abstracts

Abstracts

Plenary Session 2: Mechanisms of Bone Loss(Thursday, June 15, 0900±0930)

1. GENE THERAPY WITH IL±1Ra OR TNF-asR REDUCESOVARIECTOMY INDUCED BONE LOSS

A. W. A. Baltzer, J. D. Whalen, P. Wooley1, C. Lattermann, R.Krauspe, P. D. Robbins, C. H. Evans, 1University of Dusseldorf,Germany; 2Wayne State University, MI, USA; 3University ofPitsburgh, PA, USA

Objectives: We tested the hypothesis that gene transfer is anappropriate method to administer cytokine-inhibitors to reducingthe rapid bone loss after ovariectomy (ovx).

Methods: All experiments were conducted in six week oldfemale white balb/C mice. The effect of i.v. injection andintrafemoral vector application was tested. Adenoviral vectorsencoding IL±1Ra (1x1010 particles) were injected retroorbitally orintrafemorally, systemic levels were measured by ELISA. Theability of the adenoviral vectors to transduce bone were evaluatedby injecting Ad-b-galactosidase (Ad-LacZ) and X-gal staining. Thebody-distribution and the duration of transgene expression, wereevaluated after application of the marker gene luciferase (Ad-luc).The dry bone weight was determined twelve days afterovarectomy and Ad-IL±1Ra injection. The effect of solubletumor necrosis factor-alpha receptor (Ad-TNF-a sR) and Ad-IL±1Ra on bone resorption was evaluated by histomorphometry ®veweeks after transduction. Controls were completed with shamoperated and sham-injected animals. Analysis was done usingStudent's unpaired t-test.

Results: A highly ef®cient transduction mainly of liningosteoblasts is demonstrated. Systemic IL±1Ra levels werehigher, transgene expression was longer after intrafemoralinjection. Injection of Ad-luc demonstrates local transduction.Low levels of a transient marker gene expression were found onlyin the liver for two days and in the draining lymph nodes for twoweeks. Ovx decreased dry bone weight of humeri, tibiae, and®bulae, and the bone matrix content in humeri and femora. Boneloss was signi®cantly reduced by both, intrafemoral application ofAd-IL±1Ra (p<0.01) and Ad-sTNF-aR (p<0.01).

Discussion: We demonstrate that gene therapeutic neutraliza-tion of IL±1 and TNF-a does prevent ovarectomy induced loss oftrabecular and cortical bone. Adenoviral gene transfer to boneinduces prolonged systemic expression of transgenes in vivo,and proves to be more ef®cient than intravenous administration ofadenoviral vectors encoding marker genes. Using adenoviral-mediated in vivo delivery of cytokine-inhibitors is a new conceptthat has potential to become a treatment option in systemic orlocal bone resorption.

2. ALENDRONATE AND RISEDRONATE ARRESTKERATINOCYTE CELL GROWTH IN A MODEL FORESOPHAGEAL IRRITATION VIA EFFECTS ON CYCLIN-DEPENDENT KINASES

A. A. Reszka, J. M. Halasy, G. A. Rodan, Dept. of Bone Biologyand Osteoporosis Research, Merck Research Laboratories, WestPoint, PA, USA

Clinical and animal studies show that bisphosphonates have thepotential to irritate the esophagus. Strati®ed squamous epithe-

lium lines the esophagus, providing a protective barrier that iscontinually replaced, in part through cell growth in the stratumbasale. To model effects of nitrogen-bisphosphonates onepithelial growth, we examined the effects of alendronate (ALN)and risedronate (RIS) on normal human epithelial keratinocytes(NHEKs). While neither induced apoptosis, both inhibited NHEKgrowth. Consistent with this, the cell growth regulator, retino-blastoma (pRb), was hypophosphorylated, and p53 expressiondeclined, which accounts for inhibition of growth in the absenceof apoptosis. Expression of cdks 2 and 4, which phosphorylatepRb, declined 50%±80%. Co-precipitation analyses showed thatcdks 2 and 4 were more tightly associated with their inhibitors,p21wat1 and p27kip1. Consistent with their effects on themevalonate to cholesterol pathway and on geranylgeranylation,responses to ALN and RIS were best mimicked with inhibitors ofsqualene synthase, HMG-CoA reductase, or type I geranylgeranyltransferase. Furthermore, speci®c growth inhibitory effects ofALN were blocked through addition of LDL or geranylgeraniol.Together these data suggest that nitrogen-bisphosphonateeffects on esophageal strati®ed squamous epithelium may bemechanism-based. As with the osteoclast, geranylgeranylationmay be rate-limiting. However, unlike in the osteoclast, inhibitionof cholesterol biosynthesis may also play a critical role in theseeffects.

3. WHO LOSES MOST BONE AFTER HIP FRACTURE?

L. E. Wehren, S. I. Zimmerman, J. Yu-Yahiro, W. Hawkes, J. R.Hebel, K. Fox, D. Orwig, J. Magaziner, University of Maryland,Baltimore, MD, USA

Average bone loss after hip fracture is 2±5% in the ®rst year, butsome groups are likely to lose more bone than others. Are thereidenti®able characteristics that predict who will lose more (or less)bone mineral density (BMD) after fracture? We examined datafrom 205 women aged 65 and older in the Baltimore Hip Studiesto identify characteristics associated with differing rates of boneloss during the year following fracture. Patients or proxies wereinterviewed and had BMD measured at the contralateral hip atbaseline and 2, 6, and 12 months after fracture. Mean age of thewomen was 81.0 � 7.8 yr; 52.5% had intracapsular fractures.Comorbidity included cancer (18%), stroke (9.8%), DM (14.1%),and CVD (27.3%). Pre-fracture ADL impairments were common:25.6% in walking 10 feet; 79% in climbing 5 steps. BMD waslost at every site in the hip in the ®rst year, from 2.1%intertrochanteric BMD (.675 gm/cm2 at baseline to .659 gm/cm2)to 4.6% of femoral neck BMD (.547 gm/cm2 to .521 gm/cm2), withrate of loss greatest during the ®rst 2 months. Low levels ofpre-fracture activity, later post-surgical ambulation, serious post-operative complications, lower pre-fracture comorbidity(modi®ed Charlson index), and higher intensity physicaltherapy were associated with greater BMD loss. Women withthe lowest baseline BMD consistently demonstrated the greatestlosses, even after adjustment for other factors. This suggests thatuse of bone-strengthening medication in osteoporotic womenmay have bene®ts both before fracture, in decreasing fractureincidence, and after fracture, in improving recovery and functionaloutcome.

Osteoporos Int (2000) Suppl 2:S57–209ß 2000 International Osteoporosis Foundation and National Osteoporosis Foundation Osteoporosis

International

4. REVISION OF T-SCORE BMD DIAGNOSTIC THRESHOLDS

D. M. Black, for the Joint NOF/ISCD/ASBR Committee onSimpli®cation of the BMS Reporting

In 1992, the WHO proposed that a BMD score 2.5 SD belowyoung adult peak be the threshold of osteoporosis. This de®nitionwas intended to compare prevalence of osteoporosis acrosspopulations, when BMD was assessed using the same technique.However, the prevalence of osteoporosis (% with T-score 5±2.5)and hip fracture risk among women with BMD T-scores 5±2.5varies greatly across sites and techniques. Thus, T-score baseddiagnoses across techniques are not comparable.

To address this problem, a NOF/ISCD/ASBMR committeeevaluated several methods to increase technique comparability.The following system will create site-speci®c threshold valuesbased on hip fracture risk-the most important clinical outcome:

1. De®ne a hip fracture risk index level:5 year, age-speci®c hip fx risk among women with femoralneck BMD T-score 5±2.5.

2. Create analogous (``risk-equivalent'') thresholds for non-femoral neck techniques:

Those below the device-speci®c threshold have a hip fx risk equalto the index risk.

This process can produce a threshold BMD value for anytechnique for which there is data relating the method to hip fxrisk. For those above the threshold, the probability of FN BMD T5±2.5 should be reported, to determine referral for hip BMD. Thisrisk-based procedure is ¯exible and can incorporate other riskfactors (e.g., previous fx or biochemical bone markers).

While a number of important issues remain to be resolved, webelieve this method provides a powerful, yet ¯exible frameworkfor a uni®ed diagnostic strategy in osteoporosis.

Plenary Session 3: Bone FragilityThursday, June 15, 1100±1230)

5. IDENTIFICATION OF WOMEN AT RISK OF OSTEOPOROSIS:COMPARISON OF DIGITALX-RAY RADIOGRAMMETRY WITH DXA MEASUREMENTS ATTHE SPINE AND HIP

L. Hyldstrup, T. K. Sùrensen, L. Baeksgaard, D. Arnbjerg, J. T.Jùrgensen, Dept. of Endocrinology, Hvidovre Hospital, Universityof Copenhagen, and Pronosco A/S, Vedbaek, Denmark

BMD of the spine and hip are the best predictors of laterosteoporotic fracture. BMD can also be measured by digital X-rayradiogrammetry (DXR-BMD), a new technology that can be widelyapplied without major capital investments. In the present studyDXA-BMD were compared to DXR-BMD, using the Pronosco X-posure SystemTM with respect to identifying women with lowbone mass. 420 women were studied. 80 of these wereosteoporotic according to WHO criterias, giving a `prevalence'of osteoporosis in this sample of 20%. BMD was measured atthe spine and hip by DXA and by DXR using a standard x-rayof the distal forearm and hand. Using The WHO de®nition of5T-score 5±2.5 SD in either hip or spine as reference forosteoporosis, speci®city, sensitivity and predictive values ofDXR-BMD in the classi®cation of these women were calculated.T-scores of these 3 sites were all tightly intercorrelated. Resultsfor different cutoff levels of DXR-BMD are shown in table.

cutoff for DXR-BMD (T-score) Sensitivity Speci®city PV pos Pv neg

5±1.0 .98 .72 .42 15±2.0 .92 .88 .60 .985±2.5 .89 .93 .74 .985±3.0 .86 .96 .83 .97

In conclusion, measurements of DXR-BMD using the PronoscoX-posure SystemTM can predict risk of osteoporotic fracture aswell as conventional BMD measurements by DXA.

6. AN INTERLEUKIN 6 PROMOTER POLYMORPHISM ISASSOCIATED WITH HIP BONE LOSS IN OLDER WOMEN

J. Zmuda1, J. Cauley1, K. Stone2, M. Nevitt2, K. Ensrud3, E.Harris4, M. Hochberg5, P. Morin6, R. Saiz6, G. Joslyn6, S.Cummings2, for the SOF Research Group, 1Univ. Pittsburgh; 2SanFrancisco, CA; 3Minnesota; 4Maryland; 5Kaiser Permanente, OR;6Axys Pharmaceuticals, CA, USA

Interleukin 6 (IL6) promotes osteoclast formation and boneresorption. A single nucleotide substitution (G?C) at ±174 bp inthe IL6 promoter region affects IL6 gene transcription. Wedetermined if this polymorphism is associated with bone density(BMD) and bone loss by genotyping 3,529 women (565 yrs) in theStudy of Osteoporotic Fractures. Total hip BMD was measured anaverage of 3.5 yrs apart. Despite similar initial BMD, women withthe more active ± 174G allele experienced greater bone losscompared to women with the less active ±174C allele (Table). Thisassociation remained signi®cant after adjusting for age, bodymass index, weight change, walks for exercise, smoking, healthstatus, use of oral estrogen, glucocorticoids, and calciumsupplements, and study center (p=0.01). These results suggestthat elderly women with the ±174G allele at the IL6 gene locusexperience more rapid hip bone loss with advancing age.

Genotype (%) BMD{ Bone Loss(g/cm2) (%/yr) (mg/cm2/yr)

C/C (18.6) .76(.13) -.22(1.31) ±1.6(9.7)G/C (48.1) .76(.13) -.41(1.46) ±2.9(10.3)G/G (33.2) .76(.13) -.47(1.42) ±3.4(10.3)P (ANOVA) .765 .004 .006

{ Values are mean (�SD).

7. AGE AND BONE MINERAL DENSITY HAVE SIMILAR EFFECTSON THE RISK OF INCIDENT VERTEBRAL DEFORMITY IN MENAND WOMEN : RESULTS FROM THE EUROPEANPROSPECTIVE OSTEOPOROSIS STUDY (EPOS)

M. Lunt, T. W. O'Neill, D. Felsenberg, A. Silman, J. Reeve, theEPOS Study Group, ARC Epidemiology Unit, ManchesterUniversity, UK

Background: There are few data concerning the in¯uence of bonemineral density (BMD) in explaining gender differences in theoccurrence of osteoporotic fractures. The aim of this study was toassess the in¯uence of BMD in explaining differences in theincidence of vertebral deformity between men and women.

Methods: The subjects who took part in this analysis wererecruited from population registers for participation in a pro-spective study of osteoporosis ± the European ProspectiveOsteoporosis Study (EPOS). At baseline subjects had aninterviewer administered questionnaire, lateral spine x-rays anda subsample had BMD assessment. Repeat spinal x-rays wereperformed a mean of 3.8 years later. Radiographs were assessedmorphometrically. An incident vertebral deformity was de®ned asa vertebra that both a) showed a decrease in at least onevertebral height of more than 20% since baseline, and b) wasclassed as a new prevalent deformity (using the McCloskeymethod). The association between vertebral deformity incidence,age and BMD was determined using poisson regression.

Results: Paired spinal radiographs were available in 3000 menand 3500 women. 70 men and 141 women developed one or moreincident deformities. After adjustment to age 65 years, theincidence of vertebral deformity, per 100 person years, was in

S58 Thursday,June15, 2000

women, 1.02 (95% Con®dence Interval [CI] 0.86, 1.21) and in men,0.56 (95%CI; 0.44, 0.72). Incidence increased with age, RR=2.1(95%CI; 1.8,2.5) per decade of age. Incidence increased withdecreasing BMD, RR=1.5 (95%CI; 1.3, 1.8) per 0.1g/cm2 decreasein BMD at the spine, and RR=1.7 per 0.1g/cm2 decrease in BMDat the femoral neck and trochanter. None of these effects differedsigni®cantly between men and women. After adjusting for BMD(at any site) the difference in age-adjusted incidence in men andwomen was no longer statistically signi®cant.

Conclusions. At a given age (>50 years), the difference inincidence of vertebral deformity between men and women maybe accounted for by differences in BMD.

8. HOW WELL DOES BONE MASS PREDICT LONG-TERM RISKOF HIP FRACTURE?

D. M. Black, L. Palermo, D. Bauer, for the Study Of OsteoporoticFractures Research Group, Univ. of California, San Francisco, CA,USA

Most previous estimates of the relationship of bone massmeasurements and fracture risk have been based on only shortperiods (1±2 years) of follow-up. In order to assess the ability ofbone mass to predict longer term fracture risk, we compared therelationship of several measurements of bone mass to hipfracture risk using data from the Study of Osteoporotic Fractures(SOF). 9704 women (mean age 71 years at baseline) were enrolledin SOF in 1985±87 and have been prospectively followed for hipfractures (con®rmed by x-ray reports) since that time. Measure-ments of BMD in the proximal radius and calcaneus (Osteon,Osteometer) was measured at baseline (1985±7), BMD at thespine and hip (Hologic QDR 1000) 2 years later and calcanealultrasound (BUA, Walker-Sonix) 4 years after baseline. Wetruncated follow-up at 3, 5 and 8 years following each bonemass measurement in order to examine and compare the abilityof each measurement to predict hip fracture risk over increasingfollow-up time. Approximately 250 hip fractures occurred in the®rst 5 years of follow-up. Relative hazards per SD and 95% CI's(age adjusted) are shown below: These data suggest that bonemass measurements continue to predict hip fracture risk for aslong as 8 years although the strength of prediction varies greatlyamong measurement sites. The results also show the long-termadvantage of hip BMD for predicting hip fracture.

Bone mass measurement site

Follow-up Calcaneus CalcaneusYears FN hip Spine P. Radius (BMD) (BUA)

3 2.8 1.6 1.5 1.8 1.5(2.2,3.5) (1.3,1.9) (1.1,1.7) (1.5,2.2) (1.3,1.7)

5 2.7 1.5 1.4 1.8 1.5(2.3,3.2) (1.3,1.7) (1.2,1.6) (1.5,2.1) (1.3,1.8)

8 2.3 1.4 1.4 1.7 (Insuf®-cient

(2.0,2.6) (1.3,1.6) (1.2,1.5) (1.5,1.9) follow-up)

Basic Cell Biology

9 (1). MINERAL AND MATRIX QUALITY AND QUANTITY INILIAC CREST BIOPSIES FROM HIGH- AND LOW-TURNOVEROSTEOPOROSIS: AN FTIR MICROSPECTROSCOPIC STUDY

A. L. Boskey, E. P. Paschalis, 1Hospital for Special Surgery, NewYork, NY, USA

The quality and architecture of the mineral and matrix in bonedetermines the tissues' mechanical integrity. Fourier-transform

infrared micro-spectroscopy (FTIRM) allows analysis of mineralcontent, mineral crystal size/perfection, and collagen maturity at~10mm spatial resolution. Previous studies comparing 4mm iliaccrest biopsy sections from post-menopausal osteoporosis, vs.normal bone, showed signi®cant differences in the aforemen-tioned parameters. The present study compares the spatial andtemporal variation in mineral and matrix quality and quantity inhigh-(HOP) and low- (LOP) turnover osteoporosis. Under an IRBapproved protocol, biopsies from 8 women with HOP (ages 56±65) and 5 women and 3 men with LOP (ages 33±78) were analyzedby FTIRM. HOP was de®ned as increased resorptive surface,higher than normal numbers of osteoclasts (OC), and normalosteoblast (OB) activity. LOP was de®ned as lower than normalresorptive surface, decreased OC number, and normal OBactivity. The ®rst 60mm from the mineralizing front of formingbone (based on H&E and tetracycline labeling) were analyzed in10 mm steps. Percent differences from values at 60mm calculatedfor both mineral crystallinity and collagen maturity in HOP hadnegative values, while in LOP, differences were positive. Becausesmall crystals are resorbed ®rst, the presence of larger/moreperfect crystals and a more mature matrix in HOP indicatesimpaired OB activity. In LOP evidence of new mineral and matrixdeposition exists, providing a possible explanation for the lowerfracture incidence in LOP patients.

10 (2). TIBOLONE MODULATES SULPHATASE IN BREAST BUTNOT IN BONE

H. J. Kloosterboer, M. E. de Gooyer, N. V. Organon, Oss, TheNetherlands

Tibolone exerts tissue speci®city by selective metabolism of thecompound. Estrogenic metabolites of tibolone are formed in theliver and intestine and are responsible for the effects on bonewhereas formation of the delta±4 isomer, a progestagenicmetabolite, in the endometrium opposes the estrogenic action.The main part of the estrogenic metabolites is in the inactivesulphated form. Previous studies have shown that tibolonediminishes tumor growth in the DMBA model. This effect maybe due to a lowering of estrogenic compounds by modulation ofsulphatase activity. In bone, a full estrogenic response isobserved consistent with high biological effects suggesting thatsulphated metabolites become active in this tissue. Apparentlysulphatase in bone and breast are differntly modulated. In orderto test this hypothesis the effect of tibolone and its metabolites onsulphatase activity in breast cells (T47D) and osteoblast-like cells(MG63; HOS TE 85) were tested. Cells were incubated withestrone sulphate and the amount of intracellular estrone plusestradiol was assessed using HPLC. In these studies EMATE wasused as a positive control. A number of sulphated metaboliteswere also studied. Tibolone and its metabolites do not inhibitsulphatase activity in the two bone cells, but in breast cells astrong inhibition was observed. EMATE has a stronger inhibitoryeffect in breast cells than in bone cells. The sulphated metabolitesof tibolone show a similar discriminatory effect in the two celltypes. From these results we conclude that tibolone and itsmetabolites show tissue selectivity with respect to sulphataseinhibition. This biological effect may serve to avoid estrogenicstimulation of the breast while the estrogenic effect on boneremains.

11 (3). RALOXIFENE DIRECTLY MODULATES OSTEOBLASTSACTIVITY IN VITRO

S. Migliaccio, A. Taranta, A. Teti, D. Agnusdei, G. Spera, J. D.Termine, 1Histol & Embr, Medic Phys Depts, Univ ``La Sapienza''Rome; 2Exper Medic Dept, Univ L'Aquila; 3Eli Lilly, Florence, Italy;4Lilly Res Lab, Indianapolis, IN, USA

Raloxifene (RAL), a selective estrogen receptor modulator(SERM), prevents bone loss in postmenopausal women and

Numbers in brackets after Publication Number refers to BoardNumber

Thursday,June15, 2000 S59

ovariectomized animals. We showed that RAL decreasesosteoclastogenesis and bone resorption in vitro. Aim of thepresent study was to evaluate if RAL modulates bone formingcells functions. Osteoblasts, obtained from neonate mousecalvaria, were exposed to increasing concentrations of RAL(10±14±10±7M) for 24 hr. Medium was then changed and cellsincubated with 3H-thymidine for 4 hr. RAL induced a dose-dependent increase in the proliferation rate of the cells (maxeffect 10±11±10±8M). Moreover, osteoblasts were exposed for 24hr to RAL or 17-b-estradiol (E2, 10±10 10±7M) to evaluate effects onosteoblast function markers. At the end of incubation, RNA wasextracted and semiquantitative RT-PCR analysis performed. RALincreased in a dose-dependent manner expression of OSF±2(~10-fold), alkaline phosphatase (~2-fold), matrix proteins col-lagene-I (~3-fold) and osteopontin (~4.5-fold). E2 increasedexpression only of OSF±2 and osteopontin, suggesting that RALand E2 modulate osteoblast homeostasis with different patterns.

In conclusion, our data show for the ®rst time that RALmodulates osteoblast activity in vitro, suggesting that this SERMprotects bone mass not only inhibiting bone resorption, but alsostimulating osteoblast function.

12 (4). EVIDENCE FOR IMPAIRED COLLAGEN FORMATION INOSTEOPOROSIS: AN FTIR IMAGING STUDY

E. P. Paschalis, R. Mendelsohn, A. L. Boskey, Hospital for SpecialSurgery, New York, NY, USA

Fourier transform infrared imaging (FTIRI) is a novel techniqueallowing visualization of variations in molecular properties ofmineral and collagen in thin histologic sections (in 400x400 mm2

areas, at the 10 mm spatial resolution level). Since there is norequirement for tissue homogenization, areas to be analyzed maybe selected based on histology and histomorphometry. Examina-tion of model compounds identi®ed spectral regions describingcollagen maturity and cross-link patterns. To test the hypothesisthat there are alterations in the collagen content and compositionof osteoporotic tissues, 4mm sections from iliac crest biopsiesobtained under an IRB approved protocol from 5 normal and 19patients diagnosed with osteoporosis were analyzed by FTIRI.The areas of analyses were selected based on Hematoxylin &Eosin and tetracycline labeling to include only actively formingareas. In the normal bone, the parameter describing collagencross-links varied from 0.8 to 2.0, indicating a reproduciblecomplementary spatial and temporal variation in betweenpyridinoline and DHLNL, whereas in osteoporotic bone it fellwithin this range, but the spatial and temporal distribution wasshifted towards the highest values (1.5±2.0). Furthermore, thesedifferences were statistically signi®cant within the ®rst 30mm fromthe mineralization front, after which the values were the same.These data support our hypothesis that in addition to theabnormal resorption pro®les in osteoporosis, there may be anirregularity in the bone formation process. Such data may proveuseful to the design and choice of therapeutic protocols.

13 (5). TRIIODOTHYRONINE (T3) ENHANCES BASICFIBROBLASTIC GROWTH FACTOR (BFGF) AND PLATELETDERIVED-GROWTH FACTOR BB (PDGF-BB) ACTION INHUMAN OSTEOBLASTIC OSTEOSARCOMA (SA-OS2) CELLS

C. E. Pepene2, R. Ziegler1, L. Gozariu2, C. H. Kasperk1,1Department of Medicine, University of Heidelberg, Heidelberg,Germany; 2Department of Endocrinology, University of Cluj-Napoca, Romania

A large body of evidence suggests that thyroid hormone effectson target tissues may involve growth factors. The present studywas undertaken to determine bFGF and PDGF effects on Sa-Os2cells proliferation, as well as to test for possible interactionsbetween T3 and these skeletal growth factors on bone cell

metabolism. Subcon¯uent Sa-Os2 cells were treated with variousconcentrations of bFGF and PDGF-BB, respectively, underserum-free conditions, for 24 h. To evaluate cell proliferation,the radiolabeled thymidine incorporation assay was used.

BFGF at 10±10±10±9 ng/ml increased [3H]thymidine incorpora-tion in Sa-Os2 cells in a dose-dependent fashion (p<0.01). Incontrast, no signi®cant effect of PDGF-BB or T3 at 10±7 M onDNA synthesis in our cell culture system has been noticed.Preexposure of cultured cells to T3 for 24 h was followed byan enhanced proliferative response to bFGF. Moreover, at 10±12

±10±11 ng/ml, bFGF induced a signi®cant increase in DNAsynthesis only in combination with T3 (p<0.01). Similarly, PDGF-BB at 10±11±10±10 ng/ml increased cell proliferation in thepresence of T3 (p<0.01).

These ®ndings indicate an interaction between T3 and bFGF/PDGF-BB, thus suggesting an additional mechanism of action ofthyroid hormone on bone cells besides direct effects.

14 (6). THE EFFECT OF ESTROGEN ON FRACTURE HEALINGIN OVARIECTOMIZED RATS

P. J. Sherman, E. P. Paschalis, C. Rimnac, A. L. Boskey, Hospitalfor Special Surgery, New York, NY, USA

Estrogen therapy has been shown to prevent bone mineral lossand increase mineral content in postmenopausal women.Impaired fracture healing following ovariectomy and estrogende®ciency has also been demonstrated. In the present study theeffect of estrogen replacement on fracture healing in the estrogende®cient rat model was evaluated radiographically, biomechani-cally, and spectroscopically (Fourier transform infrared imaging-FTIRI: a technique that provides information on mineral crystal-linity and collagen cross-links at the 10 um spatial resolutionlevel). 168 ovariectomized female rats were divided into sub-cutaneous 17B-estradiol slow release tablets within three daysafter ovariectomy (1); subcutaneous estrogen pellets at the timeof fracture (2); and placebo (3). Fracture of the mid-shaft rightfemur was produced six weeks following ovariectomy. Animalswere sacri®ced at 4, 6, 8, and 12 weeks. The outcomes measuredwere delayed union rate, maximum load to failure fracture,mineral crystallinity, and collagen cross-links (DHLNL & Pyr). Atfour weeks, group (1) had a 25% delayed union rate, while (2) and(3) had rates of 50 and 55% respectively. This rate fell to less than20% in all groups at 6 and 8 weeks. By 12 weeks there were nodelayed unions radiographically. In groups (1) and (2), astatistically signi®cant linear progression of maximum load tofailure was observed from 4 to 12 weeks. The average maximumload values of (3) increased until week 8 and plateaued, whereas(1) and (2) increased to a maximum at 12 weeks. FTIRI analysissuggested that (1) was initially under osteoclastic suppression (4weeks) followed by osteoblastic upregulation in later time points(8 weeks).

Biochemical Markers

15 (7). BONE DENSITY AND BIOCHEMICAL MARKERS INRHEUMATOID ARTHRITIS

S. Akin1, O. Gulec2, M. Beyazova2, F. Korkusuz1, 1METU MedicalCenter, Ankara, Turkey; 2Department of Physical Medicine andRehabilitation, University of Gazi, Ankara, Turkey

The purpose of this study was to assess; 1) bone mineraldensity (BMD) of the hand in women with rheumatoid arthritis(RA)2) associations of BMD and serum osteocalcin, urine N-Telopeptides, pyridinoline(Pyr)and deoksypyridinoline(Dpyr).BMD of the hand was measured by dual energy x-rayabsorptiometry (Lunar DPX-IQ). 41 RA patients and 50 healthycontrols were included into the study. BMD results of thepremenopausal RA group were signi®cantly (p = 0.002) lower


than the premenopausal control group. Premenopausal RApatients had higher BMD results than the postmenopausal RApatients, however the difference was not signi®cant (p = 0.133).Dpyr was signi®cantly higher in RA patients in both groups.Independent predictors of bone mass of the RA patients werefound to be the Larsen Index, erythrocyte sedimentation rate andDpyr. Among the biochemical markers, Dpyr re¯ects boneresorption in RA patients and this seems to be the mostsigni®cant marker presenting bone loss. In conclusion, boneloss begins at the early stages of RA and hand BMD is a usefulindicator to assess bone loss even at the premenopausal stage.Furthermore, its correlation to Dpyr is signi®cant (r2=0.299).

16 (8). BIOCHEMICAL MARKERS OF BONE TURNOVER IN THEASSESSMENT OF RESPONSE TO TILUDRONATE IN PAGET'SDISEASE

L. Alvarez, N. GuanÄ abens, P. Peris, S. Vidal, I. Ros, A. Monegal, J.L. Bedini, R. Deulofeu, F. Pons, J. MunÄ oz-GoÂ mez, A. M. Ballesta,Hospital Clinic, Barcelona, Spain

Aims: To investigate the usefulness of biochemical markers ofbone turnover for monitoring tiludronate ef®cacy in the treatmentof Paget's disease.

Methods: 43 patients with Paget's disease were prospectivelystudied. All received 400 mg tiludronate daily for 3 months. Total(TAP) and bone (BAP) alkaline phosphatases, propeptide N-terminal of type 1 procollagen (PINP), serum C-terminal telopep-tide of type 1 collagen (s-CTX), hydroxyproline (HYP) and C- andN-terminal telopeptides of collagen type 1 (CTX and NTX,respectively) were measured at baseline (G0) and after 1 (G1)and 6 (G2) months after treatment. Quantitative bone scintigraphy(SAI) was performed at G0 and G2. Response (R%), normalization(N%) and variation (V%) were analyzed for all markers.

Results:

G0& N% G1& V% R% G2& V% R% N%

TAP U/L 651�108 13 237�23# ±54 81 231�17# ±49 71 61

BAP ng/mL 86�17 6.5 22�23# ±68 96 19�3# ±68 96 79

PINP ng/mL 231�42 6.5 70�15# ±70 96 60�7# ±63 92 68

HYP nM/mg 225�19 9.7 119�11# ±46 90 103�7# ±48 46 61

CTX mg/mM 614�86 32 317�55# ±47 15 251�0# ±44 11 89

s-CTX pM/L 6370�602 14 4669�489* ±26 32 4447�327# ±24 40 44

NTX nM/mM 269�40 13 9219# ±66 85 818# ±58 78 57

SAI 9201�1671 5044�908* ±44

(&=mean�SEM) *p<0.05 versus G0 # p<0.001 versus G0

Conclusions: Serum BAP and PINP and urinary NTX are themost sensitive markers for monitoring treatment ecacy withtiludronate in Paget's disease. Data of biological variation isuseful for assessing true changes induced by treatment.

17 (9). OSTEOPOROSIS TREATMENT MONITORING: UTILITYOF BONE TURNOVER MARKERS

P. R. Bainbridge, T. S. Yap, R. A. Hannon, A. Price, I Catch, N. F.Peel, R. Eastell, Northern General Hospital, Shef®eld, UK

We have introduced bone turnover markers into our nursemonitoring clinic and report here our ®rst two years' experience.Treatment monitoring may be used to identify non-respondersand enhance compliance with therapy. Bone turnover markersmay have some advantages over bone mineral density formonitoring treatment in that their response is larger and responsemay be identi®ed as early as 3 months. We measured boneformation using the bone isoform of alkaline phosphatase (bAP)and osteocalcin (OC) in the serum. We measured bone resorptionusing free deoxypyridinoline (ifDpd) and N-telopeptide of type Icollagen (NTx) in a timed morning urine sample. We studied 49patients (35 women and 14 men) with primary (30) and secondary

(19) osteoporosis (de®ned by a BMD T-score of <±2.5, or thepresence of a vertebral fracture). They were started onantiresorptive therapy with bisphosphonates (28), HRT (16) andcalcium and vitamin D (5). Bone turnover markers were measuredtwice at baseline and at 4, 7 and 10 months. A response wasde®ned as a decrease in a marker by more than the leastsigni®cant change (P<0.05, one-tailed). The percent of respon-ders and the agreement with response by spine BMD (more than4.5%, the least signi®cant change) at 10 months (kappa) areshown in the table. We found that 59% of subjects had aresponse as assessed by spine BMD.

Marker % Responders Agreement with BMD

bAP 22 0.12OC 41 0.01Dpd 34 0.17NTx 63 0.28

We conclude: 1) Bone turnover markers are useful for earlyidenti®cation of treatment response; 2) The response rate of somemarkers is similar to that of spinal BMD; 3) The agreement ofresponder as assessed by markers if poor to fair; 4) Of the fourmarkers under test, urinary NTx had the best utility for monitoringosteoporosis treatment.

18 (10). FOLLOW-UP WITH BONE TURNOVER MARKERS CANBE MISLEADING: ROLE OF REGRESSION TO THE MEAN

R. D. Chapurlat, T. Blackwell, D. C. Bauer, S. R. Cummings,University of California, San Francisco, CA, USA

Follow-up of osteoporosis treatments with bone turnover markers(MK) may sometimes be misleading because of regression to themean (RTM).

To determine how initial change in MK may be in¯uenced byRTM, we have studied patterns of variations of urinary type Icollagen breakdown products (UCTX), serum bone speci®calkaline phosphatase (BSAP) and serum osteocalcin (OC) in theMultiple Outcomes on Raloxifene Evaluation (MORE) trial, amongthe 1585 women treated with raloxifene who had MK measure-ments and were at least 70% adherent (there were 1127 controlgroup patients with MK). We applied a formula (JAMA1991;266:1678±85) yielding an adjusted change: A = (s2

d'*D) +(s2

D*d')/s2D+s2

d', D=true change; d'=post-intervention observa-tion minus the pre-intervention predicted true value; sd'

2 and sD2 =

variances of d' and D.Patients whose initial change in MK are much larger from the

mean decrease (which was of 24% at 6 months for UCTX) oftenchange in the opposite direction in the subsequent months, e.g.among women whose UCTX decreased at least 60% in the ®rst 6months, 78% had an increase in the next 6 months. Amongwomen whose UCTX increased in the ®rst 6 months, 80% had adecrease in the next 6 months. This pattern was also observedwith BSAP and OC. The formula allowed us to adjust for RTM. Forexample, for a 60% decrease in UCTX in the ®rst 6 months, afteraccounting for RTM we estimate the true decrease to be of 36%(80% con®dence interval: ±59±0%).

We conclude that measurement of MK in raloxifene treatedwomen is in¯uenced by RTM, and the formula allows to attenuatethis effect.

19 (11). PREDICTORS OF TREATMENT VALIDITY

Z. Crncevic Orlic, Endocrinology Division, University of Rijeka-Internal Clinic, Clinical Hospital Center, Rijeka, Croatia

We analyzed usefulness of biochemical parameters in differentphases in patients with senile osteoporosis and early postmeno-pause.


In retroactive study, we analyzed 20 patients taking bipho-sphonates and 20 early postmenopausal patients taking HRT. Inevery patient we have measured BMD (bone mineral density) byDPX, calcium, phosphorus, magnesium in serum and urine, bonealkaline phosphatase, osteocalcinin serum and piridinoline anddeoxy piridinoline in urine before treatment and one year later.

There were no signi®cant differences in values of serumandurine calcium, phosphorus and magnesium before and aftertreatment. Multivariate analysis showed that the combination offour (Ca, P, Mg/creatinine ratio, piridinolin, deoxy piridinolin incomarison with BMD) differentiated bone content before and afterbisphosphonates and HRT treatment.

Biochemical parameters used together and with other clinicalfeatures can help to indicate bone loss and validity of treatment.

20 (12). EFFECT OF CONTINUOUS SEQUENTIALTRANSDERMAL ESTRADIOL/ NORETHISTERONE ACETATEVS. ESTRADIOL HRT ON BONE MARKERS INPOSTMENOPAUSAL WOMEN

P. Delmas, D. F. Archer, Service de Rhumatologie, HopitalEdouard Herriot, Lyon, France; 2Department of Obstetrics andGynecology, Eastern Virginia Medical School, Norfolk, VA, USA

OBJECTIVES: To compare the effects of a combination estradiol/norethisterone acetate (E2/NETA) transdermal patch given in asequential regimen on biochemical markers of bone turnoverversus an E2-only patch in healthy postmenopausal women.

METHODS: A 52-week multicenter, parallel-group, randomized,double-blind study enrolled 646 postmenopausal women withvasomotor symptoms. Subjects received either transdermal E2 50mg/day twice weekly for weeks 1±4, or a combination of E2 50 mg/day twice weekly for weeks 1±2 and a patch releasing E2 50 mg/day plus NETA 140, 250 or 400 mg/day for weeks 3±4 of eachcycle. Serum bone formation markers (alkaline phosphatase andosteocalcin) and urinary bone resorption markers (N- and C-telopeptide) were measured at baseline, week 24 and week 52.

RESULTS: The C-telopeptide/creatinine and N-telopeptide/creatinine ratios were reduced from baseline to week 52 withthe majority of the reductions occurring within 24 weeks. Meanbone formation levels decreased in all groups by week 24 andfurther decreased by week 52.

CONCLUSIONS: A sequential E2/NETA transdermal HRT*regimen was as effective as transdermal E2 alone for exertingpositive bene®cial effects on biochemical markers of boneresorption and formation.

*trademark: ESTALIS1 SEQUI.

21 (13). OVERVIEW OF THE EFFECT OF TRANSDERMALESTRADIOL AND NORETHISTERONE ACETATE VS.ESTRADIOL TRANSDERMAL HRT ON BONE MARKERS INPOSTMENOPAUSAL WOMEN

P. Delmas1, D. F. Archer2, E. G. Luftkin3, 1Hopital Eduard Herriot,Service De Rhumatologie, Lyon, France; 2Department ofObstetrics and Gynecology, Eastern Virginia Medical School,Norfolk, VA, USA; 3Department of Endocrinology, Mayo Clinic,Rochester, MN, USA

OBJECTIVES: Two studies compared the effect of combinationtransdermal estradiol (E2) 50 mg/day, with 1 of 3 doses ofnorethisterone acetate (NETA) 140, 250 or 400 mg/day comparedwith E2 50 mg/day alone on markers of bone metabolism inpostmenopausal women.

METHODS: In one study, estradiol was administered continu-ously with NETA whereas in the other study, estradiol wasadministered throughout the cycle, and NETA was administeredin weeks 3 and 4 of each cycle. For each study, markers of boneformation (serum bone speci®c alkaline phosphatase, totalosteocalcin) and bone resorption (N-and C-telopeptide) weremeasured at baseline and weeks 24 and 52.

RESULTS: Mean bone turnover in all groups from both studiesdecreased from baseline to week 52. At baseline, bone turnoverexceeded the premenopausal range; however, under E2/NETAand E2, the markers approached the normal premenopausalrange.

CONCLUSION: A continuous combined or continuous sequen-tial E2/NETA transdermal HRT* regimen is as effective astransdermal E2 alone for exerting positive bene®cial effects onbiochemical markers of bone resorption and formation.

*trademarks: ESTALIS1 (continuous combined) ESTALIS1

SEQUI (sequential)

22 (14). RELATIONSHIP BETWEEN BIOCHEMICAL ANDHISTOMORPHOMETRIC PARAMETERS OF BONE TURNOVER

T. Eidner, G. Lehmann, P. Oelzner, A. Muller, G. Stein, G. Hein,Department of Internal Medicine IV, Section Rheumatology &Osteology, Friedrich-Schiller-University of Jena, Germany

Parameters of bone turnover provide additional information fordifferential diagnosis and therapy of metabolic osteopathies.Bone turnover can be assessed by biochemical markers orinvasively by histomorphometry. Therefore we investigated therelationship between biochemical and histomorphometric para-meters of bone turnover.

In 186 patients (126 women, age 58.9�10.6 yr, 60 men 49.9�13.4yr), who had undergone an iliac crest biopsy, we determined theexcretion of desoxy-pyridinolin in urine (DPyd, HPLC, nmol/mmolKrea) as marker of bone resorption and serum osteocalcin (OC,n=126) as marker of bone formation. Included histomorphometricparameters were: osteoid surface (OS), osteoblast coveredsurface (ObS), tetracyclin labeled surface (TCO), mineral apposi-tion rate (MAR), resorption surface (ES), osteoclast coveredsurface (OcS) and number of osteoclasts (NOc).

We found a weak, but signi®cant correlation of OC with OS,ObS (r = 0.22, p = 0.02) und TCO (r = 0.35), but not with resorptionmarkers or MAR. Similar correlation was found for DPyd with OcS(r = 0.20) und NOc (r = 0.20), but not with ES. DPyd also correlatedwith parameters of osteoblast function (OS: r = 0.27, ObS:r = 0.22).

In conclusion, biochemical markers (OC, DPyd) and histomor-phometric parameters of bone turnover showed only weakcorrelations. It has to be supposed, that either biochemicalmarkers are only poor markers of histomorphometrically mea-sured bone turnover or histomorphometry of iliac crest onlypoorly re¯ects bone turnover of the whole skeleton.

23 (15). THE EVALUATION OF THE EFFECTS OF CALCIUM,MAGNESIUM AND VIT D DERIVATES ON BONE DENSITY ANDBIOCHEMICAL MARKERS OF BONE TURNOVER IN CASES OFPOSTMENAPAUSAL OSTEOPOROSIS

N. Eskiyurt, S. Akt, A. Aydogan, B. Aksac, N. Sen, G. AkyuÈ z, A.

ÈOncel, 1Ist. Med. Fac. Dept. of Physic. Med. and Rehabil;2Marmara Med. Fac. Dept. of Physic. Med. and Rehabil, Istanbul,Turkey

The aim of this study is to evaluate the effectiveness of combinedtherapies for 12 months consisting of Magnesium (magnesiumcitrate 300 mgs/day); Calcium (1000 mgs/day) plus Magnesium(300 mgs/day) and Calcium plus Magnesium plus Vit. D derivate(0.50 mgs/day) on the marker of bone turnover and bone density.

45 patients of postmenapausal osteoporosis with a mean ageof 56, 7�5,43 years and the duration of menapause 12.4�2.32were randomly chosen and randomly distributed into threedifferent therapy groups. All these patients were evaluated byblood levels, markers of bone formation (osteocalcin, bonealcalyne phosphatase) and resorbtion (deoxypridinolin, pridinolin)and bone density measurements at the beginning and the end ofthe treatment period.


The result obtained at the end of 12 months showed astatistically signi®cant increase (p<0.001) in blood magnesiumlevels and a signi®cant inhibition (p<0.01 and p<0.05) of themarkers for both bone formation and resorbtion in all groupscomparing with the initial levels. Bone density measurement inlumbar spine and proximal femur at the end of 12 monthsrevealed that the increases seen in the third group (Ca + Mg + Vit.D derivate) were signi®cantly higher than the remaining groups.

In conclusion it can be said that the 12 months treatmentprogram consisting of Magnesium, Calcium and Vit. D derivates ismore effective in inhibiting the markers of bone turnover and theresults of the bone density measurements con®rm this fact.

24 (16). SHORT-TERM EFFECTS OF A NEW SYNTHETICCONJUGATED ESTROGENS (CENESTIN) ON BIOCHEMICALMARKERS OF BONE TURNOVER IN EARLYPOSTMENOPAUSAL WOMEN

P. Garnero1, R. E. Stevens2, S. A. Ayres2, K. V. Phelps2, 1SYNARC,Lyon, France; 2Duramed Pharmaceuticals, Inc, Cincinnati, OH,USA

In a double-blind, placebo-controlled, single-center, clinicalstudy, the effects of a new synthetic conjugated estrogens, A(Cenestin), were evaluated at baseline (3 measurements at day ±2,day ±1 and day 0), and days 30, 60 and 90 on the followingbiochemical markers: serum osteocalcin(OC)measured by auto-mated immuno¯uorescent assay(Kryptor,Cis), serum bone alka-line phosphatase by ELISA (BAP,Metra), serum N-terminalpropeptide of type I collagen(PINP)by RIA (Orion), urinary N-telopeptide of type I collagen (U-NTX) by automated ELISA (VitrosEci, Ortho-Clinical Diagnostics)and serum C-telopeptide of type Icollagen (S-CTX) by automated electrochemiluminescenceimmunoassay(Elecsys,Roche). Fifty healthy, menopausalwomen, 1±3 years after cessation of menses, 40±65 years ofage, were randomly assigned to receive either 0.625 mg/dayCenestin (n=35) or placebo (n=15). The women concomitantlyreceived 500 mg calcium supplement and one multi-vitamin daily(200 mg calcium, 400 IU Vit D). As shown in the table, Cenestinproduced a signi®cant decrease of bone resorption markers (U-NTX and S-CTX) from days 30, 60 and 90 (S-CTX only). Asexpected the decrease of bone formation markers, BAP and PINPwas delayed and signi®cant from day 60. Cenestin reduced theprogression in serum OC levels observed in the placebo group byDay 30 (+16.7 vs +0.4 in placebo and Cenestin, respectivelyp<0.02) to Day 90 (+45% vs +7.4% p<0.0001). In conclusion, thisstudy indicates that this new synthetic conjugated oral estrogendecreases bone turnover in early menopausal women, suggestingthat this treatment may be useful for the prevention ofmenopausal osteoporosis.

% Change from Baseline (*p<0.05, **p<0.01 vs placebo)

OC BAP PINP U-NTX S-CTX

30 days 0.4* ±6.9 0.2 ±31.4* ±34.2*60 days 6.5* ±12.5** ±15.4** ±58.0* ±17.6**90 days 7.4* ±20.2* ±24.5* ±34.1 ±16.9**

25 (17). BONE ALKALINE PHOSPHATASE AND VITAMIN DRECEPTOR GENE RESTRICTION POLYMORPHISM IN MALEADOLESCENTS

J. Guillemant, H. T. Le, A. Allemandou, S. Cabrol, G. Pieres, A.Raisonnier, S. Guillemant, 1Faculte de Medecine Pitie-Salpetriere,Hopital Trousseau, Paris, AFASEC, Chantilly, France

The association between BMD and VDR gene polymorphisms hasbeen studied extensively and has generated controversies. At the

end of puberty, the peak bone mass is nearly achieved and isconsidered as a major determinant of the future risk ofosteoporosis. We therefore decided to study the bone formationas a function of VDR gene polymorphism in young maleadolescents. Ninety-four caucasian young males (age: 14±17y;Tanner's stage 2±5) were explored. Their serum speci®c bonealkaline phosphatase (B-ALP) level was measured and their VDRBsmI restriction genotype was determined. Since B-ALP levelsvary according to sexual maturation and plateaus betweenTanner's stages 3 and 4, adolescents at these stages of sexualmaturity were preferently chosen. Furthermore, we checked thatthe sexual stages were equally divided among the threegenotypes. The bb group (n = 33) had the highest B-ALP level(90.3�34.1 mg/L) and the BB group (n = 14) the lowest one(65.9�20.3 mg/L); the difference between the two groups wassigni®cant (p <0.01). The Bb group (n = 48) was intermediate (B-ALP: 80.3�26.8 mg/L) and the difference between the Bb and theBB group was signi®cant (p <0.05). A very signi®cant (p <0.0001)relationship between the B-ALP serum concentrations and theBsmI genotype was observed. The present results suggest that,during the pubertal burst of growth, BB homozygotes boys have aless active bone turn-over than both bb homozygotes and Bbheterozygotes. It remains to check whether these differences inskeletal metabolism are associated with differences in peak bonemass gain.

26 (18). LOW-FAT DIETARY INTERVENTION DECREASESESTRADIOL BUT DOES NOT INCREASE MARKERS OF BONETURNOVER IN POSTMENOPAUSAL WOMEN

R. D. Jackson, D. Zaqqa, The Ohio State University, Columbus,OH, USA

Estradiol is an important determinant of bone mineral density(BMD) and subsequent risk for fracture in postmenopausalwomen. Previous data suggest that both total calories andpercent calories from dietary fat are predictors of estradiol (E2)and cholesterol intake may be a predictor of total hip BMD. Thepurpose of this study is to determine the impact of a reduction indietary fat on E2, sex hormone binding globulin(SHBG) andmarkers of bone turnover in postmenopausal women. Sixteenwomen [57.7+5.6 yrs of age, 6.7+5.1 yrs post-menopause, bodymass index(BMI) 28.7+7.7] participated in a nine month pro-spective study. All subjects followed their usual diet for 3 mo andwere then placed on a low-fat diet using a group interventionmodel for 6 mo. Testing for BMI, plasma E2, SHBG, osteo-calcin(OC), bone speci®c alkaline phosphatase(BSAP) and urinaryN-telopeptide(N-Tx) was performed at baseline and 3 monthintervals. Baseline dual energy xray absorptiometry (Lunar DPX,Madison, WI) was performed to determine spine and hip BMD,lean body mass and % body fat for use as covariates in analyses.Food frequency questionnaires were obtained at baseline andafter 3 and 6 months of dietary intervention. The results throughthe ®rst 3 months of diet intervention are presented. Theintervention was successful in decreasing the dietary fat intakeof the subjects from a baseline of 42.3+7.8% to 26.7+3.8% after 3mo of the low-fat diet. Although the diet was designed to beisocaloric, during the intervention, subjects had a signi®cant lossof weight (±3.1+3.7kg; p<0.0007) and decrease in BMI (p<0.0005).E2 levels were 10.46 pg/ml at baseline and decreased by 24.2%.There was no signi®cant change in SHBG. Despite the decreasein plasma E2, the urinary N-Tx, OC and BSAP did not changesigni®cantly with the low-fat diet. In summary, a low-fat diet candecrease plasma E2 but the magnitude of change in E2 noted inthis study had no signi®cant adverse effect on markers ofbone resorption or bone formation. Future studies are neededto determine if there is a critical level for low-fat intake or athreshold for decreasing E2 that might impact changes in boneturnover.


27 (19). THE EFFECT OF INTRANASAL SALMON CALCITONINTHERAPY ON TARTRATE RESISTANT ACID PHOSPHATASE INPOSTMENOPAUSAL WOMEN

O. Kuru1, Y. Kutlu1, A. Bedir2, A. Bilgici1, M. Tasdemir1, 1Dept. ofPM&R, Ondokuz Mayis University, Medical Faculty; 2Dept. ofBiochemistry, Ondokuz Mayis University, Medical Faculty,Samsun, Turkey

Background and objective: Acid phosphatase is a lysosomalenzyme which is present primarily in bone, prostate, platelets,erythrocytes, and spleen. The bone acid phosphatase is resistantto L(+)-tartrate, whereas the prostatic isoenzyme is inhibited. Inplasma, tartrate-resistant acid phosphatase (TRAP) originatespartly from osteoclasts and is increased after oopherectomy andin a variety of bone disorders with increased turnover. Salmoncalcitonin is a well known inhibitor of bone resorption. The aim ofthis study was to determine the value of monitoring TRAP inserum during intranasal salmon calcitonin therapy.

Methods: Forty postmenopausal women aged 51.4�0.8 yr andhad been menopausal for 4.6�0.2 yr without antiresorptivetherapy were included in the study. They all had a BMD <1 T-score at the spine (DEXA). All patients received intranasal salmoncalcitonin 100 IU/d and calcium 1000 mg/d for six months. TRAPwas measured at baseline and at the end of the study period bykinetic spectrophotometric method that uses a-naphtyl phos-phate as substrate (Boehringer-Mannheim/Hitachi 747). Totalserum alkaline phosphatase (tALP), serum calcium (Ca) andphosphorus (P) were also quanti®ed by standart techniques.

Results: There was a statistically signi®cant decrease in valuesof serum TRAP before and after treatment (2.49�0.1 and2.08�0.08, respectively)(P<0.001). We couldn't ®nd any signi®cantdifferences in values of serum tALP, Ca and P before and aftertreatment (p>0.05).

Conclusion: We can say that TRAP can be effectively usedto assess the decrease in bone resorption in response tocalcitonin.

28 (20). THE RELATIONSHIP BETWEEN MARKERS OF BONEMETABOLISM AND BONE ACQUISITION IN PERIPUBERTALGIRLS: A ONE-YEAR PROSPECTIVE STUDY

M. Lehtonen-Veromaa, T. MoÈ ttoÈ nen, K. Irjala, I. Nuotio, A. Leino,J. Viikari, 1Turku University Central Hospital; 2University of Turku,Finland

The purpose of this one-year prospective study was to evaluatethe association between biochemical markers of bone formationand resorption with bone mineral acquisition in healthy 155peripubertal Caucasian girls aged 9±15 years. Height, weight,stage of puberty, and the amount of leisure-time physical activitywere recorded. The bone mineral density (BMD) of the femoralneck, the greater trochanter, and the lumbar spine weremeasured by dual energy x-ray absorptiometry (DXA). Biochem-ical markers of bone formation in serum [osteocalcin (OC), bone-speci®c alkaline phosphatase (BAP), aminoterminal propeptide oftype I procollagen (PINP)] and bone resorption [C-terminaltelopeptide of type I collagen (CTX)] were measured. Thecorrelation of the baseline markers of bone metabolism andone-year increase of BMD were moderate at the lumbar spine(r = 0.44±0.63, p<0.001), at the femoral neck (r = 0.35±0.47,p<0.001), and at the greater trochanter (r = 0.28±0.42, p<0.001).When the one-year increase of BMD (DBMD) of the femoralneck and lumbar spine were divided into tertiles, the baselineconcentration of serum OC, BAP, PINP, and CTX were sig-ni®cantly higher in the highest DBMD tertile than in the lowest. Weconclude, that the high rate of bone turnover re¯ected assigni®cantly elevated bone markers is associated with a highone-year bone gain in peripubertal girls.

29 (21). COMPARISON OF FOUR BIOCHEMICAL MARKERSFOR THE ASSESSMENT OF THE EFFECT OF MENOPAUSEAND/OR THYROXINE (T4) TREATMENT ON BONE TURNOVER

K. Mavroudis, F. Papandroulaki, P. D. Papapetrou, 2nd Division ofEndocrinology, Alexandra Hospital, Athens, Greece

Menopause and T4 are known to accelerate bone turnover. Wemeasured serum osteocalcin (OC) and urinary free deoxypyridino-line (DPYR), the C-terminal (CTx, CrossLaps1) and the N-terminal(NTx, Osteomark1) telopeptides of collagen in double-voidedmorning fasting urine from 53 premenopausal (PRM) and 61postmenopausal (POM) control women and from 70 treated withTSH suppressive doses of T4 for simple goiter (37 PRMT4 and 33POMT4). All the patients had normal serum Ca, P, and PTH. TTest, X2 and Receiver Operating Characteristic (ROC) were usedto compare the ability of the markers to discriminate among thegroups.

Results and conclusions. Menopause caused a signi®cant riseof all four markers, although more pronounced for CTx. The effectof T4 on the markers was compared before and after themenopause: Mean Z-score values for each marker were similarbetween T4-treated PRM and POM women; however, in thePREMT4 group Z-score of CTx was signi®cantly higher than NTxor DPYR. ROC analysis showed that the performance of the threebone resorption markers was generally similar with slight super-iority of CTx. A highly signi®cant positive linear correlation wasfound between NTx and CTx (p<0.0001) in all four groups.

30 (22). SERUM BONE-RELATED DEGRADATION PRODUCTSFROM C-TERMINAL TELOPEPTIDES OF TYPE I COLLAGEN(bCTX) IN MEN

S. Minisola1, M. T. Pacitti1, P. Caravella1, S. Barberi1, S. Dionisi1,D. Diacinti1, S. Mazzaferro1, V. Carnevale3, A. Scillitani3, E.Romagnoli2, G. F. Mazzuoli1, 1Dipartimento Di Scienze Cliniche,Universita -La Sapienza-; 2Ospedale S.G. Battista, Rome;3Ospedale -Casa Sollievo della Sofferenza-, S.G. Rotondo, Italy

This study was carried out in order to evaluate serum levels ofbCTx in normal male subjects and patients with various metabolicbone disease. We enrolled 93 normal subjects (NS), 10 patientswith primary hyperparathyroidism (PHPT), 12 with establishedosteoporosis (OP), 6 with established osteoporosis while onalendronate therapy (OPT), 3 with humoral hypercalcemia ofmalignancy (HHM) and 20 with chronic renal failure (CRF, GFRvalues <70 ml/min). Each patient had a serum sample to measureserum bCTx (CrossLapsTM One Step ELISA, Osteometer BiotechA/S) and TRAP (by spectrophotometric assay). We found that, inNS, serum values of bCTx with age were best expressed by anexponential equation (y=6558.7e±0.0184x p<0.001). There was aninverse correlation between bCTx and GFR values in the rangeconsidered (y=32329e±0.0219x p<0.001). The table shows meanvalues 1SD of the two markers. In patients with PHPT and OP, Z-score values of bCTx (PHPT=6.8�6.4;OP=5.7�2.5) were signi®-cantly higher than those of TRAP (PHPT=1.3�1.7, p<0.02;OP=1.85�2.8, p<0.003). Our results suggest that an increase ofbone resorption might not be the main mechanism leading tobone loss with aging in males; the measurement of bCTx shouldnot be used in patients with GFR values below 20 ml/min. In menthe measurement of bCTx seems to be superior to that of TRAP indetecting subtle changes of bone turnover, especially thoseoccurring in osteoporotic patients.

AGE bCTx (pmol/l) TRAP (U/l)

NS 46�13 3152�1581 9.8�2.7OP 73.1�8.9 7121�1968* 14.8�7.6*OPT 65.5�5.8 2884�1174** 11.1�1.3PHPT 63�18 9609�7425* 13.4�4.6*CRF 48.1�13.4 21234�14192* 15.7�3.5*HHM 46�2.6 18082�4651* 17.9�6.7*

* p<0.0001 vs NS; ** p<0.0001 vs OP


31 (23). THE ACUTE BIOCHEMICAL RESPONSE OFPOSTMENOPAUSAL ``BONE LOSERS'' AND ``BONE GAINERS''TO A BOUT OF EXERCISE

N. M. Murphy, R. Donnelly, K. Cashman, Waterford Institute ofTechnology, Waterford, Ireland; 2University College Cork, Cork,Ireland

The purpose of the study was to investigate the acute effect ofexercise on biochemical markers of bone turnover in postmeno-pausal women whose prior rate of bone loss/gain was known.Following broadband ultrasound attenuation (BUA) measure-ments taken at the calcaneus over an 18 month period in 60women, 8 postmenopausal women were identi®ed for whom BUAdecreased signi®cantly (``bone losers'', ±5.4% to ±13%), and BUAincreased signi®cantly in 7 postmenopausal women (``bonegainers'', +8.2% to +21.9%).Twenty four hour urine samplestaken the day before, the day of, and the day after exercise wereanalysed for pyridinoline (Pyr) and deoxypyridinoline (Dpyr)crosslinks, markers of bone resorption. At these same timeperiods, fasting blood samples were taken for analysis ofosteocalcin (bone formation).The hour-long exercise bout con-sisted of jumping, skipping, stepping, resistance and aerobicwork. In the ``bone losers'' urinary Pyr was signi®cantly lower 2days post-exercise (mean (SEM), 121(7) to 102(10) nmol/d,p = 0.004), with no change in the ``bone gainers''. Osteocalcinlevels did not change in either group. Thus, exercise appears toslow bone resorption in postmenopausal women with a disposi-tion towards rapid bone loss.

32 (24). A HEAD-TO-HEAD COMPARISON OF THE EFFECTS OFFOUR WEEKS OF TREATMENT WITH ALENDRONATE ORRISEDRONATE AT THEIR PAGET'S DISEASE DOSES ON ABIOCHEMICAL MARKER OF BONE TURNOVER

T. A. Musliner1, F. L. Lanza2, H. Schwartz3, B. Sahba4, D. Y.Graham5, R. Reyes1, H. Quan1, 1Merck Research Labs, Rahway,NJ; 2Houston Institute for Clinical Research, Houston, TX; 3MiamiResearch Associates, Miami, FL; 4California ResearchFoundation, San Diego, CA; 5Baylor College of Medicine,Houston, TX

The nitrogen-containing bisphosphonates alendronate (ALN) andrisedronate (RIS) have been approved for the treatment of Paget'sdisease of bone at doses of 40 and 30 mg/day, respectively. ALNhas also been approved for the treatment and prevention ofosteoporosis (at doses of 10 and 5 mg/day, respectively), and RIShas been studied for the same indications at a maximum dose of5 mg/day. While no head-to-head comparisons of ALN and RISfor effects on bone mineral density (BMD) or bone turnover havebeen reported, observed BMD changes over a range of doses innumerous clinical trials suggest that ALN is at least as potent asRIS on a mg-for-mg basis, and also suggest that ALN 10 mg hasgreater ef®cacy than RIS 5 mg.

In the present study, serum C-telopeptide of type 1 collagen(CTX; CrossLapsTM) was measured on fasting, morning serumsamples obtained at baseline and day 29 in a double-blind,placebo-controlled study in which postmenopausal women (63%)or men (37%), ages 45 to 80, were randomized to 28 days oftreatment with ALN 40 mg/d (n=90), RIS 30 mg/d (n=89), orplacebo (PBO; n=34). The results for all subjects with bothbaseline and follow-up CTX values were as follows: Thereductions in CTX with both ALN and RSN relative to placebowere highly statistically signi®cant at p<0.001. The ALN vs RISbetween-treatment difference of 5.7% (95% CI 1.9, 9.5) was alsohighly signi®cant at p = 0.003. We conclude that at therecommended Paget's treatment doses administered over a 4-week period, ALN is a signi®cantly more effective inhibitor of boneresorption than RIS.

Treatment N Percent Changeof CTX fromBaseline

95% CI for% Change

Alendronate 40 mg/day 83 ±78.7 (±81.0, ±76.2)Risedronate 30 mg/day 87 ±73.0 (±75.8, ±69.9)Placebo 34 8.6 (±8.9, 29.4)

33 (25). CHANGES IN BONE TURNOVER FOLLOWINGOSTEOPOROTIC HIP FRACTURE IN ELDERLY MEN: THECORNWALL HIP FRACTURE STUDY

Ira Pande1, D. L. Scott2, C. Moniz2, T. W. O'Neill3, M. J. Davis1, A.D. Woolf1, 1Royal Cornwall Hospital, Truro; 2King's College,London; 3ARCUnit, Manchester, UK

Aims: 1) investigate the change in bone markers following hipfracture in elderly men and 2) compare it with the normalphysiological process in a control group.

Methods: 100 consecutive male admissions with a low traumahip fracture aged 50 and over were recruited as cases.Simultaneously, 100 matched controls were randomly selectedfrom a GP register. Fasting blood and urine samples werecollected for measuring bone markers [osteocalcin (OC), urinarydeoxypyridinoline (U Dpd)] initially and at 6 months. In casesbaseline samples were within 48 hours of the fracture. BMD wasmeasured by DXA densitometer (Hologic QDR±1000) at both thelumbar spine and femur; in cases this was within one week offracture.

Results: Fracture cases were older, had lower weight, BMI &BMD compared to controls (p<0.01). OC and U Dpd had a modestcorrelation with each other (rs=0.36, p<0.01). In controls, OC andU Dpd were within the normal range of the laboratory at baseline[mean(SD) OC: 8.3(6.2)ng/ml; U Dpd: 5.5(3.5)nM/nM] and 6months. In cases U Dpd was signi®cantly elevated within 48hours of the fracture [(mean(SD) 11.2(6.1)nM/nM] and exhibited afurther rise at 6 months (Wilcoxon signed ranks test, p<0.01).Serum OC was within the normal range both around the fracture[mean(SD) 5.6(2.7)ng/ml] and at 6 months [mean(SD) 8.2(5.3)ng/ml], but a signi®cant rise was seen between the two time points(Wilcoxon signed ranks test, p<0.01). Using multiple logisticregression there was a 40% increase in the risk of hip fracture perunit increase in U Dpd (Odds Ratio 1.41, 95%CI 1.2, 1.6). Similarly,there was a reduction in risk of fracture by 18% per ng/mlincrease in OC (OR 0.82, 95%CI 0.73, 0.92). This risk/protectionconferred was unchanged after controlling for age & BMD.

Conclusion: Men living in community exhibit normal boneremodelling. Immediately after hip fracture changes in boneresorption marker preceede formation supporting bone remodel-ling & callus formation associated with healing. Continued boneloss at 6 months may argue the need to initiate anti-resorptivetherapy in these individuals to reduce risk of further fractures.Raised osteocalcin is protective and elevated urinary deoxypyr-idinoline a risk factor for low trauma hip fracture. The risk/protection conferred is independent of age and bone density.

34 (26). BONE MINERAL DENSITY IN ASTHMATIC CHILDRENTREATED WITH INHALED BUDESONIDE OR NEDOCROMIL. A1-YEAR PROSPECTIVE, DOUBLE-BLIND, RANDOMIZEDSTUDY

S. Pedersen, L Agertoft, Department of Pediatrics, KoldingHospital, Kolding, Denmark

The aim of our study was to compare the effect of long-termtreatment with inhaled budesonide via Turbuhaler* (BUD) andnedocromil sodium (NED) pMDI on bone mineral density (BMD).Design: Randomized, double-blind, parallel group study. 91


asthmatic children (34 F, 7 ± 11 years, Tanner stage 52) wererandomized to BUD 400 mg/day for 3 months, followed by 9months at 200 mg/day, or NED 8 mg/day for 12 months. BMD wasmeasured with DEXA (total body) at baseline, after 7 months andone year. Utrasound (US) of the calcaneous and bone markerswere measured on the same occasions. Results: No statisticallysigni®cant differences in BMD or biochemical markers were foundbetween the two groups: Conclusion: One year of treatment withinhaled budesonide at daily doses of 2±400 mg and nedocromilsodium 8mg/day had similar effects on BMD and markers of boneturnover in asthmatic children.

Estimated dierence between groups for changes (BUD-NED):

BMD: Total body(%) ±0.34 (95% CI:±1.21; +0.52; (p = 0.433))

Ultrasound:

SOS (m/sec) ±6.8 (95% CI: ±21.1; +7.5; (p = 0.467))

BUA (dB/MHz) +5.7 (95% CI: ±0.3; +11.7; (p = 0.06))

Stiness (%) +2.4 (95% CI: ±3.0; +7.8; (p = 0.378))

Bioch. Markers:

Osteocalcin (%) ±51.6 (95% CI: ±52; +148; (p = 0.293))

P1CP (%) ±2.9 (95% CI: ±17.8; +11.9; (p = 696))

1CTP (%) ±6.5 (95% CI: ±16.3; +3.2; (p = 0.187))

35 (27). THE DIURNAL RHYTHM OF 1,25-DIHYDROXYVITAMIND

L. Rejnmark, P. Vestergaard, L. Heickendorff, F. Andreasen, L.Mosekilde, Aarhus Bone and Mineral Research Group andCentre of Clinical Pharmacology, Aarhus University Hospital,Denmark

Previous studies have not demonstrated a diurnal variation inserum levels of 1,25-dihydroxyvitamin D (S±1,25(OH)2D). Materi-als and methods: 12 healthy postmenopausal women. Blood andurine were sampled with intervals for 24hs for determination of S±1,25(OH)2D and serum levels of PTH (S-PTH), calcium (S-Ca), andphosphate (S-Ph), and renal excretions of calcium (U-Ca) andphosphate (U-Ph). Results: S±1,25(OH)2D exhibited a circadianrhythm (p<0.001): a decrease at night-time to a nadir in the earlymorning (at 4 a.m.: 99�12 pmol/1), followed by a rapid increase toa plateau at daytime (peak at 4 p.m.: 113�13 pmol/1) 14% abovenadir level (peak vs. nadir: p = 0.004). The diurnal rhythm of S-Ph(p<0.001) varied inversely with S±1,25(OH)2D (R = ±0.23, p = 0.03),whereas the rhythm of U-Ph (p<0.001) correlated positively withS±1,25(OH)2D (R=0.25, p = 0.002). The rhythm of S-PTH (p = 0.005)and S-Ca (p = 0.009) varied inversely (R=±0.24, p = 0.02). Con-clusion: By the disclosure of a circadian rhythm of S±1,25(OH)2D,all major hormones and minerals related to the calcium home-ostasis now have been demonstrated to shown signi®cant diurnalvariations. Furthermore, our study shows the interrelationshipbetween these parameters.

36 (28). RELATION BETWEEN BONE TURNOVER MARKERS:URINARY CALCIUM/CREATININE AND DEOXYPYRIDINOLINE/CREATININE

J. A. RoÈ man, C. FernaÂ ndez, J. Ruiz, C. CatalaÂ n, C. Vivas, L. Abad,J. MillaÂ n, A. Fuertes, 1Hospital Universitario Dr. Peset, Valencia,Spain

PURPOSE: The use of new markers of bone resorption morespeci®c and sensitive is, in our setting, restricted to the hospitallaboratories and is not available in Primary Care centers. For thisreason we have analyzed the relation between the bone turnovermarkers available in Primary Care (urinary calcium/creatinine, Ca/Cr) with those restricted to the hospital (Deoxypyridinoline/Creatinine, D-pyr/Cr).

METHODS: We have studied consecutively all patients sub-mitted with the suspicion of osteoporosis (OP) to our unit in athree months period. We have done in all patients bone mineraldensity measurements using DEXA (Norland) to establish thediagnosis of osteoporosis according to HMO criteria and we havemeasured Ca/Cr and D-Pyr/Cr levels in a sample of 2 hours urine,after 12 hours fasting. To analyze the results between both urinarymarkers we have used the correlation coef®cient of Pearson (r).P values <0.05 were considered signi®cant.

RESULTS: 60 patients were studied (58 female), with a meanage of 59.9�10.0 (39±76)

CONCLUSION: We have found a positive correlation betweenCa/Cr and D-pyr/Cr levels for the whole group and for patientswith OP. Ca/Cr levels are a valid method for the evaluation ofbone turnover in patients with OP in Primary Care.

Groups (n) r (p) Ca/Cr D-pyr/Cr

Total patients (60) 0.42 (p = 0.001) 0.16+0.07 7.7+4.5Osteoporosis (35) 0.43 (p = 0.02) 0.16+0.06 7.9+5.3Osteopenia (12) 0.18 (p = 0.18) 0.18+0.1 7.3+3.9Risk factors (13) 0.50 (p = 0.08) 0.15+0.07 7.3+2.8

37 (29). DIAGNOSTIC EFFICACY OF SERUM NTXMEASUREMENTS FOR IDENTIFYING ELDERLY WOMEN WITHLOW TOTAL BODY BONE MINERAL DENSITY

J. K. Scariano, R. H. Glew, P. J. Garry, R. N. Baumgartner,University of New Mexico School of Medicine, Albuquerque, NM

Our previous investigations in healthy elderly women detectedstatistically signi®cant inverse correlations between serum levelsof cross-linked N-telopeptides of bone collagen (NTx) and bonemineral density assessments (BMD) of the total body, lumbarspine and femoral neck regions made utilizing dual X-rayabsorptiometry (DXA). In the present study we determined thediagnostic sensitivity, speci®city and ef®ciency of the serum NTxmeasurement for identifying women with decreased total bodyBMD. Serum NTx levels and DXA were performed on 196 healthyelderly women (60±90 yrs). Twelve women were classi®ed ashaving low BMD on the basis of a total body BMD that was 1.5standard deviations or more below an age-adjusted mean (1.012g/cm2) and were compared with the other 194 women with normaltotal body BMD. The results of a receiver operating characteristicanalysis revealed that a cut-off level of more than 15.0 nMol BCE/L for serum NTx was associated with a 100% sensitivity and 70%speci®city rate for identifying women with low total body BMD.The positive likelihood ratio of an elderly woman with a serumNTx level > 15.0 nmol BCE/L who had a total body BMD 51.5 SDfrom their age-speci®c mean was 3.3. These results indicate thatserum NTx measurements are a clinically sensitive tool forscreening elderly women who are at risk for developingosteoporosis.

38 (30). ACUTE EFFECTS OF CALCIUM CARBONATE ON BONERESORPTION IN HEALTHY WOMEN

J. J. Stepan, V. Zikan, Department of Internal Medicine 3, CharlesUniversity Faculty of Medicine, Prague, Czech Republic

The purpose of this investigation was to examine whether theload of calcium affects the calcium-parathyroid axis and todetermine whether these effects are able to depress boneresorption as assessed by serum type 1 collagen cross-linkedC-telopetide (Elecsys CrossLaps, Roche). Six young healthy


women (23±27 years of age) received after overnight fasting 1000mg of elemental calcium (as an effervescent tablet of calciumcarbonate) in 250 ml of water. During the fasting period, thesubjects were given only plain water. Six healthy elderly women(63±69 years of age) with normal bone mineral density (BMD)received after overnight fasting either 1000 mg or/or 200 mg ofelemental calcium (as an effervescent tablet of calcium carbo-nate) in 250 ml of water. Blood samples were collected before andduring the 5 hours following the ingestion of calcium or wateralone and serum ionized and total calcium, plasma intactparathormone (iPTH) and serum CrossLaps were analyzed. Theload of calcium caused a signi®cant increase of the serumcalcium and a signi®cant decrease of plasma iPTH and serumCrossLaps compared to baseline values. During the ®rst 3 hrs, theload with both 1000 mg and 200 mg calcium induced a similardecrease in serum CrossLaps. After 5 hrs, however, serumCrossLaps remained signi®cantly decreased only in subjectsloaded with 1000 mg calcium. In conclusion, the results show thata single oral morning dose of calcium suppresses boneresorption as assessed by serum CrossLaps.

39 (31). BIOCHEMICAL MARKERS OF BONE TURNOVER:CLINICAL STUDY DESIGN INTERSUBJECT VARIABILITYCONSIDERATION DURING 90 DAY TREATMENT OF A NEWSYNTHETIC CONJUGATED ESTROGENS (CENESTIN)

R. E. Stevens, S. A. Ayres, K. V. Phelps, DuramedPharmaceuticals, Inc., Cincinnati, OH, USA

In a double-blind, placebo-controlled, single-center, clinicalstudy, the effects of a new synthetic conjugated estrogens, A(Cenestin), were evaluated at baseline (3 measurements at day ±2,day ±1 and day 0), and days 30, 60 and 90 on the followingbiochemical markers: S-OC, S-BAP, S-PINP, U-NTX and S-CTX.Fifty healthy, menopausal women, 1±3 years after cessation ofmenses, 40±65 years of age, were randomly assigned to receiveeither 0.625 mg/day Cenestin (n=35) or placebo (n=15). Thewomen concomitantly received 500 mg calcium supplement andone multi-vitamin daily (200 mg calcium, 400 IU Vit D). A uniquefeature of this study was to house the women 48 hrs prior tobaseline collection of a second AM urine void and 10 hours priorto urine collection at Days 30, 60 and 90. This was done in anattempt to reduce large intersubject variability, (approximately50% CV or greater) associated with AM urine collectionsobserved in published literature. Cenestin reduced the progres-sion in S-OC levels by Day 30 (p<0.02) to Day 90 (p<0.0001). Thedecrease in S-BAP and S-PINP was delayed and signi®cant fromday 60. Cenestin produced a signi®cant decrease in U-NTX andS-CTX from days 30, 60 and 90 (S-CTX only). As shown in thetable below, the housing prior to AM urine collections did notappear to reduce the inherent intersubject variability associatedwith measurement of bone markers. Cenestin was effective inreducing bone turnover in menopausal women.

COEFFICIENT OF VARIATION (% CV)

S-OC S-BAP S-PINP U-NTX S-CTX

Baseline 37 29 31 49 3830 days 38 33 36 48 5260 days 41 36 36 54 5390 days 35 28 38 54 47

40 (32). BIOCHEMICAL MARKERS OF BONE METABOLISM ASINDICATORS OF INFLAMMATORY ACTIVITY AND BONE LOSSIN RHEUMATOID ARTHRITIS

ZoltaÂ n Szekanecz, IldikoÂ KovaÂ cs, Andrea KulcsaÂ r, GabriellaLakos, SaÂ ndor Sipka, Gyula Szegedi, Third Department ofMedicine, University of Debrecen Medical Center, Debrecen,Hungary

Introduction and aims: High turnover collagen metabolism byosteoblasts and osteoclasts is crucial for the pathogenesis ofosteoporosis and joint erosions associated with rheumatoidarthritis (RA). Here biochemical markers of bone metabolismand serum cytokine (TNFa, IL±1) levels were studied andcorrelated with the clinical, laboratory activity scores of RA, andRA-associated bone loss.

Methods: 140 RA patients were recruited for the study. Bonemineral density was determined by DEXA over one year period.Osteoblast activity was indicated by serum osteocalcin, whileosteoclast function was indicated by urinary crosslink and serumCrossLaps. RA activity scores and markers included HAQ, VAS,ESR and CRP.

Results, conclusions: Urinary crosslink showed the bestcorrelation with one-year bone loss. Urinary crosslink alsoshowed signi®cant correlation with ESR and CRP (RA activitymarkers), plus urinary calcium excretion. Serum CrossLaps wascorrelated with rheumatoid factor titers, thus it may be prognosticfactor in RA. Determination of biochemical markers of bonemetabolism may have predictive value for the outcome of RA andRA-associated bone loss.

41 (33). DISASSOCIATION OF BONE/MUSCLE RATIO IN LATEPOSTMENOPAUSAL WOMEN ± IMPLICATIONS OFBIOCHEMICAL BONE MARKERS

G. Trovas, G. R. Skarantavos, P. Raptou, A. Galanos, G. P. Lyritis,Laboratory for the Research of Musculoskeletal System, AthensUniv. KAT Hospital, Ki®ssia, Greece

INTRODUCTION: Bone mass decreases with aging and aconsiderable body of data implicates the secondary hyperpar-athyroidism and increased indices of bone turnover at least inpart, the cause of the slow, age-related bone loss. Bone strengthdepends not only on the bone mass but also on the materialquality and spatial distribution of this material (geometry).Although there is a lot of data about bone mineral densitymeasured using dual-energy x-ray absorptiometry (DXA) method,there are no clinical data on the consequences of this age-relatedsecondary hyperparathyroidism on the geometrical parameters oflong bone and musculo-skeletal balance. In this study the muscleand bone cross-sectional area, along with different geometricalproperties of the lower leg have been evaluated non-invasively bymeans of a new pQCT machine, in a group of postmenopausalwomen.


MATERIALS AND METHODS: 34 women, osteoporotic by DXA,were measured at the lower leg with a XTC 2000 (StratecMedizintechnik Pforzheim, Germany). These women were dividedin two groups according to their postmenopausal status: earlypostmenopausal women within 10 years of menopause (meanage �SD = 53.8�4.2) and late postmenopausal women 10 yearssince menopause and over (mean age �SD = 62.5�7.5 years). Thedistal end of the tibia and ®bula and other bone parameters, havebeen measured at 14%, 38% and 66% of the tibia length,proximal to this point. At the 66% site the maximum muscle crosssection is measured to obtain an estimate for muscle force.

RESULTS: In comparison with the early group, the latepostmenopausal women have had increased levels of PTH andother biochemical indices of bone turnover. The cross-sectionalarea of muscle was higher in late than early postmenopausalwomen but the cross sectional area of cortical bone and the ratioof cortical bone to muscle cross sectional area was signi®cantlylower in the late postmenopusal women indicating that they hadfewer bone per unit muscle area than early postmenopausal. Byvisual inspection of the graphical plot of the data, all women as agroup presented a downward, as well as leftward displacementand in the regression analysis by group, there was a mild butsigni®cant relationship, between muscle and bone cross sectionalarea in early postmenopausal women but not in late, indicating animpairment in the relationship between muscle and bone cross-section. In the early postmenopausal women a highly signi®cantrelationship was found between muscle cross-sectional area atthe 66% site and cortical bone area at 14%, 38% and 66%. Incontrast no signi®cant relationship was revealed in the latepostmenopausal women.

At the 66% site cortical and subcortical bone content and area,as well as cortical thickness were signi®cantly reduced in the latecompared with the early postmenopausal women. This patternwas the same and at the other measurment sites although notalways reaching statistical signi®cance.

42 (34). MECHANICAL LOADING AND CALCITONIN: IS THEREANY EARLY BIOCHEMICAL RESPONSE VIA NITRIC OXIDE ANDCYTOKINES IN POSTMENOPAUSAL WOMEN?

S. TuÈ zuÈ n, M. Aslanhan, G. GuÈ lbaba, A Dirican, F. TuÈ zuÈ n,1University of Istanbul, Cerrahpasa, Istanbul, Turkey; 2Universityof Istanbul, Cerrahpasa, Istanbul, Turkey; 3RIA Lab Sisli, Istanbul,Turkey; 4University of Istanbul, Cerrahpasa, Istanbul, Turkey;5University of Istanbu, Cerrahpasa, Istanbul, Turkey

An accelerated bone loss results from estrogen de®ciency in the®rst 5 or 10 years after menopause and this appears to be themain pathogenetic factor in postmenopausal osteoporosis. Alarge number of immune and hemopoietic factors have beenshown to be responsible for this stage. The aim of this study wasto assess the early response of biochemichal determinantswhose effects on bone mineral metabolism are getting apparentsuch as nitric oxide (NO), interferon-gama(IFN-g), interleukin 1-beta (IL 1- b), tumour necrosis factor-alpha (TNF-a) and tartrateresistant acid phosphatase (TRAP). 45 postmenopausal healthywomen aged between 38 and 55 were randomly divided into threegroups. First group were applied aerobic exercise (treadmill in 5kms/h velocity) and 500 mg elementary calcium, second groupwere given 200 IU intranasal calcitonin and calcium and thirdgroup were given calcium only, for ®ve days. Serum levels of NO,IFN-g, TNF-a, IL 1- b and TRAP were measured at baseline, at the2nd and 5th day. We found NO, IFN-g and TNF-a as increasedwhereas IL1-b decreased at the 2nd and 5th day in all groups.TRAP remained in its initial value in all measurements. IncreasedNO and IFN-g levels accompanied by decreased IL1-b suggestthat bone formation could be stimulated in the early stage ofexercise, calcitonin and also calcium treatment.

43 (35). BONE TURNOVER MARKERS: DO THEY EXPLAIN RISKASSOCIATED WITH PREVIOUS FRACTURE? THE EPOS STUDY

P Vergnaud, M Lunt, C Scheidt-Nave, G Poor, G Parisi, KHoszowski, A Lopes Vaz, D M Reid, L Benevolenskaya, S Grazio,K Weber, T Miazgowski, J Stepan, P Masaryk, A Martin, J Walton,F Galan, J Bruges, R Lorenc, S Havelka, R Perez, M Seibel, GArmbrecht, D Felsenberg, A Silman, J Reeve, P D Delmas,] 1IPH,Cambridge, UK

Background. In EPIDOS markers predicted hip fractures sig-ni®cantly after adjusting for low bone density (BMD). Previousfragility fractures (fr) are associated with elevated risk of newfractures independently of BMD. In the European ProspectiveOsteoporosis Study (EPOS) a prevalent spine fracture increasedrisk of a subsequent spine fracture 3.6±12 fold according to itsclassi®cation (wedge, crush) in men and women aged 50±80, afteradjusting for BMD. We have now examined the possibility thatafter fracture, marker levels track with this BMD-independent,unexplained element of elevated fracture risk.

Methods 189 incident cases of spine or non-spine fracture wereeach matched by age, sex and study centre with 2 randomlyassigned controls who had never fractured and 1 case of fracturepre-recruitment who had no subsequent fracture in a mean 3.7years of follow up. Analyses were performed blind, in one centre,in end-of-study samples of: serum osteocalcin, bone-speci®c alkphos, CTS, total alk phos, serum creatinine, calcium, phosphateand albumin; urine CTX. Most subjects had hip DXA.

Results BMD was reduced in spine but not peripheral fr cases.Case-control analyses showed no statistically signi®cant effect(P>.18) of recent fracture on any marker except osteocalcin,which was 17.6% lower in recent peripheral cases compared tounfractured controls (P<0.05; bone sp alk phos trend similar butNS). This effect was not BMD-related. The study had an a postioripower of at least 95% to detect a difference of 0.2 population SDsbetween cases and controls for all markers.

Conclusions Spine & peripheral fracture risk factors differed.Peripheral fractures in the last 3.7 years were associated withreduced bone formation markers. For spine, high risk of futurefracture is partly related to low BMD and partly to other factors,perhaps biomechanical, which relate more closely to previousradiological fracture than to BMD or to persistent, generallyaltered bone remodelling.

44 (36). GUIDELINES ON PREANALYTICAL CRITERIA FOR THEMEASUREMENT OF PYRIDINOLINE ANDDEOXYPYRIDINOLINE AS BONE RESORPTION MARKERS INURINE

H. W. Vesper1, L. M. Demers2, R. Eastell3, P. Garnero4, M.Kleerekoper5, S. P. Robins6, A. K. Srivastava7, J. L. Pettis7, G. R.Warnick8, N. B. Watts9, G. Myers10, 1Centers for Disease Controland Prevention, Atlanta, GA, USA; 2Milton S. Hershey MedicalCenter, Hershey, PA, USA; 3Northern General Hospital Shef®eld,U.K.; 4INSERM Unite 403, Lyon, France; 5Wayne State University,Detroit, MI, USA; 6The Rowett Research Institute, Aberdeen, UK;7VAMC, Loma Linda, CA, USA; 8Paci®c BioMetrics ResearchFoundation, Seattle, WA, USA; 9Emory University, Atlanta, GA,USA; 10Centers for Disease Control and Prevention Atlanta, GA,USA

Variability in pyridinium crosslinks measurement due to pre-analytical factors highly affects the reproducibility, comparabilityand interpretation of results. Preanalytical factors comprise diet,exercise, bed-rest, pregnancy, menstruation cycle, certaindiseases and medications, age, gender and race as well assample collection, storage and treatment and creatinine mea-surement. Based on a thorough literature review from a workinggroup established by CDC, guidelines will be presented thatcover the topics mentioned above to standardize patient statusprior to sample collection, and to standardize sample collection


procedures. Interfering diseases and medications are described.Also, information to establish reference values is provided.

45 (37). BIOCHEMICAL BONE MARKERS AS INDICATORS OFDIFFERENT BONE CELLS FUNCTIONS IN OSTEOPOROSIS

I. P. Yermakova, I. A. Pronchenko, V. P. Buzulina, I. E. Borodulin,Research Institute of Transplantology and Arti®cial Organs,Moscow, Russia

The goal of the study ± estimation of bone cells functions inosteoporosis of different genesis by several biochemical bonemarkers. Markers of osteoblast [bone alkaline phosphatase(bALP), osteocalcin (OC)], carboxiterminal propeptid of type 1procollagen (C-pr)] as well as osteoclast function [tartratresistantacid phosphatase (bACP)] and resorption rate [urine deoxypyr-idinolin (UDPYD/UCr)], were estimated in 18 postmenopausal(OP) and 23 women following kidney transplantation (KT),showing osteoporosis. T-score analyses data presented in table1 (M � SE). Data suggest osteoclast activation, increase ofresorption rate and decrease of osteoblast collagen production inboth groups as well as differences in other osteoblast functions.There were discrimination power between different osteoblastfunctions in both kind of osteoporosis as well as betweenresorption rate and all osteoblast functions in OP.

bALP U/L OC ng/ml C-pr ng/ml UDPYD/Ucr bACP V/I

OP 0.9�0.5@ +1.5�0.26@ ±1.3�0.2& 3.4�0.75# 0.7�0.2KT 3.1�0.5* ±0.5�0.2 ±0.8�0.3 4.1�0.36 2.4�0.8

@± P<0.01 vs KT; #± P50.05 vs bALP, OK, C-pr; &± P<0.01 vs bALP, OC; *± P <0.01 vs

OC, C-pr.

Bone Mass Density

46 (38). QUALITY CONTROL IN ULTRASOUND: ELECTRONICPHANTOM VERSUS MEASUREMENTS IN VIVO

I. Alekxandrova, D. Hans, D. O. Slosman, Nuclear MedicineDivision, Geneva University Hospital, Switzerland

Quality control is crucial to check the long-term stability ofultrasound devices. Strict acquisition protocol is required toassure the reliability of the data when using external phantoms.As an alternative to those phantoms, an internal electronicphantom (EP) has been proposed. It represents an electronic

®lter mimicking human characteristics. The aim of this study wasto evaluate the effectiveness of the EP for monitoring the stabilityof an ultrasound device and to verify its association to conditionsin vivo. Malfunctions (e.g., loss of signal amplitude of differentdegree of severity at the reception stage) of UBIS±5000 (DMS,France) were simulated. Series of measurements on the EP andon ®ve volunteers were performed at each grade of malfunction.The results were than compared to the baseline (0 dB, equivalentto a stable device) in order to quantify: (a) the sensibility of the EPin detecting device related problems; (b) the impact of thosesimulations in vivo. The EP was found as sensitive as volunteersto small variations of gain but with different amplitude (see graph).A ratio between measurements in vivo and in vitro of 1:6 wasfound.

Conclusion: The loss of signal amplitude re¯ects the type ofmalfunction likely seen on the transducer. The fact that theelectronic phantom is as sensitive to the simulations asmeasurements in vivo allows us to propose this type of phantomas a good potential alternative to commonly used externalphantoms.

47 (39). DXR BMD HAS A SUPERIOR DISCRIMINATORYABILITY OF PATIENTS WITH AND WITHOUT VERTEBRALFRACTURES WHEN COMPARED TO DXA BMD

H. Andersen1, J. T. Jùrgensen1, A. B. Helboe1, N. H. Bjarnason2,1Pronosco A/S, Vedbaek, Denmark; 2CCBR, Ballerup, Denmark

The purpose of this cross-sectional study was to investigate theability of the X-posure System to discriminate between post-menopausal women with and without vertebral fractures. Basedon a plain radiograph of the hand and forearm the X-posureSystem estimates BMD using the Digital X-ray Radiogrammetry(DXR) technology. A total of 619 women with a mean age of 73years, range 55±80, where included in the study. Lateral radio-graphs of the thoracolumbar spine were acquired in all womenand assessed for vertebral fractures using quantitative morpho-metry. The fractures were grated from 0 (normal) to 3 (severe) byan experienced radiologist. Spine DXA BMD was measured in thelumbar spine (L1-L4). Using logistic regression to model therelation between the binary response variable (normal or deformlumbar vertebrae) and age as well as DXR BMD or DXA BMDspine results in the following odds ratios (OR):

Cut off score 51 Cut off score 54

Group N OR [95% C.I.] P value N OR [95% C.I.] P value

DXR BMD 619 1.5 [1.1 ±1.9] 0.006 546 2.9 [1.4±6.1] 0.004Spine BMD 616 1.2 [0.9 ±1.5] 0.22 546 2.6 [1.5±4.7] 0.001

Our data show that DXR BMD has a discriminatory ability,which is at least equivalent with spine BXA BMD. This con®rmsthe properties of DXR BMD as a reliable estimate of bone mass.Because DXR BMD uses another measurement site it does nothave the constraints known for spine DXA in the elderly, such asosteophytes and lumbar fractures. In conclusion, the dataindicate that DXR BMD may be advantageous in elderly, whichhas a particularly high risk of osteoporosis.

48 (40). ULTRASOUND BONE PARAMETERS IN CHILDRENWITH ASTHMA RECEIVING INHALED FLUTICASONEPROPIONATE

M. Bayer1, J. Novak2, V. Derner3, 1Dept. of Paediatrics, Ist MedicalFaculty Prague; 2Children's Dept. of Litomysl Hosp.; 3Inst. of Clin.Immunol. and Allergology, Hradec KraÂ loveÂ , Czech Republic

Aim of study ± To ®nd relation of the bone ultrasound parametersto both cumulative dose and lenght of inhaled steroids therapy.


Methods ± Anthropometric parameters and laboratory investi-gations were performed three times in nine months intervals in thegroup of 55 asthmatic children and adolescents (age range 4±17years) treated continuously with inhaled ¯uticasone propionate(FP). Calcaneal ultrasound bone parameters were measuredsimultaneously using ultrasound bone analyser CUBA McCue.Obtained values of broadband ultrasound attenuation (BUA) andvelocity of sound (VOS) were expressed as Z-score usingreference group of 818 measurements in healthy Czech pediatricpopulation aged 4±18 years.

Results ± Growth rate as well as biochemical markers in serum(calcium, phosphorus, alkaline phosphatase, cortisol) and urine(minerals and cortisol in 24 hours urine collection) were withinnormal limits. Signi®cant decrease of BUA and VOS Z-score isrelated to cumulative dose of 100±150mg/year and 50±100mg/year of FP, respectively /p<0.04; p<0.006/. These valuescorrespond to average daily dose of 200mg. The signi®cancesubsequently increases with dosing. As for the effect of lenght oftherapy, the mean borderline lies in the interval of 23±25 monthsfor BUA and 15±17 months for VOS, respectively /p<0.001;p<0.043/. Both parameters further decreased to following meanlevels: BUA= ±1.941; VOS= ±1.569 /p<0.001/ after 30±50 monthsof therapy.

Conclusions ± Despite of the fact that laboratory markers areunaffected, inhaled FP at average dose about 200ug/day havemeasurable adverse effects on bone in asthmatic children andadolescents already after 15 months of treatment. VOS seems tobe an early ultrasound sign of negative bone response to FPtreatment. Thus, new higher potency inhaled steroids as FP seemto have also increased systemic side effects. We considerultrasonometry to be a useful tool for bone status monitoring inasthmatic children treated with inhaled corticosteroids.

49 (41). COMPUTING STANDARDISED BONE MINERALDENSITY WITH THE LUNAR EXPERT

M. N. C. Beneton, J. Robinson, A. Dey, K. Kayan, J. A. Kanis, E. V.McCloskey, University of Shef®eld, UK

We wished to determine whether published algorithms forderiving standardised BMD (sBMD) applied to the Lunar Expertdensitometer. In a multicentre osteoporosis study, the EuropeanSpine Phantom (ESP) was sent to each of 5 centres operating atotal of 6 densitometers (Hologic QDR2000, n=3; QDR1000, n=1;Lunar DPX-L, n=1; Lunar Expert, n=1). At each, the ESP wasmeasured 10 times as a patient without repositioning. Themeasured vertebral areas were larger using the Lunar Expert(LE) than the other equipment. All data was subjected to non-linear regression using the published asymptotic model (1). Unlikethe other equipment, the LE measurements failed to achieveconvergence using this model. Using curve estimation, the best ®tfor the LE data was provided by a cubic model:

sBMD = 0.6568BMDLE+0.5124 (BMDLE)2±0.2218 (BMDLE)3;r2 = 1.000. Measured values for the ESP before and afteradjustment were:

Low BMD Medium BMD High BMD

BMD 0.569�0.008 1.054�0.013 1.682�0.031sBMD 0.499�0.008 1.002�0.013 1.499�0.016

We conclude that published algorithms for sBMD do not applyto the Lunar Expert but cubic non-linear regression allowsderivation of sBMD.

(1) Pearson et al, Osteoporosis Int 1995;5:174±84.

50 (42). FOREARM BONE MINERAL DENSITY (BMD) BY AGEAND SEX IN A GENERAL POPULATION

G. K. R. Berntsen1, V. Fùnnebù2, A. Tollan3, A. J. Sùgaard4, J. H.Magnus5, 1Univ of Tromsù, Norway; 2Univ of Tromsù, Norway;3Central Hospital, Hamar, Norway; 4Univ of Oslo, Norway; 5Univ ofTromsù, Norway

Population based studies of the adult life-curve of forearm BMDare few, and standardised reference values are lacking. Weinvited all men aged 55±74, women aged 50±74 and 5±10%samples of other age groups aged 25 or more years, living inTromsù (response rate 80.3%). Subjects had BMD measured bySXA at distal and ultradistal forearm sites. BMD was standardisedto the European Forearm Phantom, so our values are comparableto similarly standardised results. Distal mean BMD:

Women Men

Age N Mean,g/cm2(SD) N Mean,g/cm2(SD)

25±29 86 0.476 (0.042) 52 0.587 (0.050)30±39 220 0.483 (0.045) 122 0.592 (0.047)40±49 182 0.472 (0.050) 115 0.579 (0.053)50±59 1869 0.446 (0.057) 836 0.566 (0.059)60±69 1461 0.383 (0.068) 1311 0.542 (0.068)70±74 594 0.354 (0.066) 509 0.513 (0.076)75+ 68 0.327 (0.074) 59 0.485 (0.095)

There was a slight BMD decline before 50 years in both sexes.From age 50 the annual BMD-decline was ±0.6% in men and±1.3% in women. Male BMD-decline was stable throughoutsenescence, but in women the decline decreased to ±0.7%around 65 years of age. The eect of menopause on BMD-levelsseemed to wane o in the late post-menopause. Exclusion of 2441subjects with bone related disease and/ or medication did notaect the overall BMD-life curve.

51 (43). BONE MINERAL DENSITY OF ELDERLY WOMEN WITHSCOLIOSIS AND/OR SPONDYLOLISTHESIS

O. Cimen BoÈ lgen, G. Sahin, A. BicË er, H. GuÈ ler, S. BagÏ is, Y. Yapici,C. Erdogan, Department of PMR, Mersin University, Faculty ofMedicine, Mersin, Turkey

The aim of this study was to assess the possible effect ofscoliosis and spondylolisthesis on bone mineral density (BMD) ofelderly women. Thirty seven female patients (mean age63.27�5.64) with scoliosis and/or spondylolisthesis (17 scoliosis,20 spondylolisthesis) were included in the study. Thirty sevenfemale patients (mean age 60.62�5.64) without scoliosis orspondylolisthesis formed the control group. BMD of lomberspine and femur (neck) was evaluated by DEXA. Scoliosis andspondylolisthesis was evaluated by direct radiographic techni-ques. There was no signi®cant difference between groupsregarding age, years since menopause, body mass index,number of childbirth and lomber spine BMD.

Femoral (neck) BMD of patients with scoliosis and/orspondylolisthesis was signi®cantly lower, compared to thecontrols (p<0.001). As a result, we can say that, scoliosis andspondylolisthesis may increase lomber spine BMD of elderlywomen.

However, the numbers of patients were low, existing data ispreliminary and longterm studies with double blind controlled areneeded.


52 (44). EFFECT OF LOWER EXTREMITY AXIS DEVIATION ONBONE MINERAL DENSITY OF PROXIMAL TIBIAE

E. Czerwinski, R. T. Kukielka, K. Nowak, Department ofOrthopedics of Collegium Medicum of, Jagiellonian University,Krakow, Poland

Bone densitometry is currently widely used method for estimationof bone mineral density in many various bone metabolic diseases,particularly in osteoporosis. Nowadays a whole body devices aredisposable to evaluate measurements of bone mineral density inany point of the skeleton. That allows to make analysis of differentlocal bone disorders for example diagnosis and monitoring ofSudeck atrophy as well as evaluation of total hip arthroplasty inestimation of bone mineral density in proximal tibia in lowerextremity axis deviations.

Group of 30 women and men in age 15±72 (average 46) wereadmitted to Orthopaedic Department because osteoarthritis dueto lower extremity axis deviations on the knee level with bothvalgus and varus deformity. All patients were quali®ed for hightibial osteotomy. For preoparative planning bone density wasmeasured in lumbar spine, femoral neck and proximal tibia on ROI(region of interest). We analysed 3 ROI ± lateral, middle and themedial side. Results were expressed in g/cm2. Anthropometricmeasurements of low extremity axis deviation were performed byusing Metrecom (Faro). Before operation long standing X-ray(goniometry) was also measured. Results were compared to thecontrol group of 20 patients with normal limb axis. Increasedbone mineral density was found on the side of overweightedcompartment in comparison to the opposite side in all patients.These differences were not observed in control group. Thecoef®cient (ratio of bmd in overweighted compartment to bmd inopposite side) ranged from 1.2 to 24.5 (SD 5.7), while in controlgroup the ratio was from 0.95 to 1.4 (SD 0.15). It seems thatincreased pressure for the compartment is bound with increasedbone mineral density of the side of proximal tibia. We foundstrong correlation between differences of bone mineral density incompartments and angle of lower extremity axis deviation. Thepossibility of application bone mineral density method inprognosis of course osteoarthritis as well as outcome of hightibial osteotomy were discussed.

53 (45). 3-DIMENSIONAL EVALUATION OF BONESTRUCTURES OF THE HUMAN FOREARM IN VIVO

M. A. Dambacher, M. Neff, R. Kissling, P. RuÈ egsegger, 1UniversityClinic Balgrist and Center for Osteoporosis, Zurich, Switzerland;2Federal Inst. of Technology Zurich, Switzerland

So far only bone mass was available quantitatively. Bonestructure was analyzed qualitatively with the help of highresolution 2D CT images (hpQCT ± Densiscan 1000, ScancoLtd. Zurich). Recently real 3D examinations became available invivo and it is now possible to characterize quantitatively patientswith such microarchitectural features as trabecular number,trabecular thickness, trabecular spacing and relative bonevolume. We expect that such a characterization will give newinsights in pathogenesis and treatment of osteoporosis and mightimprove predictions of individual fracture risk in normal subjectsas well as in osteoporotics, in osteomalacia, b-thalassaemia,primary and secondary hyperparathyreoidism, in osteogenesisimperfecta and in anorexia nervosa. As an example we presenthere normal 3D structures in the radius. ``Exploted'' view oftrabecular and cortical bone.

54 (46). THE EFFECT OF BONE LOADING EXERCISE ONBROADBAND ULTRASOUND ATTENTUATION (BUA) IN PRE-AND POSTMENOPAUSAL WOMEN

R. Donnelly, N. M. Murphy, Waterford Institute of Technology,Waterford, Ireland

The purpose of the study was to monitor changes in BUA withexercise (9 months) & following a further 9 months of detraining.63 menopausal women were chosen from 200. Exercise (ex.) &control (ctrl.) groups were matched on a ratio of 2:1. BUAmeasurements were taken at 0,9 &18 months (CubaClinicalmachine). The exercise regime involved high impact boneloading. No signi®cant differences existed between ex. & ctrl.groups for age, years since menopause, initial BUA, body mass,height or %body fat (p>0.05). Following the 9 month intervention,muscular strength improved for 6 of the 7 exercises performed inthe ex. group with no change in ctrls. (p<0.05). The subjects in theex. group with the lowest initial BUA had the most positive BUAchange with exercise (p = 0.011). In the ex. group there was asigni®cant increase in %BUAchange between 0&9 months mean(SD) (8.8 (11.4)%), a signi®cant decrease between 9 & 18 months(±3.8 (7.6)%) amounting to an overall % increase in BUA of 4.5(13.2). Percentage BUAchange between 0&9 months & 9&18months was also signi®cant in the ctrl. group (p<0.05), butBUAchange between 0&18 months was not signi®cant. Nosigni®cant differences existed between ex. & ctrl. groups forBUA measured at 0, 9&18 months (p>0.05). Menopausal status,HRT use or calcium intake had no signi®cant effect onBUAchange. The variability of BUA is so large relative to theexpected changes due to exercise that it is dif®cult to observebetween group differences. If ultrasound is to be of use in futureexercise intervention studies, the precision of the instrumentsmust be improved, or large subject numbers recruited.

55 (47). CROSS CALIBRATION OF FAN BEAM AND PENCILBEAM DUAL ENERGY X-RAY ABSORPTIOMETERS

W. D. Evans, J. C. Martin, K. T. Rajan, 1University Hospital ofWales, Cardiff; 2Dewi Sant Hospital, Pontypridd, Wales, UK

The purpose of this study was to investigate the effect on boneArea, Bone Mineral Content (BMC) and Bone Mineral Density(BMD) of upgrading from a QDR1000 pencil beam densitometer toa QDR4500 fan beam device (Hologic Inc., Waltham, MA). Lumbarspine (LS) and total hip scans were performed on 128 patients (10male) on both machines. Patient age and body mass index (BMI)ranged from 24.9 to 82.7 years and 17.4 to 50.2 kg/m2

respectively. For the LS, mean values of all three variables were


smaller for the QDR4500; this was also true for hip Area and BMCbut hip BMD was greater compared with the QDR1000. Linearregression analysis of fan beam data against pencil beam datagave intercepts that were not signi®cantly different from zero,with the exception of LS Area. Forcing the regression linesthrough the origin gave slopes in the range 0.94 to 1.03 and r2

values in the range 0.73 to 0.94. These slopes can be used ascross calibration factors. Bland-Altman analysis revealed thatdifferences between corresponding variables measured on thetwo machines were not signi®cantly associated with the meanvalues. The differences in all three LS variables were negativelycorrelated with BMI while the difference in hip BMD was positivelycorrelated. The other hip variables showed no signi®cantdependence on BMI. The study con®rms that cross calibrationfactors vary between measured variables and anatomical sites,and that differences are dependent on body size.

56 (48). BONE DENSITY MEASUREMENTS IN PRIMARY CARE:COMPARISON BETWEEN PIXI AND BUA IN OS CALCIS

C. FernaÂ ndez, L. Abad, A. Fuertes, J. MillaÂ n, J. A. Roman, HospitalUniversitario Dr. Peset, Valencia, Spain

PURPOSE: Previous studies have demonstrated that PIXI heelscan can be used for screening for osteoporosis. We haveconducted this study to compare the results of bone mineraldensity (BMD) measurements using PIXI bone densitometer andBone Ultrasound Attenuation (BUA), both in os calcis.

METHODS: 50 postmenopausal women (mean age: 61 years,range: 40±80) attending a Primary Care (PC) clinic for differentcauses were selected for bone density studies. BMD measure-ments were performed using a PIXI bone densitometer (Lunar)and BUA, both in os calcis.

RESULTS: BMD results using PIXI were: normal in 16 (32%),osteopenia in 19 (38%) and osteoporosis in 15 (30%) and withBUA: normal in 12 (24%), osteopenia 27 (54%) and osteoporosis11 (22%). The Pearson's correlation coef®cient between bothtechniques was r = 0.777 (p = 0.000).

PIXI Normal PIXI Osteopenia PIXI OP Total

BUA Normal 9 3 0 12BUA Osteopenia 7 12 8 27BUA OP 0 4 7 11Total 16 19 15

Chi-square: 19.35; P=0.000. OP: osteoporosis.

DISCUSION: We have found a relation between both BMDmeasurements in os calcis. BUA could be useful in the screeningof postmenopausal osteoporosis in Primary Care.

57 (49). THE RADIOLOGICAL CHANGES IN PATIENTS WITHANKYLOSING SPONDYLITIS INFLUENCES BONEDENSITOMETRY

H. Franck, Th. Meurer, Center of Rheumatology, Oberammergau,Germany

Bone densitometry in patients with ankylosing spondylitis (AS) iscontroversly discussed in respect to different densitometrytechniques. In addition, speci®c radiological changes in AS assyndesmophytes, impair the interpretations of bone densitometry(BMD). The purpose of our study was to examine BMD in patientswith AS depending on radiological staging of the lumbar, thoracicand cervical vertebra. We measured 165 patients with AS, 116men (mean age 50.5�11.4 years) und 49 women (mean age50.2�11.8 years) with DEXA (QDR 4500 A). BMD of the lumbarspine did not differ in comparison to age matched controls. BMD

total of the hip was not signi®cantly different (0.92�0.15 g/cm2)but men had higher values (0.95�0.15 g/cm2) than women(0.87�0.14 g/cm2). The correlation between total hip in lumbarspine was r = 0.364 (p<0.01). Patients with AS and radiologicalchanges of the lumbar spine (n = 135) had lower BMD total valuesof the hip (0.919�0.15), or ward triangle (0.563 g/cm2 p<0.01) thanpatients without disease speci®c changes of the lumbar spine (hip0.941�0.15 g/cm2 ward 0.667 g/cm2 respectively). The sameapplies for patients with radiological changes of the thoracic andcervical (n = 99) spine. These data show that patients with ASpresent with BMD total of the hip which correlates signi®cantlywith radiological changes of the lumbar spine.

58 (50). COMPARISON OF 3 PERIPHERAL BONE DENSITYMACHINES TO CENTRAL DEXA

M. Gass, M. FernaÂ ndez, E. Silberstein, L. Levin, University ofCincinnati, Cincinnati, OH, USA

245 Caucasian women referred for bone density testing werescanned with the Lunar PIXI, the Lunar Achilles, the Schick ®ngerDEXA, and the Lunar DPX-L. Mean age was 57�8 yrs, range 41 to81 yrs. Using the lowest density lumbar vertebra and Ward'striangle as reference sites, sensitivity (Ss) and speci®city (Sp)were assessed for each densitometer using a T score of ±1 SD asthe cutoff on the peripheral scan to identify women with a T scorecutoff of ±2 SD at the spine and hip.

Densitometer Lumbar: Ss Sp Wards: Ss Sp

Finger DEXA 57% 87% 59% 87%Heel DEXA 52% 85% 57% 84%Heel Ultrasound 78% 62% 83% 60%

To approximate 90% sensitivity with the peripheral scan thespeci®city dropped to an average of 41%, range 31±52%:

Densitometer Lumbar: Ss Sp Wards: Ss Sp

Finger DEXA 90% 37% 90% 37%Heel DEXA 90% 39% 90% 38%Heel Ultrasound 90% 40% 90% 48%

Given the low sensitivity that results when a T score of ±1 SD isused as the cutoff for peripheral densitometers and given the lowspeci®city when 90% sensitivity is achieved, it is recommendedthat guidelines be developed for cost effective use of theperipheral densitometers.

59 (51). EFFECT OF SOCIO-ECONOMIC STATUS ON TIBIALSPEED OF SOUND (tSOS): A MULTICENTER, CASE-CONTROLSTUDY IN URBAN AREAS IN TURKEY

Y. GoÈ kce-Kutsal1, F. Inanici1, S. OÈ ncel2, M. Eryavuz3, O. Peker2, S.OÈ k3, 1Hacettepe University, Ankara; 29 Eylul University, Izmir;3Istanbul University, Istanbul, Turkey

The purpose of this study was (1) to evaluate the possible riskfactors of low tSOS, which determines cortical bone status,among residents of urban regions in Turkey, and (2) to comparegroups of different socio-economic status (SES).

A total of 1026 subjects (649 women, 377 men) between 40±70years old from 3 large cities were included in the study. Thesubjects were all volunteers from two different SES regions of thecities, which were selected randomly according to zip codes. Riskfactors of osteoporosis were determined using European


Vertebral Osteoporosis Study Questionnaire, and the bone statuswas screened by tSOS. Multivariate logistic regression analysiswas used for risk assessment.

Age, menopause, physical inactivity, SES and multiparity werethe major determinants of low tSOS in females. Major risk factorsin male were age and low SES. Tibial SOS was found lower infemales than males and in low SES group than high SES group(p<0.001). Besides the well-known risk factors such as age,gender and menopause, low SES was found to be among themajor risk factors of low tSOS in our population (Odds Ratio 0.39,%95 con®dence interval 0.26±0.58).

We concluded that SES was an important determinant ofcortical bone status. Additionally, our results con®rmed thecorrelation between tSOS and the clinical determinants of bonemass. Therefore, we propose tSOS as a useful method forscreening bone status especially for research trials involvingnormal control groups.

60 (52). OSTEOPOROSIS IN LIVER-TRANSPLANTATION:DIAGNOSIS, PREVENTION AND THERAPY

M Hommann1, K Abendroth2, U Schotte1, R Voigt1, A Kornberg1, JScheele1, 1Department of Surgery; 2Department of Medicine,FSU, Jena,

Introduction: In liver transplantation osteoporosis becomes arising problem. Since graft survival is getting prolonged over thelast years the problems of immunosuppression and its sideeffects are growing, e.g. the corticoid induced osteoporosis. Theeffect is potentiated because of the already existing osteopeniadue to hepatic disease.

Patients and methods: Our diagnostic schedule of osteoporo-sis includes X-Ray and measurement of the bone mineral density(DXA/lumbar spine and proximal femur, pQCT/ultradistal radius).We established a protocol for diagnosis, prevention and therapyof osteoporosis in Transplant-patients. Before and 3, 6 and 12months after transplantation we examine the bone mineraldensity by DXA and pQCT. In prevention and therapy of theosteoporosis we randomize our patients into two groups. Group 1receives basic therapy with calcium (1g) and vitamin D (1000 E),group 2 calcium (1g), vitamin D (1000 E) and bisphosphonates (2mg Ibandronat i.v. every 3 months). Our results and experiencesin 32 patients/24 months will be discussed.

Results and conclusions: The results in the area of the lumbarspine are different because of the preexisting ascites. Measure-ment of the proximal femur shows a clear decrease of BMD in the®rst three months, results in the ultradistal radius (pQCT) within 6months after transplantation.

Examinations in the area of the proximal femur (DXA) and theultradistal radius (pQCT) are most expressive. Because of theenormously decreased BMD of about ±5% a therapy should starton the day of transplantation. Here Ibandronat seems to be mostsuccessful. The measurement of the BMD gives preciseinformation about the actual bone mass and its quality and istherefore the best parameter to determine the risk of bonefracture due to osteoporosis after transplantation. We are able toevaluate the prognosis and monitor the therapy of osteoporosis.

61 (53). HIGH SHORT-TERM PRECISION WITH DIGITAL X-RAYRADIOGRAMMETRY

J. T. Jùrgensen1, P. B. Andersen2, A. Rosholm1, N. H. Bjarnason3,1Pronosco A/S, Vedbaek, Denmark; 2CCBR, Aalborg, Denmark;3CCBR, Ballerup, Denmark

In the present study a new bone densitometer using the Digital X-ray Radiogrammetry (DXR) technology (Pronosco X-posureSystem) was investigated with respect to its short-term precision.The BMD estimate generated by the system is referred to as DXRBMD.

The study used a balanced design with each participant having3 radiographs taken with repositioning of the hand and forearm inbetween each capture. Two groups of females where studied,one consisting of 20 pre-menopausal women, ages 30±40 years,and one of 20 post-menopausal women age 565 years. Theshort-term precision errors were calculated as root-mean-squareaverages of standard deviations of repeated measurements andexpressed as the coef®cient of variation (CV) with the corre-sponding 90% con®dence intervals. The mean age of the pre-menopausal women was 35.2 years, and the mean DXR BMD was0.578 g/cm2 (SD=0.0039 g/cm2). The mean age of the post-menopausal women was 68.2 years, and the mean DXR BMD was0.489 g/cm2 (SD=0.0030 g/cm2). The CV in the pre-menopausalgroup was 0.68% with a 90% con®dence interval of 0.57%±0.83%. The CV in the post-menopausal group was 0.61% with a90% con®dence interval of 0.52%±0.75%. In conclusion, thepresent study shows that the short-term in vivo precision error ofthe DXR technology is very low in both pre- and postmenopausalwomen. When the results of the study are compared to datareported in the literature, the performance of the DXR technologyseems to be at least equivalent with DXA.

62 (54). DUAL-ENERGY X-RAY ABSORPTIOMETRYMEASUREMENT OF BONE MINERAL DENSITY AROUNDCEMENTED AND CEMENTLESS FEMORAL PROSTHESIS

S. Kabak, M. Halici, S. Karaoglu, A. Baktir, M. Kula, Department ofOrthopaedics and Traumatology and Nuclear Medicine,University of Eeciyes Faculty of Medicine, Kayseri, Turkey

The measurement of bone mineral density (BMD) in de®ned areasaround metal implants has improved with the development ofdual -energy X-ray absorptiometry (DEXA). The purpose of thisprospective study to investigate the course of the periprostheticbone mass changes after implantation of an uncemented andcemented femoral implants over a 4-year period.

A cosecutive homogeneous group of 60 female patients with anaverage age of 58 years was operated on for unilateral hiposteoarthritis. The types of prosthetic components used were thecemented Protec MS±30 and uncemented femoral stem. Peri-prosthetic bone mineral density was measured in 7 differentzones (Zones I to VII) in femoral components. BMD of the femoralcomponents was measured preoperatively and one week, 1 yearand 4 years postoperatively. The stem of the Protec prosthesisinduced bone mass reduction in the medial femoral calcar and thelesser trochanter area (Zone VI-VII). The cementless femoral stemproduced signi®cant bone resorption in the area of the minor andgreater trochanter (Zone I-VII) 4 years after. Cemented anduncemented femoral stems induced bone mass increase in thegreater trochanter area (Zone I), and distal lateral femoral cortex(Zone III -IV). No correlation was faund between the age of thepatients and bone mineral density values.

This evaluations may be of much better prognostic value foraseptic loosening of total hip arthroplasty long before anyradiographic or clinical signs of this complication are evident.

63 (55). THE EVALUATION OF ACTIVITIES OF DAILY LIVING INPATIENTS WITH VERTEBRAL COMPRESSION FRACTURES

A. Karan, D. Diracoglu, O. Ekmekci, C. Aksoy, Deparment ofPhysical Medicine and Rehabilitation, Istanbul University, IstanbulMedical Faculty, Istanbul, Turkey

The most important clinical problem of osteoporosis is vertebralcompression fractures which may lead to severe impairment inactivities of daily living (ADL). The purpose of this study was toevaluate the impact of vertebral compression fractures on ADL.36 patients with osteoporosis who had at least one vertebralfracture were included in this study. An ADL questionnaire whichincluded eleven activities were evaluated on a ®ve point scale


according to the level of dif®culty when performing theseactivities, was applied to all the patients was found to be``carrying heavy bags'' and ``transvers with public transportationvehicles''. Bathing and dressing on the other hand were theeasiest activities for these patients to perform.

The results of this study suggets that ``carrying heavy objects''and ``public transportation'' might be harmful to osteoporoticpatients with vertebral fractures. Although ``bathing'' seems to beeasiest activity to perform. Turkish bath habit are different fromthe habit of most other countries. The patients should be carefulnot to fall while ``bathing'' in order to prevent more fractures.

64 (56). THE EVALUATION OF BONE MINERAL DENSITY INPOST-MENOPAUSAL WOMEN WITH TYPE 2 DIABETESMELLITUS

A. Karan, A. Aydogan, D. Diracoglu, S. Salman, F. Salman, N.Dincag, E. Berker, Istanbul University, Istanbul Medical Faculty,Turkey

Bone formation is stimulated in type 2 Diabetes Mellitus (DM)through peripheral insulin resistance which is more pronounced inobese patients.

The aim of this study is to evaluate Bone Mineral Density (BMD)in type 2 DM patients and to investigate the correlation betweenother clinical parameters.

28 post-menopausal women with type 2 DM between ages 43±73 were recruited for the study. All cases had a Body Mass Index(BMI) of over 29.40�3.30 and were regarded as obese. BMD wasmeasured in gr/cm2 with Dual Energy X-ray Dansitometry (DEXA)in lomber vertebraes (L1-L4), femoral neck, trochanter and wardstriangle and Hb A1c was also recorded. Disease duration, numberof births and the duration of menopause was also recorded foreach case. Student-t test and Pearson correlation coef®cient wasused for statistical analysis.

The BMD values for L1-L4 femoral neck, trochanter and wardstriangle were 0.95�0.17; 0.78�0.14; 0.63�0.16 gr/cm2 respectively.BMD in L1-L4 was shown to be signi®cantly higher than the abovementioned areas (p<0.0001). The average Hb A1c levels of8.12�2.35 recorded in these patients pointed to a dysfunction inglucose regulation.

The investigation of the correlation between BMD and BMI,disease duration, menopause duration, number of births and HbA1c showed a weak negative correlation with only L1-L4 BMD andmenopause duration (p<0.05; r = ±0.43)

As a result we may conclude that type 2 DM stimulates boneformation of trabecular bone due to high scores of BMD in L1-L4

in relation to femur BMD. Although the patient group was obesewith dysfunction of glucose regulation, the sole correlation wasbetween BMD and menopause duration which points topossibility of a variety of other factors affecting BMD other thanthose investigated. Long term randomized controlled studies areneeded to verify this fact.

65 (57). BONE MINERAL DENSITY IN VITAMIN D DEFICIENCY

R Khadgawat, S Gupta, A Mithal, Sanjay Gandhi PostgraduateInstitute, Lucknow, India

Vitamin D de®ciency (VDD) is not very common in developedcountries but is still important in developing countries. Material &Methods: We retrospectively evaluated records of all thosepatients (pts) who were referred to us between July 1996 toJune 1997 (n=107), 23/107 (21.59%, 22 females, 1 male) has S. 25(OH) vitamin D (VitD) levels <10 ngm/ml (by RIA, Incstar Corp.,USA). These pts were divided into severe VDD (VitD levels <5 ngm/ml, group A±12 patients) and mild to moderate de®ciency (VitDlevel between 5±10 ngm/ml, Group B±11 patients). S intact PTH(SiPTH, by IRMA, Incstar Corp.) and Bone mineral density (BMD)was measured by DEXA (Hologic QDR 4500). The signi®cant

differences in BMD between Gr. A and Gr. B was noted only inforearm total BMD (p = 0.047), forearm total Z score (p = 0.024),forearm ultradistal T (p = 0.028) and Z (p = 0.009). Inversecorrelation between SiPTH and total BMD (r = ±1.0) was noted.All pts were treated with VitD and calcium and reevaluated whichshowed signi®cant subjective improvement. Repeat BMD wasdone in seven patients, which showed signi®cant improvement.Conclusion: VDD is still persisting and is important cause ofsigni®cantly low BMD.

Results: BMD of different area shown in Table

Area Total Group A Group B

Forearm total T score ±1.56 ±2.99 ±1.02Forearm total Z score ±0.78 ±2.26 ±0.04Spine AP T score ±2.33 ±2.80 ±2.41Spine AP Z score ±1.53 ±2.01 ±1.51Hip total T score ±2.03 ±2.85 ±1.74Hip total Z score ±1.44 ±2.27 ±1.06Ward's T score ±2.76 ±3.44 ±2.59Ward's Z score ±1.22 ±1.86 ±0.89

66 (58). BONE MINERAL DENSITY OF THE BOTH FOREARMSIN PATIENTS WITH DISTAL RADIUS FRACTURE

P. LeszczynÄ ski, J. K. Lacki, E. Nowak, S. H. Mackiewicz,Department of Rheumatology, University School of Medicine,Poznan, Poland

Objective: The aim of our study was to compare the effect ofColles fracture on bone mineral density (BMD) and bone mineralcontent (BMC) of the forearms in postmenopausal women.

Materials and methods: A sample of 65 postmenopausalwomen who experienced the left distal radius fracture, averageage 63.0�8.8 yrs (range 50 to 80 yrs), were involved in the study.BMD and BMC of the distal both forearms (left and right) wasmeasured by dual X-ray absorptiometry using DTX±200 appendi-cular bone densitometer (Osteometer Medi-Tech A/S Denmark).The average time since Colles fracture was 7.7�7.3 yrs (range 1 to40 yrs).

Results: Average BMD and BMC values of the left (fractured)forearm were: 0.390�0.073g/cm2 and 2.768�0.570g. AverageBMD and BMC values of the right (not fractured) forearm were:0.390�0.065g/cm2 and 2.762�0.534g. There was no signi®cantdifferences between BMD and BMC of the left and right forearm.We have also found no signi®cant correlation between BMD andBMC of the fractured left forearm and time since previous fracture(r = ±0.075, r = ±0.166; respectively).

Conclusion: Our study con®rm no signi®cant densitometrydifferences of the forearms in patients with long-term previousColles fracture.

67 (59). COMPARISON OF DUAL X-RAY ABSORPTIOMETRY(DXA), HISTOMORPHOMETRY, ASH-WEIGHT AND BONEMORPHOMETRIC INDEX IN AN ANIMAL MODEL OF MALEOSTEOPOROSIS (THE ORCHIDECTOMIZED RAT)

H. Libouban, M. F. Moreau, E. Legrand, M. F. BasleÂ , M. Audran, D.Chappard, University and CHU of Angers, France

Bone mass was obtained in the orchidectomized (ORX) model ofmale osteoporosis by different methods: DXA, histomorphometry,ash weight and the bone weight per bone length index (WL index).We have examined results from 144 male Wistar rats: 48 sham-operated control rats, 48 ORX control rat, 48 ORX treated with abisphosphonate (risedronate 2 or 10 mg/kg/day, 5 days per week).Rats were sacri®ced at 2, 4, 8 or 16 w. post-orx. DXA was


performed on an Hologic QDR 2000 (small animal softwares) onthe whole body, whole tibia and tibial metaphysis. Total (C.BV/C.TV) and trabecular bone volume (BV/TV) were measured byhistomorphometry on the proximal metaphysis (including bothprimary and secondary spongiosa). Signi®cant correlation wasobtained between weight measured by DXA and scale weight(r = .993). However, DXA underestimated weight by 0.3%. Thisdiscrepancy was dependent of the rat's weight. The WL indexwas linearly correlated with BMD (r = .86), BMC (r = .96) and ashweigh (r = .97). A signi®cant correlation was found between BMCof the metaphyseal region and the bone volumes measured byhistomorphometry but this was found to explain only 27% of thevariance; correlations with BMD were poorer (r = .40). BMC andash weight were highly correlated (r = .992). However, DXAoverestimated BMC by a factor of 11% and the overestimationwas found to be dramatically dependent of the net mineralcontent.

68 (60). BONE MASS IN GROWTH-HORMONE TRANSGENICMICE ± VALIDATION AND LONGITUDINAL STUDY WITH HR-DXA

E-M. LochmuÈ ller, U. Wehr, A. Weusten, W. Rambeck, E. Wolf, F.Eckstein, 1Universitatsfrauenklinik, LMU Munchen, Germany

The purpose of this study was a) to determine the accuracy andprecision of non-invasive measurements of body compositionand bone mineral content (BMC) in mice, using high resolutionDXA, and b) to study the absolute and relative BMC (% bodyweight) longitudinally in male and female growth hormone (GH)trangenic animals.

First we examined 28 transgenic (tg) and control (con) miceaged 3 months in vitro. Four measurements were obtained atdifferent occasions with a high resolution DXA system (pDEXA,Sabre, Norland/Stratec: resolution 0.5 x 1.0 mm). These werecompared with a chemical analysis of the bone and fat tissuecontent. Next, 32 animals (16 tg, 16 con, 8 of each group male and8 female were examined in vivo from birth over 9 months.

The precision of the measurements (RMS CV% and SD) was4.4% (65 mg) for the BMC, and 13% (1.4 g) for the fat content.Thecorrelation with the ash weight was r = 0.95 (%SEE = 9%) and thatwith the chemical fat analysis r = 0.94 (%SEE = 13%). At the age of3 weeks, the BMC was around 150 mg, with no signi®cantdifferences between groups. At 9 months the females displayedvalues of 1800 (tg) vs. 1100 mg (con), and the males of 1680 (tg)vs. 1560 mg (con), showing a signi®cantly increased absolute andrelative BMC in transgenic females, but not in males.

The feasibility of measuring the BMC non-invasively andlongitudinally in transgenic mice opens new possibilities fordetermining the function of speci®c genes and gene products atvarious stages of bone development. Supraphysiologic levels ofGH are shown to exert a sex-speci®c effect, with a strongeranabolic response in females.

69 (61). CALCANEAL ULTRASOUND IN MALES AND FEMALES:NORMATIVE DATA AND RELATIONSHIP TO DXA

S. L. Low, J. C.H. Goh, S. DasDe, 1Dept of Orthopaedic Surgery,National University of Singapore,

The aim of this study was to establish the normative data of thecalcaneus using ultrasound in the local male and female Chinesepopulation and to correlate the results to DXA of the spine, hipand calcaneus. 237 females and 122 males had broadbandultrasound attenuation (BUA) and velocity of sound (VOS) of theleft calcaneus measured using a Paris ultrasound system. 174females and 104 males also had BMD of the spine, hip and leftcalcaneus measured using a Norland XR±36 bone densitometer.The coef®cient of variation (CV) was 0.90% for VOS and 3.93% forBUA. Males were found to have signi®cantly higher (p<0.001) VOSand BUA values compared to females. There was an overalldecline of 11.7% for BUA in females between the ages of 50 to 80years, which was double the rate of loss in males (6.4%).However, VOS only decreased by 1.8% in females and 0.9% inmales. Females above the age of 50 years were divided into`normal' and `osteoporotic' based on their femoral neck T scoresde®ned by WHO. The `osteoporotic' females had signi®cantlylower (p<0.05) BMD, BUA and VOS values. There was a moderatecorrelation of calcaneal BMD to BUA (r = 0.581, p50.01) whilelumbar spine BMD had the lowest correlation to VOS (r = 0.402,p50.01). In conclusion, calcaneal BUA and VOS decreases withage in both sexes and is lower in osteoporotic subjects thannormal individuals. More studies are needed to de®ne thresholdvalues in VOS and BUA in order to identify truly osteoporoticpatients.

70 (62). ETHNIC DIFFERENCES IN BONE DENSITY AND HIPAXIS LENGTH IN SINGAPORE

S. L. Low, J. C.H. Goh, S. DasDe, Dept of Orthopaedic Surgery,National University of Singapore, Singapore

In Singapore, the incidence of hip fractures in the Chinesepopulation is more prevalent than in the Malays or Indians.Studies have shown that apart from bone mineral density (BMD),hip axis length is an important predictor of hip fracture risk. Alonger hip axis length was associated with an increased risk of hipfracture.

The aim of this study is to determine whether there are anydifferences in bone density and hip axis length among the 3 majorraces in Singapore. A total of 408 females and 150 male subjectswere recruited. All subjects had BMD of the lumbar spine and lefthip measured by DXA using a LUNAR DPX-L bone densitometer.The hip axis length, de®ned as the length from the lateral boneedge below the greater trochanter through the femoral neck tothe medial bone edge of the inner pelvic brim, was measuredusing the software ruler in the hip analysis programme.

In males, there was no signi®cant differences in height, weight,lumbar spine and femoral neck BMD among the 3 races. Chinesemales were found to have a longer hip axis length compared toIndian males (P=0.029). In females, the Chinese had signi®cantlyhigher lumbar spine BMD compared to the Indians or Malays.Chinese females also had the lowest hip BMD and signi®cantlylonger hip axis length (p<0.05). Therefore the higher incidence ofhip fractures among the elderly Chinese population could bepartially due to a low hip BMD and a longer hip axis length.


71 (63). BONE MASS CHANGES IN WEIGHT LOADED ANDUNLOADED SKELETAL REGIONS FOLLOWING A FRACTUREOF THE HIP

H. Magnusson, K. J. Obrant, O. Johnell, K. M. Karlsson,Department of Orthopaedics, Malmo University Hospital, Malmo,Sweden

The aim of this study was to investigate the bone mass changesin unloaded skeletal regions in patients just sustained a hipfracture. BMD has been demonstrated to decrease in weight-loaded skeletal regions following a hip fracture. If BMD changesin unloaded regions following a fracture is not known.

BMD (g/cm2) was measured longitudinally using DXA in 44 hipfracture patients (mean age 76 years, range 53±90). Themeasurements were done in mean 11 days, 5 months and 13months after the fracture. BMD was assessed of the upper part ofthe skull representing an unloaded skeletal region and femoralneck a weight-loaded region. Data is presented as mean SEM.

BMD increased in the upper part of the skull by 1.9%�0.8%(p50.05) the ®rst 5 months and 3.7%�0.9% (p50.001) the ®rst 13months after the fracture. BMD decreased in the non fracturedfemoral neck by 4.7%�1.8% (p50.01) the ®rst 5 months and4.5%�1.7% (p50.01) the ®rst 13 months after the fracture.

In summary, BMD increased in an unloaded skeletal region anddecreased in a weight loaded region following the reducedactivity after a hip fracture. We conclude that changes in bonemass occurs differently between weight loaded and unloadedskeletal regions related to present activity level ± a bone massshift?

72 (64). L-THYROXINE TREATMENT AND BONE DENSITY:LONGITUDINAL STUDIES

C. Marcocci, F. Golia, E. Vignali, A. Picone, F. Cetani, L.Cianferotti, A. Pinchera, Dipartimento di Endocrinologia,Universita di Pisa, Pisa, Italy

Con¯icting results have been reported o the effect of L-thyroxine(L-T4) on bone density (BD). We evaluated prospectively BD in 3groups of premenopausal women given suppressive doses of L-T4: Group 1: 17 patients with nontoxic goiter in whom BD wasmeasured yearly for 5 yr after institution of therapy; Group 2: 22women treated with total thyroidectomy for differentiated thyroidcancer (DTC) for more than 5 yr (mean 11 yr), in whom BD densitywas measured twice after a mean interval of 4 yr; Group 3:included 29 women with DTC in whom BD was measured beforesurgery and after 4 yr of L-T4 therapy. The daily dose of L-T4 wasindividually adjusted in order to use the minimal amount of L-T4

able to suppress L-T4 (1.8�0.2 mg/kg body weight in Group 1,2.4�0.4 in Group 2, and 2.3�0.3 in Group 3). BD (g/cm2) wasmeasured at the lumbar spine (L2-L4) and femur (neck, Ward'striangle and trochanter) by DEXA. The results are presented in theTable. In conclusion, carefully monitored L-T4 suppressivetherapy in premenopausal women is not associated with boneloss during the ®rst 5 yr of treatment nor when given chronically.

Group 1 Group 2 Group 3

Basal 5yr 1st 2nd Basal 4 yr

L2-L4 1.20�0.1 1.18�0.1 1.24�0.1 1.22�0.1 1.14�0.2 1.15�0.1

Neck 0.93�0.1 0.94�0.1 0.97+0.1 0.98�0.1 0.92�0.1 0.92�0.1

Ward 0.86�0.1 0.85�0.1 0.93�0.1 0.93+0.1 0.84�0.1 0.84�0.1

Troch 0.75�0.1 0.74�0.1 0.76�.1 0.78+0.1 0.75�0.1 0.74�0.1

FT4 pg/ml 9.2�1.9 15.2�2.0* 15.3�4.6 15.6�3.9 10.4�2.1 15.1�2.3

FT3 pg/ml 3.2�0.7 4.3�0.5 3.6�0.2 3.7�0.8 3.3�0.6 4.2�0.5

TSH mU/ml 1.2�2.8 <0.07* <0.07 <0.07 1.40.8 <0.07

*p50.01 vs basal value

73 (65). RISK FACTORS OF OSTEOPOROSIS IN PATIENTSWITH SYSTEMIC LUPUS ERYTHEMATOSUS

P. Masaryk, A. Letkovska, J. Lukac, J. Rovensky, ResearchInstitute of Rheumatic Diseases, Piestany, Slovakia

Systemic lupus erythematosus (SLE) is a serious chronicin¯ammatory autoimmune disease. Improvement of diagnosticsand therapy results into lower mortality rate but on the other handinto increased rate of late complications including osteoporosis.Data on incidence of osteoporosis in SLE vary owing to hugeamount of risk factors with different importance.

Aim of this study is to determine incidence of osteoporosis inpatients with SLE and search for mam risk factors.

Methods: 55 in-patient (52 women a 3 men) with SLE wererecruited. Diagnosis of SLE was based on ACR criteria, diagnosisof osteoporosis on WHO densitometry criteria. Bone mineraldensity (BMD) of lumbar spine L2-L4 and femoral neck wasmeasured by means of NORLAND XR±26 equipment. Mean age ofpatients was 44,0 (13,2) yrs, 31 women were postmenopausal.The control group consist of 367 proband of EVOS study. Mean Z-score for SLE group was calculated and relative rate ofosteoporosis were determined. By means of multiple regressionanalysis the importance of 35 possible theumatology risk factorson BMD of spine and neck were performed.

Results: Mean Z-score was ±0,65 (95% CI: ±0.92, ±0.39) forlumbar spine and ± 0.75 (±1.05, ±0.42) for neck, both signi®cantlydifferent from Z = 0 of control group. In postmenopausal womenosteoporosis of lumbar spine and neck was found in 12/31(41.9%) and 4/31 (12.9%), respectively. According to multipleregression analysis the only signi®cant variable were (regr. coeff,signi®cance): age of onset (L2-L4: ±0.003, p = 0.089, neck: ±0.003,p = 0.025), duration of SLE (L2-L4: ±0.009, p = 0.045, neck: ±0.007,p = 0.019), menopause (L2-L4: ±0.002, p = 0.024, neck: ±0.004,p = 0.020), S- creatinin (L2-L4: ±0.001, p = 0.004, neck: ±0.002,p = 0.002). Neither any immunology parameters, nor any type oftherapy (including corticotherapy) were signi®cant.

Conclusion: Patients with SLE have signi®cant lower bonemineral density in lumbar spine and femural neck and the mainrisk factors are menopause, age of onset and duration of SLE andserum level of creatinin.

74 (66). IMPROVEMENTS IN PROXIMAL FEMUR BY DEXA

R. Mazess2, R. Nord2, C. D. Fogarty1, K. Nodine1, C. M. Fogarty1,1Bone Densitometry Center, Spartanburg, SC, USA; 2LUNARCorporation, Madison, WI, USA

Bone mineral (BMD) at the proximal femur using DEXA may becompromised on thin patients when high ¯ux modes are used.Suf®cient soft tissue medial to the greater trochanter is necessaryto maintain detector linearity and for accurate determination ofthe soft tissue baseline. This problem can be eliminated byplacing a tissue-equivalent bolus adjacent to the proximal femur.New software (enCORETM), recently introduced for the PRODIGYand DPX-NT densitometers (LUNAR Corp.), eliminates the needfor a tissue bolus. The SmartScanTM feature dynamically updatesscan acquisition for each subject, which should eliminate theneed for the tissue bolus. This study documents the performanceof enCORE software on the PRODIGY (fan-beam) and the DPX-NT(pencil-beam) bone densitometers with and without the use ofbolus material during acquisition of proximal femur BMD for bothsubjects and phantoms. Both left and right proximal femur BMDswere acquired on 15 normal subjects (mean age=69�8 years); twoscans were acquired at both the right and left femurs, one withand one without the bolus. Subjects were selected for small bodysize (BMI 20.2�2.3) to highlight any difference between bolus/nobolus.

Additionally, a quasi-anthropomorphic femur phantom wasconstructed to simulate a thin individual (BMI = 17), and was usedto test the need for the bolus. There was no signi®cant differencein femur neck BMD or total femur BMD related to non-use of the


bolus. The pooled precision in vivo for neck BMD and total femurBMD was 1.3% and 0.6%, respectively. There was no signi®cantdifference, with or without the bolus, on phantoms for eitherPRODIGY or DPXNT. The use of enCORE software withSmartScan eliminated the need for bolus material at the proximalfemur for both the PRODIGY and DPX-NT. This bene®ts clinicalpractice by reducing patient preparation time.

75 (67). INTERUNIT VARIATION OF FAN-BEAM AND PENCIL-BEAM DENSITOMETERS

R. B. Mazess, H. S. Barden, J. A. Hanson, Lunar Corporation,Madison, WI, USA

Studies have shown that there is good correspondence betweenfan-beam and pencil-beam DEXA densitometers from the samemanufacturer. The results obtained with any densitometer aregeneralizable because of the high degree of interunit conformityin a single model, typically �0.5% at the factory and �1% in the®eld. We have previously shown that there was only a smallvariation among 2700 DPX densitometers. We recently evaluateda large series of later models (DPX-IQ), as well as a series of therecently introduced PRODIGY fan-beam densitometer. Typicallyduring quality testing at the factory at least 3 to 5 measurementsare made of: (a) an aluminum spine phantom in 15 cm of water; (b)an actual lumbar spine embedded in 10 cm of lucite with anadditional 5 cm of water, (c) an excised low-density skeleton, (d) abody composition phantom fabricated from acrylic and vinyl. Theresults are given below:

DPX DPX-IQ PRODIGY

(n=2716) (n=2920) (n=418) DMean SD Mean SD Mean SD

Al. spine BMD 1.260 .011 1.262 .011 1.250 .010 .011

Actual spine BMD 1.032 .005 1.032 .005 1.028 .006 .003

Total body BMD 0.745 .008 0.750 .018 0.749 .013 .002

Body comp. %Fat ± ± 42.1 .90 43.0 1.44 0.9

As was the case for the DPX and DPX-IQ, the interunit variationfor BMD, and % fat with PRODIGY, was small (1%). Results forspine and total body BMD with the PRODIGY were close to DPXresults (D); BMD of the aluminum spine diered more. Thisdierence was due to measurement in water; when the samephantom was measured in 40% fat-equivalent, there was nodierence between the two densitometers. PRODIGY gave a % fatslightly higher than the DPX, but this was not observed forsubjects in vivo.

76 (68). LATERAL SPINE BMD USING THE LUNAR PRODIGY

R. Mazess2, C. D. Fogarty1, K. Nodine1, C. M. Fogarty1, D.Gorsuch2, 1Bone Densitometry Center, Spartanburg, SC, USA;2LUNAR Corporation, Madison, WI, USA

Bone mineral density (BMD) measurements at the lumbar spine(AP or PA) and the proximal femur are clinically useful forassessing fracture risk and monitoring treatment of osteoporosis.Lateral spine BMD measurements have limited clinical utility; lessthan 1% of DEXA assessments use lateral lumbar spine.However, there are clinical applications for lateral spine measure-ments of the elderly (>70 years of age) when AP spinemeasurements may be compromised due to the presence ofartifacts.

The PRODIGY densitometer (LUNAR Corp.) uses a narrow-angle fan-beam to acquire lateral spine images in less than 90

seconds, with the patient in a decubitus position. Lateral spineBMD acquired on the PRODIGY was compared to that using theQDR±4500 (Hologic, Inc., Bedford, MA) and the DPX-IQ (LUNARCorp.) densitometers. Lateral spine BMD for 12 normal subjectson the PRODIGY was highly correlated (r = 0.95, SEE=0.07g/cm2)to DPX-IQ values. Using a different set of subjects (n=12) therewas a modest correlation (r = 0.55, SEE=0.15g/cm2) between thePRODIGY and the QDR±4500 results. Precision of lateral spineBMD using the PRODIGY was determined for two subject groups:(a) young, normal volunteers (n=13, mean age 39�7 years) and (b)older female clinical subjects (n=9, mean age 48�8 years).Precision was determined from pooled calculations of 3±4repeat measurements made on each subject. The coef®cients ofvariation for groups (a) and (b) were 1.7% and 3.4%, respectively.Lateral spine measurements on the PRODIGY were relatively fastand easy to perform. The precision of lateral spine BMD is often2±3X worse than AP spine BMD. Comparability betweenPRODIGY and DPX-IQ lateral BMD was good. Lack of agreementbetween PRODIGY/DPX-IQ and QDR±4500 results may preventcross-calibration between these two instruments.

77 (69). NO SYSTEMATIC DIFFERENCES BETWEEN A FAN-BEAM (PRODIGY) AND PENCIL-BEAM (DPX-IQ)DENSITOMETER

R. Mazess, H. Barden, R. Nord, J. Hanson, LUNAR Corporation,Madison, WI, USA

Several previous studies have compared fan-beam and pencil-beam densitometers of the QDR (Hologic) series. Generally thereis only a small systematic offset, if any, for BMD, and slightlylarger offsets for body composition. However, there aredocumented differences between fan-beam and pencil-beamresults that depend on the magnitude of the variable measured,e.g., relatively large difference at low or high BMD even thoughthere is no difference at the average BMD (see Ellis and Shypailo,1998, J Bone Miner Res 13:1613±1618). We performed a Bland-Altman analysis comparing results with the PRODIGY and DPX-IQdensitometers on phantoms and on spine/femur scans (n=122)and total body scans (n=46). There were no signi®cant correla-tions (R2<5%) between densitometer differences and themeasured variable. The regression slope was negligible in eachcase over the entire biological range.

Table 1. Bland-Altman Comparison of the PRODIGY vs DPX-IQ

Dierence Relationship for dierences

Mean SD Slope Intercept R2

Total Body BMD ±0.003 0.019 ±0.019 0.02 0.010

Total Body BMC(g) 14.6 138 ±0.034 102 0.015

Total Body Lean(kg) 0.44 1.08 0.004 0.28 0.001

Total Body Fat(kg) ±0.16 1.03 ±0.016 0.26 0.031

Total Body % Fat ±0.03 1.5 ±0.011 0.07 0.007

Femur Neck BMD ±0.006 0.03 ±0.039 0.03 0.046

Lumbar Spine BMD 0.002 0.03 ±0.019 0.02 0.012

78 (70). MOST UNTREATED WOMEN LOSE BONE DENSITYAFTER MENOPAUSE

M. McClung, P. D. Ross, R. D. Wasnich, C. Christiansen, D.Hosking, D. Thompson, M. Daley, J. Yates, for the EPIC ResearchGroup, 1Oregon Osteoporosis Center, Portland, OR, USA; 2HawaiiOsteoporosis Center, Honolulu, HI, USA; 3Center for Clinical andBasic Research, Ballerup, DK; 4City Hospital, Nottingham, UK;5Merck & Co., Inc., Rahway, NJ, USA

It is well established that bone mineral density (BMD) decreasesafter menopause. However, the distribution of rates of loss


among individual women and the exact proportion of women whoactually lose bone mass is not well understood. Furthermore, thechanges in BMD and variability in changes may vary by skeletalsite. We explored these issues using data from 373 women ages45±59 (>6 months postmenopause) in the placebo group of theEarly Postmenopausal Interventional Cohort (EPIC) Study, arandomized, controlled trial of alendronate. The women weregiven general recommendations about calcium intake andexercise for bone loss prevention, but calcium supplementswere not provided. During 4 years of followup, the mean (SD)change in BMD was ±2.9 (4.1)%, ±1.9 (3.4)%, ±2.8 (2.8)%, ±4.6(4.2)%, and ±6.3 (5.4)% at the spine, hip, total body, total forearm,and ultradistal wrist, respectively. Decreases in BMD (anydecrease more than 0.001 g/cm2) were observed at the end of 4years for 76%, 70%, 86%, 90%, and 90% of women, respectively.There is a large range of changes in BMD, and a substantialproportion of women (11±52%) lost >6% over 4 years. At thespine, 24% had decreases >6% ± more than twice the averageloss. We conclude that postmenopausal women lose an averageof ~2±6% over 4 years at skeletal sites measured in this study,with greater losses at the forearm and wrist. Thus, cliniciansshould anticipate that most postmenopausal women will loseBMD progressively if not treated with more than calcium andexercise recommendations. The effects of pharmacologic treat-ment should be evaluated against the expected changes in BMDat each site rather than just the baseline value.

79 (71). BMD AND OCCUPATIONAL PHYSICAL ACTIVITY

L. C. Miranda1, M. T. CristoÂ vam2, M. E. Simoes1, 1InstitutoPortugues de Reumatologia; 2C.S. Portalegre, Lisbon, Portugal

Purpose of the study: In the relation between exercise and BMDthe available data rarely consider the role of occupationalphysical activity on bone metabolism. To compare the BMD oftwo male populations of the same airline company one with highlevel of occupational physical activity and the other with low level.

Population and Methods: Inclusion criteria: Male, over 35 years,caucasian, same occupation at least for 5 years. Exclusioncriteria: chronic diseases, regular exercise, bone metabolismmodifying drugs. Active group: 67 airplane luggage and smallcargo handling staff; Inactive group: 87 Of®ce staff. Ultrasounddensitometry and a questionaire on osteoporosis risk factorswere performed.

Results: The active group moved on average 2115 kg per day.The inactive group worked on average 73.2% sitting and only10% carry cargo (56kg). For the risk factors no statisticdifference was found between the two groups as well as fordensitometric values (QUI, T score, SOS, BUA) which were alwayshigher on the active group, however, the results are close to thatsigni®cance (QUI p = 0.06; Tscore p = 0.069; SOS p = 0.062). Whenwe classi®ed the workers, we also ®nd that the inactive group hasmore osteopenic (34.5%), (25.4% in the active) and osteoporotic(6.7%), (3% in the active) but there was not a statistic difference.

Discussion: The role of occupational physical activity in BMD isnot fully understood. This work points out the possibility of aprotective action of work related exercise on BMD.

80 (72). BONE MINERAL DENSITY IN THE FLIGHT CREWS

L. C. Miranda, M. J. Mediavilla, P. Araujo, M. Parente, E. Simoes,A. Faustino, J. Ramos, A. Vilar, Instituto Portugues deReumatologia, Lisbon, Portugal

Introduction: It is known that the absence of gravity rapidlydecreases BMD in space ¯ights. Fligth crew members are not inthe same conditions however, there are some working conditionslike atmospheric pressure, cosmic radiation, magnetic ®elds,aceleration and desaceleration whose effect on BMD are stillunknown.

Purpose of the study: To study the possible relation betweenBMD and the number of ¯igth hours ¯own by crew members.

Population and Methods: 147 crew members (74 female, 73male). Mean age 44.4�10.4 years (22±65). Inclusion criteria: pilotsor ¯ight assistants on active duty with more than 1500 hours¯own. Exclusion criteria: post-menopausal women, chronicdiseases bone metabolism modifying drugs. Monophotonicdensitometry of the distal and ultra distal radius was performedas well as heel ultra-sound measurement. A questionnaire aboutosteoporosis common risk factors was performed. Statistics:correlations coef®cient with partial correction for risk factors andsigni®cance levels were obtained. Results: Mean ¯ight hours11465�5185. Pearson correlation index between ¯igth hours anddensitometric values was signi®cati®ve for distal radius (r = ± 0.21p = 0.012) T score Ultra distal radius (r = ± 0.22 p = 0.007) and closeto signi®cance for the heel SOS (r = ±0.16 p = 0.054). Whencorrected for age and mass index the correlation is signi®cativefor BMD distal radius (r = ± 0.24 p = 0.004) BMD Ultra distal radius(r = ± 0.2 p = 0.017). The isolated analysis of the other risk factorsdid not change the way of the obtained correlations.

Conclusion: From the data we can observe that the statisticcorrelations were negative pointing to a possible inverse relation-ship between ¯ight hours and densitometric values. Thisobservation can reveal the possible role of ¯ight conditions onbone metabolism. Further studies in this area should bedeveloped. This preliminary study will be completed with a on-going case-control study.

81 (73). TIME COURSE CHANGES OF BONE MINERAL DENSITYIN HEMODIALYSIS PATIENTS USING DUAL-ENERGY X-RAYABSORPTIOMETRY

T. Nakai1, K. Masuhara2, N. Kanbara3, 1Department ofOrthopaedic Surgery, Ikeda City Hospital, Ikeda City, Japan;2Department of Orthopaedic Surgery, Osaka KoseinenkinHospital, Osaka City, Japan; 3Department of Internal Medicine,Kanbara Hospital, Japan

We have studied the change of bone mineral density (BMD) at the1/3 distal radius in 35 male and 20 female patients withmaintenance hemodialysis. BMD was measured by dual energyX-ray absorptiometry at an interval of four years (DCS 600 EX;ALOKA) (Osaka, Japan). Mean age was 54.8�11.0 (meanSD) yearsfor male (range, 32±76 years) and 59.6�12.1 years for femalepatients (range, 42±79 years). Mean duration of hemodialysis was88.5�77.9 months for male (range, 4±292 months) and 96.3�79.6months for female patients (range, 5±296 months) at thebeginning of the investigation, respectively. BMD value was0.656�0.124g/cm2 for male and 0.481�0.123g/cm2 for femalepatients at the beginning of the investigation. At the end of theinvestigation, it was 0.622�0.129g/cm2 for males and 0.444�0.126g/cm2 for females. BMD values were signi®cantly lower in femalethan in male patients at each time point (p<0.01). Signi®cantdecreases were found in both male and female patients (p<0.01).The present study showed an annual change of BMD at the 1/3distal radius of ±1.28% in male and ±1.92% in female,respectively. In conclusion, we have shown that prolongedhemodialysis could cause signi®cant bone loss.

82 (74). EVALUATION OF CALCANEAL BONE MINERALDENSITY WITH FAN BEAM DEXA

Y. Nishimura, K. Kushida, K. Yamazaki, T. Fujiwara, Y. Yamato,Hamamatsu University School of Medicine, Hamamatsu,Shizuoka, Japan

Heelscan (Kyoto Daiichi Kagaku, Kyoto, Japan) is a fan beam typedual energy bone absorptiometry (DEXA) for calcaneus. Heelscanuses a stable X-ray generator, k-edge ®lter to archive the twoenergy levels, and CdTe detector elements. The procedure takes


only 7 seconds for measurement and analysis. The purpose ofthis study is to evaluate the basic attributes of this densitometerand age related changes in normal Japanese women.

Subjects and Methods: 144 women with vertebral fracture, 84women with hip fracture, and 2557 volunteers were enrolled inthis study. T-test, ANOVA, regression analysis, and logisticregression analysis were used for statistic analysis.

Results: 1. Precision error in vivo was 0.75% for calcaneusscans. 2. Calcaneal BMD in vivo (n=120) using DXA was closelycorrelated to prior SXA osteoanalyzer (r = 0.983). There wasalmost correspondence of DXA and SXA values. 3. The cross-sectional study showed that BMD decreased by 34.4% between20 and 80 years of age, and BMD peaked at 20 to 30 years of age.4. BMD in women with vertebral fracture was signi®cantly lowerthan normal women. The relative risk of vertebral fracture was 2.1for a decline of 1SD in the bone density at the calcaneus (95%con®dence interval, 1.9 to 2.5). 5. BMD in women hip fracture wassigni®cantly lower than normal women. The relative risk ofvertebral fracture was 4.6 for a decline of 1SD in the bone densityat the calcaneus (95% con®dence interval, 3.5 to 6.2).

Conclusion: The results of this study indicate that this rapidtechnique can accurately predict women with risk of spine andhip fracture, and may be of value as an initial procedure forscreening of osteoporosis.

83 (75). NORMATIVE DATA OF A WATER-COUPLEDQUANTITATIVE ULTRASOUND DEVICE

C. F. Njeh, B. Fan, M. Grigorian, M. Chen, J. A. Shepherd, I.Saaed, T. Fuerst, D. Hans, H. K. Genant, Osteoporosis andArthritis Research Group, University of California, San Francisco,CA

Normative data are essential for the clinical utility of quantitativeultrasound (QUS). As part of a multicenter study we collectednormative data for a water-coupled imaging QUS device (UBIS5000, DMS, France). Short-term precision was also evaluated.Broadband ultrasound attenuation (BUA) and speed of sound(SOS) were acquired on 215 healthy Caucasian pre- (n = 126) andpost-menopausal (n = 89) females aged 20±89 years. In a subsetof 30 subjects triplicate measurements were carried out afterrepositioning to establish short-term precision (CV). The precisionwas standardized to the biological range (SCV). The CVs were0.60% and 0.14% for BUA and SOS, respectively. However theSCVs were 1.70% for BUA and 3.82% for SOS. The populationmean BUA was 63.2�4.8 dB/MHz and 1512�28.9 m/s for SOS.Both BUA and SOS were signi®cantly dependent on age (r = ±0.33;BUA, r = ±0.48; SOS) but displayed a large scatter around theregression line. BUA was best ®tted by a second order polynomial(r = 0.38), with values peaking around the mid thirties (64.7 dB/MHz), while SOS showed a continuous decrease from the earlytwenties. The annual change estimated from the linear regressionline was ±0.089 dB/MHz/yr and ±0.78 m/s/yr for BUA and SOS,respectively. However, there was an increase in annual changeafter age 45, namely: ±0.187 dB/MHz/yr for BUA and ±1.15 m/s/yrfor SOS. The BUA and SOS were not signi®cantly associated withyears since menopause. UBIS is a highly reproducible QUSdevice, which may be because of its temperature-controlledwater coupling. The age decline in the QUS variables is similar toage-related decline observed at the calcaneus using DXA.

84 (76). THE ASSESSMENT OF BONE WITH CALCANEALULTRASOUND IN A TURKISH POPULATION

A. Oral, D. Sindel, A. Yaliman, D. Tarakci, Istanbul UniversityMedical School, Istanbul, Turkey

The aim of this study was to provide preliminary normative data ofquantitative ultrasound (QUS) values in a total of 515 Turkishwomen aged between 20&80 years, who had no disease or

medication affecting bone metabolism. Broadband ultrasoundattenuation (BUA), speed of sound (SOS), and QUS index (QUI) ofthe right heel were measured using a Clinical Bone Sonometerwith the ``dry'' technology. The means of all QUS variables werethe highest in the youngest age group and the lowest in the oldestone and they showed a signi®cant inverse correlation with age(r = ±0.480 for BUA, r = ±0.428 for SOS, and r = ±0.478 for QUI).BUA and QUI showed a signi®cant decline after the age of 50years, whereas SOS showed a different pattern of decline. BUA,SOS, and QUI decreased by 31%, 3%, and 30% respectivelybetween 20&80 years. When compared to the Caucasian datagiven by other authors, BUA values seemed to be higher in theyounger age groups, while SOS and QUI values seemed to belower. The pattern of decline in QUS indices seemed similar. Inconclusion, this investigation presents preliminary normative datain normal Turkish women.

Age groups BUA (dB/MHz) SOS (m/s) QUImean (SD) mean (SD) mean (SD)

20±29 (n.66) 81.14 (12.7) 1554.96 (24.6) 99.76 (14.3)30±39 (n.41) 79.89 (16.3) 1543.98 (30.7) 94.81 (18.3)40±49 (n.95) 76.20 (15.1) 1542.03 (30.8) 92.69 (17.4)50±59 (n.131) 67.67 (14.8) 1531.70 (28.3) 84.57 (15.4)60±69 (n.112) 62.34 (14.5) 1524.50 (26.4) 79.65 (14.4)>70 (n.70) 55.89 (14.0) 1507.45 (29.7) 70.15 (16.2)

85 (77). BONE MINERAL DENSITY IN PATIENTS ONLONGSTANDING TREATMENT WITH SUPPRESSIVE DOSES OFTHYROXIN

V. PalicÏ ka, P. RÏ ehorÏkovaÂ , P. ZÏ ivnyÏ , T. VasÏaÂ tko, J. CÏ aÂ p, SecondMedical Clinic and Institute of Clinical Biochemistry andDiagnostics, University Hospital, Hradec KraÂ loveÂ , Czech Republic

The purpose of the study was to investigate the effect oflongstanding subclinical hyperthyroidism on bone mineral density(BMD).

BMD was measured in lumbar spine and proximal femur usingHOLOGIC QDR±4500A in 76 patients (16 men and 60 women) inthe age of 21±80 years (median 53 years). These patients havebeen treated with doses of thyroxin suf®cient to suppress TSHlevels since thyroid ablation for differentiated thyroid cancer formore than two years (median 7 years). The results were comparedwith the group of 40 persons matched for age, sex and duration oftreatment with replacement thyroxin doses for hypothyroidism.Unpaired T-test has been used for statistical evaluation ofdifferences.

No signi®cant decrease of BMD was found in patients onlongstanding thyroxin suppression (Z score: total femur0.205�1.07, neck ±0.202�1.19, lumbar spine ±0.239�1.27). Thevalues were lower than in patients treated with replacementdoses of thyroxin, the differences were statistically signi®cant,however, only in postmenopausal women in the femur region(using T-test and Z score: total femur p = 0.026, Ward' trianglep = 0.06, trochanter p = 0.05, intertrochanteric region p = 0.09). Nodifferences were found in the neck (p = 0.24) and lumbar spine(p = 0.40).

In the carcinoma group there were 14 patients in whomhypoparathyroidism was present as a complication of thyroidsurgery and who were treated with vitamin D and calcium for thewhole duration of thyroxin suppression. These patients werefound to have signi®cantly higher BMD than those withouthypoparathyroidism.

In conclusion the decrease of BMD was small in our group ofpatients with iatrogenic subclinical hyperthyroidism and wasstatistically signi®cant in postmenopausal women only. The BMDwas higher in patients with hypoparathyroidism treated withvitamin D and calcium.


86 (78). THE COURSE OF BONE MINERAL DENSITY CHANGESIN YOUNG LABORATORY RATS

V. PalicÏ ka, P. ZÏ ivnyÏ , P. RÏ ehorÏkovaÂ , A. Kasal, V. Novacek, J. CÏ aÂ p,Institute of Clinical Biochemistry and Diagnostics, UniversityHospital, Charles University, Hradec KraÂ loveÂ , Czech Republic

The purpose of this study was to assess the rate of bone mineraldensity (BMD) changes in young laboratory rats and indicate therole of castration and sexual steroid supplementation in thisprocess. After institutional approval 27 male and 37 female Wistarrats with initial body weight (bw) 180�20 g were divided into 7groups. Male: Group M1(n=7): sham operation, given withplacebo (emulgel base), M2 (n=10): castration, placebo, M3(n=10): castration, transdermally daily 2.5 mg of testosterone/kgof bw. Female: F4 (n=7): sham operation, placebo, F5 (n=10):ovarectomy, placebo, F6 (n=10): ovarectomy, transdermally dailyestradiol + progesterone (0.05 + 0.025 mg/kg of bw) and F7: (n=10)ovarectomy, transdermally daily 17b-dihydroequiline + progester-one (0.05 + 0.025 mg/kg of bw). Transdermal application wasstarted from day 20 of experiment (operation = day 0 ofexperiment). BMD measurements using DEXA (Hologic QDR4500) were performed at days 3, 17, 45 and 82 of experiment inlight aether anaesthesia. The constant part of lumbar spine wasselected for BMD evaluation. The experiments were ®nished assoon as we reached signi®cant differences in BMD betweengroups. Results are expressed as mean �SD.

Results: BMD (g/cm2) at day 3 vs. 82 was in M1: 0.146�0.01 vs.0.207�0.040, M2: 0.146�0.01 vs 0.203�0.01. M3: 0.149�0.01 vs.0.212�0.01, F4: 180�0.02 vs. 0.208�0.01, F5: 0.178�0.01 vs.0.203�0.01, F6: 0.176�0.01 vs. 0.219�0.01*, F7: 0.184�0.01 vs.0.226�0.01*. Stat. signi®cance* p<0.05, F6 resp. F7 vs. F4 and F5.We can conclude that castration resp. ovarectomy in the youngrats did not lead to decrease in BMD in comparison with shamoperated animals. The increase in BMD in placebo given groupsshould be caused by sexual steroid independent mechanisms.High transdermal doses of sexual steroids leads to signi®cantincrease in BMD, but necessary time to reach signi®cantdifferences in BMD was about 80 days.

87 (79). CORRELATION OF OSTEOPOROTIC FRACTURE RISKEVALUATED BY QUANTITATIVE ULTRASOUND BONEDENSITOMETRY (QUS) WITH BODY MASS INDEX (BMI) IN 500POSTMENOPAUSAL WOMEN

C. Poiana1, I. Virtej, C. Dumitrache, Institute of Endocrinology,``C.I. Parhon'', Bucharest, Romania

Measuring bone mineral density (BMD) forms the basis fordiagnosing osteoporosis, allowing the diagnosis in an early,asymptomatic phase and optimizing therapeutic strategies.Quantitative ultrasound (QUS) bone densitometry measuresbone mineral density (BMD) and evaluates the quality of bone.The parameters measured with QUS are; BUA (broadbandultrasound attenuation), SOS (speed of sound) and the clinicalindex Stiffness. QUS correlates with osteoporotic fracture risk.We evaluated the in¯uence of 2 independent risk factors forosteoporosis-body mass index (BMI) and number of yearspostmenopause-on. BMC and osteoporotic fracture risk in 500healthy postmenopausal women aged 43±74 years. QUS wasperformed at the os calcis with an Achilles Lunar Plus device. Allwomen were measured for BMI. Conclusions: Our study shows anincreased risk for osteoporotic fractures with increased numberof years postmenopause; the ultrasound parameter with beststatistic signi®cance was SOS with signi®cant decreased values(p<0.05) in women more than 10 years postmenopause. The riskfor osteoporotic fractures is increased in women with low BMI,independent of number of years postmenopause.

88 (80). PERIMENOPAUSAL BONE DENSITY IS PREDICTIVE OFFUTURE BREAST CANCER

D. M. Reid1, J. P. Harvie1, D. J. Torgerson2, 1Departments ofMedicine & Therapeutics, University of Aberdeen; 2HealthEconomics, University of York, UK

The critical task in the prevention of osteoporosis is to identifythose women to whom treatment should be targeted. Todetermine cost-effective targeting we have examined the role ofperimenopausal screening of bone mineral density (BMD) andsubsequent changes in bone mass from a unique randomlyselected cohort of 5,119 women aged 45±54 at their initialassessment carried out between 1990 & 1994. 5 to 7 years laterall women were invited for re-examination and 3,645 (75% ofthose available) attended. Spine and hip BMD was measured in allsubjects.

A total of 91 breast cancers (prevalence rate 2.5%) werereported of which 26 were incident cases and 36 cases werepresent at baseline. 28 women (31%) did not give a date ofdiagnosis. Incident breast cancers were twice as common inthose with baseline BMD in the highest two quartiles (F=13.23,P=0.003).

BMD at the menopause is predictive of new breast cancers, afact that can be used to improve the cost effectiveness estimatesfor the assessment of bone mass in the perimenopausal years.

89 (81). BONE MINERAL DENSITY IN TWO CHILDREN WITHMORQUIO SYNDROME

D. Rigante1, P. Ranieri2, G. Segni1, P. Caradonna2, 1Department ofPediatrics; 2Department of Internal Medicine and Geriatrics,Universita Cattolica Sacro Cuore, Rome, Italy

Morquio syndrome or Mucopolysaccharidosis type IV (MPS IV) isan autosomal recessive disorder of the connective tissue,resulting from de®cient keratan sulphate (KS) catabolism andshowing a unique pattern among lysosomal enzymopathies for itspredominant skeletal involvement, characterized by spondylo-epiphyseal dysplasia, odontoid hypoplasia deriving from partialossi®cation of dens, short trunk dwar®sm, kyphosis, growthretardation, joint laxity and normal intelligence. KS accumulationin the skeleton may interfere with the acquisition of bone massand this might place patients with MPS IV at fracture risk.

We have measured bone mineral density (BMD) in 2 childrenwith MPS IV through dual energy X-ray absorptiometry (DEXA,Hologic QDR 2000): BMD is expressed in grams/cm2 both fromlumbar vertebra L2-L4 and femoral neck; Z-scores are calculatedaccording to the Hologic database for each respective age ofnormal children.

1) P.R. (age: 11 years; height: 98 cm; weight: 16.5 kg): lumbarBMD 0.416, Z-score ± 1.46, 66 % vs normal; femoral BMD 0.356,Z-score ±2.58, 51% vs normal.

2) C.V. (age: 9 years; height: 102 cm; weight: 19 kg): lumbarBMD 0.521, Z-score ± 0.64, 97% vs normal; femoral BMD 0.323,Z-score ±2.07, 55 % vs normal.

MPS IV involves electively the skeleton and in®ltration with KSis associated with a number of potential problems, includingosteoporosis and possibility of fractures. Osteopenia or osteo-porosis may be explained with multiple other contributingfactors: a limited deambulation because of hypotonia of theinferior limbs, subsequent to cervical spinal cord compression,or a sedentary life on wheel-chair. Through DEXA remarks wehave documented an osteopenia at the lumbar site in patient 1and a severe osteoporosis at the femoral site in both patients.We believe that the capacity of deambulation must be stimulatedin such patients in order to maintain a good mineralization rate ofthe skeleton and that DEXA represents a useful means tomonitor BMD in children with MPS IV.


90 (82). BONE MINERAL DENSITY (BMD) IN CUSHING'SSYNDROME(CS) AND EXOGENOUS HYPERCORTISOLISM

L. Rozhinskaya, E. Marova, T. Chernova, N. Sazonova, L.Dzeranova, National Research Center for Endocrinology,Moscow, Russia

Chronic exposure to excessive concentrations of endogenouscortisol or to exogenous glucocorticoids (GC) causes osteope-nia, osteoporosis and bone fractures. The object of our studywas to determine frequency of osteopenia and osteoporosis inpatients with CS and in patients taking GC, and to estimatein¯uence of age, BMI, duration of amenorrea, activity ofhypercortisolism in CS or duration of GC therapy on BMD andbone loss. We have studied 187 patients with CS, 58 patientstaking GG and 300 healthy subjects (HS) divided according toage and sex. BMD was measured using ``Expert XL'' Lunardensitometer in lumbar spine and femoral neck. Data arepresented as mean �m in the table. Vertebral and femoralBMD were signi®cantly lower and frequency of OSP and OP washigher in patients in active phase of CS than in remission CS.BMD reduce did not depend on age, sex and BMI.. GC patientshad a signi®cantly lower BMD and higher frequency of OSP andOP, than in age and sex matched controls.

Analysis of our data showed: BMD reduce in CS depends onhypercortisolism activity. Bone loss restores after treatment CS;Bone loss in GC patients closely relates with GC doses andduration of GC therapy.

Groups Age n BMD L2-L4

T-score

BMD NECK

T-score

OSP %

L2-L4

OP %

L2-L4

CS, male, a/f 20±50 18 ±3.2�0.26 ±2.2�0.23 22 78

CS, male, rem 20±50 15 ±1.36�0.31 ±0.84�0.32 40 13

CS, fem., a/f 20±39 32 ±2.1�0.15 ±1.3�0.19 66 25

CS, fem., a/f 40±65 22 ±2.2�0.24 ±1.4�0.21 45 42

CS, fem., rem 20±39 45 ±0.5�0.16 ±0.32�0.19 24 9

CS, fem., rem 40±65 55 ±0,3�0,12 ±0,28�0,13 24 0

GC, male 20±50 15 ±2,2�0,32 ±1,9�0,35 40 40

GC, female 20±55 43 ±1.66�0.22 ±1.57�0.14 45 28

HS, male 20±50 42 ±0.42�0.18 ±0.39�0.21 28 2

HS, female 20±39 88 ±0.05�0.12 +0.13�0.12 16 0

HS, female 40±65 170 ±1.08�0.1 ±0.75�0.08 32 8

a/f- active phase of CS; rem± remission; OSP- osteopenia; OP- osteoporosis

91 (83). BONE INVOLVEMENT IN GAUCHER DISEASEPATIENTS

L. Russo, L. Gregorio, M. De Paula, C. Petriz, R. Vivaldi

Gaucher disease, also called glucosylceramide lipidosis is themost common of the sphingolipidoses, a group of diseases thatare inherited in an autosomal recessive manner. Its character-ized by the accumulation of glucocerebroside in tissuemacrophages, that causes hepatomegaly, splenomegaly andpancitopenia.

All patients with GD have some degree of bone involvementand skeletal deterioration like: generalized osteopenia, Erlen-meyer ¯ask deformity of the distal femur, lytic lesions, osteo-sclerosis, pathologic fractures, and soap bubble appearance ofbones. Although the cause of osteopenia is not de®ned clearly, itis thought that the osteoclast-in GD is overly active leading toosteoporosis and weakening of the bones in affected patients.

GD has become the ®rst intracellular enzyme de®ciency to betreated with a recombinantly produced enzyme. For monitoringthe focal skeletal complications we reviewed of plain X-ray ®lmsand Dual energy X-ray absorptiometry (DEXA, Lunar DPX-L WI)exams, far more sensitive method for detecting subtle changes inbone mineral density and promises to be and excellent mean ofmonitoring clinical progress in GD patients.

During one year we follow with bone densitometry scans (zero-time and 12 months) 16 patients, aged from 4 to 61(median=23�2.5) years with GD receiving Cerezyme R (Imiglucer-ase for injection, median doses for adults was 27.6 UI/kg, and forchildren was 38.5 UI/kg) and both received also 500 mg (twice aday) of calcium carbonate.

The median results of BMD in lumbar spine was 0.742�0.23g/cm2 before the treatment and 0.816�0.22 after (p<0.0001), withan increase of 7.9�5.7% in this region of the skeleton. T-score inthis region was ±1.7�1.1 before and ±1.3�1.0 after treatment(p = 0.0093).

The median results of BMD in femur was 0.979�0.23 g/cm2

before and 0.992�0.23 g/cm2 after (not statistically signi®cant)with na increase of 1.1�1.6%. T-score median was ±0.5�2.2before and ±0.6�2.1 after treatment (not signi®cant).

In total body median BMD was 0.838�0.14 g/cm2 before and0.835�0.15 g/cm2 with na increase of 2.1�4.2% in this region. T-score median was ±1.3�1.2 before and ±1.5�1.2 after treatment(not signi®cant).

Our results showed clearly that enzyme treatment plus calciumwas important for bone involvement in Gaucher disease, meanlyfor spine, and bone densitometry is an important tool forfollowing-up this GD patients.

92 (84). PERFORMANCE OF AN AUTOMATIC ANALYSISALGORITHM FOR A DXA BONE DENSITOMETER

C. Ruth, T. Richardson, E. von Stetten, H. Weiss, K. Wilson, T.Kelly, G. Rappolt, E. Yapchian, M. Barrick, Hologic, Inc., Bedford,MA, USA

Inter-operator variability in BMD results has been recognized asan important factor in clinical performance of DXA systems. Analgorithm (auto-analysis) was developed to automatically locatethe regions of interest used in the analysis of AP spine and hipimages. Auto-analysis facilitates ease of use and decreases inter-operator variability in results. We evaluated the performance ofauto-analysis relative to manual analysis performed by expertoperators. AP spine and hip scans (Hologic QDR 4500) of 96 peri-and post-menopausal women (mean age = 56�5 yrs) wereanalyzed separately by two expert operators and by automaticanalysis. Auto-analysis was considered successful if no adjust-ments to the regions were deemed necessary by an expertoperator. The mean and standard deviation of the differences inBMD results between two expert operators, and between eachoperator and auto-analysis were computed and averaged over allscans successfully analyzed for all regions. Auto-analysissuccessfully analyzed 87% of spine and 87% of hip scans.Expert operator and auto-analysis BMD results were highlycorrelated (R>0.95). Absolute differences between an expertoperator and automatic analysis were not signi®cantly differentthan the differences between two expert operators. When allscans are included in the analysis, the mean differences andcorrelation coef®cients are similar and the SD of the differencesincreases slightly. In conclusion, this auto-analysis algorithmsuccessfully analyzed the vast majority of hip and spine scansobtained in a peri- and post-menopausal population. Agreementbetween auto-analysis and an expert operator was as close asthe agreement between two expert operators. This algorithmsimpli®es analysis, minimizes operator intervention, and mayreduce inter-operator variability.

Mean differences (SD) in g/cm2 expert operators (OP1, OP2), and auto-analysis (AUT)

Region OP1 ± OP2 OP1 ± AUT OP2 ± AUTNeck 0.001 (.012) ±0.004 (.014) ±0.005 (.014)Hip Total 0.006 (.014) 0.0 (.016) ±0.006 (.019)Spine Total ±0.007 (.018) 0.003 (.015) 0.010 (.012)


93 (85). VARIABLE INTERPRETATIONS OF BONE MINERALDENSITY RESULTS IN A GROUP OF FILIPINOS USINGCAUCASIAN AND ASIAN REFERENCE VALUES

S. T. Saavedra1, T. P. Torralba1, S. H. Dy1, S. V. Navarra1, 1Sectionof Rheumatology, Immunology and Osteoporosis, Santo TomasUniversity Hospital, Manila, Philippines

OBJECTIVE: To determine variability in the interpretation of bonemineral density (BMD) using Caucasian and Asian referencevalues.

DESIGN: Cross sectional, descriptive study.SETTING: Joing and Bone Center (JBC) of Santo Tomas

University Hospital (STUH), tertiary private hospital in Manila.PARTICIPANTS: All patients referred to JBC for bone

densitometry from January to December 1999.INTERVENTION: BMD measurements were made by dual

energy x-ray absorptiometry (DXA) using Lunar DPX-IQ. TheBMD results were interpreted by World Health Organization(WHO) criteria using reference values derived from two popula-tions: Caucasians (American) and Asians (Chinese). Variability ininterpretations using either reference population was measuredby paired t-test.

RESULTS: A total of 1070 Filipinos (944 females, 126 males)were enrolled in the study. The mean age was 51.9 years withbody mass index (BMI) ranging from 13.1 to 45.3 (mean 23.97).Using the Caucasian reference values for spine BMD, 354(33.08%) were categorized as normal, 390 (36.45%) withosteopenia, and 182 (17.01%) were osteoporotic; for femoralBMD, 544 (50.84%) were normal, 446 (41.68%) osteopenic and 80(7.48%) osteoporotic. Lumbar spine and femoral neck BMDinterpretation by T-score signi®cantly differed using eitherCaucasian or Asian reference populations, p50.0001. Femoralneck BMD z-scores also showed signi®cant variability ininterpretation using Caucasian vs. Asian reference populationswith p value of 50.0001; no difference was noted using lumbarspine z-scores.

CONCLUSION: Interpretation of BMD values relies signi®cantlyon the reference population used. This will have signi®cantimplications in therapeutic recommendations.

94 (86). BONE MINERAL DENSITY AND KNEEOSTEOARTHRITIS IN ELDERLY WOMEN

G. Sahin, O. Cimen BoÈ lgen, A. BicË er, H. GuÈ ler, S. BagÏ is, Y. Yapici,C. Erdogan, Department of PMR, Mersin University, Faculty ofMedicine, Mersin, Turkey

To examine the possible inverse relationship between osteo-porosis (OP) and osteoarthritis (OA) we evaluated the associationbetween bone mineral density (BMD) and knee OA. Ninety-twopatients were enrolled to the study. Bone mineral density of theproximal femur (neck) was measured by densitometry. Knee OAwas assesed from a weight-bearing anterior-posterior radiographand graded on a scale of 0 (no OA) to (severe OA) according toKellgren-Lawrence.

The subjects included 92 women with an age range of 40±75years (mean 61,5870�7,4068 years). Of these 21 had no OA, 39had grade 1 OA, 22 had grade 2 OA, 8 had grade 3 OA and 2 hadgrade 4 OA. Mean femoral BMD (neck) was 0.7518�0.1132. Therewas signi®cant correlation between knee OA and BMD of femur(neck) statistically (r = ±0.235), (P<0.05). For BMD, there was nosigni®cant difference in the distribution of knee OA gradesbetween groups (p = 0.305). There was also no statisticallysigni®cant correlation between groups having knee OA (grade1,2,3,4) and no knee OA (grade 0) for BMD (p = 0.691).

So we conclude that relationship between OA and OP may bein¯uenced by other factors apart from osteophytosis and jointspace narrowing. However, the numbers of patients were low,existing data is preliminary and longterm studies with doubleblind controlled are needed.

95 (87). ULTRASOUND VELOCITY AND AMPLITUDE IN THEMETAPHYSIS OF FINGER PHALANGES DEPENDS ONCORTICAL POROSITY AS WELL AS GEOMETRY AND DENSITY

S. Sakata1, R. Barkmann1, E. M. LochmuÈ ller2, C. C. GluÈ er1,1Diagnostische Radiologie, CAU Kiel, Germany; 2Universitats-frauenklinik der LMU Muenchen, Germany

The cortical shell of long bones gets thinner and more porous dueto aging and disease. In this study we tested if ultrasound velocityin the metaphysis of ®nger phalanges correlated with porosity aswell as geometry and cortical density of each other.

We used 44 proximal phalanges, age 52 to 98 (15m, 29f) withremoved soft tissue, ®xed in formalin. Cross-sectional area of themetaphysis of ®nger phalanges were measured using Quantita-tive Ultrasound (DBM Sonic 1200, IGEA), High ResolutionQuantitative Computed tomography (HRQCT, Somatom Plus,Siemens) and High Resolution Magnetic Resonance Image(HRMRI, Siemens Medizintechnik, Erlangen). We used Speed ofSound (SOS) as a ultrasound velocity parameter and Area 2 Peaks(A2P) as a amplitude parameter. From HRQCT we calculatedcortical bone mineral density (cBMD), from HRMRI we calculatedthe site matched relative cross-sectional cortical area (RCA) asthe retio of cross-sectional areas of the cortex and the wholebone and cortical porosity (CP) as the ratio crosssectionalporosity areas in cortex and cortex areas.

SOS was signi®cantly correlated with RCA (R2=0.39,p50.0001), cBMD (R2=0.47, p50.0001) and CP (R2=0.30,p50.0001), while A2P was correlated with RCA (R2=0.20,p50.01), but not with cBMD and CP. The combination of RCAand cBMD using ANOVA model improved the correlationcoef®cient to R2= 0.58. RCA and BMD contributed signi®cantlyat p50.05 (RCA) and p50.01 (cBMD). SOS decreased withdecreasing cBMD as well as decreasing RCA and with increasingCP.

We conclude that these results could prove the impact ofphalanx geometry, cortical bone density and cortical porosity onultrasound velocity and only geometrical factor on amplitude.

96 (88). DOSE RELATED ASSOCIATION OF BONE MINERALDENSITY (BMD) AND HIGH IMPACT ACTIVITY INPREPUBERTAL GIRLS

T. A. Scerpella, C. M. Morganti, M. Davenport, L. M. Johnson, J.A. Kanaley, 1SUNY Upstate Medical University; 2SyracuseUniversity, Syracuse, NY, USA

The purpose of this study was to determine whether there is adose-dependent association between high impact activity andBMD in prepubertal girls.

Methods: Forty-nine 7±11 year old Caucasian female gymnasts,practicing at 3 different frequency levels [low, 2±5 hrs/wk (n=11);mid, 5±10 hrs/wk (n=20); and high, >10 hrs/wk (n=18)] werecompared to 23 sedentary controls, matched for height, weight,age, and Tanner stage. Hip, spine, arm, total body BMD and fatfree mass (FFM) were determined by dual energy X-rayabsorptiometry (DXA) (Hologic QDR4500). Anthropometrics,strength, calcium intake, gymnastics and total physical activitywere measured during the 6 months prior to DXA scanning.

Results: No difference in BMD between controls and low groupwas observed at any site. Mid and high groups had greater totaland regional BMD than controls and greater arm and hip BMDthan low group (p<0.05). Analysis of covariance revealed greaterBMD in mid and high groups than in controls when BMD wasadjusted for strength or FFM (p<0.05).

Conclusions: Total and regional BMD in prepubertal girls areincreased with ®ve or more hours per week of high impactactivity.


97 (89). STANDARD X-RAY WITH INTENSIFYING SCREENSFOR RADIOGRAPHIC ABSORPTIOMETRY: A PILOT STUDY

D. Silver1, L. Al-Dayeh2, X. Bi2, K. Hudson3, S. Silverman4, 1CedarsSinai Medical Center, OMC, UCLA, Los Angeles, CA, USA;2CompuMed, Los Angeles, CA, USA; 3OMC; 4Cedars SinaiMedical Center, VAGLAHS, OMC, UCLA, Los Angeles, CA, USA

Radiographic Absorptiometry (RA) is a reliable and inexpensivemethod for assessing BMD. Phalangeal BMD based on handradiography using RA predicts future fracture risk of the hip andspine. RA has required a two view hand x-ray without intensifyingscreens. We evaluated the use of RA using a standard radio-graphic technique and intensifying screens.

101 Caucasian and Asian females between the ages of 20 to 79had two consecutively acquired x-rays of the non-dominant hand.Phalangeal BMD was performed using an automated PC basedsystem (automated OsteoGram1, CompuMed, Inc., Los Angeles,CA). BMD results obtained with and without intensifying screenswere strongly correlated (r = 0.994, p<0.001).

The study suggests that standard radiographic techniques withminimal radiation exposure can be used for RA. We conclude thatautomated OsteoGram1 can provide an inexpensive method todetermine phalangeal BMD with readily available conventional x-ray equipment and technique.

98 (90). LONG-TERM INHALED STEROIDS AND BONEMINERAL DENSITY IN ASTHMA PATIENTS

D. Sindel1, A. Yaliman1, A. Oral1, E. Klyan2, D. Tarakci1,1Department of Physical Medicine and Rehabilitation, Istanbul,Turkey; 2Pulmonary Department, Istanbul University MedicalSchool, Istanbul, Turkey

The aim of the present study was to investigate trabecular andcortical bone density in asthma patients taking long term inhaledsteroids (range: 18±120 months, mean�SD: 40.06�22.06 months)and compare with results from normal controls. The mean diseaseduration was 9.40�6.45 years (range 2 to 20 years). We evaluatedbone status by dual energy x-ray absorptiometry (DEXA) andcalcaneal quantitative ultrasound (QUS) in 30 patients (16 females,14 males) aged 40 to 71 years (mean�SD: 57.168.29 years) havingbronchial asthma, treated with inhaled steroids and comparedthem with healthy subjects individually matched for age and sex.The mean avarage dose was 906.66�331.07 mg (range 400 to1200mg). Paired samples T test and Pearson correlation analysiswere used for statistical analysis. The bone mineral density (BMD)of the lumbar spine and of the hip were all signi®cantly lower thanthose of the matched control subjects (p<0.001). The calcanealQUS measurements were also lower in the patient group.Broadband ultrasound attenuation (BUA) showed a signi®cantinverse correlation with disease duration (r = ±0.421), whereasBMD did not. In conclusion, this study demonstrate that long-termuse of inhalational steroids for the treatment of asthma isassociated with decreased BMD and QUS variables.

99 (91). BONE MINERAL DENSITY IN PATIENTS WITH GRAVESDISEASE

L. Sipina, N. Kouznetsov, G. Kolesnikova, N. Goncharov, T.Chernova, National Endocrinology Research Center, Moscow,Russia

The objective of the research was to assess the correlationbetween Osteocalcin level and bone mineral density in womenwith Graves disease. There have been examined 36 patients,aged 22±70 years with hyperthyroidism. The BMD of lumbar spinefemoral neck was assessed using dual-energy X-Ray absorptio-metry (DEXA) LUNAR EXPERT XL. All patients received thyro-

static therapy for 2.4�0.9 years. The analysis of obtained datashowed the correlation between Osteocalcin level and bonemineral density (p<0.05). The data of the research show thevariability of Osteocalcin level in patients with Graves disease.The increase of Osteocalcin level in the majority of patients withGraves disease shows the presence of increased bone formation.The decreased bone mineral density in young (age<23 years) andpostmenopausal women with Graves disease associates with theincrease of Osteocalcin level. BMD in lumbar spine in women ofreproductive age with hyperthyroidism was signi®cantly lower ingroup of patients with overweight (BMI ±25.0±29.0) in comparisonwith the group of patients with normal weight (BMI ±18.5±24.9).BMD in femoral neck in premenopausal patients was slightlylower in group with normal weight (BMI ±18.5±24.9) than in groupof overweight patients, but this decrease was less signi®cant,than in the the previous case (p<0,75). Postmenopausal womenhad no correlation between BMD and BMI.

I II III

Age 20.5�4.2 35.9�8.1 58.2�6.4BMI 24.3�2.5 23.0�3.8 22.8�5.2TSH(mIU/ml) 0.1�0.3 0.3�0.5 0.2�0.7FT4 18.7�10.3 12.6�5.4 20.6�8.2Osteocalcin 50.1�7.9 13.4�8.2 57.7�5.6BMD (g/cm2)Neck 0.928�0.115 1.018�0.383 0.796�0.10

2Wards 0.758�0.120 0.827�0.289 0.595�0.09Trochanter 0.762�0.109 0.825�0.125 0.638�0.11

0L2-L4 1.024�0.076 1.347�0.129 0.896�0.09

100 (92). SRI JAYAWARDENEPURA COMMUNITY SURVEY OFOSTEOPOROSIS REFERENCE DATA FOR BROADBANDULTRASOUND ATTENUATION (BUA) & STIFFNESS INDEX

S. H. Siribaddana, U. Hewage, D. J.S. Fernando, Department ofMedicine, Sri Jayawardenepura University, Nugegoda, Sri Lanka

Hypothesis; Measurement of the Stiffness Index from a rando-mized representative sample of sub-urban women will provide a``young adult'' reference, and an age regression curve for thecalculation of T-scores and Z-scores.

Methods: Ambulatory women age 21 to 80 years were randomlyselected from electoral list in a suburban area. The computationof broad band ultrasound attenuation and speed of soundmeasured Stiffness Index by heel ultrasound (Lunar Achilles).

Results: BUA & Stiffness Index results were obtained from 700women. The stiffness Index demonstrated age regressiondescribed by: Age Regression of Stiffness Index =70.179+ AGE* (±0.319). BUA & Stiffness Index begins to decline dramaticallyafter 50 years. The reference value can be taken from womenaged between 20±50 years (n=446). The mean value for BUA was116.55 with standard deviation (SD) of 12.12. The mean value forstiffness index was 80.77 with a SD of 14.67. These values areused in calculating the T score.

Conclusion: The study provides representative, reference datafor assessment of osteoporotic fracture risk in Sri Lankan sub-urban women.

Age 21±30 31±40 41±50 51±60 61±70 71±80Number 143 144 159 160 70 24Stiffness 80.90 79.84 81.59 71.87 63.17 56.39SD 15.35 15.42 16.73 18.78 15.53 13.40BUA 115.61 115.77 117.94 110.33 100.59 95.04SD 14.86 13.23 12.96 20.55 15.30 12.66


101 (93). BONE MINERAL STATUS OF FEMALE ADOLESCENTS14 MONTHS AFTER THE CESSATION OF A CALCIUM ANDEXERCISE INTERVENTION

S. J. Stear, A. Prentice, S. C. Jones, T. J. Cole, MRC HumanNutrition Research, Cambridge, UK

Our recent 15-month Ca supplementation (1 g/d) and exerciseintervention enhanced bone mineral status in 16±18 year oldfemale adolescents. A follow-up study 14 months after with-drawal of Ca supplements and exercise sessions was conductedin 84 (64%) girls to investigate the intervention's lasting effect.Whole body and regional measurements of bone mineral content(BMC) and bone area (BA) were made by DXA (Hologic QDR 1000/W). Table gives mean percent difference (SE) between Casupplemented and placebo groups, for those with high com-pliance (>75% tablets taken) in change in BMC since baseline,corrected for BA, body weight, height and baseline BMC. Asigni®cant difference of 2.6% remained at the femoral neck, butdifferences at other sites were no longer signi®cant. If the effect ofCa supplement persists it could be of considerable clinicalsigni®cance, as it represents nearly quarter a SD in thispopulation, and which, if maintained into old age, might reducethe relative risk of hip fractures by a quarter.

(a=P40.05; b=P40.001) InterventionCa=21, P=23

Follow-upCa=21, P=23

Whole-body +0.9 (0.4)a +0.4 (0.5)Spine L1±4 +2.3 (0.6)b +1.0 (0.9)Hip ± total +2.8 (0.7)b +1.5 (1.1)Hip ± neck +2.7 (0.7)b +2.6 (1.1)aHip ± trochanter +5.3 (0.9)b +1.7 (1.6)

102 (94). IMPACT OF A CALCIUM AND EXERCISEINTERVENTION ON BONE MINERAL STATUS OF FEMALEADOLESCENTS

S. J. Stear, A. Prentice, S. C. Jones, T. J. Cole, MRC HumanNutrition Research, Cambridge, UK

To test the hypothesis that increasing Ca intake and taking partin regular exercise are important for the optimisation of peakbone mass, 131 female sixth-form students, 17.3�0.3 y, took partin a 15-month intervention study. Girls were randomly assigned,double-blind, to Ca (1000mg/d) or placebo and then strati®ed bysupplement type, were randomly allocated to an exercise(3 x 45min/wk) or control group. Whole body and regionalmeasurements of bone mineral content (BMC) and bone area(BA) were made by DXA (Hologic QDR 1000/W). Table gives meanpercent difference (SE) between intervention and control groups,for those with high compliance (Supplement >75%, exerciseattendance >50%) in BMC at outcome, corrected for BA, bodyweight, height and baseline BMC. Ca supplementation andexercise enhanced bone mineral status in these female adoles-cents. If it proves to be a lasting bene®t, leading to theoptimisation of peak bone mass, the risk of fragility fracturesshould be reduced.

(a=P40.05; b=P40.001) CalciumCa=32, P=30

ExerciseE=20, N=56

Whole-body 0.8 (0.3)a 0.4 (0.4)Spine L1±4 1.9 (0.5)b 0.6 (0.7)Hip ± total 2.7 (0.6)b 1.4 (0.7)aHip ± neck 2.2 (0.7)b 1.1 (0.9)Hip ± trochanter 4.8 (0.9)b 2.6 (1.2)aRadius-ultradistal 1.3 (0.6)a 0.1 (0.8)

103 (95). VALIDATION OF BIOELECTRICAL IMPEDANCEANALYSIS (BIA) IN ASSESSING BODY COMPOSITION:COMPARISON WITH TOTAL BODY DXA AND SERUM LEPTIN

B. Sutter, O. Legrand, F. Bianchi, F. Bougon, E. Meys, InstitutCALOT, Berck/Mer, France

OBJECTIVES: BIA is a fast low-cost radiation free tool for bodycomposition measurement. We evaluate a leg-to-leg BIA system(Bodymaster, Calor) and total body fan beam DXA as thereference method (Hologic QDR±4500A) in 109 subjects (women64 men 45, BMI 28.1�7.3 kg/m2 48.3�17.7 yr.). Additionally, leptinwas obtained in 60 subjects (Quantikine, R&D).

RESULTS: BIA reproducibility is 1.0� 0.8%. Correlationsbetween BIA and DXA total fat, real and DXA measured totalweight are summarized in table. There is a signi®cative differencebetween devices: BIA underestimates fat mass, while DXAunderestimates real weight. These errors are related to weight.Leptin correlated in same extent with both methods (r2= 0.541with DXA fat and 0.532 with BIA).

CONCLUSIONS: The leg-to-leg BIA. provides simple rapid and reproducible measurements of

body composition. is a good predictor of DXA-derived body fat superior to BMI

(r2= 0.908) and leptinA discrepancy is observed between the two methods: BIA

underestimates DXA measured fat, while DXA underestimatestotal weight. These biases worsen with body weight.

Total fat BIA vs DXA Total weight DXA vs weighing

r2 0.939 0.997difference ±2.1�5.2 kg ±1.9�2.4 kg

104 (96). COMPARISON OF DISTAL RADIUS SPA, SPINAL ANDFEMORAL DEXA AND TIBIAL ULTRASOUND METHODS FORDETERMINING OSTEOPOROSIS IN POSTMENOPAUSALWOMEN

C Tezel, C Erdogan, A Karabulut

Osteoporosis is a systemic skeletal disease characterized by lowbone mass and microarchitectural deterioration of bone tissue,with a consequent increase in bone fragility and susceptibility tofracture. Diagnosis and prevention of osteoporosis are importantbecause of the cost effects, fracture risk and mortality (12±21 %in hip fractures). We investigated the role of osteodensitometrywhich is a non invasive method, in the diagnosis of osteoporosisin postmenopausal women.

Fifty-three women with back or low back pain and/or withgeneral bone pain were included in the study. The means of age,weight, height, period of time since menopause have beendetermined. Serum calcium, phosphorus, alkaline phosphataseand urinary calcium (24 hours) were measured. Dorso-lumbarantero-posterior and lateral radiographs were taken. Compres-sion fracture was investigated by the method of Yamada et al.Bone mineral density was measured at lumbar spine and femoralneck by dual photon X-ray absorptiometry (DEXA), at distal radiusby single photon absorptiometry (SPA) and at mid-tibia byultrasound (ultraScan).

In the ®rst stage, means and standart deviations of age, weight,height, time since menopause, BMD values, T and Z scores,ultrasound SOS (speed of sound) and T score were calculated.These calculations were made both for the total sample and subsamples of those with or without compression fractures. Therelevant correlations were found. In the second stage, thedifferences of the values of the variables among the sub sampleswere tested by Student's t test. In the third stage ANOVA wasdone to see the signi®cance of the differences of variousmeasurements.


The three methods yield measurements which are weaklycorrelated.

105 (97). QUANTITATIVE COMPUTED TOMOGRAPHY IN THEEVALUATION OF VERTEBRAL BONE MINERAL DENSITY:COMPARISON BETWEEN 2-DIMENSIONAL AND 3-DIMENSIONAL IMAGING APPROACHES

D. J. Theodorou, S. J. Theodorou, D. Kubota, M. Andre, J.Weigert, D. J. Sartoris, Department of Radiology, Veterans AffairsMedical Center, and University of California, School of Medicine,San Diego, CA, USA

Purpose: Quantitative computed tomography (QCT) has longbeen used for the evaluation of bone mass and density. Ourpurpose was to correlate the diagnostic precision of 2-dimensional (2D) QCT with that of 3-dimensional (3D) QCT inthe assessment of bone mineral density (BMD) in the lumbarspine.

Patients and Methods: 21 women (age range, 42±82 years)referred for BMD evaluation were selected to participate in thepresent study. In all patients, a single-energy QCT scan at theL1-L2 vertebral levels was performed, and 10mm thicknesstransverse midvertebral slices were also obtained. Similarly, 3DQCT studies were performed at the same vertebral levelsselected for the 2D studies. Utilizing the scanner special analysissoftware, measurements of BMD were performed in prede®nedregions of interest (ROIs) of trabecular vertebral bone. Each dataacquisition was analyzed twice, yielding 2 pairs of BMD valuesper patient, and statistical analysis of resultant data wasconducted. To validate precision of our measurements, however,variability in values obtained by both imaging techniques wasestimated.

Results: No signi®cant difference in variability was observed inthe 2D and 3D QCT acquired measurements. 3D QCT BMDmeasurements were 8% larger than 2D QCT BMD measurements,likely owing to the incorporation of higher bone mass within theROI measured.

Conclusion: Our results indicate a non signi®cant differencebetween the BMD values derived from the 2D and 3D QCTimaging approaches, and suggest an important role for 3D QCT inthe evaluation of BMD in the lumbar spine.

106 (98). DISTRIBUTION OF BONE DENSITY IN CHILDREN 4±6YEARS OF AGE

J. Torner, S. Levy, T. Burns, M. Willing, J. Warren, K. Janz,University of Iowa, Iowa City, IA, USA

The purpose of this study is to describe and characterize factorsof bone development. A cohort of 305 children (160 girls and 145boys) was evaluated for bone density using an Hologic 2000 aspart of their annual exam. The children ranged in age from 4.3 to6.5 years with a mean of 5.2 years. Even within this restricted agerange bone mineral density (BMD) had a wide distribution.Correlations of bone mineral content (BMC) between sites werehigher (r = .77-.83) than correlations with BMD (r = .42-.58). Weightshowed the strongest individual correlation for BMD of the hipand spine and age had the largest for the whole body. A linearmodel with age, body mass index, height and gender accountedfor 27% of the variation for hip BMD, 28% for spine BMD and 11%for whole body BMD. Body size (body mass index and height) andgender was more signi®cant than age at all sites for BMD. Incontrast, regression models for BMC accounted for 55% of thevariation for hip, 53% for spine and 74% for whole body with bodymass index and height as the strongest variables.

BMD (gm/cm2) by Site

Location Mean Low High

Hip .563 .409 .736Spine .502 .382 .685Whole Body .719 .609 .850

107 (99). PREVALENCE OF LOW BONE MASS AMONG YOUNGFILIPINO FEMALE NURSES AT SANTO TOMAS UNIVERSITYHOSPITAL

T. P. Torralba1, S. V. Navarra1, S. T. Saavedra1, C. C. Bermudez1,M. T. Ong1, S. H. Dy1, L. B. Mercado-Asis1, 1Section ofRheumatology, Immunology and Osteoporosis; Section ofEndocrinology and Metabolism, University of Santo TomasHospital, Manila, Philippines

OBJECTIVE: To determine the prevalence of low bone massamong young Filipino nurses at STUH.

STUDY DESIGN: Cross sectional, descriptive study.SETTING: Joint and Bone Center of Santo Tomas University

Hospital, tertiary private hospital.PARTICIPANTS: All actively menstruating Filipino female

nurses at STUH ages 20±40 years old who underwent bonemineral density at Joint and Bone Center, STUH.

INTERVENTION: Lumbar spine (L1 to L4), femoral neck andforearm bone mineral density were made by dual energy x-rayabsorptiometry (DXA) using Lunar DPX-IQ. The prevalence ofosteoporosis was determined using the Asian (Chinese) referencepopulation de®ned according to the WHO criteria.

RESULTS: A total of 100 women were enrolled in the study witha mean age of 27.7. On lumbar spine examinations, 86 (86%)patients had normal results and 14 (14%) had osteopenia. On thefemur, 79 (79%) patients had normal results and 21 (21%) hadosteopenia. Seventy-seven (77%) had normal results, 22 (22%)had osteopenia and 1 (1%) had osteoporosis at the forearm.

CONCLUSION: The prevalence of low bone mass was 14 to22% in the group of Filipino nurses studied, especially at theforearm. It is important to review the factors underlyingosteopenia in this nurses, and perform repeat DXA in thefuture, to evaluate improvement re¯ecting peak bone massachievement.

108 (100). PREVALENCE OF OSTEOPOROSIS AMONGPERIMENOPAUSAL AND POSTMENOPAUSAL FILIPINOWOMEN STUDIED AT SANTO TOMAS UNIVERSITY HOSPITAL

T. P. Torralba1, S. T. Saavedra1, C. C. Bermudez1, M. T. Ong1, H.S. GoÂ mez1, S. V. Navarra1, S. H. Dy1, L. B. Mercado-Asis1,1Section of Rheumatology, Immunology and Osteoporosis;Section of Endocrinology and Metabolism, Santo TomasUniversity Hospital, Manila, Philippines

OBJECTIVE: To determine the prevalence of osteoporosis in agroup of perimenopausal and postmenopausal Filipino women.

STUDY DESIGN: Cross-sectional, descriptive study.SETTING: Joint and Bone Center (JBC), Santo Tomas

University Hospital (STUH), tertiary private hopsital.PARTICIPANTS: All perimenopausal and postmenopausal

Filipino women with ages 40 to 49 (n=32), 50 to 50 (n=30), and60 to 69 (n=43) who were referred for bone mineral density studyat the Joint and Bone Center, STUH.

INTERVENTION: Lumbar spine (L1 to L4), femur (neck) andforearm (total) bone mineral density (BMD) measurements weremade by dual energy x-ray absorptiometry using Lunar DPX-IQ.The prevalence of osteoporosis (T-score SD) was determined


using the Asian (Chinese) reference population based on theWCO criteria.

RESULTS: A total of 105 women were enrolled in the study.

AGE LUMBAR SPINE

Normal Osteopenia Osteoporosis40±49 (25) 78% (7) 22% 050±59 (13) 43% (13) 43% (4) 13%60±69 (23) 19% (23) 53% (12) 28%AGE FEMUR

Normal Osteopenia Osteoporosis40±49 (27) 84% (5) 16% 050±59 (18) 60% (4) 37% (1) 8%60±69 (11) 26% (28) 65% (4) 9%AGE FOREARM

Normal Osteopenia Osteoporosis40±49 (21) 66% (11) 34% 050±59 (8) 27% (18) 60% (4) 13%60±69 (10) 23% (14) 33% (19) 44%

CONCLUSION: Osteoporosis involving the lumbar, femoral andforearm areas is highest among the postmenopausal Filipinowomen aged 60 to 69 years.

109 (101). BONE MASS, BODY COMPOSITION AND BONEULTRASOUND MEASUREMENTS IN ANKYLOSINGSPONDYLITIS

E. Toussirot, F. Michel, B. AugeÂ , D. Wendling, Rheumatology,Besancon, France

Objectives: 1- to examine bone mass using dual energy X-rayabsorptiometry (DEXA) and quantitative ultrasound in ASpatients. 2- to determine the changes in body composition.

Methods: 57 AS patients (modi®ed NY criteria)(41 M, 16 F, meanage 38.02) were compared to 60 healthy controls (HC)(43 M, 17 F,mean age 36.4)(no post-menopausal women). Lumbar spine (LS)and femoral neck (FN) bone mineral density (BMD) wereevalutated using a DPX-IQ scan (Lunar). Broadband ultrasoundattenuation (BUA) and speed of the sound (SOS) were measuredat the calcaneus (Achilles, Lunar). Body mass parameters (DPX-IQ) included total BMD, total bone mineral content (BMC), leanmass (LM), fat mass (FM).

Results:

LS BMD FN BMD BUA dB SOS Total BMD Total BMC LM FM

g/cm2 gcm2 /MHz m/s g/cm2 g g g

AS 1.075 0.977 122.2 1555. 1.202 2896. 47906 16967

HC 1.185 1.047 124.1 1566. 1.251 3196. 50806 17851

P .0002 0.01 NS NS 0.02 0.006 NS NS

Conclusions: the reduced BMD and BMC in AS patients re¯ecta bone impairment. In contrast, no changes were evidenced byultrasound measurements and no modi®cations in body compo-sition (lean/fat mass) were observed. As opposed to DEXA,quantitative ultrasound does not appear to be a suitable methodfor screening AS patients with osteoporosis.

110 (102). CHARACTERISTICS OF CHANGES IN BONEMINERAL DENSITY BEFORE AND 6 MONTHS AFTEROVARIECTOMY IN AGED CYNOMOLGUS MONKEYS

Hideshi Tsusaki, Shuichi Kamata, Koichiro Fukuzaki, HiroakiMiyajima, Ryoichi Nagata, Shin Nippon Biomedical Laboratories,Ltd., Kagoshima, Japan

The purpose of this study is to clarify characteristics of changesin bone mineral density (BMD) of the lumber and femoral neck of

the cynomolgus monkey, using double X-ray absorptiometry(DXA) and peripheral quantitative computed tomography (pQCT)before and after ovariectomy (OVX). Aged female cynomolgusmonkeys (9 years or older) were used. The animals were used forthe measurement of BMD before, and 6 months after OVX orsham-operation. Each animal was held in the supine positionunder ketamine hydrochloride anesthesia. The BMD of thefemoral neck was measured by XCT±3000 (Norland Stratec).The BMD of the 3rd to 5th lumber vertebrae was measured by(DPX-a, Lunar). Compared with the sham-operated group, astatistically signi®cant decrease in BMD in the lumber (assessedwith DXA) was noted. BMD in the femoral neck (assessed withpQCT) in the OVX group tended to be lower than that in the sham-operated group, but no apparent differences were noted betweentrabecular and cortical bone densities.

111 (103). EVALUATION OF BONE MINERAL DENSITY IN ATURKISH POPULATION

F. Tuzun, S. Tuzun, I. Karacan, N. Selim, 1University of Istanbul,Cerrahpasa, Istanbul, Turkey; 2University of Istanbul, Cerrahpasa,Istanbul, Turkey; 3University of Istanbul, Cerrahpasa, Istanbul,Turkey; 4Bestas Group, Lunar, Turkey

The aim of this study was to determine the range of bone mineraldensity (BMD) in normal Turkish adults using a Lunar DPXdensitometer. Four sites (total body, AP spine, femur andforearm) were investigated in 370 healthy subjects of bothsexes (91 male and 246 female) aged between 20 and 82 yearsfrom 29 different centres. There was a positive correlationbetween BMD, body weight and height in both sexes, especiallyin postmenopausal women. The timing of peak bone density atAP spine and distal radius was 4th decade in both genderswhereas it was 3rd decade in men and 4th in women at femurneck. Total body BMD was signi®cantly higher in men in alldecades. BMD values at distal radius and femur neck were foundto be higher in men in the 3rd decade. The major fall in the BMDwas observed in women related to the menopause after 50 years.There was no relationship between BMD and both age atmenarche and parity whereas there was an inverse relationshipbetween BMD and the duration of menopause.

112 (104). MULTIPLE SCLEROSIS; THE ROLE OFCORTICOSTEROIDS AND IMMOBILITY ON BONE MINERALMETABOLISM

S. Tuzun, A. Altintas, I. Karacan, S. Tangurek, A. Siva, Universityof Istanbul, Cerrahpasa, Istanbul, Turkey

Bone mineral metabolism can be affected in MS due to severalfactors such as corticosteroid treatment, decreased mobility andpotential vitamin D de®ciency. 83 clinically de®nite MS patients(60 female.23 male) with a mean age of 39.14+9.37 and 62 age-matched controls were enrolled to the study. Besides detailedclinical examination, EDSS, Barthel Index, Functional indepen-dence measure(FIM), cumulative corticosteroid (CCS) dosages astotal peroral (PO), total parenteral (PE) and cumulative PE dose ina year before enrollment were recorded. BMD was measuredusing a Holojic QDR 4500 Plus. Serum Ca,P, Mg, bone alkalinphosphatase, PTH, 25OHD3, 1,25(OH)2D3, osteocalcine, urinedeoxypridinoline and 24 hour urinary Ca/creatinine exretion werestudied. Patients were categorized in ®ve groups according to theadministration and cumulative dosages of CS as follows: Groupla, <1500mg, PO, group Ib; >1500mg, PO, group IIa; <10000mg,PE, group IIb; 10000±30000mg PE, group IIc; >3000mg, PE, BMDvalues at lumbar spine and femur (neck, trochanter, ward's area)were signi®cantly decreased in MS patients (p = 0.000). EDSS,Barthel and FIM scores were correlated with BMD values in allevaluated regions. Signi®cance was prominent for trochanter andneck regions but not for lumbar spine. There was no correlation


between BMD scores and the CCS dosages in any treatmentgroup. Serum vitamin D levels were within normal limits in MSpatients and evaluated biochemical markers did not show anycorrelation with both CCS dosage and disability scores.Signi®cantly decreased BMD values was found in MS groupthat was correlated with disability scores but was independent ofthe CCS dosage received. Disability scores that were consistentwith preserved ambulation in our study group and the lack ofsigni®cance between osteoporosis at lumbar spine and disability,further that disability is not the only factor responsible forosteoporosis in MS. Immune factors like cytokines those have arole both in MS pathogenesis and bone metabolism could be analternative explanation of our results.

113 (105). MODEL-FITTING AND PREDICTION OF BONEMINERAL DENSITY IN THE LUMBAR SPINE, FEMORAL NECK,AND RADIUS OF HEALTHY WOMEN AFTER NATURALMENOPAUSE IN A LONGITUDINAL STUDY BY USING ANEXPONENTIAL-TYPE NONLINEAR MIXED-EFFECT MODEL

H. Watanabe1,3, M. Fukunaga2, Y. Ohashi1, 1University of Tokyo,Tokyo, Japan; 2Kawasaki Medical School, Okayama, Japan;3Teijin Ltd, Tokyo, Japan

The subjects of this study were 89 healthy women after naturalmenopause. An exponential-type nonlinear mixed-effect modelwas used to estimate and predict bone mineral density (BMD) ofthree sites: the lumbar spine, femoral neck, and distal 1/3 of theradius. The year since menopause (YSM) and age at menopause(AAM) were used as explanatory variables. The exponential-typenonlinear mixed-effect model was analyzed as (BMD)ij = a + ai + (b+ bi)exp(g . (YSM)ij) + d((AAM)i ± sÃ ) + eij, ai ~ iidN (0,s2

a), bi ~ iidN(0,s2

b), eij ~ iidN (0,s2e) (i:subject, j:time point, a, b, g, and d as the

means of the population, and ai and bi as random effects amongsubjects). The results were as follows: lumbar spine: (BMD)ij =(0.792 + ai + (0.179 + bi) exp(±0.185 x (YSM)ij) ± 0.00250((AAM)i ±50.6), sÃ 2a = (0.106)2 sÃ 2b = (0.0450)2 sÃ 2e = (0.0185)2 femoral neck:(BMD)ij = 0.595 + ai + (0.156 + bi) x exp(±0.105 x (YSM)ij) ±0.00511((AAM)i ± 50.6), sÃ 2a = (0.0880)2 sÃ 2b = (0.0659)2 sÃ 2e =(0.0181)2 and radius: (BMD)ij = 0.476 + ai + (0.122 + bi) exp(±0.106x (YSM)ij) ± 0.00196((AAM)i ± 50.6), sÃ 2a = (0.0680)2 sÃ 2b = (0.0513)2

sÃ 2e = (0.0138)2. These formulae were also used to derive aprediction formula for each individual by using Bayesianapproach.

114 (106). THE IMPORTANCE OF PRECISION-NEW HOPES FORMONITORING OSTEOPOROSIS TREATMENT BY QUS

M. Weiss1, E. Segal2, S. Ish-Shalom2, 1Endocrine Institute andDepartment of Medicine C, ``Assaf Harofeh'' Medical Center,Zeri®n; 2Rambam Medical Center and Bruce Rappoport Facultyof Medicine, Technion, Haifa

The use of quantitative ultrasound (QUS) measurement in thediagnosis of osteoporosis is growing. The role of QUS stillrequires the de®nition of diagnostic criteria and not less importanta proof for treatment monitoring capability.

A short-term precision of SOS measurements of the SunlightOmnisense [Omnisense], an ultrasound device that measuresspeed of sound (SOS) at multiple sites, was determined by threeoperators, each performing repeated measurement after reposi-tioning in 15 women age 20±70. The data obtained indicates intra-operator measurement CV of 0.40% at the Distal 1/3 Radius(RAD), 0.45% at the Mid-Shaft Tibia (TIB), 0.66% at the MetatarsalV (MTR) and 0.81% at the Proximal Phalanx III (PLX). Computed inT-score units, the intra-operator precision is 0.16, 0.18, 0.12 and0.20 for the RAD, TIB, MTR and PLX respectively. The Inter-operator CV was 0.8% at the RAD, 1.3% for the TIB, and 1.4% atthe MTR and the PLX, RAD, TIB, MTR and PLX range-normalizedstandardize precision sCV was 3.3%, 3.3%, 3.0% and 4.5%

respectively. Within the Caucasian population, following meno-pause (age group 54±61), SOS declined sharply at an annual rateof 16, 35, 37 and 13 m/sec for the RAD, PLX, MTR and TIBrespectively. Largest annual decline was 16 m/sec/y for the RAD,35 m/sec/y for the PLX, 37 m/sec/y for the MTR and 13 m/sec/yfor the TIB. This rate is close to the short-term CV, and could beused to compute the Monitoring Time Interval (=2.8*Rate/Precision SD) or the Trend Assessment Interval (=1.8*Rate/Precision SD). We conclude that the time interval between SOSmeasurements in normal women in this age range who donot have a bone-affecting disease and are not treated withbone affecting drugs should be at least two year apart. Onlythen, a meaningful change of at least two SD units could beexpected.

Prospective studies to investigate the monitoring capability ofthe Omnisnese are currently being performed.

115 (107). QUANTITATIVE ULTRASOUND OF THE CALCANEUSIN HEALTHY TURKISH MEN

A. Yaliman, A. Oral, D. Sindel, Department of Physical Medicineand Rehabilitation, Istanbul University Medical School, Turkey

The aim of this study was to determine the ultrasound parametersof the calcaneus in a healthy men population and to assess theeffect of age, body mass index on the measurements and therelationship between measurements. We measured broadbandultrasound attenuation (BUA), speed of sound (SOS) andquantitative ultrasound index (QUI) of the calcaneus of left feetin 416 healthy men aged 18 to 87 years (mean 45.54�17.43 years).Pearson correlation and lineer regression analyses were used forstatistical analysis. BUA ranged from 33.50±136.60 dB/MHz(mean 76.67�17.25); BUA signi®cantly correlated with SOSr = 0.836), QUI (r = 0.921). SOS ranged from 1472.9±1658.7m/s(mean 1544.54�33.16), SOS signi®cantly correlated with QUI(r = 0.977). QUI ranged from 49.9±165.1 (mean 93.58�19.71).Body weight, height, body mass index were not correlated withultrasound parameters in the study group; measurementscorrelated with age negatively but nonsigni®cantly.

116 (108). SEPARATED MEASUREMENT OF TRABECULARAND CORTICAL BONE IN QUANTITATIVE COMPUTEDTOMOGRAPHY (QCT) OF LUMBAR SPINE

Akio Yokoi, Tetsuya Katou, National Tokyo Medical Center,Tokyo, Japan

Purpose: QCT is thought to be one of the useful methods formeasuring the bone mineral density (BMD) in osteoporosis,because of its ability to measure BMD limited to trabecularbone. Placing the region of interest (ROI) at the lumbar spine, weset the three different ROIs; vertebral body spongiosa (SPG),vertebral body cortex (CTX), and vertebral posterior part (PST).We have evaluated the differences of BMD between the arealimited to spongiosa and the area including the surroundingcortical bone like as DEXA method.

Methods: QCT value was measured in 189 women (31±94year-old, mean 65.9) by GE±9800 CT-scanner. BMD was determinedwith a phantom B-MAS (Chugai Pharma. Co.) calculating into theweight of CaCO3. Three ROIs were traced by author after CTscan. The ROI of SPG was placed by the traced line along theinner margin of body cortex without nutritional sinus at the baseof body. The ROI of CTX was from the outer margin of bodycortex to the front of transverse process without SPG. The ROI ofPST was along the base of transverse process, vertebrallamina, facet joint, and spinal process excluding the spinalcanal space.

Results: Average QCT-value by conventional method was 84.6mgCaCO3/cm 3. Patients were compared by dividing into twogroups: mid-age (<66yo.) vs old-age (66<=), and low-QCT (SPG<=


96) vs high-QCT (96<SPG). All QCT-values of SPG, CTX, and PSTin each groups were multiplied by their areas respectively, whichimplies each BMC (mgCaCO3). Then, BMD in SPG+CTX+PSTwhich resembles AP-method in DEXA, and BMD in SPG+CTXwhich resembles lateral method in DEXA were calculated.

BMD SPG AP-method Lat-method

mid-age 120 283 179old-age 84 218 141low-QCT 66 207 122high-QCT 140 294 199

Summary: BMD in AP-method was 2.1~3.1 times of BMD inSPG, and in Lat-method 1.4~1.9 times, suggesting that BMD inDEXA is possibly evaluated so high as at least 1.4 times than BMDin trabecular bone of vertebral body.

Osteoporosis ± Epidemiology

117 (109). NUTRITIONAL RISK FACTORS IN LITHUANIANWOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS

Vidmantas Alekna, Elena Cheremnych, Marija Tamulaitiene,Institute of Experimental and Clinical Medicine, Vilnius, Lithuania

Introduction. Many behavioral factors are believed to bedeterminants of bone mass and bone mineral density. One ofthem is calcium intake from milk and diary products.

Patients and methods. A total of 73 women with postmeno-pausal osteoporosis and 80 controls (random sample) werestudied retrospectively as to determine the risk factors. Thedietary calcium intake was assessed by the special lifestylequestionnaire.

Results. The mean age of women with osteoporosis was61.9�1.2 years, controls aged 60.7�0.8 years. The differencebetween groups in their nutrition was disclosed by the ques-tionaire. In osteoporotic group 52.2% women were not consum-ing enough milk and diary products. In control group only in28.4% cases adequate intakes of calcium-rich milk products werelow.

Conclusion. These results suggest that low milk and diaryproducts consumption may be important in the genesis ofosteoporosis.

118 (110). INCIDENCE OF OSTEOARTHRITIS (OA) IN PATIENTSWITH DIFFERENT MEAN VALUES OF BONE MINERAL DENSITY(BMD) OF THE LUMBAR SPINE AND FEMORAL NECK FROMEPIDEMIOLOGICAL SAMPLE OF MOSCOW

L. Alexeeva, L. Benevolenskaya, E. Mikhailov, A. Smirnov,Institute of Rheumatology of RAMS, Moscow, Russia

Aim: to determine the incidence of knee-, hip±and nodal OA inpatients with different mean values of bone mineral density (BMD)of the lumbar spine and femoral neck from epidemiologicalsample of Moscow.

Materials and methods: 103 females from epidemiologicalsample of one of the Moscow regions had bone massmeasurements of the lumbar spine (L1 ± L4) and femoral neck(Hologic QDR±1000) and X-ray of knee and hip joints. Presence ofknee and hip OA was de®ned by Kellgren-Lawrence grade 52Nodal OA was diagnosed clinically according ACR criteria. Theirage ranged from 50 to 79 yr.

Results: patients with normal BMD had more frequently tibio-femoral OA of knee (78.6%), patello- femoral OA of knee (53.6%)

and nodal OA (53,6%) in comparison with OP females (p50.05)(53.3%, 13.3% and 38.9% correspondently).

Conclusion: the patients with normal BMD signi®cantlyfrequently had knee and nodal OA in comparison with OPpatients. These data support the hypothesis that higher BMD isassosiated with OA.

119 (111). STUDY OF HIP FRACTURES INCIDENCE INMOSCOW REGION (ELECTROSTAL)

S. G. Anikin, L. I. Benevolenskaya, Institute of RheumatologyRAMS, Moscow, Russia

The goal of this study was to determine the incidence of hipfractures in Electrostal, Moscow region.Materials and Methods. We evaluated the cases of hip fracturesamong population at age of 50 years and over from Electrostal(population 150 000) in period from January 1st 1992 to December31st 1997. We used data of Electrostal hospital and town statisticboard for analyses. Incidence rates were calculated according toISD 9, code 820.

Results: hip fractures incidence was 54.6/100 000 person/years(p/y) in males, 77.4 p/y in females (in total). The incidence of hipfractures in minimal trauma was 46.9 p/y (from 34.7 in 1994 to 64.8in 1996 p>0.05) in males and 72.1 p/y (from 35.5 in 1993 to 92.0 in1997 p<0.05) in females (86% and 97% from total traumaaccordingly). The incidence increased with age: from 15.4 p/y(age 50) to 54.7 (age 65) among males (p<0.02) and from 8.6 (age50) to 60.9 (age 65) among females. It was the highest at age 80years and over: 165.5 p/y (p>0.05) among males and 361.0 p/y(p<0.002) among females. Ratio female/male was 1.5 (p = 0.01).

Conclusion: the incidence of hip fractures was higher amongmales and increased with age in Electrostal, the typical town ofEuropean part of Rassia.

120 (112). REPRODUCTIVE FACTORS, BMD, AND FRACTUREHISTORY: THE NORA STUDY

E. Barrett-Connor, L. Wehren, D. Furman, T. Abbott, E. Siris, P.Miller, K. Faulkner, M. Berger, A. Santora, L. Sherwood, Universityof California, San Diego, La Jolla, CA, USA

Since estrogen is an important determinant of bone mineraldensity (BMD) among postmenopausal women, exposure duringreproductive years has been hypothesized to affect postmeno-pausal BMD and fracture risk. NORA, a large observational studyof osteoporosis in postmenopausal, ambulatory women, providesan excellent opportunity to examine the associations of elementsof reproductive history with peripheral BMD (T-scores) andfracture history after age 45. Baseline data on risk factors andreproductive history were collected from 47,050 women who hadnot had hysterectomies. The key variable of interest was theduration of endogenous estrogen exposure (difference betweenthe ages of menarche and menopause). Other variables examinedincluded parity, lactation, oral contraceptive (OC) use, age ofmother at birth of ®rst- and last-born children, and postmeno-pausal (PM) estrogen supplementation. We estimated theseparate and collective effects of these variables on BMD andfracture risk using bivariate analyses and (linear and logistic)regression models adjusted for age, ethnicity, and level ofeducation. Using women with less than 30 years of endogenousestrogen exposure for comparison, T-scores increased .12, .25,.41, and .53 and the odds ratios for fracture were .92, .87, .76, and.76 among women with 30±34, 35±39, 40±44, and 45+ years ofendogenous estrogen, respectively. OC usage, parity, and PMestrogen usage also had signi®cant positive effects on BMD. Thestudy provides evidence that the duration of endogenousestrogen exposure has a bene®cial effect on BMD and lowersfracture risk (even after adjusting for BMD)!


121 (113). BONE MASS AND FRACTURE RISK IN THEPROXIMAL FEMUR AMONG OLDER WORLD-CLASS MALETRIATHLETES

G. Bibb, S. Farooki, E. M. Kwong, G. F. Rocha, M. L. Look, M. A.Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D.J. Sartoris, 1University of California School of Medicine, SanDiego, CA, USA

PURPOSE: To investigate the bone mineral content (BMC) anddensity (BMD) in the proximal femur among elite, highperformance male triathletes over 45 years of age.

METHODS: 95 males were randomly recruited from the 1000participants competing in the 1999 Ironman World ChampionshipTriathlon at Kona, Hawaii. Subject age ranged from 45±76 (mean54) years. Detailed information regarding diet, exercise regimen,medical problems, lifestyle habits, and personal/family fracturehistory were obtained from all study participants. BMC and BMDof the proximal femur (regions including neck, greater trochanter,Ward triangle, proximal diaphysis, and total), frontal lumbar spine,and total body were measured using a Norland Medical SystemsXR±36 pencil-beam dual-energy X-ray absorptiometry (DXA)system. Performance times for the swimming, bicycling, andmarathon components of the event were documented. Statisticalanalysis was performed using Minitab version 12 software.

RESULTS:

REGION MINIMUM T MAXIMUM T MEAN T MINIMUM Z MAXIMUM Z MEAN Z

Total ±1.89 3.13 0.007 ±0.85 3.3 0.35

Neck ±2.99 1.93 ±0.58 0.51 2.42 1.44

Trochanter ±2.81 2.18 ±0.34 ±1.78 2.83 0.29

Ward ±3.78 0.38 ±1.9 ±2.32 1.45 ±0.385

CONCLUSION: According to World Health Organization (WHO)crteria, although osteopenia and osteoporosis occur amongworld-class male triathletes over 45 years of age, prevalence isextremely low. As a group, T- and Z- scores fall within the normalrange for the regions of greatest clinical importance (total, neck,trochanter). These results are compatible with the intensephysical training regimens of these older men, and emphasizethe importance of exercise in the prevention of age-related boneloss throughout life.

122 (114). INFLUENCE OF VDR POLYMORPHISM ON MUSCLESTRENGTH IN ELDERLY MEN

H. A. Bischoff1, W. Dick1, P. Geusens2, L. Michiels3, R. Theiler4, H.B. StaÈ helin5, 1Orthopedics, University Basel, Switzerland; 2Dept.of Rheumatology, Academic Hospital, Maastricht, TheNetherlands; 3Biomedical Research Institute, Limburg UniversityCenter, Diepenbeek, Belgium; 4Rheumatology, University Basel,Switzerland; 5Geriatrics, University Basel, Switzerland

Muscle strength has been related to vitamin D receptorpolymorphism (VDRP) in elderly non-obese women with in-creased muscle strength in bb genotype compared to BBgenotype. The purpose of this study was to investigate thisrelationship in 212 ambulatory elderly men (mean age: 76.8; agerange: 66±95). Muscle strength was measured as leg extensionpower in watts (LEP) and was 12% higher for BB genotypecompared bb genotype (p = 0.04). After correction for body massindex (BMI) this association remained signi®cant. However; effectof VDR genotype on muscle strength was lost in subjects olderthan 80 years (ANOVA: age 580: p = 0.025; > 80: p = 0.85). LEPdeclined with age (r = ± 0.48, p50.0001) and was positivelycorrelated with both 25-hydroxyvitamin D and 1,25-dihydroxyvi-tamin D (r = 0.24; p = 0.0004 / r = 0.14; p = 0.045). No associationwas found between the VDRP and vitamin D metabolites orbiochemical markers of bone turnover.

These results indicate an association of an allelic variant at theVDR locus with muscle strength in elderly men in their sixth andseventh, but not eighth decade, independent of BMI, suggestingthat the effect of the VDRP on muscle strength declines with ageas previouly described for the in¯uence of VDRP on BMD. Thedifference in allelic patterns on muscle strength in men andwomen might be explained by the effect of sex steroids on theexpression of VDRP. Further studies are indicated on the effect ofVDRP on muscle strength with age and dependency on sexsteroids.

123 (115). DOES RALOXIFENE REDUCE NON-VERTEBRALFRACTURE RISK IN WOMEN WITH VERY LOW BMD: RESULTSFROM THE MORE STUDY

D. M. Black, T. Blackwell, B. Ettinger, S. Sarkar, K. Harper, K.Ensrud, S. Cummings, 1University of California, San Francisco,CA; 2Kaiser Permanente, Oakland, CA; 3Eli Lilly & Co.,Indianapolis, IN; 4University of Minnesota, Minneapolis, MN,USA

Recent studies have suggested that, among women withoutvertebral fractures (VFx), bisphosphonates reduce non-vertebralfracture risk more effectively in those with lowest BMD. Forexample, FIT recently showed that, among women with VFx, thereduction in non-vertebral fractures with alendronate was only14% overall compared to 36% in the subgroup of women withT<±2.5. To address whether this is also true for raloxifene, aselective estrogen receptor modulator, we analyzed data from theMultiple Outcomes of Raloxifene (MORE) trial in which 7705women were randomized to placebo, raloxifene 60 or 120 mg andfollowed for 3 years. The analysis was limited to the 4805 womenwithout baseline VFx. A total of 356 non-vertebral and 128 spinefractures occurred in this subset. We compared the effect ofraloxifene on all non-vertebral and incident spine (morphometric)fractures within tertiles of baseline femoral neck (FN) BMD. Theresults showed no evidence that the effect of raloxifene varied byinitial BMD. We conclude that, among women without existingVFx, raloxifene shows no greater reduction in non-vertebralfractures in women with lower BMD. Whether these resultsrepresent a more general distinction between SERMS andbisphosphonates remains to be determined.

Effect of raloxifene in 4805 women without baseline vertebral fractures:

Baseline FN BMD Non-vertebral fractures Spine fracturesTertile T-score RR 95% CI RR 95% CI

Low <±2.6 1.05 (0.75, 1.47) 0.48 (0.28, 0.82)Middle ±2.1±2.6 0.67 (0.47, 0.94) 0.81 (0.43, 1.50)High >±2.1 0.93 (0.62, 1.39) 0.42 (0.22, 0.78)Overall 0.87 (0.71, 1.07) 0.53 (0.38, 0.75)

124 (116). OCCURRENCE OF OSTEOPOROSIS IN BULGARIA ±A STUDY OF THE BULGARIAN LEAGUE FOR THE PREVENTIONOF OSTEOPOROSIS

A-M. Borissova, R. Kovatcheva, A. Shinkov, M. Vukov, R.Shigarminova, 1Medical University, So®a, Bulgaria; 2NationalCentre for Information In Medicine, So®a, Bulgaria

The Bulgarian League for the Prevention of Osteoporosis (BLPO)performed a bone density measurement in three Bulgarian cities.627 women were included, mean age 48.4, 295 (47.1%) hadmenstrual cycle and 332 (52.9%) were postmenopausal. Osteo-penia or osteoporosis was observed in 269 (42.8%), 102 (37.9%)menstruating and 167 (62.1%) postmenopausal (p<0.001). Bonedensity was signi®cantly lower in the postmenopausal group(p<0.001). Fractures after the age of 40 were reported by 38


(6.2%) women ± 27 (8.76%) postmenopausal and 12 (4.35%)menstruating (p<0.01). The T-score showed a positive correlationwith the fracture risk (p<0.05). Of all postmenopausal women only36 (10,8%) used HRT ± 1/3 had surgical and 2/3 had naturalmenopause, and 80% were married and 20% divorced. Singlewomen and widows and subjects with secondary education didnot apply HRT. Of all postmenopausal women only 14 (4,21%)had been on HRT for more than one year. Conclusions:Osteopenia or osteoporosis were observed in 42,8% of themiddle-aged Bulgarian females. Of them 6,2% had a fracture afterthe age of 40. Only 4,21% of postmenopausal women in Bulgariahave been receiving HRT for more than one year.

125 (117). INTERSITE RELATIONSHIPS OF BONE MINERALDENSITY (BMD) IN ELITE FEMALE TRIATHLETES

G. J. Boyd, E. M. Kwong, G. F. Rocha, M. Look, G. Nakamoto, M.A. Mikus, L. Musial, C. T. Norred, M. D. Bracker, D. J. Sartoris,University of California School of Medicine, San Diego, CA, USA

PURPOSE: To investigate bone mineral density in elite femaletriathletes with particular reference to intersite relationships.

METHODS: 139 elite female athletes (age 22±69, mean=39)years participating in the 1999 Ironman World ChampionshipTriathalon in Kona, Hawaii were prospectively enrolled. Wholebody DXA, non-dominant proximal femoral DXA and frontallumbar spine DXA was performed using a Norland XR±36 pencilbeam table top scanner. Detailed history regarding diet, exerciseand lifestyle habits, medical problems, family and personalfracture history, and menstrual function was obtained on eachsubject. Performance times in the event swim, cycling tour, andmarathon were also recorded.

RESULTS: Regression analysis demonstrated a statisticallysigni®cant correlation (p<0.001) between whole body BMD vstotal/regional femoral BMD, however, whole body BMD vs totalspine BMD (p = 0.86), as well as total/regional femoral BMD vstotal spine BMD (p = 0.88) did not correlate. Subsequently, BMDof individual spine segments was analyzed and compared to bothwhole body BMD and total/regional femoral BMD. BMD at the L2and L3 levels directly correlated (p<0.001) with both whole bodyBMD and total/regional femoral BMD, whereas BMD at the L4level did not correlate with either whole body BMD or total/regional femoral BMD (p = 0.77 and p = 0.89, respectively).

CONCLUSIONS: In elite female triathletes a statisticallysigni®cant relationship is demonstrated between whole bodyBMD and total/regional femoral BMD. Total spine BMD does notcorrelate with either whole body BMD or total/regional femoralBMD. BMD at L2 and L3 is signi®cantly correlated with wholebody and total/regional femoral BMD, and the absence of suchcorrelation at the L4 level (as well as visual inspection of DXAscan images) suggests a relatively high prevalence of degen-erative disease in the lower lumbar spine among this population.This association implies that excessive physical exercise inwomen may predispose to low back problems, or that thepresence of the latter does not preclude high performancetriathlon participation.

126 (118). LOW PREVALENCE OF POSTMENOPAUSALFRACTURES IN THE HONDURAN RAIN JUNGLE

W. Bronson1, J. McMillen2, S. Gondring3, E. Brooks4, W.Gondring5, 1Heartland Health Systems, (HHS), St. Joseph, MO,USA; 2HHS; 3St. Joseph, MO, USA; 4Missouri Western StateCollege, St. Joseph, MO, USA; 5HHS,

The purpose of this investigation was to estimate the prevalenceof postmenopausal hip, wrist, and vertebral fractures in anisolated indigenous population of women in a rain jungle.

During a six day period, 226 consecutive adult women werescreened in village clinics in St. Lucio, Coyolito, and San Isidrolocated in the Department of Yoro, Honduras. The Spanishversion of the Simple Calculated Osteoporosis Risk Estimation(SCORE), Merck & Co., Inc. was given. Heights and weights weremeasured. Sixty-six postmenopausal women were identi®ed.There was a history of one broken wrist and one broken hip inthis group. There was no signi®cant difference in the meanheights among postmenopausal women by decade (p = 0.84).Twenty-four women had score totals 512. In a 1998 study ofpostmenopausal American women a score total of 512correlated with osteopenia or osteoporosis. In the absence ofany hormone replacement therapy, there appears to be a lowprevalence of fractures of the hip, wrist, and spine among thesepostmenopausal women and possibly in the Honduran rain jungleregion.

SCORE Totals for Postmenopausal Honduran Women

Age N Mean Total SD

41±50 24 5.71 3.3251±60 16 9.88 2.9261±70 20 13.05 4.5171±82 6 17.67 3.88

127 (119). VALIDATION OF HISTORY OF OSTEOPOROTIC ANDNON OSTEOPOROTIC FRACTURES PROVIDED BYPARTICIPANTS OF THE SEMOF-STUDY, A PROSPECTIVECOHORT STUDY ON 7800 ELDERLY WOMEN

J. Burnand, J. Cornuz, M A. Krieg, P. Burckhardt, for the SEMOFStudy Group, University Hospital, Lausanne, Switzerland

INTRODUCTION: The validation of the self-reported clinicalevents through mailed follow-up questionnaires is crucial toensure quality of the obtained epidemiologic data.

METHODS: Between December 1997 and September 1999,7800 women aged 68±82 were enrolled in the SEMOF Study(Swiss Evaluation of the Methods of Measurement of Risk ofOsteoporotic Fracture), an ongoing prospective study comparingdifferent bone ultrasound measurements for predicting fracturerisk. The occurrence of fracture has been recorded by a self-administered questionnaire sent every 6 months. The dataprovided by the participants are compared with the informationobtained from the participants' physicians (74% response rate).

RESULTS: The physicians1 con®rmation of the ®rst 161fractures reported by the participants is shown in table:

Type offracture

Number of fracturesreported by women

Number of fracturescon®rmed by physicians

Hip 18 15 (83%)Wrist 46 43 (93%)Vertebrae 24 20 (80%)Other 73 63 (86%)Total 161 141 (88%)

Among the 73 fractures classi®ed by the participants in ``other''category, 5, 2 and 1 fractures were mentioned as hip, wrist andvertebral fractures by the physicians, respectively. Rheumatolo-gic symptoms were the most diagnosis for these non-con®rmedfractures.

CONCLUSION: 89% of osteoporotic fractures (hip, wrist andvertebrae) and 88% of all fractures have been con®rmed byphysicians. This high con®rmation rate means that participantsprovide reliable information.


128 (120). BLOOD PRESSURE AND SODIUM INTAKE AS RISKFACTORS FOR HIGH URINARY CALCIUM LOSSES IN A MULTI-ETHNIC POPULATION

F. P. Cappuccio, A. M. Blackwood, D. G. Cook, G. A. Sagnella,Departments of Medicine and Public Health Sciences, StGeorge's Hospital Medical School, London, UK

Background. Hypertension is associated with increased urinarycalcium (UCa) excretion. A high sodium intake increases bothUCa and blood pressure (BP). This may explain the higher risk ofkidney stones and bone demineralisation seen in hypertensives. Itis not clear whether this effect is modi®ed by gender or ethnicity.We examined the relationships between BP, urinary sodium(UNa), gender and ethnic origin with both daily and fasting UCaexcretions in a population-based study.

Methods. Out of 1,577 individuals taking part in a cross-sectional survey, 743 were considered for the analysis (407women). They were all untreated, provided a complete 24h urinecollection, and had all measurements of anthropometry, BP, UNaand UCa. They were 277 whites, 227 of blacks and 239 SouthAsians. Comparisons were also carried out in the 690 participantswho also provided 3h-fasting urine collections.

Results. After adjustment for confounders including age andgender, 24h UCa was signi®cantly and independently associatedwith ethnic origin, BP and UNa. Adjusted mean UCa was 4.62(0.11) mmol/d (m[se]) in whites, 3.33 (0.12) in South Asians and3.16 (0.13) in blacks (p<0.001). A 100 mmol higher UNa predicteda 1.04 mmol higher daily UCa and a 20 mmHg higher systolic BPpredicted a 0.28 mmol higher Uca (both p<0.001). The slopeswere not signi®cantly different by ethnic group. Adjusted meansfor fasting Uca were 1.64 [0.05] in mmol/min in whites, 1.08 [0.06]in South Asians and 1.13 [0.06] in blacks (p<0.001). The degree ofassociation with both BP and UNa also did not vary.

Conclusions. BP, salt intake and ethnic origin are independentpredictors of UCa in an unselected population. These relation-ships are unlikely to be the result of differences in Ca intake orintestinal absorption, suggesting that they may re¯ect differencesin renal tubular handling. The estimated effects of either BP or Naintake on UCa, sustained over many years, may contribute toincreased bone mineral loss.

129 (121). ESTROGEN METABOLITES AND HIP FRACTURE: APROSPECTIVE STUDY

J. Cauley, J. Zmuda, T. Klug, S. Cummings, D. Bauer, L. Kuller,1Universities of Pittsburgh and California; 2Immuna-Care, Inc.,Bethlehem, PA, USA

16a-hydroxyestrone (16a-OHE1) has been described as anestrogen agonist, while 2-OHE1 may have anti-estrogenic activity.To test the hypothesis that serum concentrations of 2-OHE1, 16a-OHE1 and their ratio predict the risk of hip fracture in olderwomen, we performed a prospective case-cohort study. A total of54 women experienced an incident hip fracture, over an averagefollow-up of 6�2 years. We randomly chose 94 controls; allwomen were white; age 565 years, not receiving estrogen andparticipating in the Study of Osteoporotic Fractures. Estrogenmetabolites (pg/ml) were measured in serum collected at thebaseline examination and stored at ±708C. Monoclonal antibody-based enzyme immunoassays were used (ESTRAMET 2 and 16,ImmunaCare, Inc.). We calculated the relative risk(RR) of hipfracture across tertiles of the metabolites and their ratio. Allanalyses are adjusted for age and obesity. The median (range)concentration of 2-OHE1 was lower in the fracture cases, 69 (20±217) compared with controls, 82 (20±266), p = 0.09. There were nodifferences in 16a-OHE1 in cases, 112 (28±398) vs. controls, 118(35±464), p = 0.82. The 2-OHE1:16a-OHE1 ratio was lower incases, 0.51 than controls, 0.74, p = 0.13. Women with the highest2:16 ratio had a signi®cantly reduced risk of hip fracturescompared to women with lowest ratio, (RR=0.32; 95% CI, 0.12to 0.82). An important difference in estrogen metabolism among

women who fractured their hip, and those that did not, may be thelower level of 2-OHE1 relative to 16a-OHE1.

130 (122). OSTEOPOROSIS MANAGEMENT AFTER LOWIMPACT DISTAL FOREARM FRACTURE IN POSTMENOPAUSALWOMEN

M. T. Cuddihy, S. E. Gabriel, C. S. Crowson, L. J. Melton, III, MayoClinic and Mayo Foundation, Rochester, MN, USA

The purpose of this investigation was to describe the use ofosteoporosis therapeutic interventions (OTI) among postmeno-pausal women who sustained a low impact trauma distal forearmfracture (DFF).

Methods: Using the population-based resources of theRochester Epidemiology Project, we assembled a cohort ofpostmenopausal women in Olmsted County, MN, who experi-enced a DFF between 1993±1997. We investigated OTI given andadherence up to 12 months after DFF date. Types of OTI offeredafter DFF were: ``Rx'' (Estrogen, bisphosphonates, raloxifene orcalcitonin) or ``NP'' (nonpharmacologic advice).

Results: 370 postmenopausal women had a DFF due to lowimpact trauma (fall from standing height or less) whose mean agewas 70.5 years (range 45±100). Only 30% of women were offeredOTI after DFF. No signi®cant difference was detected betweenOTI offered to women after a ®rst osteoporotic fracture vs thosewith history of fractures (p = 0.12). Adherence to initial OTI advicewas only 44% at one year.

Discussion: These data demonstrate underutilization of knowneffective osteoporosis therapeutic interventions among postme-nopausal women with osteoporotic fractures. Additional researchis needed to explore the barriers underlying such underutilization.

Table 1: Type of OTI Offered After Low Impact DFF:

Fracture Hx Rx Advice NP Advice On Rx Before DFF Total

Yes 24% 3% 8% 129No 12% 1% 14% 241% of total 16% 2% 12% 370

131 (123). DIETARY RISK FACTORS FOR HIP FRACTURE: THEBLUE MOUNTAINS EYE STUDY

R. G. Cumming, R. Q. Ivers, P. Mitchell, A. Peduto, University ofSydney, Sydney, NSW, Australia

This study was designed to examine dietary risk factors for hipfracture in a longitudinal study of an older population. Baselinedata collected for the Blue Mountains Eye Study included adetailed interview and dietary questionnaire in 3654 residentsaged 49 years and older. Hip fractures occurring during 5 yearfollow-up (n=60) were identi®ed by self-report (con®rmed byradiology reports) and/or review of medical records at the localhospital. All hip fractures were con®rmed radiologically by aspecialist radiologist. Analysis of hip fractures was carried out formedian follow-up of 5 years. Dietary variables were ranked inquintiles for analysis, and included intake from diet (energyadjusted) and supplements. For most variables examined therewas no consistent relationship between increased intake and riskof hip fracture (age and sex adjusted). The trend p value forincreasing quintiles of protein intake was 0.1, for vitamin A p = 0.7,for vitamin C p = 0.5, for zinc p = 0.7, and sodium p = 0.5. Therewas some evidence for an association between increasingcalcium intake and decreased risk of hip fracture, although thiswas not signi®cant (trend p = 0.1). For increasing quintiles ofcalcium intake the odds ratios (OR) and 95% con®dence intervals


(95%CI) were OR 1.0 (referent), 1.1 (95%CI 0.4±2.9), 0.8 (95%CI0.3±2.2), 0.6 (95%CI 0.2±1.7), 0.5 (95% CI 0.1±1.7).

132 (124). VERTEBRAL OSTEOPHYTOSIS AND VERTEBRALDEFORMITIES IN ELDERLY POPULATION SAMPLE

Selma Cvijetic1, Kristina Potocki2, 1Institute for Medical Researchand Occupational Health, Zagreb, MD, Croatia; 2Clinical HospitalRebro, Zagreb, MD, Croatia

We investigated the association between vertebral osteophytosisand vertebral deformities in the elderly population sample and thein¯uence of some risk factors on spinal osteophytosis anddeformities.

Population sample of 280 women and 263 men, all Zagrebresidents, older than 45 years participated in the study. Radio-graphs of thoracic and lumbar spine were evaluated for thepresence of osteophyte formation and vertebral deformities.Osteophyte size was graded on a scale from 0 to 4. Vertebraldeformities were determined by semiquantitative method ofMcCloskey. Data were analyzed using chi-square test anddiscriminate analysis.

The prevalence of vertebral osteophytosis was 47.9% in men(36.5% in the thoracic and 21.3% in the lumbar spine) and 56.0%in women (36.0% in the thoracic and 23.9% in the lumbar spine).The prevalence of vertebral deformities was 8.3% in men (5.3% inthe thoracic and 3.4% in the lumbar spine) and 12.5% in women(7.9% in the thoracic and 5.4% in the lumbar segment). There wasa signi®cant association between deformities and osteophytosison the lumbar segment of the spine (p = 0.0240 men, p = 0.0152women). Analyzing the in¯uence of several risk factors, age wasfound to be the most associated with both vertebral deformitiesand osteophytosis. Obesity was signi®cantly associated withosteophytosis.

Since we found a signi®cant association between vertebralosteophytosis and deformities in the lumbar segment and norelationship in the thoracic segment, it implicates differentetiologies of vertebral deformities in the thoracic and lumbar spine.

133 (125). ASSOCIATION BETWEEN NON-TRAUMAMORTALITY AND OSTEOPOROSIS IN ELDERLY WOMEN

P. Dargent, S. H. Lee, V. Ringa, G. BreÂ art, for the EPIDOS Group,INSERM Unit 149, Villejuif, France

Results of the SOF study (Lancet 1991;338:355±358) suggestedthat low BMD in elderly women could be a marker for poorunderlying health, which has important implications for preventivehealth care. We investigated the possible association betweenseveral indicators of osteoporosis and mortality in the 7598women aged 575 years who were enrolled in the EPIDOS study(mean age 80.5�3.8). Baseline indicators of osteoporosis includedfemoral neck BMD measured by DXA (Lunar DPX-Plus), ultra-sound parameters (Lunar Achilles), loss of height, and fracturehistory. During a mean of 3.9 (�0.9) years of follow-up, 741nontraumatic deaths occurred. After adjustment for age andfollow-up time using Cox models, nontrauma mortality wassigni®cantly associated with low BMD (RR= 1.14 for ± 1SD; 95%CI 1.06 ± 1.22), low BUA (1.26 for lowest quartile; 1.06 ± 1.50), lowSOS (1.17 for lowest quartile; 0.99 ± 1.40), and loss of height (1.29for ± 5 cm; 1.17 ± 1.43). These indicators of osteoporosis weresigni®cantly associated (p50.001) with several other signi®cantpredictors of mortality (IADL incapacities, gait speed, calfcircumference, subjective health, cognitive functions). Adjust-ment for these variables eliminated the association betweenmortality and BMD, BUA, and SOS. Only loss of height remainedsigni®cantly associated with an increased risk of mortality (1.20;1.06 ± 1.35). Low BMD and ultrasound measures are associatedwith increased mortality in elderly women, probably because theyare markers of ill health and frailty.

134 (126). FRACTURES AND THE LOSS OF QUALITY OF LIFE: ACOMPARISON OF AMERICAN AND DUTCH EXPERT PANELS

C.E.D.H. De Laet1, J. van Busschbach1, M. van der Klift1, P. Lips2,H.A.P. Pols1, For The Dutch Osteoporosis Consensus Committee,1Erasmus University Medical School, Rotterdam; 2VrijeUniversiteit Amsterdam, The Netherlands

Osteoporosis has little impact on mortality but can have animportant impact on health related quality of life (QOL). Therefore,costeffectiveness analyses of osteoporosis have to take intoaccount changes in health perception and associated loss ofQuality Adjusted Life Years (QALY). Relatively little experimentaldata are available, however, and for its recent review theAmerican National Osteoporosis Foundation (NOF) avoided thisproblem by using an expert panel for the evaluation of the loss ofQOL. In this study a Dutch expert panel evaluated the same post-fracture conditions. In addition, the total burden of diseaseattributable to osteoporosis was evaluated. The list of post-fracture conditions from NOF was evaluated by a Dutch panelusing the time trade-off method. Total QALY loss was recalcu-lated for ®rst and subsequent years for both the American and theDutch evaluations. Total burden of illness was evaluatedassuming average mortality after all but hip fractures, butassuming an increased mortality after hip fracture. The Dutchevaluations of QALY loss in the ®rst and subsequent years afterfracture were consistently lower than the US evaluations.Assuming average health pre-fracture the QALY loss due to hipfracture was evaluated at 0.28 for the ®rst year (0.47 in the NOFreport) and at 0.12 for subsequent years (vs. 0.17). For wristfracture this was 0.03 vs. 0.05 for ®rst and 0.002 vs. 0.006 forsubsequent years. For vertebral fractures this was 0.04 vs. 0.05for ®rst year and 0.02 vs. 0.05 for subsequent years. Average lossof life in the population due to osteoporosis in general wasevaluated for women at 23 days. Average loss of health relatedQOL was evaluated at 0.33 QALY's.

This Dutch evaluation of health related QALY loss is system-atically lower than the American evaluation. While wrist fracturesappear to have little impact on overall burden of illness, theimpact of vertebral fractures is proportionally higher thanexpected due to the long term QOL effects.

135 (127). INCIDENCE OF HIP FRACTURES IN OSLO, NORWAY:NO CHANGE DURING THE LAST DECADE

J. A. Falch, C. M. Lofthus, E. K. Osnes, T. S. Kaastad, I. S.Kristiansen, L. Nordsletten, I. Stensvold, H. E. Meyer, AkerHospital, University of Oslo, Oslo, Norway

The incidence of hip fractures in Oslo has shown a secularincrease during the past decades. The aim of the present studywas to estimate the current incidence of hip fractures in Oslo.

Using the electronic diagnosis registers and the lists of theoperating theatre for the hospitals in Oslo with somatic care, allpatients with the ICD 9-code 820.X (hip fracture) from May 1, 1996through April 30, 1997 were identi®ed. Medical records for all theidenti®ed patients were retrieved and the diagnosis veri®ed.Using the population of Oslo on January 1, 1997 (StatisticsNorway, 1997) as the population at risk, the age-and sex-speci®cannual incidence rates were calculated. These rates werecompared to those for 1978/79 and 1988/89.

A total of 1,316 hip fractures were included (78% women). Theage-adjusted fracture rates per 10 000 for the age group 50 yearsand older were 118.0 and 44.0 in 1996, 124.3 and 44.9 in 1988/89,and 104.5 and 35.8 in 1978/79 for women and men, respectively.Compared to 1996, the rates in 1988/89 were 5% higher in women(n.s.) and 2% higher in men (n.s.). In 1978/79 the rates were 11%lower in women (p<0.02) and 19% lower in men (p<0.05).

The present study shows that the incidence of hip fractures inOslo has not changed signi®cantly during the last decade. It is stillthe highest ever reported.


136 (128). COMPARISON OF RISK FACTORS FOR VERTEBRALFRACTURE BETWEEN WOMEN IN URBAN AND RURAL AREAS

S. Fujiwara1, M. Shiraki2, N. Masunari1, F. Kasagi2, Y. Shiraki3, C.Aoki3, K. Naito1, 1Departments of Clinical Studies; 2Statistics,Radiation Effects Research Foundation, Hiroshima; 3ResearchInstitute and Practice for Involutional Disease, Nagano, Japan

This study compares the risk factors for vertebral fracture (VF)between women living in urban and rural areas. Subjects were666 women (age 65.9�9.6 yrs) in Hiroshima City selected for alongitudinal epidemiological study based on the 1950 JapaneseNational Census, and 484 women in Nagano (age 63.5�10.4 yrs)who had undergone bone mineral density (BMD) measurementsat health checkup. One third of the Nagano women were farmers,while 47% in Hiroshima were housewives and less than 2%farmers. The 1150 women were followed by BMD measurementsand spine X-rays for more than two years. None were receivingtreatment for osteoporosis. Diagnosis of VF was standardized forHiroshima and Nagano.

Poisson regression analysis showed that the risk of new VF wasrelated to age, BMD, and previous VF (Table). After adjusting forage, relative risk of VF was similar for the two groups, around 1.3by 1 SD decrease in BMD. However, the relative risk for VF amongwomen with previous VF was higher in women in Nagano than inHiroshima. The difference in risk among women with VF betweenurban and rural areas may be due to occupational differences inthe two groups.

In conclusion, after adjusting for age, the relationship betweenBMD and subsequent VF was similar in urban and rural areas, butthe contribution of previous VF on new VF may differ byoccupation or daily activity.

Table. Relative risk for VF in the two areas

Risk factors Relative risk

Urban (Hiroshima) Rural (Nagano)

Age (10 yrs) 1.82 1.55

Spine BMD (±1 SD) 1.28 1.35

Previous VF 1.88 2.53

137 (129). REGIONAL DISTRIBUTION OF BONE MINERAL ANDSOFT TISSUE COMPOSITION IN ELITE FEMALE ATHLETES

R. Garcia, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L.Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J.Sartoris, University of California School of Medicine, San Diego,CA, USA

PURPOSE: To investigate the relationship between regionaldistribution of bone mineral density (BMD)/content (BMC) andsoft tissue mass (lean versus fat components) in a uniquepopulation of elite female endurance athletes.

METHODS: 139 female triathletes competing in the 1999Ironman World Championship Triathlon held at Kona, Hawaiiwere randomly recruited from the qualifying competitors. Agesranged from 22±69 (mean 39) years of age. Body weight rangedfrom 93±176 (mean=125) pounds. Detailed information regardingdietary/medical history, exercise/lifestyle habits, and menstrualfunction was elicited from each participant. Performance times inthe swimming, bicycling, and marathon components of the eventwere also recorded. Regional bone mineral and soft tissuecomposition was assessed using a Norland XR±36 pencil-beamdual-energy X-ray absorptiometry system. Statistical analysiswas performed using Minitab version 12 software.

RESULTS:

BMD vs SOF BMC vs SOF

P R2 (adj) % P R2 (adj) %

Head 0.002 6.7 0.000 26.1Chest 0.000 26.8 0.000 46.9Midriff 0.167 0.7 0.000 80.6Pelvis 0.003 6.1 0.000 36.1L Leg 0.000 40.0 0.000 64.0R Leg 0.000 36.0 0.000 63.7L Arm 0.000 18.6 0.000 69.7R Arm 0.000 28.8 0.000 69.2

LEFT vs RIGHT LEG LEFT vs RIGHT ARM

P R2 (adj) % P R2 (adj) %

BMC 0.000 94.6 0.000 75.5AREA 0.000 86.3 0.000 63.1SOFT TISSUE 0.000 95.0 0.000 78.2BMD 0.000 87.8 0.000 67.8

CONCLUSION: Both BMC and BMD are signi®cantly correlatedwith total soft tissue distribution in most regions of the bodyamong elite female triathletes. However, correlation coecients forBMD were higher in biomechanically active regions (chest, legs,arms. In contrast to previous studies demonstrating relativelyconstant ratios between BMD/BMC and muscle mass in theextremities, neither was signi®cantly related to individual softtissue components (lean versus fat) of the arms/legs in these highperformance female athletes. Relative symmetry of bone and softtissue composition in the arms and legs is present.

138 (130). BONE MINERAL DENSITY IN ADOLESCENTS WITHIDIOPATHIC SCOLIOSIS

S. Gatto, R. Gimigliano, G. Iolascon, Orthopedics Dept., IIUniversity of Naples, Italy

The purpose of our study is to assess an association ofosteopenia/osteoporosis with idiopathic scoliosis and if osteo-porosis plays a rule in primary etiology of spinal deformity. Burner(1982) demonstrated this association using Singh Index. Cook(1987), using DPA, found a signi®cant reduction in BMD.

METHODS. BMD was measured in 49 patients (31 females and18 males) with idiopathic scoliosis. Adolescents were aged from10 to 17 y.o. and Cobb angle ranged from 258 to 478. No orthosiswas used before BMD measurements. Bone mass wasmeasured by DEXA technique both spinal and femoral sites.Our results were compared with normal values published byKroger (1993).

RESULTS. 15 males and 26 females showed low BMD (Zs: 52S.D.) at spinal and femoral sites. Low bone mass wasindipendent from curve severity and was more important infemoral neck.

CONCLUSIONS. Scoliosis was associated with osteopenia/osteoporosis in 83% of our adolescents. Low bone mass,probably, is not secondary to the scoliosis because it is presentalso, and mostly, in femoral neck. Osteoporosis, probably, plays arule in the onset of vertebral body deformity and therefore incurve irreducibility.

Low bone mass has no rule in scoliosis primary etiologybecause body deformity cannot explain all pathological ®ndingsof vertebra in these patients. Further studies need to investigateabout this association.


139 (131). BONE MINERAL DENSITY IN ADOLESCENTS WITHJUVENILE KYPHOSIS

S. Gatto, R. Gimigliano, G. Iolascon, Orthopedics Dept., IIUniversity of Naples, Italy

The purpose of our study is to assess an association ofosteopenia/osteoporosis with juvenile kyphosis and if osteoporo-sis plays a rule in primary etiology of spinal deformity.Bradford(1976) and Burner(1982) demonstrated this associationusing Singh Index and postulated that transitory osteoporosis is aprimary etiology of Scheurmann's kyphosis.

METHODS. BMD was measured in 47 patients (17 females and30 males). The wedge body deformity was present in 28 patients(15 with Scheuermann's signs and 13 without). 19 patients had nostructural deformity. Adolescents were aged from 10 to 17 y.o..No orthosis was used before BMD measurements. Bone masswas measured by DEXA technique at spinal and femoral sites.Our results were compared with normal values published byKroger (1993).

RESULTS. 23 males (76%) and 11 females (65%) showed lowBMD (Zs: 52 S.D.) at spinal and femoral sites. Low bone masswas indipendent from etiology and curve severity and was moreimportant in femoral neck.

CONCLUSIONS. Kyphosis was associated with osteoporosis in76% of males and, 65% of females. Low bone mass, probably, isnot secondary to the kyphosis because it is present also, andmostly, in femoral neck. Osteoporosis could determine wedgedeformity but not other Scheuermann signs. Furthermore lowbone mass is present also in absence of vertebral deformity.Further studies need to investigate about this association.

140 (132). VERTEBRAL WEDGING AND SPINAL DEFORMITY INANKYLOSING SPONDYLITIS

P. Geusens1,2, J. Vanhoof2, D. Vosse1, D. van der Heijde1, J.Raus2, Sj. van der Linden1, 1Department of Rheumatology,Academic Hospital, Maastricht University, The Netherlands;2Biomedical Research Institute DWI, Limburg University Centre,Diepenbeek, Belgium

Fixed antero¯exion of the spine is one of the irreversible clinicalcomplications in ankylosing spondylitis (AS) that can seriouslyaffect quality of life. Thoracic hyperkyphosis has been related tothe severity of AS and to osteoporosis. However, the underlyinganatomical changes in vertebral shape have not yet been relatedin detail to the clinical changes in spinal stature in AS. Wetherefore studied the changes in shape of vertebrae in 69 patientswith AS (21 women and 48 men), having different degrees ofkyphosis as measured by wall-occiput distance (WOD). Lateral x-rays of the thoracic spine (T7-T12) were measured for anterior(Ha) and posterior height (Hp) of the vertebrae. Severe vertebralwedging was de®ned as Ha/Hp <0.80. Severe vertebral wedgingwas found in 36 vertebrae in 22 (32%) of patients (range 1 to 4). Inthe vertebrae from T7 to T12, WOD was associated with wedgingof the vertebrae [R=±0.509 (p<0.01)]. In patients with WOD >1 cm,46% had at least one severely wedged vertebra compared to 13%in patients with WOD <1 cm (p<0.05). A greater proportion ofpatients with a WOD of >10 cm had one or more severely wedgedvertebrae compared to patients with WOD of 0 cm [59% versus13% respectively of patients (p<0.001)]. Patients with 1 or moreseverely wedged vertebrae had a higher mean WOD than patientswithout severely wedged vertebrae [12 cm versus 6 cmrespectively (p<0.01)]. The mean WOD increased signi®cantlywith the number of severely wedged vertebrae in men and women(6 cm among those without severely wedging, up to 23 cm amongthose with >2 severely wedged vertebrae, p = 0.001 for trend).There were no signi®cant differences between men and women.

We conclude that in patients with AS and WOD >1 cm, severewedging of the thoracic vertebrae contributes signi®cantly to the

®xed and irreversible antero¯exion of the thoracic spine in 46% ofpatients. These ®ndings open new perspectives for therapy,which should not only aim to prevent in¯ammation, but also toprevent vertebral wedging. Insofar osteoporosis is involved in thedevelopment of severe wedging of vertebrae, prevention of boneloss should be considered.

141 (133). RISK FACTORS FOR OSTEOPOROSIS IN TURKISHWOMEN

A. Gokman1, U. SecË ckin1, H. Bodur1, O. H. GuÈ nduÈ z1, G. Pekcan2,1Dept. of Physical Medicine and Rehabilitation, Ankara NumuneEducation and Research Hospital; 2Dept. of Dietetics,Samanpazari, Hacettepe University, Ankara, Turkey

We evaluated the relationships between bone mineral density(BMD) and nutrition, calcium (Ca) intake, age, number ofpregnancy, age at menopause, menopausal period, lactationperiod, body weight, and height, body mass index (BMI), andphysical activity level. 151 subjects were evaluated in arandomized manner. There were signi®cant differences betweenage, number of alive children, menopause period and the twogroups which are designed according to the BMD's of L1-L4lumbar spine and Ward's triangle. In groups with lower BMDvalues, patients had more alive children, longer menopausalperiods and higher average age. There were signi®cant differ-ences between the number of pregnancy, lactation period, fatintake, meal frequency and the BMD of the Ward's triangle.Patients with higher BMD values had higher BMI, higher bodyweight and physical activity levels. Patients with low BMD valueshad a tendency towards having more pregnancies, longerlactation periods and more fat intakes. We didn't ®nd anyrelationship between Ca intake and BMD values. This could bedue to insuf®cient Ca intake in our subjects.

142 (134). PREVALENCE OF OSTEOPOROTIC VERTEBRALFRACTURES IN FRENCH ELDERLY WOMEN FROM EPIDOSSTUDY

F. Grados1, C. Roux2, J. F. Vergnol1, C. Marcelli3, P. Dargent-Molina4, P. J. Meunier5, P. Fardellone1, 1Rheumatology CHUAmiens; 2CEMO CHU Cochin, Paris; 3Rheumatology CHU Caen;4INSERM U 149 Paris; 5INSERM U 403 Lyon, France

The prevalence of osteoporotic vertebral fractures was evaluatedin 770 randomly selected women participants of the Epidos study.Epidos is a multicenter study performed in ®ve French centers(Amiens, Lyon, Paris, Montpellier, Toulouse) among 7598 healthyfemale volunteers aged 75±95 years living at home. Anteropos-terior and lateral radiographs of the thoracic and lumbar spinewere reviewed by two trained rheumatologists using thesemiquantitative (SQ) method described by Genant et al (JBMR1993;8:1137±48). Vertebral deformities that could be related tocauses other than osteoporosis (i.e Scheuermann's disease orosteoarthritis) were not taken into account. The ®nal analysis wasmade on 745 women after exclusion of 25 women whose spineradiographs were incomplete or of poor quality. The mean agewas 80.1�3.4 years. We veri®ed in 39 women that theconcordance of SQ method was excellent. The interobserveragreement was 98% with a corresponding kappa score of 0.95.Vertebral fractures related to osteoporosis were found in 170women: 22.8% (95% CI = 19.8±25.8%). The prevalence ofvertebral fractures rose with age from about 18.2 per 100women 75±79 years old to 25.8 per 100 in those 80 years of ageand over.

We concluded that the prevalence of osteoporotic vertebralfractures is high in French elderly women living at home.


143 (135). THE INFLUENCE OF ESTROGENS ON BONE MASSIN WOMEN WITH BREAST CANCER

P. Hadji, G. Emons, K.-D. Schulz, Philipps University Marburg,Marburg, Germany

This study was aimed to evaluate the relation between bone massand breast cancer and to investigate if cumulative exposure toestrogens could explain this association. Speed of sound (SOS),broadband ultrasound attenuation (BUA), and Stiffness index (SI)of the Os calcaneus were measured in 2492 women, mean age54.4 years. 242 patients had a history of breast cancer, while 2250women had not. Due to the signi®cant group differences, werandomly formed an equally sized sample of healthy women whowere matched for confounding variables such as age, BMI,cumulative exposure to estrogens and others.

Women with breast cancer were older, showed a higher weight,BMI, number of parity and lactation, and a longer exposure toestrogens. SOS and SI were signi®cantly higher in women withbreast cancer even after matching for confounding variables(p<0.001). Odds ratios for the risk of breast cancer were 1.0, 1.6,3.4 and 2.9 from the lowest to the highest quartile of SI (p for trend<0.001).

Women with breast cancer have higher bone mass thancontrols, even after matching for confounding variables. Womenin the higher quartiles of bone mass are at higher risk for breastcancer. Although the link of bone mass and breast cancer is notfully understood, factors other than cumulative exposure toestrogens must play a role.

144 (136). PRIMARY PREVENTION OF OSTEOPOROSIS WITHSPECIAL PATIENT-EDUCATIONAL PROGRAM FOR CHILDREN

K. HalaÂ sz, Rheumatology Unit Kutvolgyi Clinical Dept.,Semmelweis University Budapest, Hungary

The peak-bone mass is genetically determined. This geneticprogram is in¯uenced by environmental factors, such as suitablenutrition, lack of harmful habits, and appropiate sport activitythroutout the life. Since osteoporosis /OP/ cannot be cured evennow all efforts have to be done forprimary prevention that has tobe started as young as possible. Age suited educational programis necessary to increase the knowladge and awareness of OP.

450 children aged 5±17 years were involved in the study. Theauthor presented the main facts of OP in 45 min sessions atschools. After the class children were encouraged to drawanything they picked from the presentation. 177 drawings weremade. The bests were exhibited and awarded on OsteoporosisDay 1999.

After the age of 13 yrs children dislike to draw. Therefore anintroductory and assessement questionnaire were developed forhigh-school children. The goal was to assess their originalknowladge on OP and what they have learned from thepresentation.

The evaluation of drawins made by kindergarden and primaryschool-children showed that they already knew quite a fewinformation on OP, and the targeted presentation helped them toorganiz the data and form positive opinions for prevention.Presentations at high schools provided an emotional strategy forolder children to reorganize their everyday lifestyle aiming toreach the highest peak-bone mass.

The evaluation of questionnaires were statistically analized.

145 (137). RESULTS OF A NATIONAL SURVEY ON RISKFACTORS FOR OSTEOPOROSIS IN URUGUAY

J. HernaÂ ndez, A. Ronco, V. Chijani, R. Souto, G. GonzaÂ lez, C.Uboldi, R. Tejeiro, A. Ramagli, L. Tuso, E. GoÂ mez, M. Albanese, L.Bairo, M. Moyano, B. Mendoza, C. Belzarena, S. Lima, StudyGroup On Osteopatic, 1Uruguayan Society of Rheumatology,Montevideo, Uruguay

The ®rst nationwide survey on selected risk factors forosteoporosis has been carried out in Uruguay, in order to know

their prevalence and to furtherly enhance the prevention of thedisease. During the period June-August / 1999 a number of 3,500fourty-years-old and above patients (84% women) who went tomedical examination for control or under symptomatic conditionsto general practitioners or specialists received a short ques-tionnaire form queries about education, lifestyle, selectedconsuptions and medial issues. Patients came from the wholecountry (62% from Montevideo, the capital city), from bothhealtcare systems (81% from the pre-paid system) and wereethnically rather representative of the general population (97%white). A risk score was calculated on the basis of answers, with arange of 4±24 points. The threshold of susceptibility toosteoporosis was established in 12 points, as in the originalMedGuide version. While 67% of women fell into the risk group,only 16% of men did it (OR= 4.01. 99% CI 2.99 ± 5,46). Main®ndings are herewith presented and discussed.

146 (138). ORTHOPEDIC PATIENTS WITH COGNITIVEIMPAIRMENT HAVE INCREASED HIP FRACTURE RISK ANDMORTALITY

K. Hindsù, J. B. Lauritzen, Department of Orthopedic Surgery,Hvidovre Hospital, University of Copenhagen, Denmark

Aim To evaluate cognitive impairment as a prognostic risk factorfor hip fracture and mortality.

Design & patients A total of 1,590 patients more than 74 yearsof age were consecutively included in the study after admittanceto one of two orthopedic departments in Copenhagen. Thepatients participated in a hip protector trial, and for analysesrelated to hip fracture risk 642 controls were included. Atinclusion all patients were interviewed and examined. Cognitiveimpairment was evaluated using a short questionnaire. Duringfollow-up hip fractures and deaths were recorded. Multivariatesurvival analysis (Cox proportional hazard model) was used.

Results In the cohort 32 % (95% CI: 30±34%) (503/1,590) werecognitively impaired. The overall annual mortality was 20% (437deaths / 2,172 person-years). The mortality rate for cognitivelyimpaired was 41 % and for non-impaired 13 %, SMR 3.2 (2.7±3.9).Adjusted for the effects of gender, age, medical conditions andnursing home the SMR was 2.5 (2.0±3.2). Annual hip fracture riskfor cognitively impaired was 5.9% versus 2.8% for non-impaired;relative risk 2.1 (1.0±4.5), adjusted for gender, age, fall tendencyand smoking.

Conclusion Cognitive impairment is a common occurrenceamong elderly orthopedic patients, and leads to increased risk ofhip fracture and mortality.

147 (139). DETERMINANTS OF BONE MINERAL DENSITY ANDQUANTITATIVE ULTRASOUND INDEX IN WOMEN WITHRHEUMATOID ARTHRITIS

M. C. Hochberg, J. C. Scott, W. Yap, University of MarylandSchool of Medicine, Baltimore, MD, USA

The objective was to determine whether measures of diseaseactivity and severity are independently associated with bonemineral density (BMD) and quantitative ultrasound index (QUI) inwomen with rheumatoid arthritis (RA). A convenience sample of100 women with RA (mean [SD] age 58.6 [12.2] years, height 160.2[5.6] cm, and weight 72.6 [17.2] kg) completed a detailedosteoporosis risk factor questionnaire identical to that used inthe Study of Osteoporotic Fractures and the Stanford HealthAssessment Questionnaire Disability Index (HAQDI), had BMDmeasured at the right hip and total body with a Hologic QDR±2000and QUI measured at the right heel with a Hologic Sahara, andunderwent a 28-joint count performed by a trained nurse. Multipleregression analyses were performed to adjust for factors knownto be associated with bone mass. Mean (SD) BMD (g/cm2) at the


femoral neck, greater trochanter, total hip and total body was 0.67(0.14), 0.92 (0.20), 0.78 (0.19) and 1.06 (0.12), respectively; mean(SD) QUI was 80.7 (22.9). Signi®cant predictors of BMD by sitefollow:

Femoral neck: age, weight, heightTrochanter: age, weight, height, HAQDITotal hip: weight, height, menopausal statusTotal body: weight, menopausal status

The only signi®cant predictors of QUI were age and height.Neither the number of painful/tender joints or swollen joints, northe current use of prednisone or methotrexate, were signi®cantlyassociated with BMD at any site or QUI. These data suggest that,in women with RA, measures of disease activity and severity havelittle eect on BMD and bone microarchitecture over and abovefactors known to be associated with bone mass.

148 (140). CHANGES IN BONE DENSITY IN JAPANESE WOMENOVER THREE YEARS AND DETERMINANTS OF THE BONELOSS

M. Iki, A. Morita, Y. Ikeda, H. Aihara, S. Kagamimori, Y. Kagawa, T.Matsuzaki, H. Yoneshima, F. Marumo, for JPOS Study Group,Kinki U Schl Med, Osaka-Sayama, Japan

This study aimed to clarify the changes in bone mineral density(BMD) of several skeletal sites in Japanese women of various ageand to investigate the determinants of these changes.

We randomly selected 50 women each from 5-year agestrati®ed populations (15±79 year) according to the residentregistration in each of 3 areas located north, middle and southparts of Japan. The follow-up study was conducted 3 years afterthe baseline. Both studies comprised bone densitometry of thespine, hip (QDR4500A, Hologic) and distal forearm (pDXA,Norland/Stratec), and interviews on medical histories and lifestylefactors.

In total, 1651 women underwent the baseline study and 1137completed the both studies. Among 1137 women, 1000 had neverhad any diseases or administration of drugs which may affectbone mass and were analyzed further. Signi®cant bone loss in thespine was observed in the subjects aged 45±74 at baseline andthat in the femoral neck was in those under 25 or over 40 years.The greatest loss was seen just after menopause in the spine andneck and in the subjects aged 75 or older in the femoral neck. Wefound signi®cant differences in BMD change in most sitesexamined among the study areas. These differences reducedafter allowing for the effects of height, weight, BMD at baseline,habitual exercise, dietary calcium intake, and consumption offermented soybean on the BMD change but still remainedsigni®cant.

The regional differences in BMD change were attributed partlyto the difference in physique and lifestyles. Other unknownfactors, however, operated in generating such differences inJapan.

149 (141). DIETARY CALCIUM INSUFFICIENCY IN ELDERLYFREE-LIVING WOMEN: AN ITALIAN MULTICENTER STUDY

G. Isaia1, R. Giorgino2, on behalf of the Italian Multicenter StudyGroup, 1Turin, Italy; 2Rome, Italy

Few studies are available at national level on dietary calciumintake in elderly Italian people: the aim was to measure theprevalence of dietary calcium insuf®ciency and its majordeterminants in postmenopausal free-living women. On a periodbetween Feb. 15th and March 15th 1999, an observational study

was conducted in 43 Italian out-patients centers. Medical historyand a life-style questionnaire was recorded in 799 hundredninety-nine postmenopausal women (age range 60±80 years,median 67) at their ®rst Osteoporosis work-out were adminis-tered: a validated food frequency questionnaire was planned forcalcium intake measurement. Each woman self-administered a 3-item daily based calcium intake score sheet. The nutritionalanalysis showed a 784 mg/day median calcium dietary intake; ageographic subanalysis indicated a signi®cantly lower calciumintake in Southern Italy (710 mg/day vs. 810 and 835 mg/dayrespectively in Northern and Central Italy, p<0.001). This datamainly re¯ects different regional habits in cheese consumption(p<0.01): however the proportion of dietary calcium coming frommilk and dairy products was about 70% without signi®cantgeographic patterns. The following table shows the proportion ofsubjects with different ranges of Ca intake in the 3 majorgeographic areas. Low calcium intake was associated withActivities of Daily Living impairment (p<0.01): lower Ca intakelevels were detected in diabetic patients (p<0.05). The 3-itemcalcium score was signi®cantly correlated with calcium intakelevels measured by the extended food-frequency questionnaire(p<0.0001). In conclusion, this study con®rms the relevance ofdietary calcium insuf®ciency in Italian elderly population: thisemphasizes the need of wide-scale educational programs tocorrect one of the major determinants of senile osteoporosis. Wevalidated an easy-to-use tool to be tested on a large scale in GPs'of®ces to stimulate physicians and patients awareness on thispublic health issue.

All North Center South

No. of cases 799 333 206 260Calcium Intake0±500 mg/day 25% 24% 24% 28%501±1000 mg/day 50% 49% 47% 54%1001±1500 mg/day 20% 23% 23% 15%>1500 mg/day 5% 5% 6% 3%

150 (142). LIFESTYLE FACTORS HAVE ONLY A MODESTINFLUENCE IN PREDICTING INCIDENT VERTEBRALDEFORMITY : RESULTS FROM THE EUROPEAN PROSPECTIVEOSTEOPOROSIS STUDY (EPOS)

A. A. Ismail, J. D. Finn, M. Lunt, C. Cooper, D. Felsenberg, O.Johnell, J. Reeve, A. J. Silman, T. W. O'Neill, the EPOS StudyGroup, ARC Epidemiology Unit, Manchester University, UK

Background: Little is known about risk factors for incidentvertebral deformity. The aim of this analysis was to determine,in women, whether lifestyle factors in¯uence susceptibility toincident vertebral deformity.

Methods. Women aged 50 years and over were recruited frompopulation registers in 15 European countries for participation ina screening survey of vertebral osteoporosis (European VertebralOsteoporosis Study). Subjects underwent an interviewer admi-nistered questionnaire and lateral spinal radiographs using astandard protocol. The questionnaire included questions aboutsmoking, alcohol, milk consumption (at ages 15±25yrs, 25±50 yrs,and 50 years+) and physical activity. Paired spinal radiographswere evaluated morphometrically. An incident vertebral deformitywas de®ned as a vertebra which ful®lled criteria for a prevalentdeformity on the second ®lm, and in which there was evidence ofa change of 20% or more in vertebral height (anterior, middle orposterior) between ®lms. Poisson regression was used todetermine the in¯uence of lifestyle factors on the risk of incidentvertebral deformity.

Results. 3,569 women, mean age 62.1 years (SD= 7.5) hadduplicate spinal radiographs performed (median 3.7 yrs apart).


After adjustment for age and centre, none of the lifestyle factorsstudied were associated with a statistically signi®cant increase inthe risk of incident vertebral deformity : walking (per day : 530mins vs 530 mins) relative risk (RR)=0.8, smoking (ever vs never)RR=1.2, milk consumption (per day: 51 glass vs 51 glass)RR=0.8±1.0 (depending on consumption at different ages),alcohol (number of days per week : 5 days vs 51 day) RR=1.5.

Conclusion: Lifestyle factors appear to have limited impact indetermining susceptibility to incident vertebral deformity inpostmenopausal women.

151 (143). HEALTH AND VITAMIN D STATUS INOSTEOPOROTIC PATIENTS WITH AND WITHOUT VERTEBRALFRACTURE

T. Jalava, B. Mawer, S. Sarna, L. Pylkkanen, J. A. Kanis, E.McCloskey, University of Shef®eld, UK

We have examined differences in several measures of skeletaland non-skeletal health in 677 patients with osteoporosis (PMOP,n=483; women with secondary osteoporosis, n=110 and osteo-porotic men, n=84). Of these, 55% had prevalent vertebralfractures at entry. Patients with fractures were older (67.9 yearsvs 64.3 years, p<0.0001), had a higher number of concomitantdiseases (p<0.0009) and treatments (p<0.0001), a higher ESR(p = 0.032) and poorer renal function (p = 0.0097). Finally, theserum calcium (p = 0.006) and 25-OHD3 were lower (21.2 vs 25.0ng/ml, p = 0.0001).

Over 3.2 years, mortality was higher in secondary (8.2%) andmale (11%) osteoporosis than in PMOP (3.9%). A multivariate Coxregression analysis revealed that increased mortality wasassociated with prevalent vertebral fractures (HR 3.9, 95%CI1.3±11.5), low (<9ng/ml) 25-OHD3 (4.4, 1.7±4.9) and moreconcomitant treatments (1.3, 1.1±1.4). Higher serum albuminwas associated with lower mortality (0.9, 0.8±1.0). When themultivariate analysis was restricted to PMOP alone, onlyprevalent vertebral fractures were associated with an increasedmortality (10.3, 1.3±80.1). It is unclear whether the associationbetween low 25OHD3 and mortality, particularly in secondary andmale osteoporosis, is causative or simply re¯ects general ill-health.

152 (144). IS GENERAL HEALTH RELATED TO OSTEOPOROTICFRACTURES? A POPULATION-BASED STUDY

O. Johnell, A. Holmberg, P. Nilsson, J. A. Nilsson, G. Berglund,Department of Orthopaedics and Department of Medicine, MalmoUniversity Hospital, Malmo, Sweden

The purpose of this investigation is to study general health issuesin relation to different osteoporotic fractures in both sexes. InMalmo Preventive Study 10,902 women and 22,444 men wereexamined. The mean age for men was 46 years and women 48years. The participants were followed-up to a maximum time of 18years. The fractures were recorded prospectively and during thefollow-up 1,700 had any fragility fracture. The questions in thisstudy were: Have you got full health? (health) Have your appetitechanged? (appetite) Do you often wake up? (wake up). A logisticregression model was used adjusting for age. Only low energyfractures were selected. For individuals with fracture of the distalend of the forearm there was no signi®cance, neither in men nor inwomen. For hip fractures there was a signi®cance for health RR =0.66 and wake up 1.76. For women there was only signi®cance forhealth 0.57. For clinical vertebral fractures in men there was asigni®cance for all questions: appetite 2.70, health 0.52, wake up2.30, for women only wake up was signi®cant 1.76. It seems thatthere is a difference between different osteoporotic fractures inrelation to these health questions and also a difference betweenthe sexes.

153 (145). SOCIAL FACTORS PREDICT FRAGILITYFRACTURES IN AN MIDDLE-AGED POPULATION. APOPULATION-BASED STUDY OF 33,000 MEN AND WOMEN

O. Johnell, A. Holmberg, P. Nilsson, J. A. Nilsson, G. Berglund,Department of Orthopaedics and Department of Medicine, MalmoUniversity Hospital, Malmo, Sweden

Several risk factors have been identi®ed for osteoporoticfractures. Less attention has been paid to social predictors forfractures. The purpose of this investigation was to studybiological, social and life style predictors in a population ±Malmo Preventive Study. Baseline variables were obtained from22,444 men and 10,902 women with a participation rate of 72%.Mean age men 46 and women 48 years. The follow-up was up to18 years. The fractures were recorded from the ®les of theDepartment of Diagnostic Radiology and the ®rst incidencefragility fracture was identi®ed. Social data were obtained froma questionnaire and the Swedish Population and HousingCensus. In a stepwise logistic regression the following signi®cantrelations were found for incidence fragility fractures: Men ±alcohol problem OR 1.54 (1.27±1.86), manual work OR 1.35 (1.20±1.52), unmarried OR 1.33 (1.14±1.56), divorced OR 1.31 (1.10±1.55)and for continuous risk factors per SD change: Body mass index0.88 (0.83±0.94), gamma GT 1.10 (1.04±1.17). For women we onlyfound the following signi®cant relations: Body mass index 0.92(0.86±0.99), gamma GT 1.08 (1.01±1.14). Besides known riskfactors, social factors could be important especially in middle-aged men.

154 (146). RELATIVE RISK OF HIP FRACTURE ACCORDING TOWHO CRITERIA FOR OSTEOPOROSIS

J. A. Kanis, O. Johnell, A. Oden, B. Jonsson, C. De Laet, A.Dawson, Centre for Metabolic Bone Diseases, University ofShef®eld Medical School, Shef®eld, UK

In the assessment of patients it is appropriate to quantifyfracture risk in relation to the risk of the general population. Bycontrast, the predictive value of bone mineral density (BMD) iscommonly expressed as an increase in fracture risk per standarddeviation difference in BMD. For example, hip fracture riskincreases 2.6-fold per standard deviation difference in femoralneck BMD. Thus, an individual with a Z-score of ±1 has a 2.6-foldincrease in risk compared to an individual with a Z-score of 0(RRmean). The risk of fractures with BMD is non-linear however,whereas BMD at each age is normally distributed. For thisreason an average BMD (eg Z-score = 0) is associated with alower than average risk of fracture. The aim of this paper is tocharacterise risk, based on BMD to the risk of the generalpopulation (RRpop) rather than RRmean based on mathematicalmodelling using the NHANES reference material applied to thepopulation of Sweden.

Women at the age of 50 years at the threshold for osteoporosis(T-score = ±2.5 SD) had a RRmean of 4.6 decreasing to 0.98 at theage of 85 years. By contrast, the RRpop was 2.9 and decreasedwith age to 0.62 at the age of 85 years. In men at the age of 50years the RRmean was 14.6 and the RRpop 4.6 and fell to 9.2 and2.9 respectively at the age of 85 years.

The use of relative risks applied to average bone mineraldensity overestimates the impact of osteoporosis in thecommunity. The use of RRpop gives relative risks that are 27and 32% of values for RRmean in women and men respectively.Similar transformations for other fractures and other technologieswill be required to assess risks in individuals to effectively targetinterventions.


155 (147). HIP FRACTURE INCIDENCE RATES IN SINGAPORE1991±1998

L. Koh, S. M. Saw, J. Lee, K. H. Leong, J. Lee, National WorkingCommittee On Osteoporosis, Singapore

The purpose of this population-based study was to determine theincidence rates of hip fracture among Singapore residents aged50 years and above. Information was obtained from a centralizeddatabase system which captured admissions with the primarydiagnosis of a closed hip fracture (ICD±9 codes 820, 820.0, 820.2and 820.8, n = 12,927) from all health-care establishments in thecountry from 1991 to 1998 inclusive. After removing duplicates,hospital transfers, readmissions and non-acute care admissions,the total number of hip fractures was 9,406. The age-standardizedhip fracture rates per 100 000 (standardized to USA population1985) for 1991±8 were 152 in men and 402 in women, 1.5 and 5times higher than corresponding rates in the 1960s respectively.From 1991 to 1998, hip fracture rates increased annually by 0.7%in men and 1.2% in women. Age-standardized hip fracture ratesamong the three major racial groups were as follows:

Chinese* Malay* Indian*

Male 168 (158,178) 71 (54,88) 128 (105,152)Female 410 (395,425) 264 (225,303) 361 (290,432)

*rates (95% con®dence intervals)

Hip fracture rates in Singapore have risen rapidly over the past30±40 years. Signi®cant racial dierences in hip fracture rates arepresent within the same community.

156 (148). INTERSITE RELATIONSHIPS OF BONE MINERALDENSITY IN OLDER ELITE MALE TRIATHLETES

E. M. Kwong, G. F. Rocha, M. Look, M. A. Mikus, L. Musial, G.Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, Universityof California San Diego School of Medicine, La Jolla, CA, USA

OBJECTIVE: To investigate relationships among bone mineraldensity (BMD) and content (BMC) measurements at the lumberspine, proximal femur, and whole body in high performance maletriathletes over forty-®ve years of age.

METHODS: 95 clite male athletes of aged 45 to 76 (mean 54)years competing in the 1999 Ironman World ChampionshipTriathlon in Kona, Hawaii were recruited as subjects at the siteof the competition. BMD and BMC at the lumber spine (L2-L4),proximal femur, and whole body were assessed using a NorlandXR±36 pencil-beam tabletop dual-energy X-ray absorptiometrysystem. Detailed histories regarding diet, exercise/lifestyle habitsand medical history were elicited from each participant. Eventperformance times in the swim, cycling tour, and marathon wererecorded. Data analysis employed Minitab release 12 statisticalsoftware.

RESULTS: Regression analysis indicated a signi®cant correla-tion between whole body BMD and proximal femoral BMD(p50.0001). BMD correlations between whole body and totallumber spine (p = 0.390) and between promimal femur and totallumber spine (p = 0.602) were not statistically signi®cant. How-ever, when both whole body and proximal femur BMD werecompared to individual lumber spine levels L2 and L3, signi®cantrelationships were found (p50.0001). In contrast, when comparedto L4, the correlations were again insigni®cant (p = 0.449 and0.839, respectively).

CONCLUSIONS: Among elite male triathletes over 45 years ofage, signi®cant intersite relationships exist between total body,proximal femoral, and upper lumbar spine BMD. The failure ofBMD in the total lumbar spine and L4 alone to correlate with otherskeletal sites suggests a relatively high prevalence of degen-erative spinal disease in the low back among this population. Thisimplies that intense physical activity among older men either

predisposes to the latter, or that its presence does not precludetriathlon participation.

157 (149. OSTEOPOROTIC VERTEBRAL FRACTURES INPATIENTS WITH CROHN'S DISEASE

L. Landgraf1, D. Felsenberg1, S. Ljunghall2, G. Bianchi Porro2, R.Stockbrugger2, M. Vatn2, 1Univ. Hospital B. Franklin, Berlin,Germany; 2Steering Committee of The Matrix Study Group

Objective: To study the prevalence of vertebral fractures inpatients with Crohn's Disease (CD), where osteoporosis is acommon problem.

Methods: Baseline values were analysed in a trial conducted at34 European centres. In total 137 women (mean age 37.2 years)and 136 men (mean age 36.5 years) with CD were randomized toreceive treatment with budesonide or prednisolone. Vertebralfractures (fx) were assessed by one radiologist using the ``EVOS''criteria.

Results: 60 vertebral (45 wedge and 15 concavity) fractureswere found in 39 (14%) of 273 patients. In men, the prevalence ofvertebral fractures was similar in all age groups; in women, itincreased signi®cantly with age (P=0.0042; linear regression).

Conclusion: In this predominantly young study population withCD, the vertebral fracture rate was strikingly high, both in menand women, a problem deserving further clinical attention.

Total Age 17±30 31±40 41±50 51±60 61±69

Patients 273 111 64 48 34 16

Patients with fx 39 (14%) 12 (11%) 8 (13%) 8 (17%) 6 (18%) 5 (31%)

Women 137 50 36 28 16 7

Women with fx 17 (12%) 3 (6%) 4 (11%) 4 (14%) 3 (19%) 3 (43%)

Men 136 61 28 20 18 9

Men with fx 22 (16%) 9 (15%) 4 (14%) 4 (20%) 3 (17%) 2 (22%)

158 (150). LIFE COURSE PREDICTORS OF ULTRASONIC HEELMEASUREMENT IN A CROSS-SECTIONAL STUDY OF WOMENFROM SOUTHEAST ASIA

D. S. Lauderdale1, T. Salant1, K. L. Han2, P. Tran2, 1University ofChicago; 2Weiss Health Center, Chicago, IL, USA

We conducted a cross-sectional study of bone mineral density(BMD) estimated from ultrasonic calcaneal measurement inwomen born in Southeast Asia and now living in Chicago. Thestudy addressed three questions: was there a trend towards lowestimated BMD? what factors before and after immigration wereassociated with BMD? and were factors which re¯ected theenvironment before age 18 equally associated with BMD forpostmenopausal and premenopausal women? An intervieweradministered a bilingual questionnaire collecting immigration,reproductive and lifestyle data for 213 women (age 20±80) born inVietnam, Cambodia or Laos. Average age at immigration was 39.Postmenopausal Southeast Asian women had lower estimatedmean BMD than reference values for white women. Foursummary indicators of the childhood and adolescent environmentwere predictive: education, remembered age at menarche, height,and coastal birth. These factors were more strongly associatedwith estimated BMD for premenopausal (multiple-partial R2=0.21)than postmenopausal (R2=0.06) women. Adjusting for thesefactors and age, young adult exposures were also associated:early ®rst birth (lower BMD), farming at age 18 (higher BMD), andage at immigration (inverse association). Consistent with otherstudies, smoking and physical inactivity were associated withlower BMD. Distinctive proximal factors ± vegetarian diet (lowerBMD) and betel nut use (higher BMD) ± were weakly associated.


Although early life factors in¯uenced BMD, modi®able risk factorswere also predictive.

159 (151). PREVALENCE OF LOW BONE MASS IN THEPROXIMAL FEMUR AMONG WORLD-CLASS FEMALETRIATHELETES

P. Lee, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L.Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris,University of California School of Medicine, San Diego, CA, USA

PURPOSE: To investigate the prevalence of low bone mass in theproximal femur among elite, high performance athletic women.

METHODS: 139 females were randomly recruited from the 500participants competing in the 1999 Ironman World ChampionshipTriathlon at Kona, Hawaii. Subject age ranged from 16±69 (mean39) years. Detailed information regarding diet, exercise regimen,medical problems, lifestyle habits, personal/family fracturehistory, and menstrual function were obtained from all studyparticipants. Bone mineral density (BMD) and content (BMC) ofthe proximal femur (regions including neck, greater trochanter,Ward triangle, proximal diaphysis, and total), frontal lumbar spine,and total body were measured using a Norland Medical SystemsXR±36 pencil-beam dual-energy X-ray absorptiometry (DXA)system. Performance times for the swimming, bicycling, andmarathon components of the event were documented. Statisticalanalysis was performed using Minitab version 12 software.

RESULTS: The mean BMC and BMD of the femoral neck were4.46 g and 0.96 (range: 0.71 to 0.97) g/cm2, respectively;trochanter values were 9.0 g and 0.75 (range: 0.45 to 1.01)g/cm2, respectively; diaphyseal values were 17.4 g and 1.12(range: 0.75 to 1.58) g/cm2, respectively. Standardized totalfemoral BMC and BMD were 32042 mg and 992 (range: 1348 to691) mg/cm2, respectively. Mean total femoral T-score was 0.52(range: ±2.15 to 2.19); mean Z-score was 0.811 (range: ±1.34 to3.19). Mean T- and Z-scores for the femoral neck were ±0.54(range: ±3.26 to 2.07) and 0.0619 (range: ±1.52 to 2.9),respectively. Mean T-and Z-scores for the trochanter were ±0.29(range: ±2.77 to 2.21) and 0.202 (range: ±1.99 to 3.27).

CONCLUSION: In contrast to previous studies which havefocused on amateur female athletes competing in a single sport,we conclude that these world-class triathlete women generally donot suffer from low bone mass or osteoporosis in the proximalfemur. Relative preservation of bone mass in this population maybe related to optimized dietary and training regimens thatmaintain body fat at a reasonable level (mean: 12.9%), andthus, their ability to produce suf®cient estrogen.

160 (152). RISK FACTORS FOR FRACTURES OF PROXIMALHUMERUS

S. H. Lee, P. Dargent, G. BreÂ art, for the EPIDOS Group, INSERMUnit 149, Villejuif, France

Fracture of the proximal humerus is one of the major osteoporoticfractures, yet it has seldom been studied. Two types of factors(related to bone fragility or to falls) were evaluated to identify riskfactors for humeral fractures (HF), as well as to examine possibleinteractions between them. 6901 women aged 75 years and olderhad a baseline examination including femoral neck bone mineraldensity (BMD), calcaneal ultrasound parameters (speed of sound± SOS and broadband ultrasound attenuation ± BUA), personaland maternal history of fractures, as well as physical capacity,mobility, neuromuscular and visual function assessements.During a mean of 3.6 (�0.8) years of follow-up, 165 humeralfractures occurred. Using Cox regression models, we identi®edthree bone fragility-related risk factors ± low BMD (RR= 1.4 for ±1SD; 95% CI 1.1±1.7), low SOS (1.3 for ±1SD; 1.0±1.6), maternalhistory of hip fracture (1.8; 1.0±3.0), and four fall-related riskfactors ± pain in the ankle or foot (1.4; 1.0±2.1), bad performance

in a test of balance (1.8; 1.1±2.9), low level of physical activity (2.2;1.1±4.4), history of fall in the past 6 months (1.1; 0.6±2.0 for the®rst year to 3.0; 1.5±6.1 for the fourth year of follow-up). The effectof these fall-related predictors varied according to the level ofBMD: in osteoporotic women (BMD T-score 4±2,5), they weresigni®cantly associated with HF, whereas in non osteoporoticwomen they were not. These results suggest that programsaimed at preventing HF should target, in priority, women whohave both types of risk factors.

161 (153). PREVALENCE OF OSTEOPROSIS IN PATIENTSREFERRED FOR BONE DENSITOMETRY IN SRILANKA

S. Lekamwasam, Faculty of Medicine, University of Ruhuna, SriLanka

This study estimates the prevalence of osteoporosis at differentskeletal sites in 236 patients, who underwent Duel EnergyAbsoptiometry for the ®rst time in Sri Lanka.

Method: 236 patients, who were suspected to have osteo-porosis were scanned using Norland Eclipse Densitometer. AsianReference data set provided by manufactures was used toestimate the T score. The diagnosis of osteoporosis was madeusing WHO criteria based on the T score.

Results: 90% of patients were women and 83% of them werepostmenopausal. The Mean age of the population was 55 (+11.2)yrs, their height 148 (+21.7) cm, weight 51 (+11.9) kg and BMI 22(+4.8). Osteoporosis was detected in 29% of patients at distalradius and ulna, 42% at proximal radius and ulna, 55% atproximal radius, 48% at lumbar spine and 17% at the neck offemur.

Discussion: High % of post-menaopasal women would havecontributed to osteoporosis of lumbar spine detected in 48%.Unlike in western countries, the highest prevalence of osteo-porosis was seen at the proximal radius. This raises thepossibility of associated vitamin D and Calcium de®ciency inthe etiology. Further studies are required to prove this possibility,which will have direct relevance on the prevention and treatmentof osteoporosis in Asian countries.

162 (154). DEFINITION OF INCIDENT VERTEBRAL DEFORMITYIN POPULATION STUDIES : CASES SHOULD ALSO SATISFYCRITERIA FOR A PREVALENT DEFORMITY

M. Lunt, A. A. Ismail, C. Cooper, D. Felsenberg, O. Johnell, J.Kanis, T. W. O'Neill, J. Reeve, A. J. Silman, the EuropeanProspective Osteoporosis Study Group, ARC Epidemiology Unit,Manchester University, UK

Background: Several morphometric criteria have been proposedto de®ne incident vertebral deformities, however, there are fewdata comparing their relative performance. The aim of this studywas to compare the performance of two established morpho-metric methods.

Methods: The subjects who took part in the analysis wererecruited from population registers for participation in a pro-spective study of osteoporosis ± the European ProspectiveOsteoporosis Study (EPOS). At baseline subjects had aninterviewer administered questionnaire, lateral spine x-rays anda subsample had BMD assessment. Repeat spinal x-rays wereperformed a mean of 3.8 years later. Radiographs were assessedmorphometrically and clinically by an experienced radiologist.Incident deformities were de®ned using 2 morphometric criteria:a) a change in vertebral height by more than 20% since baseline,b) a new prevalent deformity (using the McCloskey method). Adiscriminant function was developed using several risk factorsincluding BMD, which differentiated between subjects in whomboth methods agreed were normal and those both agreed hadincident deformities. This function was then applied to thesubjects who were positive by only one de®nition.


Results: Paired spinal radiographs were available in 3500women and 3000 men. Using the discriminant function there wasno signi®cant difference between subjects positive only bymethod a and those positive only by method b, although therewere more subjects positive by method b. The risk factor pro®leof subjects who were positive by only one de®nition was moresimilar to subjects agreed to be normal than to subjects agreed tohave an incident deformity. If only subjects satisfying both criteriawere regarded as having incident deformities, the number ofsubjects with deformities not diagnosed as having a clinicalfracture (according to the radiologist) dropped from 56 (method a)or 201 (method b) to 22, whilst the number with clinical fracturesdropped from 188 (method a) or 202 (method b) to 184.

Conclusions: In this analysis, using data from a populationsurvey, there was no difference in the risk factor characteristics ofsubjects classi®ed as having an incident deformity by twoestablished morphometric criteria. A combination of these criteriawas more strongly associated with the potential risk factors andthe clinical evaluation than either method separately.

163 (155). INCIDENCE OF OSTEOPOROSIS IN A WOMANPOPULATION OF BUENOS AIRES CITY

Z. Man, P. Antunez, TIEMPO Medical Center, Buenos Aires,Argentina

In order to determine the incidence of spinal and hip Osteo-porosis (OP) and Osteopenia (O) in a group of women ([,]])without obvious risk factors in our city, a random selected groupof 280 postmenopausal [,] from 46 to 82 years old (y) has beenevaluated densitometrically (dtm), measuring Bone MineralDensity (BMD) in lumbar spine (R), Femoral Neck (FN) andTrochanter (T). There have been excluded from the researchthose [,] with early menopause (less than 45 years old), hyper orhypothyroidism, hyper or hypoparathyroidism, renal failure,Cushing syndrome or adrenal de®ciency, kidney stones, severegastrointestinal pathologies, cerebral-vascular injure, pathologi-cal fractures, Paget disease, multiple mieloma or other cancers,hypopituitarism or GH de®cit, hyperprolactinemia; drugs (formore than 2 months): any drug used for OP treatment, corticoids,T4, heparine or oral anticoagulants, diuretics, high doses of AINEor raloxiphene. The 130 patients (age X = 60, 46�12,1 y) which didnot present any of the above mentioned OP risk factors, wereasked about number of y from menopause (MY) and their BodyMass Index (BMI) was calculated. The patients were classi®edaccording to: a) BMD: Normal (N = T up to ±0.99), O (O = T from ±1to ±2.49) or OP (OP = T >±2.49); b) MY: 1 to 4.9; 5 to 9.9; 10 to 19.9and >20; c) BMI: Normal Weight (NW, >24.9), Overweight (OW,from 25 to 29.9) and Obesity (OB, >30).

Results (respectively R/FN/T,): N-N-N, 31 [,], 23.84%; O-O-O,16 [,], 12.3%; OP-OP-OP, 6 [,]], 4.61%; O-N-N, 11 [,], 8.46%; OP-N-N, 2 [,], 1.53%; OP-O-O, 10 [,], 7.69%; OP-O-N, 12 [,], 9.23%;O-OP-O, 3 [,], 2.3%; N-O-N, 13 [,], 10%; O-O-N, 17 [,], 13.07%;OP-OP-O, 8 [,], 6.15%; N-O-O, 1 [,], 0.76%. a) Neither NW [,] with>5 YM nor any [,] >20 YM had the 3 dtm measured regions N; b)None of the OW or OB [,], independently of YM, had OP in the 3zones, only NW [,] presented OP in the 3 zones; c) None of theNW [,] had R with O or OP with N hip (FN and T); d) None of the [,]had FN OP with R and T N, but 3 [,] showed FN OP with R and T Oand 13 [,] FN O with R and T N; e) None of the [,] with > 20 YMhad N FN; f) OB [,] only change T after 10 YM; g) Only 2 [,] shownOP in R with hip (FN and T) N; h) In all YM groups were found [,]with OP-O-N, O-N-N and O-O-N, but only 1 [,] had N R with hip(FN and T) O; i) It has been found that more [,] OW or OB showedBMD dissociation between R and T.

Conclusions: 1) The 23.84 % of postmenopausal [,] didn'tpresent O or OP, but neither any [,] YM >5 nor any [,] YM >20 hasthe 3 regions N; 2) Only a 4.61 % of postmenopausal [,], all NW,have OP in R, FN and T; 3) The 41.61 % of the patients presented

O at least in one region; 4) The 31.53 % of the patients has OP atleast in one region; 5) The T is the most preserved region, which isshown N in a 66.15 % of the examined patients; 6) It doesn't existan affection sequence in which R should precede FN; 7) Theweight dissociates the R from the T.

164 (156). COMPARATIVE PREDICTIVE ABILITY OF SKELETALMEASUREMENTS FOR FRAGILITY FRACTURE

E. V. McCloskey, D. de Takats, J. Bernard, K. Pande, R. Ashford,M. Beneton, T. Jalava, J. Kenraali, L. Pylkkanen, J. A. Kanis,University of Shef®eld, UK

We wished to compare the predictive abilities of a number ofdensitometric and ultrasound techniques for fragility fractures. Inan interim analysis of a prospective double-blind, placebo-controlled study of hip fracture prevention, 4348 women agedat least 75 years underwent a variety of skeletal assessments atentry. They were then randomised to receive clodronate 800mgdaily or placebo. The present analysis remains blinded totreatment.

During a median follow-up of 15 months, a total of 195 validatedfragility fractures were documented, including 51 hip fractures.The age and weight adjusted odds ratio for fracture for each 1SDdecrease in measurement was computed by logistic regression(Table). All of the assessments showed signi®cant predictiveability for any fragility fractures. The relative performance of totalhip BMD appears superior to the other assessments.

Measurement Any OP fracture Hip fracture

Total hip BMD 1.6 (p<0.0001) 2.1 (p<0.0001)Forearm BMD 1.4 (p<0.0001) 1.7 (p<0.0001)Heel BUA 1.2 (p = 0.0038) 1.3 (p = 0.0062)Tibial SOS 1.2 (p = 0.0082) 1.1 (p = 0.4404)

165 (157). INCIDENCE OF HIP AND DISTAL FOREARMFRACTURES AMONG URBAN POPULATION IN RUSSIA

E. E. Mikhailov, L. I. Benevolenskaya, S. G. Anikin, E. A. Besedina,U. A. Doroshenko, O. B. Ershjva, E. V. Zhuravleva, O. M. Lesnyak,L. V. Menshikova, E. N. Otteva, Institute of Rheumatology RAMS,Moscow, Russia

Retrospective multicentral study among the population aged 50year and over from 12 Russian cities in the period of 1992±1997was aimed at the study of hip and distal forearm fracturesincidence. Total numbers of the examined population was1,394,250 persons (M=529, 796; F=864, 454). Among males hipfracture incidence varied from 25.7 to 176.2/100 000 whichaveragely is 78.8/100 000. Fracture incidence among females inthe majority of the cities statistically signi®cant prevailed over thatamong males and varied from 61.4 to 259.5 being in average105.9/100 000. Fracture incidence grew with age with maximalvalues in age groups >70 y/o. Distal forearm fractures incidenceamong males varied from 71.2 to 1247.3 which averagely is 235.1/100 000 for all period of observation. Fracture incidence of thislocalisation among females statistically signi®cant prevailed overthat among males and varied from 242.4 to 1213.3 whichaveragely is 684.9/100 000. Three groups of cities were isolated:with high, medial and low fractures incidence. The differencesbetween groups were statistically reliable. Analysis of fracturesdynamics during the studies years enabled us to reveal thestatistically signi®cant increase of fractures incidence of bothlocalisations for the last years.


166 (158). OBSERVATIONAL STUDY ON ARTHROSIS ANDOSTEOPOROSIS: RESULTS FROM 1880 WOMEN

O. Moreschini, S. Conte, M. Nocente, University of Rome ``LaSapienza'' Orthopaedic Department, Italy

Abstract. We studied the possible relationship between Os-teoartrhitis (OA), Osteoporosis (OP), and correlated risk factors, ina cohort of female subjects over 45 years.

Severe OA was de®ned as a variation of grade 4, inacccordance with the criteria described by Kellgren andLawrence; OP was diagnosed by means of densitometricexamination performed with double X-ray mineralometric techni-ques (DEXA).

Complete data, including anthropometric charateristics, gona-dal function, eating habits during both adolescence and adultage, smoking, physical intensity of working activities, articularand somatic pain and disability, were available in 1880 women(mean age 65.2�8 years). Statistical analysis was made.

Our results show an inverse correlation between bone densitydistribution in terms of the degree of OA, (r = ±0.89; p = 0.042)regardless of the age factor.

We found an highly signi®cant difference (p50.01) in bodyweight, number of children, body mass index, articular pain(always higher in the OA group) and quality of life (lower in thesevere OA group).

No signi®cant differences (p > 0.05) were observed for height,menarchal age, period of breastfeeding, eating habits duringadolescence and adulthood, comsumption of alcohol or coffee,smoking, somatic pain.

Our study con®rms the existence of a marked inversecorrelation between OA and OP, particularly in the most severeclinical and diagnostic conditions.

To conclude, far from presuming a de®nite pathological causelinking these two conditions, we consider the factor ``presence ofsevere OA'' as an additional diagnostic element for managementof post-menopausal osteoporosis.

167 (159). HIGH BMD INCREASES THE RISK OF NEW HIP OA INELDERLY WOMEN, BUT OSTEOPOROSIS IS NOT PROTECTIVE

M. Nevitt, N. Lane, M. Hochberg, E. Williams, for the SOFResearch Group, Universities of California, San Francisco;2Baltimore, Maryland, USA

In cross-sectional studies women with radiographic hip OA(RHOA) have increased BMD at the hip and peripheral sites. Weperformed a prospective study of the relationship betweenbaseline BMD, prevalent vertebral fractures (PVFX), and newRHOA among women age 565 in the Study of OsteoporoticFractures (SOF). AP pelvis x-rays were obtained 8.0 (SD 0.4) yearsapart in 5,987 women, 73% of survivors. Paired x-rays wereassessed blinded to order for individual radiographic features(IRFs) of hip OA and measurement of minimal joint space (MJS).Total hip BMD was assessed by DXA (Hologic QDR 1000) andradius BMD by SPA (Osteon Osteoanalyzer). PVFX were assessedby morphometry from lateral spine x-rays. In women withoutRHOA at baseline, we calculated odds ratios (OR) for theassociation of age-adjusted quartiles of BMD and PVFX withnew RHOA ([get] 2 new IRFs), new osteophytes and new MJS41.5 mm. Logistic regression was used to estimate ORs in a hip-based analysis, with GEE to account for within subjectcorrelation, adjusted for age, estrogen use, weight, height,physical activity, and smoking. Women with high hip BMD hada greater risk of new RHOA and osteophytes, but not loss of jointspace, a marker for severe OA. Results were similar for radiusBMD. In contrast, women with 2 or more (vs. none) PVFX had anincreased risk of RHOA, osteophytes and loss of joint space. Weconclude that high BMD is a risk factor for an osteotrophic variantof RHOA in elderly women. However, osteoporosis may increasethe risk of developing severe hip OA with loss of joint space.

% new RHOA (OR) by Age-adj. BMD Quartile

Q1 Q2 Q3 Q4

RHOA 2.3% (1.0) 2.5% (1.2) 3.2% (1.6) 4.7% (2.3)**Osteophytes 2.7% (1.0) 3.6% (1.4) 3.9% (1.5)* 4.7% (1.9)**MJS 1.5 mm 2.7% (1.0) 2.2% (0.8) 2.6% (1.0) 2.6% (1.0)

*P<.05 **P<.01

168 (160). REGIONAL BONE MINERAL DENSITY AND SOFTTISSUE COMPOSITION IN OLDER ELITE MALE ATHLETES

D. Nguyen, E. M. Kwong, G. F. Rocha, M. L. Look, M. A. Mikus, L.Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris,University of California School of Medicine, San Diego, CA, USA

PURPOSE: To assess the relationships among regional bonemineral density (BMD), bone mineral content (BMC) and leanversus fat soft tissue composition in highly trained athletic menover 45 years of age.

METHODS: 95 elite male athletes ranging in age from 45 to 76(mean 54) years who competed in the 1999 Ironman WorldChampionship Triathlon in Kona, Hawaii were examined. Totalbody and regional BMC and BMD, as well as total and regionalsoft tissue mass (including lean versus fat components) weremeasured using a Norland XR±36 pencil-beam tabletop dual-energy X-ray absorptiometry scanner. Dietary/medical history,exercise/lifestyle habits, and personal/family fracture history,along with performance times in the swim, cycling tour, andmarathon components of the event, were documented for eachparticipant. Statistical analysis of data was performed usingMinitab version 12 software.

RESULTS: Signi®cant correlation was found between (BMC)and soft tissue (lean plus fat) mass in all body regions, with thestrongest relationship in the abdomen (p50.0001, R-Sq = 77.8%).However, BMC in the arms and legs was not statistically relatedto either fat or lean mass individually in these areas. Correcting forskeletal size, BMD correlated signi®cantly with total soft tissuemass only in the chest, legs, and arms (p ranging from <0.0001 to<0.005). No statistical relationship was found between regionalBMD and separate fat versus lean tissue components. BMC,BMD, bone size, and total soft tissue mass of the right versus leftextremities were signi®cantly correlated (p50.0001), indicatingsymmetry.

CONCLUSIONS: BMC correlates well with total soft tissuemass in all regions of the body among older male triathletes.However, the BMD:soft tissue relationship is signi®cant only in thebiomechanically active regions of the body (chest, arms, legs),suggesting an in¯uence of their intense physical training. Incontrast to previous studies demonstrating relatively constantratios between BMD/BMC and muscle mass in the extremities,this investigation suggests that BMD/BMC in the arms and legs isrelated to total soft tissue mass as opposed to lean versus fatcomponents separately among older elite male athletes.

169 (161). EXERCISE AND MILK INTAKE ARE DETERMINANTSOF BONE MASS IN ELITE MALE MILITARY CADETS

J Nieves, M Zion, J Ruf®ng, R Lindsay, F Cosman, Helen HayesHospital, NY, USA

Peak bone mass is clearly related to genetic and lifestyle factors.A sample of 557 male cadets entering the United States MilitaryAcademy (USMA) had multiple bone density assessments todetermine the relative importance of milk intake and physicalactivity on bone mass at various skeletal sites. Dietary intakes ofcalcium, salt, caffeine and physical activity over the yearpreceding entry to the USMA were assessed by writtenquestionnaire. Calcium intake was almost solely determined by


milk intake in this population. A Lunar DPX-IQ Dual x-rayabsorptiometry (DXA) was used to assess bone density (BMD)at the lumbar spine and total hip in a randomly chosen subset of131 male cadets. A peripheral DXA (Lunar) was used to assessheel BMD in 557 male cadets and a peripheral pQCT (Norland)was used to measure tibial bone content and cortical thickness in503 male cadets. On average the cadets had spine, hip and heelBMD values that were one standard deviation above themanufacturers young normal reference population. Higher milkintakes (3 cups/day or more) were signi®cantly related to greatertotal tibial content (p = 0.01); cortical thickness (p = 0.02) and heelBMD (p = 0.05). There was also a trend toward higher BMD of thespine and hip in those with higher milk intakes. In male cadets,intense physical activity in the past year (exceeding 12 hours perweek) was associated with signi®cantly higher bone massthroughout the skeleton including the spine, hip, heel and tibia(3 and 6% higher; all p<0.02) as compared to cadets with lessintense levels of physical activity. Salt and caffeine were notassociated with bone mass. In conclusion, males with bone massat the high end of normal, can still maximize bone mass at allskeletal sites by high levels of exercise and adequate calciumintake through milk consumption.

170 (162). GENETIC CONTRIBUTION TO BONE MINERALDENSITY VARIATION AT MAJOR SKELETAL SITES IN TWINS

T. Niu1, J. Ni2, C. Chen1, D. Chen,1,2, B. Wang,1,2, X. Liu2, S. R.Cummings3, C. J. Rosen4, X. Xu,1,2,5, 1Program for PopulationGenetics, Harvard Schl Pub Hlth, Boston, MA; 2Inst. for Biomed,Anhui Med. Univ., Hefei, China; 3Dept. of Med., UCSF, SanFrancisco, CA; 4Maine Ctr. for Osteoporosis Res. & Education,Bangor, ME; 5Channing Lab, Dept. of Med., BWH, Harvard Med.Schl., Boston, MA, USA

Twin studies offer unique opportunities in estimating the geneticcomponent of quantitative traits. We measured bone mineraldensity (BMD) using DEXA at various skeletal sites and for thetotal body in 605 twin pairs in Anqing, China. Estimates ofheritability for age-, sex-, smoking status-, and body mass index(BMI) -adjusted BMD of head, arms, legs, trunk, rib, pelvis, spine,and total body were 0.65, 0.82, 0.71, 0.75, 0.73, 0.45, 0.78 and0.58, respectively for twins under age 18, and were 0.60, 0.53,0.70, 0.70, 0.67, 0.75, 0.45, and 0.66 for twins at least 18 years old.The intrapair difference of BMI was found to be a signi®cantpredictor of the intrapair difference of age- and sex-adjustedBMD of trunk, rib, pelvis, and total body among adult MZ twins(P<0.001). This study suggests that the variance of BMD atvarious anatomical sites is largely genetically determined in bothchildren and adults. Furthermore, our results demonstrate thatBMI is a signi®cant predictor of BMD values at various skeletalsites examined.

171 (163). TOTAL BODY CALCIUM AND BODY COMPOSITIONIN OLDER ELITE MALE TRIATHLETES

C. T. Norred, E. M. Kwong, G. F. Rocha, M. Look, M. A. Mikus, L.Musial, G. Nakamoto, M. D. Bracker, D. J. Sartoris, University ofCalifornia School of Medicine, San Diego, CA, USA

PURPOSE: To evaluate total body bone mineral content (BMC)/density (BMD) and soft tissue composition among elite maletriathletes over age 45 years, with reference to regionaldistribution and interrelationships.

METHODS: 96 male triathletes ranging in age from 45±76 (mean54) years participating in the 1999 Ironman World ChampionshipTriathlon at Kona, Hawaii were prospectively recruited. Dual-energy X-ray absorptiometry studies of the total body, frontallumbar spine, and proximal femur were performed on eachsubject using a Norland XR±36 pencil-beam tabletop scanner.Questionnaire data solicited from each participant included

dietary/medical history, exercise/lifestyle habits, and personal/family fracture history. Performance times in the swimming,bicycling, and marathon components of the event were alsorecorded. Statistical analysis was performed using Minitabversion 12 software.

RESULTS: Height ranged from 59±75 (mean 69) inches. Weightranged from 129±193 (mean 159) pounds. Maximum lifetimeweight averaged 175, with a high of 230, pounds. Total body BMCranged from 2368±3918 (mean 3109) grams. Total body BMDranged from 0.859±1.235 (mean 1.080) grams/cm2. Total softtissue mass ranged from 55.6±82.1 (mean 69.7) kilograms. Leanbody mass ranged from 35.1±69.3 (mean 51.6) kilograms. Fatbody mass ranged from 4.7±20.8 (mean 11.1) kilograms.Corrected percentage body fat ranged from 4.0±25.6 (mean12.5) %. Total body BMC was signi®cantly correlated with totalsoft tissue mass (p50.0001, R-Sq = 29.6%). Total body BMD wassigni®cantly correlated with total soft tissue mass (p50.0001, R-Sq = 14.0%). However, neither total body BMC nor BMD waspredicted by lean versus fat components of total body soft tissuecomposition (p = 0.657, p = 0.14 for BMC, p = 0.393, p = 0.107 forBMD, respectively). Lean body mass was not signi®cantly relatedto fat body mass (p = 0.287).

CONCLUSIONS: Older elite male triathletes as a group do notdiffer signi®cantly from the general population in terms of totalbody BMC and BMD, despite intense physical training regimens.Similarly, percentage body fat is not below the generally acceptedideal range of 10±20% for the general population of men. Totalbody BMC and BMD are predicted by total soft tissue mass, butnot by lean or fat body mass independently.

172 (164). BMD IN CALCANEUS IN 1392 18 YEAR OLD MEN INRELATION TO MUSCLE STRENGTH

C. Nyman, O. Johnell, K. Landin-Wilhelmsson, L. Hulthen, R.Kullenberg, L. Samuelsson, R. Lorentzon, E. Norjavaara, D.MellstroÈ m, 1Dept of Geriatrics, Internal Medicine andRadiophysics, University of Gothenburg, The National ServiceAdministration, Regional Of®ce, Gothenburg; 2Dept ofOrthopaedics, Umea and Malmo, AstraZeneca, Lund, Sweden

BMD is a predictor of fractures and survival in men. Most studiesshow a close relation between BMD and muscle strength in men.The question is if BMD is a predictor of muscle strength andendurance corrected for anthropometric factors and years oftraining. Most (96 per cent) of 18 year old men in Swedenparticipate in a two days test of functional capacity and ®tness forthe compulsary military service. BMD in right calcaneus wasmeasured with DXA. Calscan. A questionnaire included nutritionalhabits, physical activity, life style factors and heredity.

BMD in calcaneus correlated to heigth (r = 0.14), weight(r = 0.21), years of training (r = 0.39), muscle strength (r = 0.33),oxygen uptake (r = 0.21) and endurance test (r = 0.40). In acovariance analysis BMD remainded signi®cant in a model withage, heigth, weight and years of training as a predictor for musclestrength. In summary BMD in calcaneus was an independentpredictor of muscle strength and endurance in a communitybased population of 18 year old men.

173 (165). A METHOD OF CALCULATING THE LONG-TERMPROBABILITY OF FRACTURE

A. Oden, J. A. Kanis, O. Johnell, D MellstroÈ m, B. Jonsson, C. DeLaet, A. Dawson, Consulting Statistician Romelanda, Sweden

Whereas hip BMD provides diagnostic criteria for osteoporosis,treatment thresholds depend upon other factors includingabsolute risk and the cost effectiveness of interventions. Absoluterisks are preferable to relative risks and 10-year risks areconsidered appropriate for the development of practice guide-


lines. In this paper we have devised a method of determininglong-term risks.

The easiest way of determining the long-term risk of fracture isto follow a cohort for a given period of time but this is not alwaysfeasible. A more appropriate approach is to estimate the fractureand death hazards separately with varying follow up periods andwithout restriction to time by the use of Poisson regressionmodels. The general relationship between the probability on oneside and the two hazard functions on the other one is then appliedin order to calculate the probabilities for different subgroups.Adjustments of the death hazards to future hazards or to othercountries are possible by this method as well as adjustments tothe general level of the fracture hazard of the country. The relativeimportance of risk variables such as bone mineral density(re¯ected by beta coef®cients in regression models) is probablymore stable from country to country than the general level of therisk of a country. In many cases the estimations of the two hazardfunctions can be done with a greater accuracy than the estimationsay, of the ®ve years probability by logistic regression. Forexample, a low bone mineral density gives a higher risk of deathwhich to some extent makes the bone mineral density lessimportant for the probability than for the hazard function. Inaddition, the data after these ®ve years can be used.

This methodology has been applied to the Gothenbergpopulation in Sweden to examine the effects of age, sex, bonemineral density, body mass index and other risk factors on the tenyear probability of hip fracture.

174 (166). EXCESS COSTS: OSTEOPOROTIC FRACTURES INVETERANS

A. Ohldin, K. Kiefe, University of Alabama, Birmingham, AL, USA

Background: Osteoporosis affects over 20 million Americans.Complications of osteoporosis such as hip and other fracturesresult in signi®cant incremental health care costs. Hip fracturesaccount for 300 000 hospital admissions and annual costestimates range from $15 billion to $30 billion. The majority ofhip fractures are attributed to osteoporosis.

The prevalence of osteoporosis and associated fractures areexpected to increase among the aging Veteran population.Osteoporotic hip fractures are associated with one-year excessmortality of 10±20%. Less than one third of elders with hipfractures return to their previous level of function.

Purpose: Identify frequency and incremental medical costsassociated with hip fractures among Veterans.

Methods: Medical cost inferences based on VA and Medicaredischarge and cost data.

Results: Hip fractures annually result in 11 million dollars ofexcess costs to Veterans and the VA.

Conclusions: Osteoporotic hip fractures are preventable. Useof primary and secondary preventive measures, in the VA,represent an opportunity for substantial cost savings andenhanced quality of life.

175 (167). DOES THE PREDICTIVE VALUE FOR HIP FRACTUREOF A CALCANEAL BONE MINERAL MEASUREMENT CHANGEWITH TIME?

J. O Olsson1, J A. Kanis2, A. Oden3, O. Johnell4, C. Johansson1, A.Rundgren1, D. MellstroÈ m1, 1Dept. of Geriatrics, University ofGothenburg, Sweden; 2Metabolic Bone Diseases, Shef®eldUniversity, Shef®eld, UK; 3Dept. of Statistics, ChalmersGothenburg, Sweden; 4Dept. of Orthopaedics, Malmo, Sweden

Bone mineral density measurement predicts future hip fracture,with a relative risk per SD from 1.5 to 2.6 depending on site ofmeasurement in a metaanalyse.

The question is, if a single BMD measurement among elderlycould predict hip fracture after 5±10 years.

Population and method: From the longitudinal population studyof the elderly in Gothenburg, 1628 individuals (944 women) with amean age from start of 77.6 years (range 70±85 years), wereincluded. Bone mineral density was measured with DPA-technique in calcaneus. The occurrence of hip fractures wasensured by coordination with the medical register of the NationalBoard of Health and Welfare and x-ray archives. A Poison modelwas used to study the impact of time after BMD measurement topredict hip fractures.

Results: The total follow up time was 12.223.8 years. Thenumber of patients with hip fracture were 216. Mean value of BMDwas 0.381 g/cm2 and SD was 0.137. The predictive power of abone density measurement declined during a period of 10 yearswith a relative risk per SD from &1.5 year one to 1.2 the ®nal year.The study indicates that gender has no signi®cant importance forthe risk of hip fracture if bone density was included in the modeland smokers and subjects with low BMI had an independentincreased risk for hip fracture.

Conclusion: This study demonstrates that a bone densitymeasurement in calcaneus is a strong independent predictor forfuture hip fracture also at age 80. It also indicates that thepredictive power signi®cantly decrease during a period of 10years after the measurement.

176 (168). HIGH CHOLESTEROL LEVELS ARE ASSOCIATEDWITH LOW BONE DENSITY IN POSTMENOPAUSAL WOMEN

P. Orozco, I. Hurtado, ABS Gotic & Universitat de Barcelona &Unitat Recerca Experimental, Barcelona, Spain

Recent studies suggest that osteoporosis and cardiovascular riskfactors may be associated.

Objective: To evaluate the lumbar and femoral bone density (byDXA) in early postmenopausal women aged 553 years withnormal (5240 mg/dl) and high cholesterol levels (>240 mg/dl).

Patients: 55 women (32 normal and 23 with high cholesterol),with no treatment that interfere lipids or bone metabolism. Allwere no heavy smoker, no sedentary, no early menopause.

Results: Women with high cholesterol had lower BMD thanthose with normal cholesterol. Both group had similar age, timesince menopause, weight, height, blood pressure, but calciumintake was lower in those with high cholesterol.

Cholesterol (mg/dl) p<240 >240X (SD) n=32 X (SD) n=23

Tscore L2 ± L4 ±1.0 (1.4) ±1.6 (0.7) 0.02Tscore neck ±0.7 (0.9) ±1.1 (0.8) 0.07Tscore troch ±0.4 (1.4) ±0.7 (1.1) 0.4Tscore inter 0.2 (1.3) ±0.6 (1.0) 0.02Tscore F-tot ±0.1 (1.3) ±0.8 (1.0) 0.02Tscore Ward's ±1.0 (1.4) ±1.6 (0.8) 0.06Cholesterol 207 (24) 275 (27) 0.0001Years since mp 5 (2) 5 (2) 0.7BMI (kg/m2) 27.4 (2.2) 27.3 (1.6) 0.9Calcium intake 1213 (426) 928 (281) 0.007

Conclusions: These data suggest that women with hypercho-lesterolemia have lower bone density, but other confoundingfactors like nutrition should be considered.

177 (169). RISC FACTORS FOR OSTEOPOROSIS IN CITIZENSOF BELGRADE

N. PilipovicÂ , N. VujasinovicÂ - Stupar, D. Palic-ObradovicÂ , G.Radunovic, P. Vukojevic, S. BrankovicÂ , Institute of Rheumatology,Belgrade, Yugoslavia

We examined 667 citizens of Belgrade, randomly selected fromthe population register to estabilsh risc factors for osteoporosis.


The study was carried out in Institute of rheumatology in Belgradeand bone mineral density (BMD) of lumbar spine were performed,using a Lunar DPX-L device. There were 541 female agedbetween 20 and 78 years (mean 48.60�11,84) and 126 maleaged between 20 and 77 (mean 50,89�15.09). Osteopenia wasfound in 26.6% women and 28.6% men, and osteoporosis in 9,1% and 8.7% women and men, respectively. Analysis have beendone using Chi square test, T-test for independent samples andANOVA. Study con®rmed that age and menopause havesigni®cant effect on BMD. Also, in this study the other factorswere found to be of substantial importance for bone mass:sedentary life (recreation end sport activity, as well as hard workhave positive corelation with BMD), low calcium intake (intake ofdiary products every day has positive corelation with BMD), lowsun exposure, low BMI, surgical treatment ± especially earlyoophorectomy, malignancy, thyreoid disases, joint disease andextensive smoking. The most of these risc factors could bemodi®ed for prevention of osteoporotic fractures.

178 (170). THE INCIDENCE OF VERTEBRAL DEFORMITY INHUNGARIAN MEN AND WOMEN

Gyula Poor1, Csaba Kiss1, Dieter Felsenberg2, Terence W.O'Neill3, Marianne Szilagyi1, Alan J. Silman3, 1National Institute ofRheumatology, Budapest, Hungary; 2Steglitz Medical Centre,Freie Universitat Berlin, Berlin, Germany; 3ARC EpidemiologyResearch Unit, University of Manchester, Manchester, UK

There is no reliable vertebral fracture incidence data in Hungary.We studied prospectively 223 women and 198 men aged >50 for amean of 5.1 years in Budapest. Baseline and follow-up lateral X-ray of the spine (T4-L4) was digitised centrally. Film pairs withcandidate fractures were submitted for reevaluation by skeletalradiologist. Data were examined for inconsistencies and data-base cleaning in the statistical centre. Mc Closkey -Kanis 3 SDdeformities were identi®ed on the second X-ray and incidencede®ned by a 53 SD vertebral hight reduction. Clinical fractureswere judged on new endplate infraction and vertebral shapechange.

There were 17 incident deformities in 9 women and 12 in 6 mencompatible with osteoporosis. Adjusted to age 65, 1.21 (0.65±1.42, 95% CI) woman suffered an incident deformity per 100 yearsfollow up and 0.61 (0.42±0.79, 95% CI) men suffered an incidentdeformity per 100 years follow up.

179 (171). BONE DENSITY EVALUATION IN SYSTEMIC LUPUSERYTHEMATOSUS

Z. Pospisil, P. Horak, V. Scudla, L. Faltynek, IIIrd Department ofInternal Medicine, University of Olomouc, Czech Republic

Background: The actual accurrence of osteopenia in patients withSLE has not been established as yet and the causes have notbeen adequately elucidated.

Objective: To assess the accurrence rate of osteopenia inwomen with SLE, the severity of skeletal damage (ostepenia,osteporosis) in the region of lumbar spine and in the neck offemur, to determine and assess causal relationships involve in thedevelopment of osteopenia.

Patients and methods: The study is based on the analysis of agroup of 26 women (9 in the productive, 17 in postmenopausalage). Their degree of bone tissue mineralisation was measuredusing the method of double-energy x-ray absorbtiometry (LUNARDPX-L).

Results: In young women of productive age skeletal affectionwas but rarely observed, ostepenia was present in 4/9 (44%),while none of them had osteoporosis. In women of postmeno-pausal age ostepenia was recorded in 7/17 (41%), osteoporosis in6/17 (35%), only 4/17 (24%) had a normal densitometric ®nding.The differences observed between two groups were statistically

signi®cant, concerning both the accurence rate of osteopenia andosteoporosis and severity of bone affection (T and Z score) oflumbar spine (p = 0.007), as well as of the neck of the femur(p = 0.035). The incidence of osteopenia and osteoporosisincreases with the duration of the underlying disease, withduration of corticosteroid therapy and the presence of otherserious diseases may also have been involved. The region of thelumbar spine was signi®cantly more frequently affected than theneck of the femur.

Conclusions: Management of patients with SLE should involveprevention of the development of osteopenia, particularly inwomen of menopausal age, in the presence of several risk factorsof osteoporosis, especially in long-term therapy with corticoster-oids and a prolonged course of underlying disease with frequent¯ares of disease activity.

180 (172). AGE-RELATED BONE LOSS IN NORMALPOPULATION OF UKRAINE: DATA OF ULTRASOUND BONEDENSITOMETRY

V. V. Povoroznyuk, Institute of Gerontology, AMS Ukraine, MD,Ukraine

The bone tissue state in the residents of Ukraine, subjects of bothsexes, was studied. The total of 1866 persons (1364 women and502 men; 20±89 years old) were included. Patients with diseasesin¯uencing their bone tissue metabolism were excluded from thestudy. The heel bone examinations were performed by means ofan ultrasound bone densitometer 5Achilles+4 (Lunar Corp.,Madison, WI). The speed of sound (SOS, m/s), broadbandultrasound attenuation (BUA, dB/MHz) and a calculated 5Stiff-ness4 index (SI, %) were measured. It was found out that theultrasound parameters characterizing state of spongy bonetissue, and its density decrease after the age of 45 years old inwomen and after the age of 70 years old in men (®g. 1).

Fig.1. SI values in population of Ukraine associated with ageand sex Note: *±p50.05; **±p50.01; ***±p50.,001 compared tothe age group of 35±39 years old; #±p50.05; ##±p50.01;###±p50.001 compared to women.

SI lower than the fracture threshold was found in: 2.4% ± men;13.4% ± women in age group of 50±59 years; 9.6% ± men; 24.6%± women in age group of 60±69; 22.6% ± men; 50.0% ± women inage group of 70±79 years, 20.,1% ± men; 53.3% ± women in agegroup of 80±89 years.

Thus, in the process of aging ultrasound parameters char-acterizing bone tissue state decrease signi®cantly and number ofthe examined with indices lower than the fracture thresholdincreases.


181 (173). ULTRASOUND DENSITOMETRY OF THECALCANEUS IN CHILDREN AND ADOLESCENTS OF UKRAINE

V. V. Povoroznyuk, Institute of Gerontology, AMS Ukraine, MD,Ukraine

The bone tissue state in children and adolescents of Ukraine,subjects of both sexes, was studied. The purpose of this study isto determine normal values in Ukrainian children and adolescents.The total of 577 healthy children and adolescents (205 males and372 females; 7±18 years old) were examined by means ofultrasound bone densitometer ``Achilles+'' (Lunar Corp., Madison,WI). The speed of sound (SOS, m/s), broadband ultrasoundattenuation (BUA, dB/MHz) and a calculated ``Stiffness'' index (SI,%) were measured. Ultrasound parameters increased with age inboth sexes (®g.1). It was found out that the ultrasound parameterscharacterizing state of spongy bone tissue and its densityincrease during the age of 10±14 years. Results of linearregression analysis revealed a signi®cant correlation betweenultrasound parameters and beight (SOS = 1413+0.99 x Height;r = 0.45; R2=20.2; p<0.001; BUA = 7.0+0.62 x Height; r = 0.60;R2=36.1; p<0.001; SI = 0.69 x Height ±19,6; r = 0.60; R2=36.1;p<0.001). Using the method of step-by-step multiple regression,mathematical models for determination of the structural-func-tional age of bone system (SFA BS) in children and adolescentsare worked out:

SFA BS (males) = 9.01 x H +0.06 x W +0.04 x BUA±7.7 (r = 0.88;R2=78%; p<0.0001);

SFA BS (females) = 8.02 x H +0.05 x W ±0.008 x SOS±13.9(r = 0.78; R2=61%; p<0.0001), where: H ± height (m), W ± weight.

In summary, basic preventive measures against the develop-ment of ``future'' osteoporosis in children need to be carried outduring the period from 10±15 years.

182 (174). AFRICAN-AMERICAN(A-A) WOMEN WITH LUPUSHAVE A GREATER RISK OF LOWER LUMBAR SPINE (LS) BONEMINERAL DENSITY (BMD) THAN CAUCASIAN(C) WOMEN WITHLUPUS

R. Ramsey-Goldman, D. Dunlop, C. F. Huang, E. Koch, C.McCray, S. Cunanan, S. Spies, S. Manzi, Northwestern University,IL, and University of Pittsburgh, PA, USA

A-A women are af¯icted with lupus 3±4x more frequently than Cwomen. However, little is known about the bone health of A-Awomen with lupus. The objectives of this study were to measureLS BMD by DXA and to estimate the effect of risk factors for lowBMD in A-A and C women with lupus. 179 women [139 C and 40A-A] were studied to date. There were signi®cant differences(p = 0.05) between A-A and C lupus women in disease severity as

measured by current mean steroid dose 7.8 mg vs. 4.1 mg andmean lupus damage score [excluding osteoporosis] 1.7 vs. 1.1,and personal characteristics as measured by mean BMI 29.0 kg/m2 vs. 26.5 kg/m2 and mean daily calcium intake 910 mg vs. 1185mg. Mean unadjusted LS BMD was 0.996 g/cm2 and 0.966 g/cm2

in C and A-A lupus women, respectively (p = 0.000). A-A lupuswomen had signi®cantly lower LS BMD compared with C lupuswomen in multiple regression analysis, after controlling for BMI,lupus damage score and menopause. A-A lupus womencompared with C lupus women had lower LS BMD equivalent to1SD. Race was not protective for LS BMD in A-A lupus womenand may indeed be a risk factor. Therefore, preventive measuresmust be incorporated into the care of all lupus patients,irrespective of race.

183 (175). DETERMINANTS OF SIZE OF INCIDENT SPINEDEFORMITIES

J. Reeve, M. Lunt, G. Armbrecht, T. O'Neill, A. J. Silman, DFelsenberg, the EPOS Study Group, Institute of Public Health,Cambridge, UK

Background: The personal impact of a vertebral fracture dependspartly on its size. To help understand the biological mechanismsunderlying the development of disabling spinal osteoporosis wehave investigated the determinants of fracture size in a largeEuropean population-based prospective study (EPOS).

Methods: 3800 women and 3300 men were followed in 31European centres. Lateral spine radiographs were taken a meanof 3.7 years apart. Bone mineral density (BMD) measurementswere made, using DXA, at the spine or hip in all but 9 centres.Paired digital ®lm images were adjusted to the same magni®ca-tion and each candidate fracture was subjected to rigorous QA.Incident deformities were de®ned by the McCloskey-Kanisalgorithm on the second ®lm (6 point method) and had at leastone height reduced by 20% between ®lms. 66 men and 142women had at least 1 incident deformity, for each of which loss ofheight (LOH) was calculated as the percentage reduction in thesum of the three vertebral heights. Clinical fractures wereclassi®ed as wedge(we), concave(co), biconcave(bi) or crush(cr).Backwards stepwise regression was used to determine aparsimonious model for LOH.

Results: LOH increased with age (4%/decade), previous bi or crand was not signi®cantly different between men and women. LOHalso increased by 2% /0.1g.cm±2 decrease in BMD. Modelsincluding BMD accounted for >30% of the variance in LOH. WhenLOH for all newly fractured vertebrae was summed and made thedependent variable, the model retained the same determinantsand the variance accounted for increased to 70%. LOH fortheworst new fracture was more than 2-fold greater in subjectswith a pre-existing bi or cr deformity (mean 30 vs 13% P<0.001).

Conclusions: Second fracture size, like second fracture risk, ispredicted independently of BMD by a previous fracture.Meticulous radiological evaluation of spine ®lms is crucial in theprognosis and management as well as in the diagnosis ofvertebral osteoporosis.

184 (176). PREVALENCE OF LOW BONE MASS ANDDEGENERATIVE SPINAL DISEASE IN OLDER HIGHENDURANCE MALE TRIATHLETES

G. F. Rocha, E. M. Kwong, M. L. Look, M. A. Mikus, L. Musial, G. I.Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris, Universityof California School of Medicine, San Diego, CA, USA

OBJECTIVE: To investigate bone mineral content (BMC), bonemineral density (BMD) and resulting mean T-scores and Z-scoresat the lumber spine of high endurance male triathletes 45 years ofage and over.

METHODS: 95 high endurance male athletes ages 45±76 (mean54) years competing in the 1999 Ironman World Championship

Fig. 1. SI values in children and adolescents associated with ageand sex Note: *±p50.05; **± p50.01; ***± p50.001 in comparisonwith the 10 year-old males and females


Triathlon in Kona, Hawaii were randomly recruited as subjects atthe competition site. BMD, BMC, T-scores, and Z-scores of thelumber spine (L2-L4) were assessed using a Norland XR±36pencil-beam tabletop dual-energy X-ray absorptiometry (DXA)system. Detailed information regarding dietary/medical history,exercise/lifestyle habits, and personal/family fracture record wereobtained from each participant. Event performance times in theswimming, cycling tour, and marathon components of the eventwere recorded. Data analysis employed Minitab release 12statistical software.

RESULTS: Visual and quantitative analysis of total lumbar spineand individual levels (L2-L4) indicated a relatively high prevalenceof degenerative spinal disease. Mean BMC values for L2-L4 were0.333, 0.329, and 0.41 g, respectively. Average BMD values forL2-L4 were 0.017, 0.016, and 0.161 g/cm2, respectively. Mean T-scores for L2-L4 were ±0.57, ±0.39, and ±0.95, respectively.Average Z-scores for L2-L4 were 0.031, 0.145, and 0.319,respectively.

CONCLUSION: Among high endurance male triathletes over 45years of age, DXA results suggest a relatively high prevalence ofdegenerative spinal disease in the lower back. This implies thatintense physical activity among older males either predisposes tothe latter, or that its presence does not preclude world-classtriathlon participation. According to World Health Organization(WHO) criteria, the prevalence of low bone mass and osteoporo-sis in this population is extremely low; as a group, vertebral T-and Z-scores fall within the normal range even at levelsunaffected by signi®cant degenerative changes. These resultsare compatible with the intense physical training regimens ofthese older men, and emphasize the importance of exercise in theprevention of age-related bone loss throughout life.

185 (177). AWARENESS, ATTITUDES AND OPINIONS ONOSTEOPOROSIS OF PRIMARY CARE PHYSICIANS WORKINGIN THE METROPOLITAN AREA OF ROME

E. Romagnoli1, S. Minisola2, 1Ospedale San Giovanni Battista;2Dipartimento di Scienze Cliniche, Universita degli Studi ± LaSapienza-, Rome, Italy

This study was aimed to determine the awareness and opinionsof family physicians regarding prevention, diagnosis and treat-ment of osteoporosis.

One hundred out of 115 family physicians were randomlyselected among the 2562 primary care physicians working in thelarge metropolitan area of Rome. The doctors were asked tocomplete a survey including ten closed-ended questions. As faras the level of awareness is concerned, approximately one-thirdof the physicians (38%) do not know that the WHO hasestablished precise criteria for diagnosis of osteoporosis incaucasian females; moreover, thirty-seven percent of doctorsbelieves that the disease, in the elderly, is not relevant in respectto other chronic diseases. Thirty-six percent of physicians makethe diagnosis of osteoporosis exclusively on the basis of BMDresults. Seventeen percent of doctors never use BMD fordiagnosing the disease. Forty-seven percent rely on BMD aswell as on X-ray of the spine and/or reported symptoms. Once thepresence of osteoporosis is suspected, ®fty-three percent ofdoctors require the measurement of biochemical markers of boneturnover. As far as the choice of treatment is concerned, 44% ofthe doctors start therapy autonomously, according to thesuggestions of editorials in journals (38%) and/or pharmaceuticaladvertising (18%). Answers related to the follow-up of treatmenthave been brie¯y grouped for the sake of clarity as correct orinadequate, according to widely accepted criteria. Fifty-sixpercent of physicians appropriately rely on BMD measurement,with or without other parameters, after at least twelve months oftreatment; the remaining 44% either request BMD before 12months of treatment or evaluate the response to the treatment bymeans of unaccepted criteria. Regarding the issue of biochemicalmarkers of bone turnover 35% of doctors assess them within sixmonths after starting therapy.

In conclusion, more attention should be paid by the experts onosteoporosis to the education of primary care physicians aboutthe management of the disease.

186 (178). WORKSHOPS IN OSTEOPOROSIS IN PRIMARYCARE: EXPERIENCE OF ONE YEAR

J. A. Roman, C. FernaÂ ndez, A. Fuertes, J. MillaÂ n, L. Abad, HospitalUniversitario Dr. Peset, Valencia, Spain

PURPOSE: In order to improve the knowledge, management andcontrol of osteoporosis of Primary Care (PC) physicians weorganize four workshops in our area and evaluate the resultsobtained after the workshops.

METHODS: All of workshops have a ®rst part of theory and asecond practice section. 20 PC physicians participated in theworkshops, each of them selected three consecutive postmeno-pausal females (n=60) for the evaluation. Risk factors, dailydietary calcium intake, previous fractures, bone resorptionmarkers (Urinary Calcium/Creatinine, Ca/Cr and Deoxypyridino-line/Creatinine, D-pyr/Cr, after 12 hours fasting) and bone mineraldensity (BMD) measurements were analyzed in all women.

RESULTS: Risk factors: only 8 women performed dailyexercise, 28% have an estimated calcium daily dietary intake5500 mg/day. 90% of patients had non-speci®c pain in any partof the squeleton. 24% had a previous fracture, from which 33%had more than one fracture site (Colles and vertebral). 36% (n=22)had hypercalciuria and 61.6% had high turnover, de®ned as atleast one of the bone resorption markers raised (Ca/Kr in 40%and D-pyr/Cr in 44%). BMD results (n=54): normal in 32,osteopenia in 16 (30%) and osteoporosis in 6 (11%). In patientswith hip fracture the mean t-score was ±2.7 (mean age: 80 years).

DISCUSION: We have found osteoporosis in 11% of post-menopausal females attending a PC clinic, most of them withnon-speci®c esqueletal pain. Previous fractures, low calcium diet,hypercalciuria and high bone turnover were the factors morefrequently founded between these women.

187 (179. PELVIC INSUFFICIENCY FRACTURES INOSTEOPOROSIS

S. Samdani, B. Lachmann, W. Nagler, New York PresbyterianHospital, New York, NY, USA

Pelvic insuf®ciency fractures (PIF) are a commonly overlookedcause of hip and low back pain that can occur without trauma. PIFare a type of stress fracture that can occur with repetitive stressto already weakened or abnormal bone. Insuf®ciency fracturesoften occur in bone with decreased mineralization and elasticresistance, with postmenopausal osteoporosis as the main riskfactor. It is estimated that 40% of Caucasian women in the UnitedStates will sustain at least one osteoporotic fracture after the agoof 50. The lifetime risk of fracture among women aged 50 andolder may be as high as 70% if all skeletal sites are included.Other predisposing factors for pelvic inauf®ciency fracturesinclude prolonged corticosteroid use, rheumatoid arthricis, renaldisease, and local irradiation. The clinical presentation is oftenvariable. Patients often complain of severe low back, groin, or hippain accompanied by dif®culty or inability to ambulate. Diagnosiscan be challenging as initial imaging studies are often negative inthe ®rst two to four weeks following onset of symptoms.Sensitivity of early ®lms may be as low as 15%. Technitium±99bone scintigraphy typically reveals increased radiotracer uptakeat the site of the fracture and is nonspeci®c and may bediagnostic within 24 hours of symptom onset. Increased uptakeof bone scans can occur with almost any increase in osteoblasticactivity often seen with trauma from a fall, infections, neoplasms,and bone infarcts. Computed tomography con®rms the diagnosisand can be helpful to rule cut a malignancy. Magnetic resonanceimaging is considered to be the most sensitive and speci®c test.


Diagnosis of pelvic insuf®ciency fractures is often based on highclinical suspicion, a thorough physical exam, and the appropriatecon®rmatory imaging study.

We conduoted a retrospective chart review of 90 patients withpelvic insuf®ciency fractures. The review assessed initial pre-sentation, past medical history, ®ndings on physical exam, anddiagnostic imaging studies obtained. We also reviewed overallmorbidity and functional status of patients after such fracturesand will discuss clinical ®ndings, radiological ®ndings, andfunctional outcome at discharge. Through our extensive review,we documented that the majority of patients with pelvicinsuf®ciency fractures can be treated conservatively withoutsurgical intervention and can safely weight bear as toleratedwith use of an assistive device with good functional outcome.

188 (180). INFLUENCE OF THE MENTAL STATE OF OLDPEOPLE ON OSTEOPOROTIC FEMORAL FRACTURES

O. V. Semenova, A. V. Urivaev, O. B. Ershova, V. G. Evstratov,Yaroslavl Center of Osteoporosis, Yaroslavl Medical Institute,Yaroslavl, Russia

A number of mental states parameters of 116 patients sufferingfrom fractures (average age 69,41�9, 07) and 84 (average age 71,57�10, 56) people without fractures have been examined. Thestudy was carried out for the purpose fo evaluation of mentalstate of old people as one of the factors in osteoporotic femoralfractures. To achieve this the psycho diagnostic (Mini-Mental-Status Test, MMST) was utilized. This test is a screening methodfor founding cognitive deviations of people of advanced age). Thetest contained 30 questions. The highest number of points being30. The average rating for patients suffering from fractures was25, 91�4, 67 and for the people without fractures ± 27, 83�2, 36.The difference proved to be statistically correct, p = 0.02. Lowrating as per the results of the MMST was discovered withpatients who had deviations in realization of movement process,which in its turn causes falls and fractures.

On the whole the results of the test prove importance of optimalstate of old people the nervous activity in prevention of falls.

189 (181). SRI JAYAWARDENEPURA COMMUNITY SURVEY OFOSTEOPOROSIS; DIETARY CALCIUM INTAKE

S. H. Siribaddana, U. Hewage, D. J.S. Fernando, 1Department ofMedicine, Sri Jayawardenepura University, Nugegoda, Sri Lanka

Introduction: Risk of osteoporosis in any given person isdependent on peak bone mass. Although genetic factorscontribute mainly to the peak bone mass exercise and calciumintake are modi®able contributing factors.

Methods: 988 ambulatory persons, aged 21 to 80 years wererandomly selected from electoral list in a suburban area. Calciumintake was calculated from semi-quantitative food frequencyquestionnaire.

Results:

Males

Age 21±30 31±40 41±50 51±60 61±70 71±80

Number 75 58 54 44 33 13

Mean/mg 1382 1359 1635 1336 1355 1214

SD/mg 600 638 543 546 524 384

Main contributor (mg) Sprats

(383)

Sprats

(391)

Sprats

(425)

Sprats

(358)

Sprats

(329)

K'murunga

(312)

Females

Age 21±30 31±40 41±50 51±60 61±70 71±80

Number 143 144 159 166 70 24

Mean/mg 1458 1481 1452 1456 1372 1301

SD/mg 578 534 469 536 492 463

Main contributor (mg) Sprats

(387)

Sprats

(407)

Sprats

(448)

Sprats

(368)

Sprats

(340)

Sprats

(351)

Conclusion: Average calcium intake is quite high in sub-urbanSri Lankan men and women. The intake declines at the old age.The main source of calcium is dried ®sh and sprats.

190 (182). THE EFFECT OF DIETARY CALCIUM ON BONEMINERAL DENSITY IN POSTMENOPAUSAL WOMEN

Y. Suzuki1, S. J. Whiting1, P. D. Chilibeck2, K. S. Davison2,1College of Pharmacy and Nutrition, Saskatoon, SK, Canada;2College of Kinesiology, University of Saskatchewan, Saskatoon,SK, Canada

The objective of this study was to examine the effect of usualdietary intake of calcium (Ca), vitamin D (vD), and retinol on BMDat various bone sites in postmenopausal women. Dietary intakewas determined by using food frequency and diet historyquestionnaires. Subjects were 58 women, mean (SD) age was57(7.2)y, 7.9(7.1)y since menopause (YSM). Subjects' mean totalintake of Ca was 1163 mg, of vD was 9 mg, and of retinol was 0.71mg. There was a negative correlation between age (or YSM) andBMD, as well as between weight (or BMI) and BMD. There was apositive correlation between total Ca intake and BMD at hip(r = 0.294, P<0.05), femoral neck (r = 0.364, P<0.01), trochanter(r = 0.270, P<0.05), and wards (r = 0.306, P<0.05). There was apositive correlation between total vD and BMD (r = 0.287, P<0.05)and between total retinol and BMD (r = 0.229, P<0.1) at trochanter.Ca, vD, and retinol intakes were correlated with each other.Stepwise multiple linear regression showed a major effect of ageor YSM and weight or BMI at most bone sites except total body. Italso showed the positive effect of total Ca on BMD at corticalbone sites such as hip (5.9 %), femoral neck (9.8 %), wards (6.8%), and total body (5.5 %). There was a positive effect of totalretinol on the BMD at trochanter (6.8 %). There was no dietaryeffect on BMD at the spine, which is mostly trabecular. Our studyshowed the positive effect of total dietary Ca on BMD ofpostmenopausal women and supported the hypothesis that theeffect of Ca is mostly on cortical bone rather than on trabecularbone.

191 (183). DIRECT MEDICAL COSTS OF OSTEOPOROTICPROXIMAL FEMUR FRACTURES

M. Tamulaitiene, V. Alekna, I. Diliunaite-Breiviene, NationalOsteoporosis Center, Institute of Experimental and ClinicalMedicine, Vilnius, Lithuania

The aim of this study was to determine the direct medical costs ofthe osteoporotic proximal femur fracture in Lithuanian population.A 1-year retrospective study was carried out applying it to all thepatients over 50 years old with osteoporotic hip fractures treatedin traumatological-orthopaedical departments in 3 Vilnius hospi-tals in 1998.

The direct medical cost of hip fracture includes acute hospitalcare and subsequent restore treatment, i.e. rehabilitation ex-penses. Cost of acute hospital care mainly depends on themethod of surgical treatment. The total direct medical costs forhip fracture were calculated, where acute hospital care costsrepresented the larger proportion. On the contrary, evaluation ofthe mean cost per fracture showed that larger proportion wasformed by rehabilitation expenses.

The most expensive method of proximal hip fracture treatmentis the prosthetic replacement followed by extended rehabilitationprogram. The largest proportion of the direct medical costs wasformed by costs of treating hip fracture by internal ®xation with orwithout rehabilitation.


192 (184). SCREENING FOR LOW BONE MASS IN CROHN'SDISEASE: INCIDENCE OF OSTEOPENIA AND OSTEOPOROSISIN 500 UNSELECTED CASES

R. Tanger, B. Weidmann, H. Malchow, J. D. Ringe, Leverkusen,Germany

Patients with Crohn's disease have an increased risk ofosteoporosis and associated fractures compared to a healthypopulation. The prevalence of different clinical stages and thecorrelation with different contributing risk factors, however, hasnot been studied in a large cohort of affected patients includingthose with a mild course of the disease.

Methods: Bone mineral density (BMD) was measured by DEXA-technique at the lumbar spine and femoral neck in 500 unselectedpatients with established Crohn's Disease. The mean age of thepatients was 35.1 years (range: 10.1 ± 80.3). The average durationof disease was 8.2 years (range: 0 ± 43.8). Lateral x-rays of thespine were performed in cases with back pain or signi®cantlyreduced BMD at the lumbar spine (T-score 5±2.5 SD). A vertebralfracture was diagnosed if loss of anterior, median or posteriorheight of 20 % or more was observed. Accompanying risk factorsfor bone loss (e.g. dosage and duration of corticoids, diseaseactivity, vitamin D levels, previous operation, smoking habits)were recorded.

Results: Normal values of BMD (T-score above ±1.0) werefound at the lumbar spine in 275 cases (= 55.0%) and at thefemoral neck in 252 patients (= 50.4%). Osteopenia or preclinicalosteoporosis (T-score ±1.0 to ±2.5) was documented in 157(= 31.4%), and 196 patients (= 39.2%), and established osteo-porosis (T-score below ±2.5) in 68 (= 13.6%) and 52 patients(= 10.4%) at the two measuring sites, respectively. 30 patients(6.0%) had severe osteoporosis with one or more vertebralfractures (range: 14 ± 63 years). There was a signi®cantcorrelation between BMD and duration of disease, (n = 500),cumulative dose of corticoids (n = 104) and tobacco consumption(n = 106).

Conclusion: We conclude that in unselected patients withCrohn's disease preclinical and established osteoporosis can beexpected at an average rate of 41% and 18%, respectively.Screening for osteoporosis with osteodensitometry and preven-tive measures are mandatory. Patients with long-term disease, ahigh cumulative dose of corticoids, and smoking are atparticularly high risk. Further studies on contributing risk factorsand longitudinal measurements of BMD with and withoutintervention are of high interest.

193 (185). TOTAL BODY CALCIUM AND SOFT TISSUECOMPOSITION IN ELITE FEMALE TRIATHLETES

V. A. Tatsis, E. M. Kwong, G. F. Rocha, M. L. Look, A. M. Mikus, L.Musial, G. I. Nakamoto, C. T. Norred, M. D. Bracker, D. J. Sartoris,University of California School of Medicine, San Diego, CA, USA

PURPOSE: To investigate total body calcium, lean body mass,and percentage body fat in elite female athletes, with reference tointerrelationships among the various components of bodycomposition.

METHODS: 139 high performance female endurance athletescompeting in the 1999 Ironman World Championship Triathlonheld at Kona, Hawaii were randomly recruited from the qualifying®eld. Age ranged from 16±69 (mean 39) years. Height ranged from51±71 (mean 64) inches. Weight ranged from 93±176 (mean 125)pounds. Maximum lifetime weight ranged from 101±198 (mean137) pounds. Total body bone mineral content (BMC) and density(BMD), lean body mass, fat body mass, and percentage body fatwere measured using a Norland XR±36 pencil-beam tabletopdual-energy X-ray absorptiometry system. Questionnaire dataelicited from each subject included dietary/medical history,exercise/lifestyle habits, personal/family fracture background,and menstrual function record. Performance times in the swim,

cycling tour, and marathon components of the event were alsodocumented. Data analysis was performed using Minitab version12 statistical software.

RESULTS: Total body BMC ranged from 1675±3528 (mean2631) grams. Total body BMD ranged from 0.77±1.218 (mean1.024) g/cm2. Mean values for lean body mass, fat body mass,and percentage body fat were 48.8 kg, 11.2 kg, and 12.9%,respectively. Total body BMC (p50.0001, R-Sq = 48.9%) andBMD (p50.0001, R-Sq = 27.2%) correlated signi®cantly with totalsoft tissue mass. However, total body BMC was not statisticallyrelated to lean body mass (p = 0.16), fat body mass (p = 0.71), orpercentage body fat (p = 0.45). Similarly, total body BMD was notstatistically related to lean body mass (p = 0.082), fat body mass(p = 0.75), or percentage body fat (p = 0.89). Of the two soft tissuecomponents, lean body mass appeared to be more stronglyrelated to BMC and BMD than did fat body mass.

CONCLUSIONS: In contrast to previous studies relating bodycomposition to physical activity levels among amateur womenathletes, the elite female triathletes in this investigation generallydid not suffer from extremely low bone mass or osteoporosis.This difference may be explained by maintenance of percentagebody fat at a reasonably high level (mean = 12.9% versusgenerally accepted ideal range of 15±30% for women) despiteintense physical training, with the skeletal risk:bene®t ratio of thelatter thus being acceptable.

194 (186). EVALUATION OF BONE MASS AND OSTEOPOROSISSUSCEPTIBILITY IN THE LUMBAR SPINE OF ELITE FEMALETRIATHLETES

D. J. Theodorou, S. J. Theodorou, E. M. Kwong, G. F. Rocha, M. L.Look, M. A. Mikus, L. Musial, G. I. Nakamoto, C. T. Norred, M. D.Bracker, D. J. Sartoris, University of California School ofMedicine, San Diego, CA, USA

PURPOSE: To investigate the effects of endurance athletictraining on bone mineral density (BMD) and content (BMC) inthe spine of high performance female athletes, and to developpotential recommendations for levels of physical exercisecompatible with optimal skeletal health in women.

METHODS: Frontal spine (L2-L4), proximal femoral, and totalbody BMC and BMD measurements were performed in 139randomly recruited female participants in the 1999 Ironman WorldChampionship Triathlon at Kona, Hawaii athletes, using a NorlandXR±36 dual-energy X-ray absorptiometry (DXA) system. Ageranged from 16±69 (mean 39) years. Body weight ranged from93±176 (mean 125) pounds. Height ranged from 51±71 (mean 64)inches. Questionnaire data elicited from each subject includeddietary/medical information, exercise/lifestyle habits, personal/family fracture history, and menstrual function. Performancetimes in the swim, cycling tour, and marathon components ofthe event were recorded. Data analysis was performed usingMinitab version 12 statistical software.

RESULTS: Average BMD values for the L2, L3, L4 and L2-L4regions were 1.064, 1.082, 1.022 and 1.108 g/cm2, respectively.Corresponding mean T-scores were ±0.46, ±0.09, ±0.63, and70.51, while mean Z-scores were ±0.085, ±0.125, ±0.385, ±0.13,respectively. Although in individual athletes or vertebrae in-creased bone loss could be identi®ed, BMD values in thepopulation as a whole were within normal limits according toWorld Health Organization (WHO) criteria. Visual inspection ofDXA scan images and statistical analysis of BMD values by leveldocumented a high prevalence of degenerative disease in thelower lumbar spine among these female triathletes.

CONCLUSIONS: In contrast to prior investigations of physicalactivity versus bone mass among amateur female athletes, world-class triathlete women generally maintain acceptable levels ofbone mass in the spine. This may be secondary to relativepreservation of body fat (mean 12.9% versus generally acceptedideal range of 15±30% for women) and hence suf®cient estrogenlevels. Degenerative spine disease in elite female athletes may be


related to intense physical training regimens, and/or does notpreclude high performance triathlon participation.

195 (187). VERTEBRAL OSTEOPOROTIC DEFORMITY:ASSOCIATION WITH RISK FACTORS

N. V. Toroptsova, L. I. Benevolenskaya, Institute of RheumatologyRAMS, Moscow, Russia

Aim: To study the prevalence of vertebral deformities in womenwith osteopenia aged 55 and elder and establish risk factors forthem.

Methods: 697 women with osteopenia (T-score less than ±2 SDin one vertebrae measured by DEXA, Hologic 4500A) wereexamined by X-ray and deformities were evaluated by morpho-metric analysis of T4-L5 on the lateral images. Also, we selected agroup of age matched women (N=110) with osteopenia in L1-L4(without vertebral deformities) and performed a case-controlstudy to evaluate the in¯uence of some factors on developmentof vertebral fracture.

Results: Spine osteoporotic fractures were revealed in 107patients (15.3%). The deformity of 1 vertebrae occurred in 44.8%of pts, 2 ± in 26.7% pts, 3-in 20.4% pts, 4 and >± in 8.6% pts.Mean value of BMD was 0.736�0.0095 (g/cm2) for L1-L4 in womenwith osteoporotic deformities. In control group mean value ofBMD was 0.726�0.0077 (g/cm2). We analysed some individualfactors, including medical and family history, and revealed anassociation between osteoporotic spine deformities and bodymass index (BMI): patients with higher BMI signi®cantly moreoften had osteoporotic vertebral fractures (p<0.05). No otherfactors had associations with deformities of vertebrae in thiscase-control study.

Conclusion: Our data presents the prevalence of osteoporoticdeformities in women with osteopenia. The analysis of somefactors revealed association between BMI and osteoporoticfractures.

196 (188). SCREENING FOR RISK OF HIP FRACTURE IN THEELDERLY

N. M. Van Schoor, L. M. Bouter, P. Lips, EMGO-Institute, VrijeUniversiteit, Amsterdam, The Netherlands

A randomized clinical trial is performed to examine whetherexternal hip protectors can reduce the number of hip fractures inDutch elderly persons at high risk of fracturing a hip. Elderlypersons from nursing homes, homes and apartment houses forthe elderly are included when having a: (1) broadband ultrasoundattenuation (BUA) 440 or (2) 40 5BUA 460 and at least 2 riskfactors for falls or (3) 60 5BUA 470 and at least 3 risk factors forfalls. Risk factors for falls: one or more falls in the past, dizziness,stroke, impaired mobility, low physical activity, urinary incon-tinence, and cognitive impairment. Recently 248 elderly personswere screened for risk of hip fracture. 40.3% of these personssustained a fall in the previous half year, 42.7% reporteddizziness, 18.1% reported a stroke, 50.4% had low physicalactivity, 30.7% had impaired mobility, 54.8% reported urinaryincontinence and 47.8% had cognitive impairment. 195 of the 248screened persons had a bone density below 70 dB/MHz; 32persons with a low bone density were excluded because they hadtoo few risk factors for falls. 53 persons were excluded becausetheir bone density was too high. The mean number of risk factorsfor falls in the bone density groups with a BUA 440; 40 5BUA460, 60 5BUA 470 and BUA >70 was respectively 3.9; 3.3; 3.3and 3.1.

It appears that persons in homes for the elderly have a high riskfor falls. This study suggests that the number of risk factors for

falls is a less discriminating criterion when screening for risk ofhip fracture than bone density.

197 (189). DESCRIPTIVE STUDY OF OSTEOPOROTICFRACTURES AND HIP FRACTURE RISK EVALUATION OFSUBJECTS WITH PAST MINOR FRACTURES

P. A. Vendittoli1, D. Major2, A. Simpson2, S. Jean2, J. P. Brown1,1Centre Hospitalier Universitaire De Quebec, Universite Laval;2Service de Depistage Provincial PARLAB Ste-Foy, QC, Canada

Osteoporotic fractures, especially hip fractures, represent a majorhealth problem in terms of morbidity, mortality and cost. Sincethe availability of new treatments for osteoporosis, a betterunderstanding of the disease is needed to de®ne the indicationsfor treatment. A descriptive study of all osteoporotic fractureswas done on a population aged 45 years old and older from 1980to 1997 (2.5 million individuals, 1997). During the follow-up periodthere was a total of 220, 120 fractures (hip, wrist, proximalhumerus and ankle). The incidence of fracture was stable overtime. The wrist fracture was the most frequent (42.2%) followedby the hip fracture (32.5%). Although the proportion of fracturesites were similar for both sexes, 75% of the fractures occurred infemales. The peak incidence of wrist fracture is between 45±65years old. The hip fracture follows an exponential curve ofincidence after 65 years of age. The mortality 1 year after a hipfracture is increased by 14±27% for men and 9±13% for womenafter 60 years of age. Men and women aged 45 years old andolder have a risk for hip fracture after a minor fracture of 2.3±17.3time the risk of people without previous minor fracture. Becauseactual medical osteoporosis treatment is effective and minorfractures represent a signi®cant risk for future hip fracture, allthese patients should be evaluated for osteoporosis and receivethe appropriate treatment.

198 (190). RELATIONSHIP BETWEEN MUSCLE STRENGTH INFUNCTIONAL MOVEMENTS, ACTIVITIES OF DAILY LIVING ANDBONE MINERAL DENSITY IN OSTEOPOROTIC WOMEN

L. A. Verbruggen, A. Lenaerts, W. Duquet, C. Pauwels, T. Mets,1University Hospital VUB; 2Free University Brussels, Brussels,Belgium

Potential relationships were investigated in osteoporotic womenbetween muscle strength in functional leg extension movementsand handgrip, ability to perform activities of daily living (ADL), andbone mineral density (BMD) by lumbar QCT or calcanealultrasound.

The following evaluations were made in 103 outpatients (age 60to 93 years): power and force of leg extension at 2 speeds using alinear isokinetic dynamometer (Aristokin1 Lode, Netherlands),handgrip strength using a Martin vigorimeter, lumbar BMD byQCT, broadband ultrasound attenuation (BUA) of the calcaneus,and the Lawton-Instrumental-ADL (IADL) scale.

The IADL scale weakly but signi®cantly correlated withextensor strength (r 0.27±0.29, p<0.001) and with QCT (r 0.28,p<0.001). Furthermore, using age as a controlling variable, legextension strength correlated with lumbar BMD (r 0.39±0.43,p<0.001) and to a lesser extent with handgrip strength (r 0.24±0.31, p<0.01). The latter also weakly correlated with BUA of thecalcaneus (r 0.28, p<0.005).

The use of a linear isokinetic dynamometer allows to measureforce and power in functional movements involving more thanone articulation, such as leg extension: its relevance wascon®rmed by signi®cant correlations with handgrip strength,ability to perform ADL, and BMD in this group of osteoporoticwomen.


199 (191). AVERAGE TOTAL LIFETIME ALCOHOL INTAKE ANDBONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN

J. Wactawski-Wende, M. Trevisan, R. Brennan, S. G. Grossi, R. J.Genco, C. Klemenz, University at Buffalo, Buffalo, NY, USA

This study assesses the relationship between average totallifetime alcohol intake and bone mineral density (BMD) in 608Caucasian postmenopausal women from Buffalo, NY participat-ing in a larger study of the relationship between BMD andperiodontal disease, an ancillary study of the NIH Women'sHealth Initiative. After consent, all women completed question-naires on health history and risk exposure, and had a physicalexam. BMD of the hip (total femur region) was assessed by dualenergy X-ray absorptiometry (DXA; Hologic QDR±4500). BMD wasdichotomized for logistic regression analyses (lowest tertile vs.highest 2 tertiles). Alcohol intake (mean daily ounces total alcohol)was the primary independent variable of interest. Other factorsassessed in the analysis were: age at interview, cigarette smoking(ever), education (4high school, college, graduate school), bodymass index (BMI), diabetes (ever), thyroid disease (ever), physicalactivity (daily hours standing), fracture 5 age 40 (ever), and yearsof estrogen de®ciency (years since menopause-years of estrogenreplacement therapy). Alcohol intake was found to be signi®cantlyassociated with higher BMD (OR=1.84, p = .0486). Other factorsfound to be related independently with higher BMD included: nohistory of adult fracture (OR=2.23, p = .0003), higher BMI(OR=1.18, p = .0000), younger age (OR=1.08, p = .0001), andfewer years without estrogen (OR=1.03, p = .0086). This studysupports the hypothesis that moderate lifetime alcohol intake isassociated with higher BMD of the total femur, even aftercontrolling for factors known or suspected to be associatedwith bone mineral density.

200 (192). THE RELATIONSHIP OF BONE MINERAL DENSITYTO ORAL BONE LOSS IN POSTMENOPAUSAL WOMEN

J. Wactawski-Wende, S. G. Grossi, E. Hausmann, R. Dunford, R.J. Genco, C. Klemenz, M. Trevisan, University at Buffalo, Buffalo,NY, USA

This study assesses the relationship between bone mineraldensity (BMD) and oral bone loss in 608 Caucasian postmeno-pausal women from Buffalo, NY participating in a study of BMDand periodontal disease, an ancillary study of the NIH Women'sHealth Initiative. After consent, women completed questionnaireson health history, risk exposures and had a physical exam. Oralbone loss was de®ned as mean loss of alveolar crestal height(ACH) dichotomized for logistic regression analyses (worst ACHtertile vs. best tertiles). BMD of the total femur (lowest vs. highest2 tertiles) was the primary independent variable of interest andwas assessed by dual energy X-ray absorptiometry (DXA; HologicQDR±4500). Other factors assessed included: age at visit,cigarette smoking (ever), education (4high school, college,graduate school), body mass index (BMI), diabetes (ever) andyears estrogen de®ciency (years since menopause ± years onestrogen). Lower ACH was signi®cantly associated with lowerBMD (OR=1.81, p = .0134). Other factors independently asso-ciated with lower ACH included: older age (OR=1.11, p = .0000)and ever smoking cigarettes (OR=1.84, p = .0033). This studysupports the hypothesis that lower BMD is associated with lossof oral bone even after controlling for factors known or suspectedto be associated with either ACH or BMD. This study is one of thelargest to date and supports previous ®ndings by us and othersthat lower BMD is related to oral bone loss, that may lead to toothloss. Additional research is needed to better understand thisrelationship.

201 (193). OSTEOPOROSIS: PREVALENCE IN TAIWANESEWOMEN

T. S. Yang, C. R. Chen, Department of Ob/Gyn, Veterans GeneralHospital Taipei and National Yang-Ming University, Taipei, Taiwan

Objectives: this paper aims to clarify the bone mass values in theTaiwanese female population and to further analyze the closerelationship among the bone mass values // body height // bodyweight and BMI (body mass index). We also assess the numberand proportion of Taiwanese women considered to haveosteoporosis according to the WHO diagnostic guideline.Method: A total of 4689 female subjects were recruited. Allbone mass measurements were performed by means of dualenergy X-ray densitometry: DXA (Lunar, DPX-L,USA) at two sites:lumbar vertebrae L2-L4 and femoral neck. These values areexpressed with reference to the mean bone mineral densityvalues, height, weight and BMI of the group aged 30±39 years.Results: the study revealed respectively that there is no clearrelationship between the bone mineral density and the bodyheight // body weight nor BMI. The diagnostic value forosteoporosis is set at 0.827 g/cm2 for lumbar vertebrae and0.605 g/cm2 for femoral neck. According to the de®ning values oflumbar vertebrae, the prevalence of osteoporosis in the differentage groups is detailed as follow: 40±49 years, 8.24%; 50±59 years,8.62%; 60±69 years, 14.14%; 70±79 years, 14.25%; >80 years,16.07%. Those diagnosed to have osteoporosis by femoral neckis detailed as follow: 40±49 years, 5.24%; 50±59 years, 5.27%; 60±69 years, 11.16%; 70±79 years, 17.30%; >80 years, 24%. Thewhole proportion for osteoporosis included 10.08% for lumbarvertebrae and 7.45% for femoral neck. Conclusion: there is noclose relationship among the bone mineral density // body height// body weight nor BMI in Taiwanese female population, whichcoincides with most of the recent reports' results. The prevalenceof osteoporosis is also lower in comparing with the females ofwestern societies, and this may be related to the alimentaryhabits, life style, cultural background and ethnicity. Nevertheless,the acceptance rate of HRT in the Taiwanese female population isalso lower, which is calculated to be no more than 5%. Themaintenance of traditional culture and habits and the HRT policypropagation will both be the tasks to be accomplished in thefuture.

202 (194). A SEVEN-YEAR FOLLOW UP STUDY OF BONE LOSSIN A RURAL JAPANESE COMMUNITY: THE MIYAMA STUDY

N. Yoshimura, K. Sakata, T. Hashimoto, Wakayama MedicalCollege, Wakayama, Japan

Purpose: To assess the rate of bone loss and characterise itsdeterminants among general inhabitants of Miyama village, a ruralJapanese community.

Method: A cohort of 1543 residents consisting of all inhabitantsaged 40±79 was established in 1989, using the residentregistration of December 1988. A total of 400 individuals,comprising 200 males and 200 females, were then recruitedrandomly from following age strata; 40±49, 50±59, 60±69, 70±79(giving a total of 50 subjects in each age-sex group.) They wereperformed the interviewer-administered questionnaire surveyincluding information on past medical history, physical activity,calcium intake, a menstrual history and so on. The follow up studywas performed three and seven years later. Subjects participatingin the baseline study were recontacted. Dual energy X-rayabsorptiometry (DXA: Lunar DPX) was used for the measurementof bone mineral density (BMD) in both the initial and follow-upstudies.

Results: A total of 148 men and 170 women participated thefollow up study (79.5%). The annual rates of change of lumbarspine BMD between 1990 and 1993 in men in their 40's, 50's, 60'sand 70's were ±0.20%, ±0.06%, ±0.34% and ±0.31% per yearrespectively. Rates in women were ±0.43%, ±1.45%, ±0.72% and±0.69%. Annual rates of change in BMD from 1993 to 1997 among


men in their 40's, 50's, 60's and 70's were 0.16%, 0.81%, 0.44%and 0.17% respectively. Those among women were ±1.03%,70.72%, ±0.31% and ±0.26%. The rates of change of lumbarspine BMD was also assessed by classi®ed by menstrual status.Menstrual status at baseline was related signi®cantly to change inbone density.

Conclusion: The fastest bone loss was observed on women intheir 50's. Menstrual function were suggested to be importantdeterminant of bone loss.

203 (195). EPIDEMIOLOGICAL CHARACTERISTICS OF HIP ANDWRIST FRACTURES IN METROPOLITAN AND RURALHOSPITALS OF CAMEROON

M. R. D. Zebaze, E. T. Magny, C. Djeumen, L. M. Ebah, G. T.Mbonda, S. Eko, S. Mba, Medicine, University of Yaounde,Yaounde, Cameroon

Purpose: to assess the occurrence of hip and wrist fractures inCameroon, Africa.

Osteoporosis and related fractures are reported rare in Africa.To assess this concept, a two years retrospective study in tworural and two urban hospitals were taken. All patient admitted forfractures, age 35 and above were recruited. We found 70 (13.6%of all fractures) hip and wrist fractures in urban hospitals and 6(15%) in rural's both being the third cause of admissions forfractures. They affect mostly postmenopausal women and weredue to minimal low-energy trauma like falling 61.4% of them.8.3% of all fractures were hip and wrist fractures due to fall, a®gure of which is high being the third cause of admission forfracture. Using the 1997 report on the population in Cameroon,the minimal age-speci®c incidence rate per 100 000 for the 35years and above based on the discharged diagnosis alone in thetwo urban hospitals were 7; which is not negligible. Our studyshows that the problem of involutional bone disorders isimportant in Africa. This challenges the concept of rarity ofosteoporosis in Africa and may change the view of this disease inthis part of the world.

Plenary Session 4: Fracture Risk(Thursday, June 15, 1500±1700)

204. FRACTURE RISK BEFORE AND AFTER SURGERY FORPRIMARY HYPERPARATHYROIDISM

P. Vestergaard, C. L. Mollerup, V. G. Frokjaer, P. Christiansen, M.Blichert-Toft, L. Mosekilde, 1Department of Endocrinology andMetabolism, Aarhus Amtssygehus, Aarhus, Denmark

Aim: To study fracture risk before and after surgery in patientswith primary hyperparathyroidism.

Design: Case-control study with historical follow-up.Material and methods: 674 patients primary hyperparathyroid-

ism (median age 61, range 13±89 years, 74% women, 90%adenomas, 25% with previous kidney stones at the time ofsurgery) with operated between January 1 1979 and December 311997 and 2021 age and gender matched normal controls. Theoccurrence of fractures in the patients was compared to that ofthe controls.

Results: There was an increased relative risk of fractures before(RR=1.8, 95% CI: 1.3±2.3) but not after surgery (RR=1.0, 95% CI:0.8±1.3) among the patients. The fracture risk was increased forfractures of the vertebrae, the distal part of the lower leg/ankles,and the non-distal part of the forearm. The increase in fracturerisk began approximately 10 years before surgery followed by alower but still signi®cant level within the last ®ve yearsimmediately prior to surgery.

Conclusions: An increased fracture risk can be found up to 10years prior to surgery in primary hyperparathyroidism. Thefracture risk is normalised after surgery.

205. THE NOF ESTIMATES FOR FRACTURE RISK REVISITED

C. E. D. H De Laet1, M. van der Klift1, A. Hofman2, H. A. P. Pols,2,3,1Institute for Medical Technology Assessment; 2Dept ofEpidemiology and Biostatistics; 3Dept of Internal Medicine, TheErasmus University Medical School, Rotterdam, The Netherlands

The American National Osteoporosis Foundation (NOF) proposeda fracture risk assessment (all fractures) for women based on datafrom the Study of Osteoporotic Fractures (SOF) using 5 riskindicators. However, this prediction algorithm was not validatedelsewhere. In this study we tested the selected risk indicators inthe female population from the Rotterdam Study. We assessedthe performance of the proposed risk indicators for (low bodyweight, current smoking status, fracture history and parentalhistory of fracture) with and without bone mineral density (BMD)measurement at their proposed thresholds, in the femalepopulation of the Rotterdam Study. Incident hip fractures andother peripheral fractures were reported and veri®ed duringfollow-up. At baseline, the risk factors proposed by the NOFincluding BMD were measured. Prior fracture, however, was onlyassessed for the 5 years preceding baseline. All relative risks (RR)were corrected for age, with and without correction for BMD.Valid follow-up of fractures was obtained for 4268 women, and for3078 of those we also had valid baseline BMD data. Averagefollow-up was 3.9 years for all non-vertebral fractures (338fractures) and over 6 years or hip fractures (166 fractures). Fromthe 5 risk indicators selected for the NOF guidelines, only priorfracture and BMD carried a similar and signi®cant relative risk forthe risk of any fracture. The RR for all non-vertebral fractures forBMD was 1.5 (2.2 for hip fractures). For all non-vertebral fracturesthe RR for prior fracture was 1.4 corrected for age and 1.3corrected for both age and BMD. Both relative risks weresigni®cant but lower than in the NOF guidelines. The relativerisks for the other risk indicators, however, were lower than in theNOF report and not signi®cantly different from 1. Risk indicatorsderived from only one study overestimate predictive power.Validation in other populations is needed before a risk indicator ora risk score can be used with con®dence.

206. BMD CHANGES AFTER 1 YEAR PREDICT BMD CHANGESAFTER 4 YEARS

M. McClung, P. D. Ross, R. D. Wasnich, C. Christiansen, D.Hosking, D. Thompson, M. Daley, J. Yates, for the EPIC ResearchGroup, 1Oregon Osteoporosis Center, Portland, OR, USA; 2HawaiiOsteoporosis Center, Honolulu, HI, USA; 3Center for Clinical andBasic Research, Ballerup, DK; 4City Hospital, Nottingham, UK;5Merck & Co., Inc., Rahway, NJ, USA

Many women experience declines in bone mineral density (BMD)after menopause. However, it is not obvious how short-termchanges (1 year) relate to changes over longer periods. Weexplored this issue using data from 373 women ages 45±59 (>6months postmenopause) in the placebo group of the EarlyPostmenopausal Interventional Cohort (EPIC) Study, a rando-mized, controlled trial of alendronate. At baseline, these womenhad a mean age of 53 years, and were an average of 6 yearspostmenopause. During 4 years of followup, the mean (SD)change in BMD was ±2.9%, ±1.9%, ±2.8%, ±4.6%, and ±6.3% atthe spine, hip, total body, forearm, and ultradistal wrist,respectively. In general, BMD changes measured over 1 yearprovided a good indication of the total BMD changes over 4years. The subset of 122 women who lost 0±2% (mean = 1.0%) atthe spine during year 1 had a total 2.8% decrease in spine BMD atthe end of 4 years. Women with extreme changes at year 1 tended


to have subsequent BMD changes that were less extreme;however, the total changes after 4 years remained more extremethan the average for other women. For example, those who lost>4% (n = 41; mean = 5.2%) at the spine during year 1 had anaverage 5.7% decrease in spine BMD at the end of 4 years (twicethe losses compared to women with decreases of 0±2% at year1). These data suggest that the BMD change measured at 1 yearis a good indicator of long-term changes, on average. However,the ability of short-term changes to predict long-term changes inindividuals may not be as good.

207. HIP FRACTURE IN ASIA ± WHAT IS THE SCALE OF THEPROBLEM AND HOW SHOULD IT BE PREVENTED?

E. M. C. Lau1, P. Suriwongpaisal2, J. K. Lee2, S. Das De2, M. R.Festin2, A. Khir2, T. Torralba2, A. Sham1, P. Sambrook2,1Department of Community and Family Medicine, The ChineseUniversity of Hong Kong; 2Asian Osteoporosis Study Group

Objectives The Asian Osteoporosis Study was conducted in fourAsian countries to study the incidence of hip fracture and toidentify risk factors for public health strategies for its prevention.

Methods National hospital discharge surveys on hip fracturewere conducted in 1997, and a casecontrol study was conductedon 451 men and 725 women with hip fracture and an equalnumber of age-matched community controls.

Results Incidence rates (per 100 000 population) of hip fracture(Age-adjusted to 1997 US white population) are as follows:

Hong Kong Singapore Malaysia ThailandMen/women 189/453 180/417 90/291 125/356

Adjusted relative risk (RR) and population attributable risk(PAR%) for hip fracture in Singapore, Malaysia, Thailand andPhilippines are as follows:

Men WomenRR PAR (%) RR PAR (%)

Fell twice in last year 2.9 9.3 2.6 8.9Cigarette smoking 1.4 19.5 0.8 NAAlcoholism 1.7 6.1 2.7 2.2Calcium intake (<498g/day) 1.6 30.5 2.0 40.1No regular load-bearing activities 3.8 55.6 1.9 33.9A history of stroke 3.1 7.4 5.5 13.3

Conclusion The incidence rates of hip fracture in Asiancountries varied by 50±100%. Hip fracture may be preventableby maintaining physical activity, calcium intake, preventing fallsand stroke and avoidance of cigarette smoking and alcoholism indeveloping Asian countries.

208. USE OF THE NOF GUIDELINES WITH PERIPHERALDENSITOMETRY TO PREDICT FRACTURES

P. Miller, E. Siris, K. G. Faulkner, T. Abbott, D. Furman, J. Panish,E. Barrett-Connor, M. Berger, A. Santora, L. Sherwood, ColoradoCenter for Bone Research, Lakewood, CO, USA

NORA is a longitudinal observational study of US womendesigned to study osteoporosis (OP). Study participants wereambulatory, postmenopausal women with no prior diagnosis ofOP or BMD test in the past year. Heel (SXA) or forearm (pDEXA)density data and risk assessment questionnaires were collectedfrom 167,892 Caucasian women at baseline. These women wereclassi®ed into two groups: those who met the NOF treatmentguidelines (NOF Tx group: T-score 5±2.0 or 5±1.5 with a riskfactor) and those who did not (non-NOF Tx group). For 52,050 ofthese women, prospective self-reported fracture data werecaptured by follow-up surveys completed an average 8 months

after baseline. Fracture rates (per 100 person years) were twice ashigh in the NOF Tx group compared to the non-NOF Tx group.Both devices identi®ed approximately 30% of the women asmeeting NOF criteria. The fracture rates and odds ratios for theNOF groups were similar when based on either forearm or heelBMD sites. We conclude that peripheral BMD measurementsidentify similar proportions of women eligible for treatment of OPand yield comparable estimates of fracture risk based on the NOFtreatment guidelines.

Device Forearm (pDEXA) Heel (SXA)

NOF Tx Group: % 30.5 28.5Number 19,718 29,421Fx Rate 5.0 5.3Non-NOF Tx Gp:Fx Rate 2.8 2.6Odds Ratio 1.8 2.095% CI for Odds Ratio 1.5, 2.2 1.8, 2.4

209. INCREASED RISK OF NEW VERTEBRAL FRACTUREWITHIN 1 YEAR OF AN INCIDENT VERTEBRAL FRACTURE

R. Lindsay1, N. Watts2, Ch. Roux3, J. Brown4, I. Barton5, K.Flowers6, C. Cooper7, 1West Haverstraw, NY, USA; 2Atlanta, GA,USA; 3Paris, France; 4Ste-Foy, Quebec, Canada; 5Staines, UK;6Cincinnati, OH, USA; 7Southampton, UK

We examined data from 2725 postmenopausal women enrolled inthe control groups of 3 large clinical trials of 3 years duration inorder to determine the effect of an incident vertebral fracture onthe risk of a new fracture within 1 year. Baseline and annualradiographs con®rmed prevalent and incident fractures, respec-tively. Patients received calcium (1000 mg/day), and weresupplemented with vitamin D if baseline levels were low. Themean age of patients was 76 years and 57% had baseline(prevalent) vertebral fractures.

Of the 381 patients who experienced an incident fracture,overall 19.2% fractured again within 1 year following the ®rstincident fracture. Fracture incidence within 1 year of an incidentfracture increased as a function of the number of prevalentfractures. For example, in patients with 1 prevalent fracture,11.5% experienced an additional fracture within 1 year of anincident fracture. For patients with 2 or more prevalent fractures,24.0% had another incident fracture within 1 year of the ®rstincident fracture.

In conclusion, patients taking only calcium and Vitamin D canrapidly fracture again (within 1 year) following an incident fracture.As fractures begin to cluster, risk for additional fracture increasesand can lead to decreased quality of life. The immediate risk tothese patients suggest a need for a therapy that can provide arapid reduction in vertebral fracture risk.

Plenary Session 5: Secondary Osteoporosis(Friday, June 16, 0800±1000)

210. ASSOCIATION OF BMI AND DEPRESSION IN AN ELDERLYPOPULATION

J. A. Robbins1, C. H. Hirsch1, R. Whitmer1, J. Cauley2, T. B.Harris3, 1U. C. Davis, Sacramento, CA; 2U. of Pittsburgh,Pittsburgh, PA; 3National Institute of Aging, Bethesda, MD, USA

Background Low bone mineral density (BMD) is a major riskfactor for fractures. It has been suggested that low BMD may beassociated with depression, but results have been inconsistent.Few studies have been community based or addressed theproblem in both men and women or in races other thanCaucasian.

S112 Thursday/Friday,June16, 2000

Methods Using data from 1,566 Cardiovascular Health Study(CHS) participants, total hip BMD, after adjustment for multipleco-variates, was compared with the Center for EpidemiologicalStudies 10-item Depression Scale (CES-Dm). Risk factors forosteoporosis were compared in depressed (CES-Dm 510) andnon-depressed participants. Potential correlates were enteredinto a regression model.

Results Sixteen percent of participants showed depressivesymptomatology. Mean BMD was 40 mg/cm2 lower in those withdepression (p<0.001). Higher CES-Dm scores were associatedwith lower BMD (p<0.5) when adjusted for BMI, age, Kcals ofactivity, estrogen use, gender, race, smoking and drinking. Whenstrati®ed by race, this remained true for Caucasians (p<0.01),African-Americans (p<0.05), and Caucasian women (p<0.001).Further strati®cation yielded the results in the table, listed asparameter estimates, (bS).

Table. Relationship of Depression and BMD mg/cm2. Adjusted for covariates

ALL Women (903) Men (649)

Risk Factor Caucasian (716) Af. American Caucasian (536) Af. American

CES-D ±3.81*** ±2.92** ±0.79 ±2.52 3.47

BMI 13.98*** 13.37*** 11.86*** 15.61*** 17.85***

AGE ±4.24*** ±5.57*** ±6.21** ±5.11*** ±4.18

KCAL 0.01* 0.0008 ±0.006 0.006* ±0.009

ESTRGN # 62.4*** 62.0

PKYRS 0.35* 0.01 ±0.21 ±0.20 ±1.25

ALCOH 2.27*** 2.56** 1.79 3.05** ±0.73

*p<0.05, **p<0.01, ***p<0.001, #Only used in models with only women

Conclusions: A signi®cant association was found betweenBMD and depressive symptoms after adjustment for osteoporo-sis risk factors. We postulate that there may be an unmeasuredthird factor, such as an endogenous steroid, which is responsiblefor both low BMD and depression.

211. VISUAL IMPAIRMENT AND RISK OF HIP FRACTURE

R. Q. Ivers, R. G. Cumming, P. Mitchell, A. Peduto, 1University ofSydney, Sydney, NSW, Australia

The aim of this investigation was to examine the associationsbetween visual impairment and risk of hip fracture in alongitudinal study of eye disease in an older population.Baseline data collected for the Blue Mountains Eye Studyincluded a detailed interview and eye examination includingrefraction, measurement of visual acuity, contrast sensitivity andvisual ®eld in 3654 residents aged 49 years and older. Eyedisease was graded from photographs according to well de®nedprotocols. Hip fractures occurring during 5 year follow-up (n=60)were identi®ed by self-report (con®rmed by radiology reports)and/or review of medical records at the local hospital. All hipfractures were con®rmed radiologically by a specialist radiolo-gist. Several vision variables were associated with risk of hipfracture in the ®rst two years of follow-up: corrected visualacuity worse than 20/60 in the best eye (adjusted odds ratio(OR) 9.0, 95% con®dence interval (CI) 1.6±50.3); any posteriorsubcapsular cataract in the worst eye (adjusted OR 3.9, 95% CI1.1±13.5); ®ve or points missing in the visual ®eld (adjusted OR5.9, 95% CI 1.1±31.8). At 5 years follow up no vision variablewas signi®cantly associated with increased risk of fracture.Older people at risk of hip fracture should have their eyes testedevery 2 years, and have refractive error and cataract treatedpromptly to reduce their risk of hip fracture.

212. INHALED CORTICOSTEROIDS AND RISK OF FRACTURES

T. P. Van Staa, H. Leufkens, C. Cooper, 1Utrecht University, TheNetherlands; 2Procter & Gamble Pharmaceuticals, 0; 3MedicalResearch Council, Southampton, UK

The objective of this study was to describe the fracture risks ofinhaled corticosteroids.

Information was obtained from the General Practice ResearchDatabase in the UK which contains medical records of generalpractitioners. Inhaled corticosteroid users aged 18 years or olderwere compared to matched control patients and bronchodilatorsusers. Patients with concomitant use of systemic corticosteroidswere excluded.

The study comprised 170,818 inhaled corticosteroid users,108,786 bronchodilator users and 170,818 control patients. Therelative rates of non-vertebral, hip and vertebral fractures duringinhaled corticosteroid treatment compared to control were 1.15(95% con®dence interval 1.10±1.20), 1.22 (1.04±1.43) and 1.51(1.22±1.85), respectively. No differences were found between theinhaled corticosteroid and bronchodilator groups (non-vertebralRR = 1.00). With a standardised daily dose of less than 300 mgbeclomethasone per day, hip fracture risk was 0.95 (0.67±1.34)relative to control, rising to 1.06 (0.80±1.40) at doses of 300 up to700 mg, and 1.77 (1.31±2.40) at doses of 700 mg per day or more.

These results suggest that users of inhaled corticosteroidshave an increased risk of fractures albeit this excess risk may bepartly related to the severity of respiratory disease.

213. THE EFFECTS OF A SINGLE PAMIDRONATE INFUSIONPRIOR TO LIVER TRANSPLANTATION ON BONE LOSS: ARANDOMISED CONTROLLED SINGLE-BLIND TRIAL

M. Ninkovic, S. A. Love, B. Thom, S. Skingle, J. S. Wright, G. J.MAlexander, J. E. Compston, Department of Medicine, University ofCambridge School of Clinical Medicine and Metabolic Bone Unit,Addenbrooke's Hospital, Cambridge, UK

Osteoporosis is a common complication of liver transplantation.Increased rates of bone loss have been demonstrated aftertransplantation and fractures occur in up to one-third of patientsin the ®rst post-operative year. Since bone loss occurs early aftertransplantation and is characterised by increased bone turnover,administration of an anti-resorptive agent prior to transplantationprovides a rational strategy for prevention of bone loss. Weinvestigated the effects of a single intravenous infusion ofpamidronate (60mg) on bone loss during the ®rst year after livertransplantation in patients with chronic liver disease. Bonemineral density (BMD) was measured by dual energy X-rayabsorptiometry on an Hologic QDR4500.

99 adult patients (50 male) were randomised to treatment withpamidronate, 60 mg as a single infusion prior to transplantationor no treatment. Pre-operatively, 34% of the patients wereosteoporotic and 51% osteopenic as de®ned by WHO criteria.In the lumbar spine, no signi®cant bone loss was detected ineither group nor were there any signi®cant differences in BMDat the three time points between the two groups. In the femoralneck, signi®cant bone loss occurred during the ®rst threemonths (3.7 and 3.6% respectively compared with baseline,p<0.001 and <0.005 respectively). Signi®cant bone loss versusbaseline values was also demonstrated at 6 months (p<0.001and <0.01 respectively) and at 1 year (p<0.005 and <0.04). Nosigni®cant differences were seen between the pamidronate anduntreated groups at any time point. These results demonstratethat pamidronate, in the regimen used, does not havesigni®cant effects on BMD in the spine or femoral neckfollowing liver transplantation. The absence of bone loss inthe spine may re¯ect the use of lower doses of glucocorticoidsin recent years.

Friday, June16, 2000 S113

214. USE OF ORAL CORTICOSTEROIDS INCREASES RISK OFFRACTURE

M. Steinbuch1, R. Burge2, A. Thompson3, T. Youket4, 1Mason, OH,USA; 2Mason, OH, USA; 3Kansas City, MO, USA; 4Mason, OH,USA

The objective of this study was to assess the risk of fracture inpatients exposed to oral corticosteroids (OCS). The data sourcefor the analysis was the MEDSTAT MarketScan1 administrativeclaims database. The OCS population was de®ned as members18±64 years of age continuously enrolled for at least one yearprior to and one year after date of initial pharmacy claim for anOCS during a 24-month capture period (1995±1996). Thecomparison population was selected from all members with aclaim for a non-corticosteroid. One comparison member wasselected for each OCS member and individually matched on age(�2 years), sex, and date of ®rst claim (�3 months). The day supplyfor each script was de®ned as the reported day supply or 31 days,whichever was greater, to adjust for variation in dose tapering.Measurements of exposure included: average daily dose (high,low), duration (590, 590 days), and pattern of use (single,intermittent, continuous). Osteoporosis-related fractures wereobserved up to time of fracture (hip, vertebral, wrist, non-vertebral, any), disenrollment date, or 31 December 1997,whichever occurred ®rst.

A total of 17,957 OCS users and 17,957 comparison memberswere analyzed. The total person-years of observation for anyfracture was 32,986 and 34,206 in the exposed and unexposedgroups, respectively. The prednisone-equivalent average dailydose for OCS exposure was 7.5 mg (median=4.8 mg). Based on aCox model, the adjusted relative risk estimates for fracturesassociated with OCS exposure were as follows: hip (RR=1.87,95% con®dence interval [CI]=1.2±2.9); vertebral (RR=2.92, 95%CI=2.0±4.3); and wrist (RR=1.03, 95% CI=0.8±1.4). The combina-tion of duration of OCS exposure and pattern of use demon-strated a signi®cant 5-fold and 5.9-fold increased risk of hip andvertebral fracture, respectively, among continuous OCS userswith 590 days exposure compared to those unexposed to OCS.These data suggest a rapid deleterious effect on trabecular-richbone which has not been previously recognized.

215. THYROID HORMONE REPLACEMENT IS NOT RELATEDTO INCREASED RISK OF OSTEOPOROSIS

Martin Stenstrom, Jan-Oloph Olsson, Dan MellstroÈ m, Dept ofGeriatric Medicine, University of Gothenburg, Gothenburg,Sweden

Hyperthyroidism causes increases in bone turnover and reducedbone mass especially in elderly woman. Thyroxine (T4) stimulatedirectly bone resorption. A major clinical concern has been theissue of exogenous thyroid hormone replacement and osteo-porosis, The purpose of this study was to examine bone mass inpostmenopausal women with treatment with thyroxine andcontrols. BMD was measured in the forearm with DXA(Osteometer 200). The study population setting was a simulta-neus screening of breastcancer and osteoporosis in 10 364women aged 49 to 69 years, The population of thyroxine treatedwomen was 6,9 per cent. There were no differences in BMDbetween treated or not treated women.

The in¯uence of a great variety of variables from a healthquestionnaire and treatment with thyroxine was tested with alogistic regression model. A history of earlier fractures, treatmentwith peroral cortisone and antihypertensive drugs, smoking and ahigher current BMI was signi®cantly more frequent in women withtreatment with thyroxine compared to controls.

Conclusion: Thyroxine treatment was not related to reducedBMD.

Plenary Session 6: Nutrition and Bone Disease

216. A META ANALYSIS OF CALCIUM SUPPLEMENTATIONFOR THE PREVENTION OF POSTMENOPAUSALOSTEOPOROSIS

B Shea, C J Rosen, G Guyatt, A Cranney, P Tugwell, D Black, theOsteoporosis Research Advisory Group (ORAG), 1McMasterUniversity; 2University of Ottawa; 3UCSF; 4St. Joseph Hospital,

Introduction: Calcium supplementation is considered essential inthe prevention of bone loss for most postmenopausal women.Moreover, calcium is added to standard anti-osteoporosistreatments such as the bisphosphonates, estrogens, andcalcitonin, to optimize bone gain and prevent fractures. However,observational studies and some controlled trials have producedcon¯icting results leading to controversy concerning the ef®cacyof calcium supplementation alone in preventing fractures or boneloss in postmenopausal women. ORAG (The OsteoporosisResearch Advisory Group) has worked with the CochraneCollaboration to perform evidence based analyses of randomizedcontrolled trials (RCTs) for several osteoporosis treatments.

Methods: We performed a meta-analysis of trials with calciumsupplementation alone and excluded studies of calcium andvitamin D (i.e. >400 IU per day) in postmenopausal women. Weestablished apriori hypotheses to explore reasons for largedifferences in results between studies (heterogeneity), utilizedthree reviewers to rate methodologic quality and used anevidence based method to perform searches of RCT of calciumin women older than 45 years of age who were postmenopausal,and who were followed for at least one year with bonedensitometry.

Results: Sixty six (66) published papers addressed therelationship of calcium intake and BMD of which 22 were RCTS.Seven were excluded for various reasons leaving 15 RCTs whichful®lled pre-set criteria and for which the primary author providedadditional data. Five (5) of the RCTs reported fractures as anoutcome. Eighteen hundred and six (1806) patients were enrolledin the 15 trials, 953 receiving calcium supplementation. Pooleddifferences in percentage change in bone density from baselinebetween treatment (calcium) and control at two years are asfollows (95% CI): TBBMD: +2.05% (0.24±3.86%), LS BMD:+1.66% (0.92±2.39%), FN-BMD: +1.60% (0.78±2.4%); radialBMD: +1.91% (0.33±3.5%). The RR for vertebral fractures was0.77 (0.54±1.09) and for non-vertebral fractures was 0.86 (0.43±1.72).

Conclusion: We conclude that calcium supplementation alonehas a small positive effect on BMD at all skeletal sites but thenumber of events is too small to meaningfully address the impacton fractures.

217. CAN VITAMIN D SUPPLEMENTATION REDUCE THE RISKOF FRACTURE IN THE ELDERLY? A RANDOMISEDCONTROLLED TRIAL

H. E. Meyer, J. A. Falch, E. Kvaavik, G. B. Smedshaug, A. Tverdal,J. I. Pedersen, National Health Screening Service, Oslo, Norway

The purpose of this randomised controlled trial was to study if adaily supplement of vitamin D3 could reduce the risk of hipfracture and other osteoporotic fractures in institutionalisedelderly. The study was performed in nursing home residents intwo Norwegian cities. It was of importance to make a simplestudy design in order to facilitate its use in the great number ofwards involved. The intervention group received 5 ml ordinarycod liver oil daily containing 10mg vitamin D3 and the controlgroup 5 ml cod liver oil where vitamin D was removed. Theparticipants, the nursing staff, and the investigators were blindedto which type of cod liver oil the participants were given. Duringthe study period of two years, hip fracture, other non-vertebralfractures and deaths were registered. The fracture diagnoseswere validated in hospital discharge letters or x-ray descriptions.

S114 Friday, June16, 2000

A total of 1,144 residents from 51 nursing homes were included inthe study. Mean age at baseline was 85 years and 3/4 of thesewere women. The intervention ended summer 1999. The studyparticipants contributed with a total of approximately 1,700observation years, giving the study a 80% power to detect a42% reduction in hip fracture incidence and a 30% reduction in allnonvertebral fractures at the 5% signi®cance level. The fracturevalidation will soon be completed, and will be followed byanalysis of fracture data on the intention-to-treat basis. Mainresults from the study will be presented and discussed.

218. VITAMIN D AND CALCIUM SUPPLEMENTATION REDUCESFALLS IN ELDERLY WOMEN VIA IMPROVEMENT OF BODYSWAY AND NORMALISATION OF BLOOD PRESSURE: APROSPECTIVE, RANDOMIZED, AND DOUBLE-BLIND STUDY

H. W. Minne1, M. Pfeifer1, B. Begerow1, D. Nachtigall2, C.Hansen2, 1Institute of Clinical Osteology ``Gustav Pommer'' andClinic ``DER FUERSTENHOF''Bad Pyrmont, Germany;2Strathmann AG, Hamburg, Germany

The risk of fractures increases with age. This is a result ofincreasing bone fragility due to osteoporosis but it is also a resultof an increasing number of falls. Consequently, therapeuticinterventions should either increase bone mass and bone qualityor decrease the risk of falling. The effects of eight weeks ofsupplementation with vitamin D and calcium on body sway, bloodpressure, and biochemical measures of bone metabolism werestudied. The sample consisted of 148 women (mean [�SD] age,74�1 years) with a 25-hydroxy-cholecalciferol level below 50nmol/l. They received either 1200 mg of calcium plus 800 IU ofvitamin D or 1200 mg of calcium per day. We measured 25-hydroxyvitamin D, intact parathyroid hormone, markers of boneturnover, and blood pressure before and after treatment. Fallsand fractures among the participants were followed over a one-year period. Statistical evaluation was carried out using SAS forWindows, version 6.10 (CCDRD, Berlin, Germany). Compared tocalcium mono, supplementation with vitamin D and calciumresulted in an increase in serum 25-hydroxyvitamin D of 72percent (p<0.0001), a decrease in parathyroid hormone of 18percent (p = 0.0432), a decrease in body sway of 9 percent(p = 0.0435), a decrease in systolic blood pressure of 9 percent(p = 0.0165), and a decrease in heart rate of 5 percent (p = 0.0219).The mean number of falls per subject during a one year follow-upperiod was 0.45 for the calcium mono group and 0.24 for thecalcium and vitamin D group (p = 0.0346). Short-term supplemen-tation with vitamin D and calcium improves body sway,normalizes blood pressure, reduces secondary hyperparathyr-oidism and therefore may prevent falls and subsequent non-vertebral fractures in elderly women.

219. BONE LOSS INDUCED BY ISOCALORIC PROTEINUNDERNUTRITION IN ADULT MALE RATS IS ASSOCIATEDWITH EARLY DECREASED IGF-I AND LATE HYPOGONADISM

P. Ammann, A. Toromanoff, S. Bourrin, J. P. Bonjour, R. Rizzoli,Division of Bone Diseases, Department of Internal Medicine,University Hospital, Geneva, Switzerland

Hypogonadism and protein undernutrition can contribute to thepathogenesis of osteoporosis in elderly. We have shown thatprotein undernutrition could affect both sex hormone status andIGF-I system in adult female rats. To investigate whether proteinundernutrition could in¯uence gonadal function and/or the IGF-Isystem in males, we evaluated the time-dependent effects ofisocaloric diets with various levels of protein content (15, 7.5, 5and 2.5% casein) in pairfed 7 month-old adult male rats. Bonemineral density (BMD), and ultimate strength (US) were measuredat the level of the femur, proximal tibia (PT) and midshaft tibia,together with lower limb muscle mass. Markers of bone

remodeling and histomorphometry analysis of the secondaryspongiosa and cortex of the tibia were also investigated. PlasmaIGF-I and testosterone were determined, as well as seminalvesicles weight taken as the re¯ection of testosterone effects. At12 weeks, a marked decrease in IGF-I was observed with thelowest protein diet: 675�29, 668�23, 657�35 and 349�29* ng/ml(means�SEM; *p<0.05 vs 15% by ANOVA) in rats fed 15, 7.5, 5and 2.5% casein, respectively. The effect was still morepronounced after 24 weeks. In contrast, at 12 weeks no effecton testosterone was observed. Only at 24 weeks testosteronewas in¯uenced: 1306�251, 998�169, 707�109* and 494�65* pg/ml(*p<0.05 vs 15%), in rats fed 15, 7.5, 5 and 2.5% casein,respectively. The early fall in IGF-I was associated with decreasedbone formation and the late depressed testosterone with anincrement of bone turnover. The repercussion on BMD, US andtissues weights observed at 24 weeks are tabulated below:

Protein Intake 15.0% 7.5% 5.0% 2.5%

PT BMD (mg/cm2) 266�3 270�6 261�4 234�8**PT US (N) 156�11 137�21 140�5 114�5*Seminal vesicle (mg) 309�13 305�20 227�42 199�14*Muscle (g) 7.72�0.25 7.55�0.21 5.74�0.98* 5.56�0.16*

Bone Mass Diagnosis

Similar eects on midshaft tibia and femoral neck BMD wereobserved. Thus, bone loss occurred in male rats pairfed anisocaloric low protein diet at skeletal sites formed by cortical and/or trabecular bone. This was associated with alteration of bonemechanical properties. A dose-dependent decrease of muscleweight was also observed. In conclusion, isocaloric proteinundernutrition induces bone loss in adult male rats, throughmechanisms involving an early drop in IGF-I and in boneformation followed by hypogonadism and increased bone turn-over. This could be reminiscent to osteoporosis pathogenesis inmale elderly.

220 (196). BONE MINERAL DENSITY IN CHILDREN WITHASTHMA RECEIVING LONG-TERM TREATMENT WITHINHALED BUDESONIDE

L Agertoft, S Pedersen, Department of Pediatrics, KoldingHospital, Kolding, Denmark

The aim of our study was to assess the effects of long-termtreatment with inhaled budesonide (BUD) on total body bonemineral density (BMD), total body bone mineral capacity (BMC),total bone calcium (TBC), and body composition in children withasthma.

Dual energy X-ray absorptiometry (DEXA) was performed in 157asthmatic children treated with inhaled BUD at a mean daily doseof 504 mg (range: 189 to 1,322 mg) for 3 to 6 years (mean, 4.5years). Measurements were compared with those of 111 age-matched children also suffering from asthma but who had neverbeen treated with exogenous corticosteroids for more than 14 d(control group).

There were no statistically signi®cant differences between thetwo groups in BMD (BUD = 0.915 g/cm2 controls = 0.917 g/cm2),BMC (BUD = 1,378 g, controls = 1,367 g), TBC (BUD = 524 g,controls = 519 g), or body composition (lean body weight BUD =27,600 g, controls = 26,923 g; % body fat BUD = 20.1%, controls= 20.3%). Furthermore, there was no correlation between any ofthese parameters and duration of treatment, accumulated orcurrent dose of budesonide.

Three to six years of treatment with inhaled budesonide at anaverage daily dose of 504 mg has no adverse effect on total BMD,total BMC, TBC, or body composition in children with chronicasthma.


221 (197). EVALUATION OF THE BONE MINERAL DENSITY OFTHE LOWER EXTREMITIES OF THE HEMIPLEGIC PATIENTS

Fatma Atalay1, Oya Gulec1, Gulcin Kaymak Karatas1, Jale M.Tan1, 1Department of Physical Medicine and Rehabilitation, GaziUniversity Faculty of Medicine, Ankara, Turkey

In stroke patints, there is a risk for osteoporosis due toimmobilization. In this study bone mineral densities of bothlower extremities of hemiplegic patients were evaluated and itsrelationship with immobilisation were investigated.

Bilateral tibial bone mineral densities of 18 men and 14 women,a total of 32 patients were measured by quantitative ultrasoundand speed of sound(SOS) , t and z scores were estimated. Theparticipants were questioned for demographic properties, riskfactors for osteoporosis and for menopause durations in women.Spastisity and Rivermead Mobility Indexes were assessed andtheir relationships between bone mineral density parameterswere evaluated.

Mean age of participants was determined as 58, 1�9, 2 yearsand mean duration of illness was 24, 1�18, 5 months. Nosigni®cant differences was found in SOS, t and z scores betweenhemiplegic and normal extremities in total patients. In men, nosigni®cant correlation was found between age, duration of illnessand SOS, t and z scores of both extremities. In women, there wasnot any correlation between age, menopause duration and bonemineral density parameters, but there was a strong correlationbetween illness duration and bone mineral density parameters inboth hemiplegic and normal sides.

222 (198). DIAGNOSTIC VALUE OF A SINGLE DENSITOMETRY

Marek Bolanowski, Department of Endocrinology andDiabetology, Wroclaw Medical University, Wroclaw, Poland

Nowadays bone densitometry has been available in clinicalpractice and its consequence are many confusing results.Moreover, descriptions of a measurement without personalcontact with patient are not uncommon. In some cases theresult of a single, sometimes by chance, densitometry canprovide a false conclusion and therapeutic decision wheninterpreted without suf®cient knowledge of an individual clinicalpicture and/or methodological conditions.

The purpose of the study was to compare densitometric resultsusing different methods in healthy men. Following densitometricanalyses were carried out: forearm (SPA, SXA, pDEXA, pQCT),lumbar spine (DEXA, QCT), hip (DEXA), total body (DEXA), tibia(QUS), os calcis (QUS), phalanx (QUS). The results werecompared according to age, race and sex matched normalpopulation values.

A considerable dispersion in the results of densitometry wasshown. Especially methods used in screening studies (SPA, SXA,QUS) provided results lower in contrast to results obtained bystandard methods (DEXA, QCT).

It suggests to be very careful when interpreted or described theresult of a single densitometry without personal contact withpatient and his history, or without suf®cient knowledge ofdensitometric methods.

223 (199). COMPARISON OF QUANTITATIVE ULTRASOUNDAND BONE MINERAL DENSITY IN PRE-PUBERTAL GIRLS

S. Cheng1, H. Suominen1, A. Koistinen1, F. Tylavsky2, H. Kroger3,1University of Jyvaskyla, Jyvaskyla, Finland; 2University ofTennessee, Memphis, TN, USA; 3University of Kuopio, Kuopio,Finland

Relatively little is known about the association betweenquantitative ultrasound (QUS) parameters and bone mineraldensity (BMD) in children. We have compared calcaneal broad-band ultrasound attenuation (BUA; QUS±2, Metra Biosystems)

with areal BMD of the total body (TB), total hip (TH) and itssubregions, and lumbar spine (LS; Prodigy, Lunar). Subjects weregirls aged 11±13 years enrolled in an intervention study toevaluate the effects of supplementation with calcium, vitamin D,and cheese on the acquisition of bone mass during pre-puberty(the CALEX study). The median of the CVs for duplicatedetermination of BUA was 1.2% in 103 girls. Correlations(Spearman rho) between bone mass and anthropometric para-meters in 61 girls are shown in the table below. BUA was weaklyassociated with BMD of the total body, the hip and all itssubregions, but not the spine. Both BUA and BMD measurementswere associated with height, weight, body mass index (BMI), andage to a similar degree. Further study is required to determinewhether the differences between calcaneal BUA and axial BMDare due to the measurement technique or to differences in bonemass acquisition at different skeletal sites. QUS appears to be apromising technique for evaluating bone mass in children.

TB BMD TH BMD LS BMD Height Weight BMI Age

BUA 0.293 0.321 0.236* 0.204 0.445 0.494 0.250

TB BMD 0.814 0.755 0.471 0.495 0.407 0.317

TH BMD 0.737 0.335 0.432 0.423 0.326

LS BMD 0.504 0.527 0.386 0.392

Height 0.764 0.348 0.621

Weight 0.860 0.420

BMI 0.129*

* not signi®cant; all others p<0.05

224 (200). CAN COMMERCIALLY AVAILABLE PHANTOMS BEUSED FOR UNIVERSAL FOREARM BMD CROSS-CALIBRATION?

X. G. Cheng, J. A. Shepherd, C. F. Njeh, T. Fuerst, J. Toschke, M.Grigorian, H. K. Genant, Osteoporosis & Arthritis Research Group,University of California, San Francisco, CA, USA

There is a need for phantoms to monitor machine precision and tocross-calibrate between peripheral DXA devices for large multi-center trials. We evaluated seven commercially availablephantoms on ®ve DXA scanners.

The European Forearm Phantom II (EFPII), the ComputerizedImaging Reference Systems (CIRS) 400, 600 and 800 phantoms,the Osteometer DTX200 phantom, the Norland pDEXA phantom,and the Lunar PIXI phantom, were scanned ®ve times withrepositioning. The DXA scanners were the Aloka DCS600EX, theHologic QDR4500A, the Osteometer DTX200, the Norland pDEXA,and the Lunar PIXI. In addition, 100 female subjects (21±78 yrs)were scanned on each densitometer as part of an in vivo crosscalibration study. CVs are shown in the table. The ®gure showsthe distribution of in vivo PIXI T-scores compared to eachphantom. Precision varied due to phantom-speci®c repositioningissues. A combination of these phantoms could be used to coverthe clinical BMD range for monitoring precision and accuracy inmulti-center trials.


Device 400 600 800 DTX EFPII PDXA PIXI

Aloka 2.3 3.1 1.7 1.0 na 1.2 1.0Holo. 2.2 1.9 1.4 0.9 2.6 1.7 0.9Osteo. 2.2 1.2 0.9 0.6 0.5 0.7 0.6PDXA 2.4 1.1 2.1 0.7 0.7 0.9 1.1PIXI 1.8 1.9 1.1 0.5 1.0 1.1 0.4

225 (201). AGE RELATED INCIDENCE OF AORTICCALCIFICATION AND OSTEOPHYTE IN KOREAN AGEINGPEOPLE

W. H. Choi, C. B. Lee, Y. S. Park, T. H. Kim, University of Hanyang,Hangdangdong, Seoul, Korea

There are two basic clinical indication for performing bonedensity. The one is accurate measurement of BMD in order toidentify patients with low bone mass and increased risk offracture, the other one is precise monitoring of patients place ontherapy to determine its effect. But most of popular bone mineraldensimeter, DEXA system which has limited value for evaluationof old people who has common osteophyte and aortic calci®ca-tion in anterioposterior scan.

There are no known data about incidence of osteophyte andaortic calci®cation in ageing people. We used computedtomography (Siemens, somatom plus4) and simultaneous calibla-tion phantom(K2HPO4) and software QCT pro (Mindways, CA)with 3 dimensional evaluation.

We evaluated 128 patient who visited to osteoporosis clinic atHanyang university hospital in Seoul, Korea. We de®nedosteophyte that detected bony overgrowth around the anyregion of L1 to L2 area. Aortic calci®cation de®ned any radio-opaque calci®ed region in the same level of aorta and renal atery.

The incidence of osteophyte were 35% at 50th decade, 62% at60th decade, 68% at 70th decade and more than 95% at 80th

decade. The incidence of aortic calci®cation were 20% at 50th

decade, 42% at 60th decade, 50% at 70th decade and more than95% at 80th decade. Both are present lower than 5% at 50th

decade, but 37% at 60th decade, 40% at 70th decade and morethan 95% at 80th decade. Some patient could not evaluate thefollow up DEXA result after year treatment of antiresorptiveagents. This clinical problem might be considered ageing changeof osteophyte and or aortic calci®cation. To overcome thislimitation, 3 dimensional QCT method would be useful foralternative method.

226 (202). QUANTITATIVE ULTRASOUND OF BONE AND NEWMARKERS OF BONE TURNOVER IN CUSHING'S SYNDROME

B. Cortet, F. Blanckaert, A. Racadot, M. d'Herbomez, X.Marchandise, D. Dewailly, C. Cortet, University-Hospital of Lille,Lille cedex, France

Purpose: Quantitative ultrasound (QUS) of bone is a valuable toolin the assessment of postmenopausal osteoporosis. QUS andnew markers of bone turnover have been poorly assessed inCushing's syndrome however.

Patients and Methods: 22 patients with Cushing's syndrome (19females, 3 males, mean age: 38�10 years) were studied andcompared to 35 control patients age- and sex-matched (meanage for controls: 39�11 years, P=0.8). The following variableswere measured in both groups: QUS at the heel (Achilles, Lunar):BUA, SOS ans stiffness index (SI), bone mineral density (BMD)both at the lumbar spine (LS) and femoral neck (FN) by dual-energy X-ray absorptiometry (DXA, QDR 2000, Hologic), serummarkers of bone turnover: osteocalcin (OC), procollagen type IN-and C-terminal propeptides (PINP and PICP), procollagen typeIC-terminal telopeptide (ICTP).

Results: Both BUA and SI were decreased in patients withCushing's syndrome (P<0.01) but not SOS (P=0.08). BMD wasalso strongly decreased in Cushing's syndrome both at the LSand FN (P<0.001). The sole marker of bone turnover statisticallysigni®cantly different between the 2 groups was OC: 3.5�3.4 ng/mL versus 6.4�2.9 ng/mL (P<0.01). The areas under the ROCcurves (AUC) were 0.722 (BUA), 0.729 (SI), 0.898 (BMDLS), 0.812(BMDFN) and 0.829 (OC) respectively. AUC was signi®cantlyhigher for BMDLS than for both BUA ans SI (P<0.05). ConverselyAUC were not statistically signi®cantly different for BMDFN and forboth BUA and SI. Odds-ratios [and 95% con®dence interval -CI-]per 1 control standard deviation decrease were: 1.9 [1.1±3.3] forBUA, 1.7 [95% CI: 1±2.9] for SI, 7.8 [95% CI: 2.6±23.7] for BMDLS,4.7 [95% CI: 1.8±12.1] for BMDFN and 2.9 [95% CI: 1.3±6.3] for OC.Odds ratios for SOS and other markers of bone turnover were notstatistically signi®cant.

Conclusion: QUS of bone seems a relevant tool for assessingbone involvement in Cushing's syndrome. QUS does have a lowersensitivity as compared with DXA however. The new markers ofbone turnover (PINP, PICP and ICTP) assessed in this study donot seem of interest.

227 (203). THE ITALIAN EPIDEMIOLOGICAL STUDY ON THEPREVALENCE OF OSTEOPOROSIS (E.S.O.P.O.)

G. Crepaldi1, S. Adami2, G. Isaia3, P. Filipponi4, O. DiMunno5, S.Maggi1, R. Giorgino6, A. Menotti7, The E.S.O.P.O Study Group ,1Padua; 2Verona; 3Turin; 4Perugia; 5Pisa; 6Rome, Italy;7Minneapolis, USA

Aim of the study is to measure the prevalence of osteopenia andosteoporosis among general population across all Italian regionalareas. The study (starting Feb. 1st 2000 and ending May 31st 2000)involves about 90 hospital and university sites: the recruitmentwill be supported by 1800 General Practitioners who will invite bymail or by phone 25 000 women (aged 40±79 yrs) and 20 000 men(aged 60±79 yrs). Subjects will be randomly selected from GPs'database. A 66% redemption rate is expected in order to allow a®nal sample of 30 000 subjects. The sample has been calculatedbased on published cohort data. Each subject will undergo anultrasound densitometry at the heel on a Lunar Achilles Expressdevice for Stiffness Index measurement. Recent studies haveshown that Stiffness Index T-scores measured by the Achilles areentirely congruent with those of axial BMD. Based on WHOcriteria, Stiffness and axial BMD identify the same proportion(20%) of postmenopausal women as osteoporotic. A life-style andrisk-factor questionnaire (partially drawn by the EVOS study) willbe administered to each subject: blood pressure and BMI will bealso measured. The primary endpoint of ESOPO will be toestimate the proportion of subjects with Stiffness Index >±1 SD(osteopenia) and >±2.5 SD (osteoporosis) below the young adultmean in each decade: the secondary endpoint is to con®rm and/or identify any potential determinant of both conditions. Aprecision error test trial will be also performed in each center tomeasure Stiffness Index CV in vivo both intra- and inter-observer.A speci®c software has been developed for data collection: aninterim-analysis has been planned on early April in order to allowa preliminary presentation at the WCO meeting.

228 (204). BUA AND SOS VALUE OF THE CALCANEUS INELDERLY WOMEN DEPENDS ON MECHANICAL LOAD OF THESOLE

E Csupor1, P Soos2, L Basch3, P Vargha4, S Meszaros4, CHorvath4, 1Health Service of Budavar, St. Janos Hosp, SensitivLTD, lst Dept of Med., Semmelweis University, Budapest, Hungary

The advantage of the quantitative ultrasound (QUS) is measuringparameters in¯uenced not only by mineral density but also bystructure and qualitiy of the bone. For this reason, to study the


role of mechanical load of sole to the heel QUS parametersseemed to be promising. SOS, BUA and QUI (Sahara, Hologic)were measured at both calcaneus in 84 elderly women (age67�9.1 ys). The pressure to the right and left sole were alsoexamined by podoscope. Patients were grouped as pressingdominantly the right or left sole or pressing equally both sides.The difference in right-left side for BUA, SOS and QUI wascalculated.

Results: mean, (95% con®d. limits), *p<0.0002 Our resultssuggest the role of mechanical load in determining the speed andattenuation measured at the calcaneus.

equal load right dom. left dom.

n 42 27 15

BUA ±0.54 5.81* ±9.90*(±2.50; 1.41) (3.24; 8.37) (±14.2; ±5.56)

SOS 2.,69 12.08* ±13.74*(±0.62; 5.99) (8.55; 15.61) (±18.68; ±8.8)

QUI ±19.12 7.35* ±9,68*(±54.18; 15.95) (5.08; 9.62) (±13.08; ±6.3)

229 (205). COMPUTER AIDED HISTOMORPHOMETRICANALYSIS OF VERTEBRAL BODIES

E. Czerwinski1, A. Gadek1, L. Wojnar2, 1Depat. of Orthopaedics,Jagiell. University, Krakow; 2Inst. of Mat. Sc., Kracow Universityof Technology, Poland

The aim of study was elaboration of a automatic method ofhistomophometric analysis of trabecular bone samples usingcomputer aided image analysis. Transverse sections of decalci-®ed vertebral bodies has been chosen for examination. Digitalimages of the sections analysed have been stored in a PCcomputer. memory using the frame grabber. Further analysis hasbeen performed using the specialised software for image analysisAphelion v. 2.4. Independent analysis of the RGB channels andautomatic shade correction allowed was used.

This introductory processing has been followed by binarisationand measurements of selected parameters. Application of theprocedures offered by image analysis has enabled fast andobjective evaluation of histomorphometric parameters of thetrabecular structure. The method proposed has high sensitivity anoffers good repeatability of the results, even in the case ofsamples with poor contrast. The results of introductory testsindicates that this method can be applied in a fully automaticmode within various ®elds of view of a single specimen. Goodrepeatability of the results and high ef®ciency in measurementsmakes this method an interesting alternative for classicalhistomorphometric analysis.

230 (206). RADIUS BONE MINERAL DENSITY MEASUREMENTSAND STRUCTURE ANALYSIS IN DIAGNOSIS OFOSTEOPOROSIS

E. Czerwinski, R. T. Kukielka, A. Len, Dept. of Orthopaedics,Medical Coll. of Jagiellonian University, Kopernika, Krakow,Poland

However bone mineral density is widerly accepted criterion forosteoporosis, but is not suf®cient for bone quality and fracturesrisk assessment. Apart from BMD the bone structure is also oreven more important.

The DXA method is currently considered the golden standard indiagnosing osteoporosis. According to WHO criteria the values ofT-scores in any site justi®es the diagnosis of osteoporosis.Because of the perceived high cost of DEXA studies of the spine

and femur, there is renewed interest in small, low-cost devices forBMD measuring in the peripheral skeleton like forearm. It's alsogood place for estimation of bone microstructure, thanks to smallamount of soft tissues. One could remember that radial fracturesare common in osteoporotic patients.

The sim of this study was to estimate the value of measure-ments of the forearm in diagnosing osteoporosis in comparison tolumbar spine and proximal femur densytometric measurements.Application of computerised assessement of bone structure on X-rays is described.

Bone mineral measurement was performed in 600 patients.Forearm measurements were carried out using the DTX±200(Osteometer) in both ``distal'' and ``ultradistal'' regions. Measure-ments of the lumbar spine and proximal femur were performed onthe DPX-IQ (Lunar) densytometer. Signi®cant correlation betweenperipheral results, proximal femur and lumbar spine was found.Diagnosis of osteoporosis was also wellcorrelated in peripheraland axial measurements (about 89 %).

Radiographs of distal radial methaphysis, femoral neck andcalcaneus were selected for the research. All the radiographs hadbeen made in ordinary X-ray rooms. The elaborated methodallows for a quantitative bone structure measurement on radio-graphs of different types: distal radius, femoral neck, andcalcaneus radiographs as well as on experimental radiographs.The only condition of this method is good quality of theradiograph and access to image recording device ± CCDcamera or scanner. In the previously performed resarch,measurement precision as well as certain norm range for distalradius.

We conclude that measurements of bone mineral density in theforeann is valuable method in diaguosing asteoporosis. On thebasis of the computerised analyses of radiographx it is possibleto obtain quantitative measurement of bone structure.

Bone mineral density was assessed by using of DTX±100 andDTX±200.

Measurements are carried out in distal (mainly cortical bone)and ultradistal (trabecular bone) regious. We found highcorrelation between bone mineral density measurements in theforearm, proximal femur and lumbar spine with correlationcoef®cient (r) range from 0.66 to 0.8. Using WHO de®nitiondiagnosis of osteoporosis based on forearm densitometry wascon®rmed or excluded in 90% cases in comparison to proximalfemur and lumbar spine densitometry. Measurement of BMD inforearm is very ef®cient, precise and low cost method indiagnosis of osteoporosis.

There are also possibilities to estimate of bone structure in theforearm basing on digitalised radiogram. Such programsTrabecula and Densyt are dedicared for evaluation of bothtrabecular and cortical bone structure, mainly trabecular quantity,width, density. Basing on PC computer and standarised radio-gram patients with deteriorated bone structured can be distin-guished from patients with normal bone structure.

231 (207). CALCANEAL ULTRASOUND -INFLUENCE OFACTIVITY AND COMPARISON WITH STANDARD DEXAMEASUREMENTS IN A GENERAL CLINICAL PRACTICE

R. D. Danese, A. A. Licata, B. Richmond, C. Deal, Cleveland ClinicFoundation, Cleveland, Ohio, USA

Calcaneal ultrasound (US) is a rapid and inexpensive modality forscreening osteoporosis in daily of®ce practice. But questionsremain about its precision, correlation with standard DEXAprocedures, and applicability to WHO criteria. We compared itsresults to routine DEXA testing and evaluated the performance ofthis tool pre and post exercise. Fifty women were evaluated withultrasound (Hologic Sahara) at their scheduled DEXA testing(Lunar 4500). The mean (s.d.) age, height, weight, and years sincemenopause were 60.3(1.2) y, 1.61 (0.06) m, 65.6(9.6) kg. and 12.9(9.3) y, resp.


Ultrasound correlation

Neck Trochanter Ward Total Hip Spine

r-value 0.40 0.59 0.32 0.37 0.42p-value 0.005 <0.009 0.026 0.012 0.006

Only 4% of pts had US t-scores below±2.5 s.d., but 20.5% hadDEXA scores below ±2.5 s.d. at the spine, 21.7% at the femoralneck, 28.8% at wards triangle, 4.4% at the trochanter, and 5% atthe total hip. 42% of patients had US t-scores below ±1.0 s.d.. 18subjects were evaluated before and after a 1±2 mile ``walk forosteoporosis''. Mean US t-scores were 70.033(95% CI, ±0.48 to0.42) before the walk and ±0.24 (95% CI, 70.73 to 0.24)afterwards (p = 0.008). Pre-walk, 16.6% had t-scores below ~1.0compared to 33% post walk. Those with (-) scores at the outset(mean ±0.70 [range ±1.06 to ±0.33]) showed worse values after thewalk (mean ±0.94 [range ±1.27 to ±0.60] p = 0.01). US with thismachine failed to detect the same frequency of osteoporosis asroutine dexa when using standard WHO critical cuto criteria (i.e., ±2.5 s.d. t-score). Prior activity in¯uenced these measurementsand falsely lowered values. Conclusion: WHO criteria cannot beused to screen for osteoporosis when using this speci®cmachine. Minor physical activity may aect precision and increasethe false positive rate.

232 (208). ESTIMATION OF THE RISK OF HIP FRACTURE INTWO DIFFERENT POPULATIONS: THE EPIDOS AND SOFSTUDIES

P. Dargent, M. Nevitt, L. Palermo, F. Poitiers, G. BreÂ art, for theEPIDOS And SOF Research Groups, 1University of California, SanFrancisco; 2INSERM, Paris, France

Differences in age- and BMD-speci®c fracture risks acrossgeographic populations are an obstacle to generalizable screen-ing and treatment guidelines for osteoporosis. The goal of thisanalysis was to assess whether differences in hip fracture ratesbetween cohorts of French and American women could beexplained by differences in the distribution of BMD and age. Weused data from two large, prospective cohort studies of BMD andhip fracture in France (EPIDOS) and the US (SOF). This analysisincluded only women between 75 and 89 years of age withbaseline hip BMD; 6510 women in EPIDOS (mean age 80.4�3.4years) and 4448 women in SOF (78.0�3.1 years). Women had hipBMD assessed by DXA at baseline (Lunar DPX in EPIDOS andHologic QDR1000 in SOF). We used published equations (JBMR1997; 12:13 16) to convert manufacturer-speci®c values for totalhip BMD into standardized units (sBMD). Follow-up for hipfracture was truncated at 4 years in each cohort. In SOF, 140hip fractures occurred during 3.7 ( 0.7) years while in EPIDOS, 245hip fractures occurred during 3.6 (�0.8) years. Crude rates of hipfracture per 1000 woman-years were 27% higher in EPIDOS (10.7;9.4 ± 11.9) than in SOF (8.4; 7.0 ± 9.8). The mean age-standardizedsBMD was higher in SOF than EPIDOS up to age <83 (746.2 and727.5 mg/cm2, respectively, p50.001), but was lower in SOF afterage 583 (686.2 and 693.9 mg/cm2, p = 0.21). In both cohorts, therisk of hip fracture showed nearly identical strong associationswith sBMD and age in Cox proportional hazards models. Incombined models, adjustment for sBMD and age eliminatedstudy differences in risk of hip fracture (RR for SOF vs. EPIDOS:1.12; 95% CI: 0.91±1.39). There were no signi®cant sBMD or ageby study interactions. In conclusion, the 4-year age- and hipBMD-speci®c risks of hip fracture are similar for women in theEPIDOS and SOF cohorts. This suggests that simple screeningand treatment guidelines utilizing risk of hip fracture in risk groupsde®ned by age and hip BMD may have similar validity in the USand France. Studies are needed to test the generalizability offracture risk estimates across other geographic areas.

233 (209). DXA INSUFFICIENCY IN PRIMARY DIAGNOSIS OFOSTEOPOROSIS

R. Dreher, M. Hesse, G. Lingg, G. Sommer, 1Hospital forRheumatic Diseases, Bad Kreuznach; 2Hospital EvaluationSystems, Kaiserslautern, Germany

Aims: To de®ne osteoporotic patients by triple bone mineraldensity (BMD) measurements. To compare DXA and QCT BMDmeasurement values.

Methods: BMD measurements were performed by LUNARlumbar DXA (LDXA) and femoral neck DXA (FNDXA) measure-ments and additionally by QCT measurements of lumbarvertebrae (General Electric 3000 single energy scanner) inwomen (n = 250), women 51±70 years (n = 141), women >70years (n = 109) and men (n = 74), men 51±70 years (n = 60), men>70 years (n = 14). 1. De®nition of osteoporosis on the basis ofabsolute BMD values for women/ men: LDXA 50,90/ 50,93mg/cm2 and/or FNDXA 50.73/ 50.80mg/cm2 and/or QCT lumbarvertebrae 591.5mg HAE (Hydroxy Apatite Equivalent), the samefor women and men. 2. Comparison of numbers and percentagesof osteoporotic patients depending on the BMD measurementmethods and age of patients. 3. Comparison of triple BMDabsolute values by Spaerman correlation coef®cients betweenQCT-LDXA, QCT-FNDXA and FNDXA-LDXA. 4. Spaerman corre-lation coef®cients betwen BMD values and number of grade 3lumbar vertebrae fractures.

Results: Numbers (n) and percentages (%) of osteoporosis bytriple BMD measurements (LDXA, FNDXA, QCT) women, 51±70years (n=141); LDXA (n=38/27%), FNDXA (n=43/31%), QCT (n=93/66%), women, >70 years (n=109); LDXA (n=35/32%), FNDXA(n=51/47%), QCT (n=96/88%) men, 51±70 years (n=60); LDXA(n=10/17%), FNDXA (n=27/45%), QCT (n=39/65%), men, >70years (n=14); LDXA (n=5/36%), FNDXA (n=9/64%), QCT (n=13/93%). Spearman correlation coef®cients of BMD values women,51±70 years; QCT vs LDXA (r = 0.56, p = 0.000), QCT vs FNDXA(r = 0.51, p = 0.000), LDXA vs FNDXA (r = 0.56, =0.000) women, >70years: QCT vs LDXA (r = 0.44, p = 0.000), QCT vs FNDXA (r = 0.45,p = 0.000), LDXA vs FNDXA (r = 0.50, p = 0.000) men, 51±70 years:QCT vs LDXA (r = 0.49, p = 0.000), QCT vs FNDXA (r = 0.45,p = 0.000), LDXA vs FNDXA (r = 0.27. p = 0,19), men, > 70 years;QCT vs LDXA (r = 0,67, p = 0.003), QCT vs FNDXA (r = 0.91,p = 0.000), LDXA vs FNDXA (r = 0.61, p = 0.010)

Spearman correlation coef®cients between grade 3 lumbarvertebrae fractures (G 3 LF) and BMD values, all patients: G 3 LFvs QCT (r = 0.44, p = 0.000), G 3 LF vs FNDXA (r = 0.31, p = 0.000),G3 LF vs LDXA (r = 26, p = 0.000)

Conclusion: If only DXA techniques are used in patients withvarious underlying rheumatological diseases, osteoporosis willoften be overlooked. FNDXA is only moderately correlated withLDXA and lumbar QCT with the exception of elderly men, whereFNDXA correlates strongly with the QCT values of the lumbarspine. Grade 3 lumbar vertebrae fractures correlate best withlumbar QCT values.

234 (210). INTERRELATIONSHIPS BETWEEN BONE MASS,SERUM PTH LEVELS AND BONE TURNOVER IN PATIENTS ONCHRONIC MAINTENANCE HEMODIALYSIS

C. Dumitrache, D. Grigorie, Elena Neacsu, Carmen Barbu, M.Grabovschi, C. I. Parhon Institute of Endocrinology, NephrologyDepartment of the Carol Davila Hospital, Bucharest, Romania

The aim of the study was to assess the pattern of bone loss in theaxial and appendicular skeleton and its relationships with serumPTH levels and bone turnover in patients on chronic hemodia-lysis. We measured the total body bone mineral density by DEXAin 15 patients (6 women and 9 men) with a mean of 7.4 years(range:1±18 years) of chronic hemodialysis. Mean value of Z scorewas signi®cantly decreased in the arms (Z=±2.21). There was nocorrelation between bone mineral density measured at any region


and serum levels of intact PTH (IRMA), intact serum osteocalcinor total alkaline phosphatase. We found a signi®cant inverserelationship between bone loss (Z score) and serum levels of iPTH(r = ±0.6, p<0.05) and years of hemodialysis (r = ±0.58, p<0.05),respectively. We found a signi®cant increase in mean values ofserum iPTH (782.4 pg/ml) and osteocalcin (155.23 ng/ml) levels. Inconclusion, 1) the cortical bone loss is signi®cant and is due tochronic renal failure, 2) signi®cant increase in serum PTH levelsand bone turnover markers suggests that long-term hemodialysisproduces a high-turnover bone loss, 3) secondary hyperparathyr-oidism is pathogenically involved in the bone loss, 4) theincidence of high-turnover renal osteodystrophy seems to behigh among chronic renal failure patients treated by hemodialysis.

235 (211). BONE MINERAL DENSITY AND BONESCINTIGRAPHY IN CHILDREN AND ADOLESCENTS WITHOSTEOMALACIA

M. El Desouki, N. Al Jurayyan, King Khalid University Hospital,Riyadh, Saudi Arabia

In order to demonstrate the role of bone mineral density (BMD)measurements and bone scan in the management of patients withosteomalacia, radioisotope bone scintigraphy using Tc±99mMethyline Diphosphonate (MDP) and BMD measurements of thelumbar spine and femur by means of Dual X-ray Absorptiometry(DXA) were performed at the time of diagnosis, and six monthsafter therapy in 26 Saudi patients (17 females and 9 males). Theirmean age was 13.5 years (range, 5±16). BMD measurements werecompared with those of normal Saudi subjects matched for ageand sex. Bone scan showed an increase in tracer uptakethroughout the skeleton (``superscan'') in all children anddemonstrated multiple stress fractures in eight. The mean BMDfor the lumbar spine was 0.53 gm/cm2 (Z-score, ±3.1) and for thefemoral neck 0.55 gm/cm2 (Z-score, 2.8). Repeated bone scanand BMD after 6 months of therapy with oral Vitamin D, calciumand proper sun exposure, demonstrated signi®cant increase(P<0.001) in BMD and healing of pseudofractures. In conclusion,as a non-invasive method with minimal radiation exposure,measurements of BMD in children with osteomalacia are to berecommended in the initial assessment of the severity ofosteopenia and in the follow up to monitor the response totherapy. Bone scintigraphy is valuable in demonstrating the siteand severity of stress fractures.

236 (212). BONE MINERAL DENSITY (DXA) AND BONE SCAN INADULT SAUDI FEMALE PATIENTS WITH OSTEOMALACIA

M. El Desouki, King Khalid University Hospital, King SaudUniversity, Riyadh, Saudi Arabia

Objectives: This prospective study was conducted to demon-strate the role of bone mineral density (BMD) and bone scan in themanagement of patients with osteomalacia. Patients andMethods: Bone scans using 99m Tc-Methylene Diphosphonate(MDP) and BMD of the total body, lumbar spine and femur usingDual X-ray Absorptiometry (DPA), Lunar Radiation Corp.,Wisconsin) were performed at the time of diagnosis, and 6months after treatment in 96 Saudi female patients, aged between18 and 73 years (mean 42 yr) with clinical and biochemicaldiagnosis of Osteomalacia. BMD measurements were comparedwith that of normal Saudi female subjects. Results: Bone scanshowed the features of ``Superscan'' in all patients anddemonstrated multiple stress fractures in twenty seven. In 19patients with chronic bone pain and the diagnosis was made bybone scan as the ®rst modality. The BMD (mean � SD in gm/cm2)was 0.781�0.156 (T-score: ±3.01) for the lumbar spine,0.666�0.177 (T-score: ±2.44) for the femoral neck, 0.562�0.190

(T-score: ±2.66) for the femoral wards, 0.577�0.174 (T-score:71.75) for the femoral trochanter and 0.903�0.137 (T-score:72.04) for total body. Repeated bone scan and BMD after 6months of therapy with oral Vit-D, calcium and proper sunexposure demonstrated a signi®cant increase (P<0.00) in BMDand healing of pseudofracture.

Conclusion: Measurements of BMD in patients with osteoma-lacia are of value and recommended in the initial assessment ofthe degree of osteopenia. Bone scintigraphy is valuable indemonstrating the site and extent of stress fractures as well asdiagnosis.

237 (213). BONE SCINTIGRAPHY AND BONE DENSITOMETRYIN CHILDREN WITH OSTEOPETROSIS

M. El Desouki, N. Al Jurayyan, A. Al Herbish, S. Al Rasheed, KingKhalid University Hospital, King Saud University, Riyadh, SaudiArabia

Bone scintigraphy and dual x-ray absorptiometry were per-formed in 18 children (8 males, 10 females) with clinical andradiologic diagnoses of osteopetrosis in order to demonstratethe scintigraphic features of this rare disorder and to measurethe bone mineral density. Their mean age was 9 years (range, 3±16 years). Bone scintigraphy demonstrated characteristicfeatures of a widened metaphysis of all long bones thatshowed increased tracer uptake, particularly in the distal femurand proximal tibia. Dual x-ray absorptiometry of the lumbarspine, three femoral sites, and total body showed a markedincrease in bone mineral density. The mean values for bonedensity of the lumbar spine and greater trochanter weremarkedly elevated than were other sites. Compared with anormal group matched for age and gender, the increase in bonemineral density was 181 % for the lumbar spine and 193% forthe greater trochanter. The authors concluded that bone imagingand bone densitometry are useful in establishing the diagnosisof osteopetrosis by demonstrating increase tracer uptake in thewidened metaphysis and increased bone density. Bonedensitometry may be of prognostic value in followup, especiallyin monitoring the response to therapy.

238 (214). OSTEOPOROSIS IN POSTMENOPAUSAL SAUDIWOMEN USING DUAL X-RAY BONE DENSITOMETRY

M. El Desouki, King Khalid University Hospital, King SaudUniversity, Riyadh, Saudi Arabia

Objective: A pilot study to evaluate prevalence of osteopenia andosteoporosis in postmenopausal Saudi women.

Patients and Methods: Lumbar spine bone density wasmeasured in 483 postmenopausal Saudi women 52±62 years ofage (average 55 years), using dual x-ray absorptiometry (DXA).

Results: The results of the bone mineral density (BMD) in gm/cm2 was compared to the peak bone density (PBD) in younghealthy Saudi females (T-score) and to age matched group (Z-score). Based on the de®nition of WHO the T-score value wasconsidered for analysis. Accordingly, 203 (42%) patients werenormal (mean BMD of 1.098�0.109, mean T-score of ±0.513 SD;Z-score of 0.434), 164 (34%) with osteopenia (mean BMD of0.893�0.134, mean T-score of ±2.36 SD; Z score of ±1.05), and 116(24%) patients with osteoporosis (mean BMD of 0.795�0.142,mean T-score of ±3.2 SD; Z score of ±1.76).

Conclusion: Osteopenia and Osteoporosis are not uncommonamong postmenopausal Saudi women and should be considereda matter of public concern. Bone densitometry should be used toclassify patients, identify those who need therapy. Further studiesare needed to investigate the secondary causes of osteoporosisand to determine the Vitamin-D level.


239 (215). INTERPRETATION OF PROXIMAL FEMORAL DUAL-ENERGY X-RAY ABSORPTIOMETRY (DXA) SCANS: REGION-OF-INTEREST CONTROVERSIES LAID TO REST

S. Farooki, R. J. Smith, K. Hoyte, D. Cla¯in, D. J. Sartoris,Department of Radiology, University of California School ofMedicine, San Diego, CA, USA

PURPOSE: To critically examine the variability in bone mineralcontent (BMC) and density (BMD) among the various manufac-turer-speci®ed regions-of-interest (ROI) in the proximal femur inorder to develop guidelines for DXA scan interpretation in theclinical detection and management of osteoporosis.

METHODS: We retrospectively reviewed the proximal femoralDXA reports of 1227 patients from August 1998 ± August 1999 (81males; 1146 females, average age 58.7. BMD and T-scorescalculated for the femoral neck, Ward's triangle, greatertrochanter, and the total proximal femur were compared withone another using analysis of variance (ANOVA) for determinationof statistical signi®cance. All scans were performed on a LunarDPX-IQ pencil-beam DXA system. Statistical analysis wasperformed using Minitab version 12 software.

RESULTS: The distribution of the lowest T-scores for sub-regions was: 67.7% (831/1227) Ward's triangle, 9.6% (118/1227)neck, 6.2% (76/1227) trochanter, 7.3% (90/1227) total proximalfemur, and 9.2% with multiple subregions being equal. The meanT-scores for Ward's triangle, femoral neck, greater trochanter,and total proximal femur were ±1.54, ±1.08, ±0.59, and ±0.99,respectively, and there was a statistically signi®cant differencebetween the T-score means (F = 784.72, p50.001 with repeatedmeasures ANOVA). There was a very high degree of correlationbetween T-scores in Ward's triangle and femoral neck (Pearson'scorrelation coef®cient r = 0.93) and an intermediate degreebetween the total proximal femur and Ward's triangle (r = 0.88),total and neck (r = 0.89), and total and trochanter (r = 0.87).There was a low correlation between Ward's triangle andgreater trochanter (r = 0.77) and between neck and trochanter(r = 0.78).

CONCLUSIONS: The lowest T-score among the major ROIsshould always be used for diagnosis. However, Ward's triangleshould not be used for diagnosis or follow-up due to itsuniformly low T-scores and small sample volume. Our datashow that only the femoral neck or the greater trochanter shouldbe used for diagnosis of osteoporosis. For follow up examina-tions, either the greater trochanter or the total proximal femurcould be used.

240 (216). T-SCORE DISCREPANCIES IN MEN AT DIFFERENTSKELETAL SITES

K G Faulkner1, E von Stetten2, E Orwoll3, 1Synarc, Portland, OR;2Hologic Inc., Bedford, MA; 3Oregon Health Sciences University,Portland, OR, USA

Recently it has been acknowledged that signi®cant T-scoredifferences exist at various skeletal sites in Caucasian women(1). At the heel, few women have T-scores below ±2.5, while mostpostmenopausal women will fall below this level with lateral DXAor QCT. As a result, a single T-score criterion cannot beuniversally applied to all BMD measurements and skeletal sitesin women. However, potential normative database discrepancieshave not yet been fully investigated in men. In this study, wecompared the prevalence of osteoporosis in men (based on a ±2.5SD criterion compared to young normal Caucasian males) atdifferent skeletal sites using manufacturer's normative data. Wedetermined the expected mean T-score for a 65-year-old male atthe heel (ultrasound), femoral neck (DXA), total hip (DXA), spine(DXA and QCT), and forearm (DXA). Assuming a normaldistribution of T-scores, we computed the expected percentage

of 65-year-old men that would be classi®ed as osteoporotic foreach measurement. Differences in age-related T-scores for eachskeletal site are shown below. At age 65, the mean T-scoreranged from ±0.6 for total hip, to ±1.9 for QCT spine. Prevalenceestimates were 3% at the total hip, 4% for DXA spine, 5% for theforearm, 6% for ultrasound heel, 8% for femoral neck, and 27%for spinal QCT. We conclude that T-score discrepancies exist inmen as have been previously reported for women. Thesediscrepancies raise important concerns about the use of BMDmeasures in assessing fracture risk in men.

Reference1. Faulkner KG, von Stetten E, Miller P 1999 Discordance in patient

classi®cation using T-scores. J Clin Densitometry 2(3):343±350

241 (217). ANY PERIPHERAL FRACTURE OCCURRING AT ANYAGE IS ASSOCIATED WITH DECREASED BONE MINERALDENSITY IN POST-MENOPAUSAL WOMEN

C. Fiorano-Charlier, A. Ostertag, J P Aquino, M. C. de Vernejoul,C. Baudoin, Inserm U349, Centre Viggo Petersen, HopitalLariboisiere, Paris, France

Women who experienced any peripheral fractures at any age arethey at risk of osteoporosis? For this purpose, we selectedamong a cohort of 503 women, 460 women (mean age�SD: 65�6)without vertebral or femoral neck fractures and without previoustreatment with bisphosphonate or ¯uoride. Among them, 49women (10%) had a total of 60 wrist fractures at a mean age of49�17 years (WF) and 74 (16%) had a peripheral fracture atanother site (OPF) (ribs, humerus, tibia, feet ankles . . .) at a meanage of 49�18 years. These two fractured groups and the 337women without any previous fractures (NF) had the same age,weight, height, nutritional calcium, prevalence of femoral neckfracture in the family and proportion (40%) and duration (7�7years) of HRT use. Wrist fracture group and other peripheralfracture group had a decreased bone mineral density atboth the lumbar spine (WF: 0.99�0.15, OPF: 0.98�0.16, NF:1.07�0.17 g/cm2, p<0.0001) and the femoral neck (WF: 0.77�0.09,OPF: 0.77�0.10, NF: 0.82�0.11 g/cm2, p<0.0001). Women whohad a wrist fracture before menopause (n=13, age at the fracture:25�13, Z-score at the lumbar spine: ±0.60�0.82) were comparablewith women who had a wrist fracture after menopause (n=35, ageat the fracture: 58�7, Z-score: ±0.09�0.89). Both were decreasedcompared to women without fractures (Z-score: 0.21�0.90). Thesame differences were observed at the femoral neck and for theother peripheral fractures.

Conclusion: 1) Women with any previous peripheral, fracturesbesides wrist fractures, have an increased osteoporotic risk. 2)peripheral fractures occurring before menopause are associatedwith a decreased bone mineral density. This suggest that thesepre-menopausal women had a dcreased peak bone mass at theime of the fracture.


242 (218). MONITORING THERAPY RESPONSE WITH BONEDENSITOMETRY AND QUANTITATIVE ULTRASOUND INWOMEN PARTICIPATING IN A REHABILITATION PROGRAM

M. G. GluÈ er1, H. Minne2, A. Lazerescu2, M. Pfeifer2, B. Begerow2,T. Schlotthauer2, C. GluÈ er1, W. PollaÈ hne2, 1Universitatsklinik CAUKiel; 2Institut fur klinische Osteologie, Bad Pyrmont, Germany

We investigated if therapy effects of a 2-year rehabilitationprogram can be demonstrated by Bone Densitometry (HologicQDR) and Quantitative Ultrasound (QUS, Lunar Achilles).

All women had been diagnosed with postmenopausal osteo-porosis. Depending on their disease status they got recommen-dations for adequate drug. Women of group A (n=19, age67.4�8.4) actually took mild medications (calcium, Vitamin D),while women of group B (n=48, age 62.4�6.6) took strongertreatments (bisphosphonates, hormones). After two years womenof both groups gained bone mineral density (BMD) but their QUSparameters (SOS ± Speed of Sound and BUA ± BroadbandUltrasound Attenuation) were reduced (see table). Women in thestrong treatment group gained more BMD and lost less in QUSparameters. Whether loss in QUS parameters was due to lack oftreatment effect or was caused by download drift needs to beclari®ed. Our results demonstrate the effectiveness of therehabilitation program in increasing the BMD of the patients.

Var Mild treatment Strong treatment

BMD Lumbar spine 2.7%* 6.8%***BMD Total hip �0% n.s. 3.2%***BMD Whole body 1.6%* 4.4%***SOS Calcaneus ±0.7%** ±0.4%**BUA Calcaneus ±1.8% n.s. ±0.9% n.s.

Signi®cant change: *p50.05; **p50.01; ***p50.001

243 (219). BONE STRUCTURE EVALUATION WITH MEASURESOF COMPLEXITY

W. Gowin1, P. Saparin1, P. Kurths2, D. Felsenberg1, 1Univ. -Hosp.B. Franklin, Free Univ. Berlin, Germany; 2Inst. of Physics, Univ.Potsdam, Germany

Objective: The purpose of this study was to develop parametersbased on physical complexity to evaluate the architecturalcomposition of human vertebral trabecular bone.

Methods: 50 L3 and 57 L4 specimen (age:24±92) wereexamined by QCT (BMD: 18±144 mg/ml) and HRCT in axial1mm slices. The method was developed on 1 mm slices and latertransferred to the QCT-slices. The images were encoded withsymbols using symbolic dynamics. 5 measures of complexitywere derived from the data. The parameters describe thearchitectural composition (IGE), the regional complexity (SCI),the disorder of composition (SDI), the homogeneity, and therelation to the marrow space of the trabecular network.

Results: The ®gures show IGE, SCI, and SDI in relation to BMD.D = L3, & = L4, osteopenia = 80±100 mg/ml.

The trabecular network of normal vertebrae has a orderlycomplex and differentiated composition, whereas osteoporoticlumbar vertebrae are much simpler composed. Osteopenic andmild osteoporotic vertebrae appear to be in a compositionaltransition with increased disorder of the trabeculae. In contrast toBMD, we found no age dependency for the structural parametersSCI, IGE, and SDI.

Conclusion: The structural measures are remarkably sensitiveto architectural composition and show no dependency of age inadult lumbar vertebrae.

244 (220). CORRELATION OF BONE AREA WITH MUSCLEAREA IN LOWER LIMBS

M. Hartard, A. Arians, D. Jeschke, M. Schwaiger, Working Groupof MusculoSkelatal Interactions, Universities of Munich, Germany

Positive correlations of bone mass to muscle mass, of bone massto muscle force or of bone strength to muscle force have beencorroborated many times over.

The goal of this cross-sectional study was to correlate crosssectional areas of muscle and bone of the right lower limb. Innearly 300 healthy subjects of both sexes (9- 80 years) the crosssectional areas were determined from peripheral quantitativecomputed tomography (pQCT) using a STRATEC XCT 2000.Images were taken at 4%, 14%, 38% and 66% of tibia length,starting at the distal ankle joint of the right limb.

Muscle cross sectional areas at 66% of tibia length correlatedhighly (R2=0,8) with pQCT derived bone cross sectional areas at38% of tibia length.

The high age-, gender- and motivation-unrelated correlationbetween the cross sectional areas of bone and muscle supportsthe hypothesis that muscle could be a leading variable estimatingbone health. The strong correlation of cross sectional areas ofbone and muscle might be valuable as a tool for diagnosis ofbone diseases.

245 (221). ULTRASOUND AND DEXA BONE MEASUREMENT INFEMALE RHEUMATOID ARTHRITIS PATIENTS COMPAREDWITH RANDOMLY SELECTED SUBJECTS IN THEPOPULATION. PRELIMINARY RESULTS

G Haugeberg1, R E Orstavik1, T Uhlig1, T K Kvien1, J A Falch2, J IHalse3, 1Oslo City Dept. of Rheumatology, DiakonhjemmetHospital, Oslo; 2Dept. of Internal Medicine, Aker Hospital, Oslo;3Osteoporosis Clinic, Oslo, Norway

Background and Objective: The risk of vertebral fractures inrheumatoid arthritis (RA) patients seems to be less dependent onbone mass than in primary osteoporosis, suspecting a poorerbone quality in RA patients. Quantitative ultrasound is suggestedto measure aspects of bone quality. The aim was to examinebone mass in female RA patients compared with randomlyselected subjects in the population measured in spine and hipwith dual energy x-ray absorptiometry (DEXA) and in the heel withquantitative ultrasound.

Methods: A total of 28 female RA patients randomly selectedfrom a RA register and 28 age matched female controls recruited


randomly from the population were examined. Mean diseaseduration for the RA patients was 17.6 yrs and 35% wererheumatoid factor positive. Bone mineral density (BMD) measure-ments were performed in spine and in the hip using DEXA (LunarExpert). Speed of sound (SOS), broadband ultrasound attenua-tion (BUA) and Stiffness were measured at the heel usingquantitative ultrasound (Lunar Achilles+). The associationsbetween DEXA and ultrasound measurements in the two groupswere tested using Pearson's correlation coef®cients.

Results: No difference in age (61.9 vs. 61.8 yrs, P=0.96) andweight (64.5 vs. 68.8 kg, P=0.12) were found between the RApatients and the controls. No statistically signi®cant differences inBMD (g/cm2) were found between RA patients and the controls atthe spine (1.04 vs 1.07, p = 0.56) and the hip (femoral neck: 0.80vs. 0.84, P=0.29; total hip: 0.85 vs. 0.88, P=0.39). In RA patients astatistically signi®cant reduction was found in SOS (1493 vs. 1516m/s, P=0.007) and Stiffness (67.2 vs. 75.9, P=0.043) but not inBUA (103.5 vs. 106.9 dB/MHz, P=0.30).

The correlation coef®cients (Pearson's r) between quantitativeultrasound (Stiffness) and DEXA (BMD in hip and spine) in RAwere 0.59*, 0.65* and 0.44* for femoral neck, total hip and spineand for the controls 0.58*, 0.62* and 0.47*, respectively (*allP<0.02).

Conclusion: A statistical signi®cant reduction was found forultrasound (SOS and Stiffness) but not for BUA or BMD in RApatients compared with controls. Studies evaluating both DEXAand quantitative ultrasound and risk of fracture in RA patients areneeded.

246 (222). PREDICTION OF PERIPROSTHETIC BONE LOSSAFTER HIP ARTHROPLASTY BY DEXA OF THE SPINE

T. H. Hennigs, University of Frankfurt/M, Germany

A periprosthetic bone loss occurs after total hip arthroplasty(THA) attributed to initial operative irritation, immobilization andstress shielding. Recent studies showed only a weak correlationbetween the BMD of the proximal femur and the amount of thepostoperative bone loss. The aim of our study was to evaluate thepredictive capacity of DEXA for the periprosthetic bone loss. In 38subjects (f+m) aged 22±65, with un-cemented THA, withoutsuspected conditions affecting bone metabolism, we measuredthe BMD (Hologic, 4500 A) of the spine (L1-L4), the periprostheticfemur and the contralateral femur in the ®rst week and one yearafter surgery. Regions of interest (ROI) were de®ned according toGruen. ROI 7 (calcar femoris) showed the highest amount of boneloss with a range up to 60 %. We found a high correlationbetween this bone loss and the BMD of the lumbar spine(r = ~0.74): with decreasing lumbar BMD (T-score) (x), the relativebone loss (y) was increasing (y = 0.7x2 ± 6.1x + 19.1). Thecorrelation of the BMD of the periprosthetic femur or of thecontralateral femur with the bone loss was much weaker (r = ±0.35and ±0.39, resp.). We conclude, that the predictive capacity forthe early periprosthetic bone loss is much higher in the DEXAmeasurement of the lumbar spine than in that of the ipsi- orcontralateral femur. A preoperative assessment of the expectedbone loss is possible and represents a valuable aid in theplanning and postoperative treatment of THA, mainly in supposedhealthy candidates.

247 (223). BONE MINERAL DENSITY, BODY COMPOSITION,AND PHYSICAL ACTIVITY IN MEDICAL STUDENTS

M. Hogstrom, H. Alfredson, R. Lorentzon, K. Thorsen, 1SportsMedicine, Department of Surgical and Perioperative Science,Umea University; 2Department of Musculoskeletal Research,National Institute for Working Life, Umea, Sweden

The purpose was to examine the relationship between bonemineral density, body composition, and physical activity in

medical students. Peak bone mass is considered to be animportant predictor for future fractures. Physical activity is,besides heredity, one of the main determinants of the observedvariance in peak bone mass.

Material and Methods: One-hundred and twenty-four healthy,non-smoking, Caucasian medical students, 62 women, 25�4years (mean�SD) and 62 men, 28�4 years, were investigated.Bone mineral density (BMD; total body, lumbar spine, and hip)and body composition were determined by DEXA (Lunar DPX-L).The current level (hrs/w) and type (hi, medium, and low) of impactloading activities were registered.

Results: There were no differences in the amount or theparticipation rates in different impact loading activities betweenfemale and male students. In the female students, no associationwas found between current physical activity and BMD. Asigni®cant positive association (r = 0.31, p = 0.014) was observedbetween age and fat mass. Using stepwise multiple regression,body weight was the only determinant of total body (b = 0.43,p = 0.001), trochanter (b = 0.37, p = 0.003), and lumbar spine BMD(b = 0.40, p = 0.001), while lean body mass was the only predictorof femoral neck BMD (b = 0.26, p = 0.038). In male students, thecurrent level of high impact loading was positively correlated toBMD on all locations (r = 0.29±0.42, p 0.001±0.023) and lean bodymass (r = 0.27, p = 0.035). A signi®cant decrease in hip BMD(r =70.33±0.37, p = 0.03±0.09) was observed with age. Age andfat mass was positively correlated (r = 0.25, p = 0.047). Afterstepwise multiple regression, lean body mass was a predictor(b = 0.39±0.45, p = 0.001±0.004) of BMD on all locations, but thelevel of physical activity also predicted total body and hip BMD(b= 0.26±0.30, p = 0.008±0.028).

Conclusions: In female medical students, the level of currentphysical activity is not related to BMD. Body weight is the mainpredictor of BMD. In male students, high impact activities arerelated to BMD and lean body mass is the major determinant ofBMD.

248 (224). QUANTITATIVE ULTRASOUND OF PHALANGES INPATIENTS WITH END-STAGE RENAL FAILURE TREATED WITHHEMODIALYSIS

C Horvath, S Meszaros, E Hosszu, J Szucs, N Szedelyi, G Deak, IMucsi, 1st Dept Medicine, 2nd Dept Pediatrics, SemmelweisUniversity, Budapest, Hungary

End-stage renal failure is frequently resulted in low bone densityand fractures. The aim of this study was to evaluate the ability ofbone ultrasonometry to detect bone disease due to renal failure incomparison to bone densitometry. 32 patients (18 men and 21women, age 54.11�4,3 ys) with end-stage renal failure treatedwith hemodialysis and 21 age- and sex-matched controls werestudied. All patients were normocalcemic with a slightly increasedserum PTH level. Bone densitometry was performed at lumbarspine and femoral neck (XR26, Norland) as well as at forearm(NK364, Gamma). Speed of ultrasound transmitting the phalanges(SOS) was also measured (DBM Sonic 1200, IGEA). Negativecorrelations were found between SOS and age and positivecorrelations between SOS and femur or radius BMD. In womenthe SOS positively correlated to bone-speci®c alkaline phospha-tase, too. Our results suggest the phalangeal ultrasound to be auseful method in the diagnosis of renal bone disease.

Results:

women men

patients controls patients controls

LBMD 0.937** 1.078 1.100 1.090FBMD 0.724** 0.895 0.811* 0.942RBMD 0.724 0.778 1.180 1.220SOS 1888.7* 1997.0 1909.9** 2024.0

(p<0.05*, p<0.01**)


249 (225). AGE-RELATED DECREASE IN BONEULTRASONOMETRY IN DENSITY-ADJUSTED WOMEN

E Hosszu, V Ferencz, S Meszaros, E Csupor, E Toth, K Bors, E VMcCloskey2, C Horvath, 12nd Dept Pediatrics, 1st Dept Medicine,Semmelweis University, Budapest, Hungary; 2WHO CollaboratingCentre for Metabolic Bone Diseases, University of Shef®eld,Shef®eld, UK

A growing body of evidences suggest that bone ultrasonometry(QUS) re¯ects not only density but also non-mass properties ofthe bone. To test this hypothesis QUS was done in young andmiddle-aged women with the same bone mineral density.

Patients: Y ± 22 healthy young women (age 21.7�2.1 ys) and forcomparison: S ± 25 women (age 48.3�5.3 ys) adjusted for spineBMD, F ± 20 women (age 48.8�6.2 ys) adjusted for femur BMD, R± 24 women (age 48.1�7.7 ys) adjusted for radius BMD,respectively. All women were premenopausal.

Methods: BMD measurement was performed by DEXA atlumbar spine and femoral neck (DPX-L, Lunar) and by SPA atforearm (NK±364, Gamma). Heel ultrasonometry was also done(Sahara, Hologic) and BUA, SOS, QUI and estimated heel BMD(eBMD) were calculated.

Results: *p<0.01, **p<0.001

Y S F R

S BMD 1.27�0.03 1.26�0.03

F BMD 1.06�0.03 1.06�0.03

R BMD 0.86�0.02 0.84�0.01

BUA 85.9�3.4 69.4�3.5* 62.3�3.3** 66.0�3.3**

SOS 1597�7.5 1552�5.5** 1540�5.7** 1548�5.7**

QUI 119.1�4 93.9�3.3** 85.7�3.2** 90.6�3.4**

eBMD 0.68�0.03 0.52�0.03** 0.46�0.02** 0.50�0.03**

All QUS parameters correlated negatively with age andpositively with spine or hip BMD.

Conclusion: our results suggest that changes in bone quality/structure occured with ageing can be responsible for the QUSdifferences between young and middle-aged women. Boneultrasound re¯ects de®nitely more than density alone.

250 (226). HORMONE REPLACEMENT THERAPY ANDBISPHOSPHONATE TREATMENT EVALUATED BY NEWQUALITATIVE MEASURES OF CORTICAL BONE

L. Hyldstrup, J. T. Jùrgensen, L. Baeksgaard, T. K. Sùrensen,Dept. of Endocrinology, Hvidovre Hospital, University ofCopenhagen, and Pronosco A/S, Denmark

To evaluate longitudinal changes in BMD following treatment withHRT or bisphosphonate (BP), 121 postmenopausal women (75controls, 32 using HRT and 14 on BP) were measured twice over2 years with digital X-ray radiogrammetry (DXR) by Pro-nosco X-posure System and DXA of the spine, hip and forearm. Long-itudinal changes in DXA-BMD were compared to changes in DXR-BMD, cortical thickness of the 2nd metacarpal (MT2), porosity ofcortical bone and striation of the distal radius.

The expected annual reduction in BMD in the control group wasdetected by BMDspine (±0.8%,p<.02), BMDhip (±1.6%, p<.001),BMDforearm (±1.5%, p<.001), DXR-BMD (±0.8%, p<.001), and MT2(±1.1%, p<.001). In the HRT group only signi®cant reductionswere seen in DXA-BMDhip, (±1.0%, p<.01) and distal forearm(71.0%, p<.02), while striation increased (p<0.05). Comparing theHRT group with the untreated, the reduction in MT2 wassigni®cantly smaller. In the BP group, only cortical porosity wassigni®cantly reduced (p<.025). Comparing changes in the BPgroup with an age-matched subsample of controls, both DXR-BMD, MT2, and porosity of cortical bone differed signi®cantly(p<.01, p<.05, p<.05, respectively), while the DXA measurementsdid not.

In conclusion, DXR provides a densitometry equivalentmeasurement of the distal forearm and hand and seems to offernew information on the structure of cortical bone. This may proveuseful in the evaluation of bone loss, fracture risk and treatmenteffect.

251 (227). LONG-TERM EFFECT OF INHALED BUDESONIDEON BONE METABOLISM IN ASTHMA AND CHRONICOBSTRUCTIVE PULMONARY DISEASE (COPD)

O. G. Johnell1, R. KarlstroÈ m2, C-G LoÈ fdahl3, 1University Hospital,Malmo, Sweden; 2AstraZeneca R&D, Lund, Sweden; 3UniversityHospital, Lund, Sweden on behalf of the EUROSCOP steeringcommittee

To assess the long-term effect of inhaled budesonide on bonemetabolism, two groups of patients were investigated in tworandomized trials. 165 asthmatic patients (86 F, 18±59 years) weretreated with Pulmicort Turbuhaler1 (BUD) at daily doses adjustedaccording to the severity of the disease, or non-steroid referencetherapy for 2 years. 912 patients (254 F, 25±65 years) with chronicobstructive pulmonary disease (COPD) were treated with BUD800 mg/day or placebo for 3 years. In 161 COPD patients and in allasthmatics, BMD (lumbar spine and femoral neck) was measuredat baseline, after 6 months, and at yearly intervals. In 653 COPDpatients and in all asthmatics, the frequency of vertebral fractureswas assessed at baseline and at the end of the treatment period.No statistically signi®cant difference in BMD and in the frequencyof vertebral fractures was recorded between patients treated withPulmicort Turbuhaler1 and control patients. After long-termtreatment with BUD, no signi®cant effect could be detected onBMD or frequency of vertebral fractures in asthmatic patients orin patients with COPD compared with control patients.

Estimated differences between groups for change (%) in BMD over 2years. Asthmatic patients

BUD vs. Est diff. Lower Limit Upper Limit p-value

Control CI CIL2-L4 ±0.35 ±1.46 0.76 0.5380Fem. Neck ±0.70 ±2.00 0.60 0.2900

Estimated differences between groups for change (%) in BMD over 3years. COPD patients

L2-L4 ±0.52 ±1.91 0.88 0.4667Fem Neck ±0.87 ±2.58 0.85 0.3205

252 (228). BONE MINERAL DENSITY IN WOMEN WITH COLLES'FRACTURE. A CASE CONTROL STUDY

E. Kanterewicz, A. Yanez, A. Perez-Pons, I. Codony, L. Del Rio,Hospital General De Vic and Cetir Medical Center, Barcelona,Spain

Colles' fracture in postmenopausal women has been linked withlumbar and femoral osteoporosis. However, the direction of theassociation has not been not clearly established.

Objectives: To evaluate the association between Colles'fracture and low bone mineral density (BMD).

Methods: We undertook a case-control study including 58postmenopausal patients with recent Colles' fracture and 83population-based controls of similar age and menopausal status.Age of participants ranged from 45 to 80 years. BMD wasmeasured by DXA (Lunar Expert) at the non-fractured wrist,lumbar spine and hip. WHO criteria (t-score <2.5 SD) were used tode®ne osteoporosis.


Results: Cases were, on average, older than controls (mean age65.8 years vs. 58.7, p<0.05). Mean body mass index (BMI) was thesame in both groups (27.2 kg/m2). BMD was signi®cantly lower incases than controls for all three areas (p<0.001). Osteoporosiswas more prevalent in cases than in controls at wrist (60% vs.35%, p<0.001), lumbar spine (47% vs. 20%, p<0.005) and total hip(19% vs. 6%, p<0.005). Osteoporosis (at lumbar spine and/or hip)remained signi®cantly associated with Colles' fracture: (OR 2.3,95% Cl 1.1±5.1) after adjusting for age and BMI in a multivariateanalysis.

Conclusions: Colles' fracture in postmenopausal women isassociated with osteoporosis in other areas commonly affectedby osteoporosis as well as osteoporosis of the forearm.

253 (229). T-SCORE IS USEFULL TO DETERMINEPROBABILITY OF RISK OF VERTEBRAL FRACTURES BY QCTIN ELDERLY PATIENTS

S. Kudlacek, O. Freudenthaler, J. WeissboÈ ck, H. Resch, B.Schneider, R. Willvonseder, Med. Dep. Barmherzige Bruder &Ludwig Boltzmann, Inst. of Aging Research, Vienna, Austria

Bone mineral density determined by the DEXA (Dual X RayAbsortiometry) method is expressed as T-Score and/or Z-Score.T-Score has been accepted to classify osteoporosis of post-menopausal females. QCT has remained the gold standard ofbone mineral density measurement but it is uncertain if T-Scoreclassi®cation can be adopted from results obtained by the DEXAmethode. We have determined bone density by QCT andvertebral fractures in 534 postmenopausal females (60.9�8years, median 60; 40±83). Statistical analysis was performed toevaluate the predictive value of fracture probability between QCT(mg/cc), T-Score and Z-Score. ROC analysis and differences ofAUC (area under curve) were calculated by a non-parametriccontrast test. We found an overlap of QCT, T-Score and Z-Scorein women beow age 55. When the whole study populationincluding women up to 83 years was calculated, QCT and T-Scorewere superior. Occurence of vertebral fractures can be explainedby T-Score and QCT (mg/cc) in 90%, by Z-Score in 77%(p50.0001). Our results demonstrate that T-Score classi®cationis suitable for the QCT method to determine probability of fracturerisk. If the same score classi®cation can be adopted remainsuncertain.

254 (230). PREDICTING BONE MASS IN PREADOLESCENTGIRLS

C. K. Kwoh, E. Trapl, L. Morgan, G. Warner, Case Western Res. U.and DVAMC, Cleveland, OH, USA

We examined predictors of bone mass in a cohort of 8 to 10 yearold girls. Bone mass was assessed using quantitative heelultrasound (QUS). Bone mass parameters included Bone Ultra-sound Attenuation (BUA), Speed of Sound (SOS) and a calculatedstiffness index (STIFF). Girls with chronic diseases or onmedications known to affect bone mass were excluded.Assessment included, height, weight, Tanner stage, dietarycalcium intake by 3-day food diary (CA), and level of weightbearing activity (WBA).

The mean age of the 160 girls was 9.3�0.6 years (mean�sd) and91% were white. Forty percent were in pre-puberty or earlypuberty and 88% were in mid-puberty. Anthropomorphic char-acteristics were height 1.4�0.07 m, weight 36.5�9.0 kg, and leanbody mass 28.9�7.7 kg. Mean bone mass parameters were94.4�11 for BUA, 1538�23 for SOS, and 73.7�12 for STIFF. Meandietary CA by food diary was 1090�442 mg/day and mean WBAwas 2.9�5.2 hours/week. Level of WBA (by tertiles) was asigni®cant predictor of SOS and STIFF after controlling for

Tanner stage, weight and shoe size, but dietary CA was not. Incontrast, for BUA, neither dietary CA or level of WBA weresigni®cant predictors after controlling for anthropomorphicparameters.

The results of this cross-sectional study suggest, that prior topuberty, the level of WBA seems more important than dietary CAin the determination of QUS parameters.

255 (231). EVALUATION OF DUAL-X-RAY ABSORPTIOMETRYAND QUANTITATIVE ULTRASOUND IN POLISH WOMEN

P. LeszczynÄ ski, J. K. Lacki, S. H. Mackiewicz, Department ofRheumatology, University School of Medicine, Poznan, Poland

Objective: The aim of our study was to analyze BMD of theforearm, lumbar spine, hip and BUA and SOS of the calcaneus inPolish women.

Materials and methods: A sample of 297 healthy women,average age 55.0�10.3 yrs (range 27 to 81 yrs) were involved inthe study. BMD of the forearm was measured by DXA using DTX±200 and QUS parameters by DTU-ONE (all systems produced byOsteometer Medi-Tech A/S Denmark). BMD of lumbar spine andhip were measured by DXA using ECLIPSE densitometer (NOR-LAND Medical Systems, Inc., Fort Atkinson, WI).

Results: Average BMD values of the forearm (BMDF), lumbarspine (BMDL) and hip (BMDH) were: 0.408�0.069g/cm2,0.920�0.139 g/cm2, 0.766�0.105 g/cm2 (respectively). AverageBUA and SOS values were: 48.4�8.3 db/MHz and 1542�12 m/s(respectively). We have found signi®cant correlation betweenBUA and BMDF, BMDL, BMDH (r = 0.477, r = 0.398, r = 0.421;respectively) and between BMDF, BMDL, BMDH and SOS(r = 0.379, r = 0.422, r = 0.392; respectively).

Conclusion: QUS and DXA correlate relatively closely but it isquestionable whether the combination of these measurementsimprove the discrimination of women with increased risk offractures.

256 (232). LUMBAR VERSUS THORACIC VERTEBRALFRACTURE LOADS AND CORRELATION WITH IN-SITU ANDEX-SITU DXA

E.-M. LochmuÈ ller, D. BuÈ rklein, N. Krefting, J. Grimm, R. MuÈ ller, F.Eckstein, C.-C. GluÈ er, Universitatsfrauenklinik, LMU Munchen,Germany

The purpose of this study was to determine the correlation ofmechanical failure loads in the thoracic and lumbar spine, and toassess their association with DXA of the lumbar spine in-situ(including soft-tissues) as well as ex-situ.

We studied 130 specimens (79�10 yrs), measuring the BMC of L2±4 with DXA in situ (AP) and ex situ (lateral and AP). Twosegments of the thoracic (Th 5±7 and Th 9±11) and one of thelumbar spine (L 2±4) were tested as a functional unit in an axialcompression test (400 mm/min).

The failure load (but not the failure stress) of Th 6 wassigni®cantly lower than that of Th 10 and L 3. In men, the fractureloads were signi®cantly higher than in women, also after adjustingfor the vertebral cross-sectional area. The correlation of thefracture loads of Th 6 and 10 was r = 0.86, and those of Th 6 andTh 10 with L 3 0.65 and 0.71, respectively. Measuring the BMC inlateral (but not in AP) projection under ex-situ conditionsimproved the prediction of lumbar, but not of thoracic failureloads, compared with the AP in situ measurements (Table 1). Thestudy shows that lateral ex situ DXA of the lumbar spine predictslumbar failure loads with higher accuracy than in situ measure-ments. However, the prediction of thoracic failure loads is similarfor both types of measurements.


Table 1: Correlation (r) of BMC vs. failure load

L3 Th10 Th 6

L2±4 in situ AP 0.73*** 0.74*** 0.68***L2±4 ex situ AP 0.66*** 0.69*** 0.69***L2±4 ex situ lat 0.84*** 0.74*** 0.68***

257 (233). A STUDY OF LUMBAR BONE MINERAL DENSITYAND ITS MORPHOLOGICAL EXAMINATION

E. Matsuyama, Y. Sen, Nara Medical University, Kashihara, Nara,Japan

The purpose of the present study is to investigate the sexualdifference in the morphology of the lumbar vertebrae includingnot only the vertebral body itself but the posterior elements, andto analyze the relation between the morphological change andBMD. All the subjects who consisted of 220 female and 86 maleunderwent roentgenography and the BMD measurement usingDXA method. The BMD of the lumbar vertebrae ranging from L2 toL4 showed little statistical difference between men and women.The measured values of area, width, and height were greater inmen than in women, because of the difference in physicalconstitution. In morphology of the lumbar vertebrae, it wasnatural that all the parameters except the interpedicular distanceshould be smaller in women than in men, because of theirphysical constitution. In order to compare the morphology of thelumber vertebrae, it should be corrected by the size of the skeletalstructure. Therefore we used the relative values to comparebetween each parameter. From the results of this study, weconcluded that the difference between men and women in thesize of the bony structure was natural and that the shape of thevertebrae was the most important factor in the vertebralmorphology. The cross section of the vertebral body to theheight of the vertebral body was smaller in women, and theposterior elements were relatively larger in women than in men, inspite of smaller size of the vertebral body. However, it isimportant that the absolute value of the posterior elements wassmaller in women. Moreover, it is suggested that the real BMD ishigher in women than in men.

258 (234). IS BMD RELATED TO COGNITIVE FUNCTION? APOPULATION-BASED STUDY

D. MellstroÈ m, C. Nyman, K. Landin-Wilhelmsson, L. Hulten, L.Samuelsson, R. Lorentzon, E. Norjavara, O. Johnell, DeptGeriatrics and Internal Medicine, University of Gothenburg, TheNational Service Administration Regional Of®ce, Gothenburg,Depts Orthopedic, UnicaÊ and MalmoÈ , Astrazereca, Lund, Sweden

BMD is useful to predict fractures as well as mortality. Ourquestion is whether BMD is related to cognitive function-intelligence quotient (IQ)? At 18 years of age all men in Swedenmust perform a 2-day test before selection to compulsory militaryservice. 96% attend this test. The test consists of several parts:questionnaire, anthropometric measurements, physical tests(muscle strengths, oxygen uptake etc) and cognitive function.We added a BMD measurement of the right calcaneus, DXA-Calscan. 3,015 men were included. Mean age 18.3 (0.3), weight73.1 (11.0) kg, height 180.4 (6.7)cm. IQ was signi®cantly correlatedto height (r = 0.14), BMD (r = 0.05), muscle strength (r = 0.10),endurance test (r = 0.15). In a covariance analysis BMD remainedsigni®cant in a model with age, height and weight. For quintiles ofIQ BMD was 0.62, 0.64, 0.64, 0.65, 0.64. In young men thesigni®cant correlation with BMD remained also after controllingfor age, height, weight, but was not signi®cant after including

muscle strength in the model. The question is whether BMD is aproxy for another variable like muscle strengths?

259 (235). BONE MINERAL DENSITY (BMD) OF TOTAL BODY(TB) AND LUMBAR SPINE (LS) DURING PUBERTY. A CROSS-SECTIONAL STUDY

O. D. Messina1, A. M. Armatta2, G. L. Araujo1, C. Bianculli2, J. C.Barreira1, J. A. Maldonado Cocco1, 1Rheumatology; 2PediatricsServices, Hospital Dr. Cosme Argerich, Buenos Aires, Argentina

Objective. To establish regional normative values for TB and LS-BMDs and total body bone mineral content (BMC) derived fromhealthy children of both sexes, according to pubertal develop-ment.

Method. 100 Females and 100 Males, aged 10 to 20 years werestudied; 20 at each stage were sexmatched. Pubertal stage (byTanner 5-grading scale) and anthropometric measures wererecorded. Posteroanterior LS-BMD, TB-BMD and TB-BMC weremeasured by DEXA (Lunar DPX L).

Results. Mean values and SD in early and late pubertywere respectively: LS-BMD F: 0.814 (0.120) g/cm2 and 1.154(0.107) g/cm2; M:0.740 (0.111) g/cm2 and 1.114 (0.121) g/cm2; TB-BMD F: 0.914 (0.072) g/cm2 and 1.102 (0.065) g/cm2; M: 0.918(0.058) g/cm2 and 1.184 (0.087) g/cm2; TB-BMC F: 1442 (264) gand 2181 (288) g; M: 1518 (339) g and 2922 (404) g. Increments oneither BMDs and BMC in F among Tanner stages 1±2±3±4 and inM among Tanner stages 1±2 and 3±4±5 were statisticallysigni®cant. Higher mean LS-BMD values were shown in F atstages 3 and 4 than in M at same pubertal stages (p<0.05),re¯ecting the impact on trabecular bone of the earlier femalegonadal maturition and menarche. However, males showedhigher TB-BMD at stage 5 (p<0.05) and higher TB-BMC atstages 2 and 5 (p<0.05) than females at same pubertal stages.High correlations were determined between TB-BMD and weightin M (r: 0.81) and between TB-BMC and weight in both sexes (Fr: 0.85, M r: 0.90) and height in M (r: 0.84).

Conclusions. A large amount of the observed changes on LS-BMD, TB-BMD and TB-BMC during puberty is accounted for bygrowth and pubertal development, showing marked sex differ-ences.

260 (236). DIFFERENCES IN BMD BY USING DIFFERENTDENSITOMETERS OR BY MEASURING DIFFERENT SITES OFSPINE IN OSTEOPOROTIC VERTEBRAL FRACTURES

W. N. Moon1, H. J. Oh2, 1Orthopedic Surgery, SungkjunkawnUniv.; 2Family Medicine, Sungkyunkawn Univ., Samsung CheilHospital, Seoul, Korea

Purpose: This study was done to see whether types of DEXA andlevels of lumbar vertebrae show any differences in makingstandard values of lumbar bone mineral density (BMD) inosteoporotic vertebral fracture.

Materials and Methods: Sixty osteoporotic vertebral fractureout of 462 postmenopausal patients were subdivided into QDRgroup and DPX group according to densitometers (QDR 39patients, DPX 21 patients). The BMD was compared between twogroups. The difference between BMD measured in L3 and thatmeasured in L2±4 was analyzed by student t-test.

Results: There was no difference between BMD of L3 and L2±4standard level (p>0.05). The mean BMD measured by QDR andDPX using L2±4 standard were 0.667�0.127g/cm2 and0.756�0.123g/cm2 respectively and showed statistically signi®-cant difference (p = 0.012).

Conclusion: The type of bone mineral densitometer should betaken into consideration in follow-up of osteoprosis patients and


the L3 standard level might have no superiority over theconventional L2±4 standard level in measuring BMD in osteo-porotic vertebral fracture patients.

261 (237). RELATIONSHIPS OF SPINAL BMD ANDREPRODUCTIVE HISTORY IN POSTMENOPAUSAL KOREANWOMEN

H. J. Oh, W. N. Moon, H. K. Yoon, I. K. Han, SungkyunkwanUniversity, Seoul, Korea

The purpose of this study was to determine the associations ofspinal BMD and reproductive risk factors including YSM, weight,BMI and gravidity and numbers of delivery of Korean menopausalwomen. We have evaluated general characteristics, spinal BMD,and reproductive histories those were assessed by simplequestionnaires of 625 peri and postmenopausal women. Ourresults revealed that: 1) In simple correlation analysis, BMD wasassociated positively with weight (r = 0.261, P<0.01) but negativelywith YSM (r = ±0.47, P<0.001). 2) After controlling age, BMI andYSM, spinal BMD was negatively correlated with numbers ofdelivery (r = ±0.159, P<0.001). 3) YSM, weight, number of deliveryand age were revealed as important factors that predicting spinalBMD by multiple stepwise regression analysis. These resultscould suggest that YSM is one of the most important factor thatpredicting BMD. And numbers of delivery also might affect BMDin postmenopausal women.

262 (238). BONE MINERAL DENSITY IN PATIENTS WITHANOREXIA NERVOSA

J. M. Olmos, J. MeneÂ ndez-Arango, J. L. PenÄ a, J. MartõÂnez, J. A.Amado, J. GonzaÂ lez-MacõÂas, Dpto. Medicina Interna Y (*), S.Psiquiatria Hospital Universitario MarqueÂ s de Valdecilla,Santander, Spain

Objectives: A) To evaluate spinal and femoral bone mineraldensity (BMD) in patients with anorexia nervosa (AN) and itsrelation with clinical data. B) To determine the course of BMD inAN patients after two years of follow-up.

Patients and methods: We studied 25 women with AN (DSM-IV)aged 15±36 years (mean SD; 275). Mean body mass index (BMI)was 15.4�2.3 Kg/m2 and duration of AN was 5.5�3.4 years. BMDwas determined in lumbar spine (LS) and femoral neck (FN) bydual-energy-X-ray absorptiometry (Hologic QDR, 1000). Clinicaland densitometric studies were repeated in 8 patients twoyears later. 38 healthy women (26�5 years) with a normal BMI(20�2 Kg/m2) were utilized as a control group.

Results:

BMD (g/cm2)

Spine Femoral neck

A.Nervosa 0.819�0.124 0.720�0.125Controls 1.009�0.097 0.839�0.110p <0.001 <0.01

Both spinal and femoral BMD were inversely correlated with theduration of AN (r = ±0.43; p<0.05 and r =70.41; p<0.05 respec-tively). BMI was slightly increased (1.3�1.2 kg/m2) in patients after2 years of follow-up. However, BMD decreased in LS andremained unchanged in FN.

Conclusions: A) Women with, AN have a reduced spinal andfemoral BMD that is correlated with the duration of the disease.B) Bone loss in LS persisted in patients followed during twoyears, in spite of the stabilization of BMI.

263 (239). QUANTITATIVE ULTRASOUND AT THE HANDPHALANGES AND ANTHROPOMETRIC PARAMETERS INPOLISH NORMAL CHILDREN AGED 8±13 YEARS: APROSPECTIVE STUDY

W. Pluskiewicz, Z. Halaba, Silesian School of Medicine, Zabrze,Poland

In the prospective study 288 normal Polish children (146 girls and142 boys) aged 8±13 y. were evaluated. The time interval betweenthe 1st and 2nd examination was 12 months � 1 month. Followinganthropometric parameters were measured: height, length of thetrunk with lower limbs, length of the trunk, length of the lower andupper limbs and lateral reach. Bone status was assessed usingquantitative ultrasound (QUS) at the proximal phalanges II-V ofthe hand using DBM Sonic 1200 (Igea, Italy). Amplitudedependent Speed of Sound (Ad-SoS [m/s]) was established.CV% was 0.64. sCV% was 7.13%. Results: In girls the growth rateof height and the growth rate of the length of the lower limbsdiminishes from 10 year while the growth rate of Ad-SoS and thegrowth rate of the length of the trunk increases from 11 year. Inboys we did not observe the increase of the growth rate of Ad-SoS and the length of the lower limbs while the growth rate ofheight and the length of the trunk increases from 11 year. Amongall studied children we have observed positive signi®cantcorrelation only between the growth of Ad-SoS and the growthof height r = 0.58, p = 0.009 and the growth of the lateral reachr = 0.52, p = 0.022. Menstruating girls had higher values of Ad-SoSthan non menstruating but these differences were signi®cant onlyin the group of 12 years (p = 0.009). Concluding, QUS at the handphalanges is able to detect skeletal changes during childhoodand adolescence in Polish normal children.

264 (240). PATHOGENESIS OF COLLES' FRACTURE

S. Pors-Nielsen, Xiong Xie, O. BaÈ renholdt, Hillerùd Hospital,Denmark

This investigation was undertaken after it was observed thatColles' fracture often occurs in women with normal lumbar spineand hip BMD.

Problem: Why do Colles' fractures occur where they do? (in ourhands from 7 to 20 mm from the joint gap).

Or: Are there any speci®c features of the cross-sectionalgeometry or volumetric density at that site?

Material: 70 consecutive post-menopausal women with Colles'fracture, mean age (SD) 64.1 (13.1) and 34 pre-menopausalwomen without fractures ever, mean age 49 (9.7) years.

Methods: 1) Multilayer CT with Scanco Densiscan 1000 using adedicated software was done at an ultradistal site rich intrabecular bone including the typical Colles fracture site, and amore proximal site rich in cortical bone (non-fractured armmeasured). Precision error: less that 0.1% for standardsmeasured daily over 152 days. 2) Transaxial quantitativeultrasonometry (tQUS) was done with Sunlight Omnisense ,measuring speed of sound (SOS) along the long axis of longbones.

Results: Moving proximally mean trabecular volumetric density(TVD) started to decline one cm from the joint gap in both groups;mean cortical thickness of non-fracture and fracture casesstarted to diverge at the same site. The following variables werelower (p<0.001) in the fracture cases: Mean ultradistal TVD, meanultradistal and proximal cortical volumetric density (CVD), meanultradistal and proximal cortical thickness. Cross-sectional totalbone area and cortical bending moment of inertia were identicalin the two groups, suggesting that the deforming force ofColles' fracture has a transaxial direction (fall on outstrchedarm), resulting in a crush fracture, and that it is not a bendingforce. SOS correlated with mean CVD, mean cortical cross-sectional area, and mean cortical thickness at the cortical richproximal site. However, pQCT and tQUS did not correlate


suf®ciently well to justify individual prediction of one from theother.

Conclusions: 1) The deforming force in Colles' fracture is atransaxial one; 2) Colles' fracture is a crush fracture; 3) Speci®ccross-sectional properties of the distal radius are characteristic ofColles' fracture.

265 (241). ABILITY OF A COMBINATION OF pDXAMEASUREMENTS OF THE OS CALCIS AND FOREARM TOSCREEN WOMEN AT MENOPAUSE FOR OSTEOPOROSIS

J. M. Pouilles, F. A. TreÂ mollieres, J. Gauchiran, C. Ribot,Menopause & Bone Disease Unit, Dept of Endocrinology, CHURangueil, Toulouse cedex, France

Axial DXA is currently considered the gold standard for theevaluation of osteoporosis. However, peripheral BMD measure-ments by pDXA using lower cost and portable devices are beingincreasingly used for screening. The aim of this study was toevaluate the usefulness of combining in a same patient twoperipheral measurements (os calcis and distal forearm) using anew pDXA densitometer (PIXI, Lunar) in identifying postmeno-pausal women with axial osteoporosis.

362 healthy postmenopausal women (mean age 54�6 yrs [range40±69]) had BMD measured the same day at the lumbar spine (LS)and femoral neck (FN) by DXA (DPX-IQ, Lunar) and at the os calcisand forearm by pDXA. Moreover, 228 ``young'' normal womenaged 20±39 yrs were measured for T-score calculation. The short-term precision of the PIXI densitometer assessed in 10 subjectswas 1.5 % both for the os calcis and forearm.

23% of the women were classi®ed as being osteoporotic (T-score 4±2.5) using LS and/or FN BMD measurements ascompared to only 5.2% and 6% at the os calcis and forearm,respectively. 25% of women with axial osteoporosis had a normalperipheral T-score (5 ± 1 SD) at the os calcis and 29% of thoseosteoporotic women had a normal forearm T-score. The pDXA T-score threshold value that allowed to detect 95% of women withaxial osteoporosis (either LS or FN) was similar for the os calcisand forearm and was 0. Twenty two to 34% of the women wereabove this cut-off at the os calcis and forearm, respectively andthus could be excluded from further axial measurement.Combining the two peripheral sites slightly improved theperformance of screening in increasing to 43% the number ofwomen who would not need further axial measurement. Of thewomen recommended for axial measurement, only 10% had anormal LS and/or FN T-score (5 ±1) (false positives). The resultsof this study suggest that the ability of pDXA measurements toscreen early postmenopausal women with axial osteoporosis ispoor but might be enhanced when combining 2 peripheral sites.

266 (242). STRUCTURAL-FUNCTIONAL STATE OF BONE INPATIENTS WITH PRONOUNCED FORMS OF SCOLIOTICDISEASE

V. V. Povoroznyuk1, V. Ya. Fishchenko2, D. V. Ulyeshohenko2, V.A. Ulyeshchenko, 1Institute of Gerontology, S. Ukraine; 2UkrainianScienti®c Research Institute of Traumatology and Orthopedics,Health Ministry of Ukraine, Ukraine

Studying of etiology and pathogenesis of scolictic disease plays aleading role in the problem of its treatment. Many national andforeign authors payed great attention to it in their works but anumber of unresolved problems still remain. One of them is toassess the in¯uence of structural-functional state of the bone onthe development of scoliotic disease. To study the structural-functional state of bone in children and adolescents with scolioticdisease depending on the degree of disease's severity, 82patients aged 11±16 years were examined. People examinedwere divided into the following groups; I group 25 girls (mean age± 14.7�0,4 years; height ± 1.59�0.02 m; weight ± 49.0�1.9 kg) and

8 boys (mean age ± 14.6�0.5 years; height ± 1.55�0.03 m; weight ±44.9�2.8 kg) with scoliotic disease of III and IV degree of severity;II group ± 9 girls (mean age ± 13.9�0.6 years; height ± 1.67�0.03 m;weight ± 48.6�4.2 kg). Control group (CG) was made up by girlsstandardized by age, sex etc. To evaluate the structural-functional state of bone tissue ultrasound densitometer``Achilles+'' (Lunar Corp., Madison, WI) was used. Speed ofultrasound spreading (SOS, m/sec), broadband ultrasoundattenuation (BUA, dB/MHz) and Stiffness, index of bone tissue(SI, %) were determined. Compared to CG the most consi-derablechanges in structural-functional state of bone tissue wererevealed in patients with scoliotic disease of III and IV degree ofseverity (girls ± SOS: I group ± 1556�5 m/sec; CG ± 1576�5 m/sec;p<0.05; BUA: I group ± 97.5�1.8 dB/MHz; CG ± 110.1�2.0 dBMHz;p<0.001; SI: I group ± 80.8�1.8%; CG ± 94.8�2.2%; p<0.001; boys± SOS: I group ± 1540�7 m/sec; CG ± 1574�5 m/sec; p<0.05; BUA:I group ± 93.9�3.3 dB/MHz; CG ± 109.6�2,4 dB/MHz; p<0.001; SI: Igroup ± 73.7�4.0%; CG ± 94.2�2.2%; p<0.001). Ultrasonometrydata considerably deteriorated in girls with progression of thedisease's severity: SOS: I-II degree ± 1559�7 m/sec; III-IV degree± 1556�5 m/sec; BUA: I-II degree ± 109.7�3.9 dB/MHz; III-IVdegree ± 97.5�1.8 dB/MHz; SI: I-II degree ± 90.6�3.9%; III-IVdegree ± 80.8�1.8%; p<0.001.

Thus, we have revealed considerable structural-functionaldisorders of bone tissue in patients with scoliotic disease of III-IV degree of severity. Disorders become more pronounced withprogression of the disease.

Decrease in bone density, deterioration of its quality in childrenand adolescents with scoliotic disease make it necessary tocontrol its state constantly by means of densitometry and to carryout the appropriate medical and prophylactic measures.

267 (243). ULTRASOUND DENSITOMETRY INDICES AMONGWOMEN WITH COLLES' FRACTURE IN POSTMENOPAUSALPERIOD

V. Povoroznjuk1, V. Fischenko2, V. Kostuk2, 1Institute ofGerontology AMS Ukraine; 2Medical University of Vinnytcya,Ukraine

This research was aimed at studying the bone tissue state amongwomen with Colles' fracture with aid of the ultrasounddensitometry method. The total of 41 healthy postmenopausalwomen 42±74 years old (62.1�7.5) having Colles' fracture in theiranamnesis (CF) were examined by ultrasound bone densitometer``Achilles+'' (Lunar Corp., Madison, WI). The control groupincluded postmenopausal women without any osteoporoticfractures in their anamnesis (WF), being standardized by age,BMI, etc. The speed of sound (SOS, m/s), broadband ultrasoundattenuation (BUA, dB/MHz) and a calculated ``Stiffness'' index (SI,%) were measured. The main risk factors for the osteoporoticColles' fracture turned out to be a menarche after 15 years, anearly and late menopause. 29.3% of patients with Colles'fractures had a bone tissue stiffness index coinciding with thelimit of fracture risk or under it. There was no revealed relationbetween the age and the ultrasound densitometry indices amongwomen of posmenopausal age without fractures. Only 12.5% ofpatients with Colles' fractures were noticed to have a normalbone tissue. The ultrasound parameters were veritably loweramong postmenopausal women with CF than among WF (SOS:CF ± 1524�28.4; WF ± 1543�24.3, p50.05; BUA: CF ± 102�17.8;WF ± 109�12.0, p<0.05; SI: CF ± 76�14.9; WF ± 35�13.5, p<0.05;all values are the mean SD). It is caused by the decrease of bonetissue mineral density, it's accelerated aging, and the develop-ment of osteopaenia and osteoporosis. The most tangibledifferences in these indices were noticed among the elderlypatients. Colles' fracture indicates osteopaenia and osteoporosisin postmenopausal period. In summary, ultrasound densitometryis an effective screening method to reveal the women of riskgroup having future osteoporotic Colles' fracture in postmeno-pausal period.


268 (244). INTERPRETATION OF BONE DENSITY RESULTS INYOUNG WOMEN

J. Przedlacki, M. Wieliczko, W. Tlustochowicz, J. Matuszkiewicz-Rowinska, K. Ostrowski, National Center of Osteoporosis,Medical University of Warsaw, Warsaw, Poland

The purpose of this investigation was to evaluate theinterpretation of DXA results in young women (age up to 45y, Young-Adult). The BMD result depends on sex, age as wellas on the bone volume, so T-score which is taken as criterionof diagnosis of osteoporosis is simpli®ed parameter only (doesnot depend on body weight, when Z-score depends on it). BMDwas measured in 39 women aged 39.3�6.6 y (20±45 y) with lowbody weight 47.5�2.8 kg (38-arbitrary taken 50 kg) using LunarDPX-L equipment in lumbar spine region. BMI was 18.9�1.4(15.2±23.2). The indication for bone densitometry was prophy-laxis of osteoporosis in 19, bone pain in 12, X-ray suspicion ofosteoporosis in 10, bone fractures in 3, other in 3 women. Bonefractures were recognised in 5 women. Osteoporosis wasdiagnosed in 4, osteopenia in 17 and normal result in 18women on the basis of T-score value (traditional way). When Z-score was taken as the criterion of diagnosis, osteoporosis wasrecognised in 2, osteopenia in 9 and normal result in 28women. The diagnosis was changed in 12 women. We concludethat in young women (aged up to 45 y) the diagnosis of bonemineral disturbances (osteoporosis among others) ought to bebased on Z-score value and not on T-score value. Z-scorevalue ought to be taken as their own peak bone massparameter.

269 (245). TOTAL BODY COMPOSITION IN A CHILD WITHHEPATORENAL TYROSINAEMIA

D. Rigante1, P. Ranieri2, E. Holme3, G. Segni1, P. Caradonna2,1Department of Pediatrics; 2Department of Internal Medicine andGeriatrics, Universita Cattolica Sacro Cuore, Rome, Italy;3Department of Clinical Chemistry, Sahlgrenska UniversityHospital, Gothenburg, Sweden

An adequate nutritional support is ®rstly re¯ected on abalanced total body composition (BC), especially for inbornerrors of metabolism receiving bene®t from dietetic regimens:therefore the evaluation of total BC and of fat/lean massdistribution are essential for assessing a personalized diet oroptimizing therapy.

Hepatorenal tyrosinaemia (HT; fumarylacetoacetase de®ciency,McKusick 276700) is an inherited metabolic disorder (incidence 1:100.000), characterized by hepatic cirrhosis, renal tubulardysfunction and acute porphyria. Children with HT improveremarkably with low Phe/Tyr medical foods and speci®c therapywith NTBC [2-(2-nitro±4-tri¯uoro-methylbenzoyl)±1,3-cyclohexa-nedione].

We report a case of a 6 year and 3/12±old female child, who -atthe age of 3 years, after having reached normal developmentalmilestones- presented signs related to invalidating rickets, whichled to the diagnosis of HT. Since then the child has been treatedwith a Phe/Tyr restricted diet (daily intake of proteins: 1.35 g/kg),Maxamaid X-Phen Tyr-SHS (75 g/day) and NTBC (1 mg/kg/day).She actually has a weight of 21.3 kg (508 centile), a height of 113.5cm (25±508 centile) and total BC has been evaluated with (1)anthropometric measurements of wrist, mid-arm, arm, waist, hip,thigh, mid-thigh, calf circumferences and triceps, biceps,subscapular, abdominal, sovrailiac, anterior/posterior thigh, calfskinfold thicknessess according Brook's equation (softwareMaster Ver. 1.1 Dietosystem) and (2) dual energy X-rayabsorptiometry (DEXA, Hologic QDR 2000) at the lumbar spine(L2-L4) and at the femoral neck. The results are shown in thefollowing table:

Anthropometry DEXA

Fat free mass 15.80 kg (79.39 % of body weight) 15.36 kg (79.9 % of body weight)

Fast mass 4.10 kg (20.60 % of body weight) 4.19 kg (21.1 % of body weight)

We have observed a mildly increased fat mass vs normal forage and sex, both on anthropometric remarks and DEXA. Thenutritional support so far settled seems to have produced anoverall correct growth in terms of total BC in this child after 3years of NTBC therapy. We believe that anthropometry and DEXArepresent useful tools to monitor dietary intake or therapy andtheir impact on BC in children with HT.

270 (246). SIMULTANEOUS DUAL-FEMUR SOFTWARE INCLINICAL PRACTICE USING DUAL-ENERGY X-RAYABSORPTIOMETRY (DXA): VALIDATION OF SYMMETRY

F. Sarter, J. Felt, G. J. Boyd, D. Cla¯in, D. Feiger, D. Schneider, D.J. Sartoris, University of California School of Medicine, San Diego,CA, USA

PURPOSE: To investigate the clinical value of simultaneous dual-femur acquisition software using DXA, with particular reference todegree of side-to-side symmetry, and to generate speci®crecommendations concerning scanning the dominant versusnon-dominant femur at institutions where such advanced soft-ware is currently unavailable.

METHODS: Approximately 400 male and female patients withclinical risk factors for low bone mass referred for two-site (spine,proximal femur) DXA were included in the study population. Allsubjects underwent femoral densitometry utilizing simultaneousdual-femur acquisition software installed on a Lunar DPX-IQpencil-beam tabletop DXA system. Bone mineral content (BMC),projected area (cm2), bone mineral density (BMD), % youngnormal mean, T-score, % age-matched mean, Z-score, neck-shaft angle, and regional % body fat were recorded for the rightversus left sides, with bone regions-of-interest including thefemoral neck, Ward triangle, greater trochanter, proximaldiaphysis, and total proximal femur. Average values for BMD, %young normal mean, T-score, % age-matched mean, and Z-scorewere also documented, along with side-to-side differences.Statistical analysis with particular reference to symmetry wasperformed using Minitab version 12 software.

RESULTS: Patients ranged in age from 27±93 (mean 63) years,with height ranging from 60±74 (mean 65.5) inches and weightranging from 90±263 (mean 142) pounds. Representative rangesand mean values (total proximal femur) for the various measuredparameters were as follows:

%FAT N-ANGLE BMD %YOUNG T-SCORE %AGE Z-SCORE

R MIN 5.7 49.0 0.42 39.0 ±5.2 46.0 ±3.8

R MAX 34.4 61.0 1.194 110.0 0.8 118.0 1.4

R MEAN 19.9 54.0 0.844 83.5 ±1.38 95.3 ±0.34

L MIN 8.3 49.0 0.501 50.0 ±4.2 65.0 ±2.5

L MAX 36.0 62.0 1.199 110.0 0.9 119.0 1.02

L MEAN 21.0 55.2 0.853 84.3 ±1.31 96.3 0.88

No signi®cant dierence was found between regional % bodyfat, BMD, % young normal mean, T-score, % age-matched mean,and Z-score for the two sides (p = 0.19 to 0.65). Signi®cantasymmetry was found between neck-shaft angle on the two sides(p = 0.0036). The right-left dierence in BMD ranged from 0±0.229(mean 0.036) g/cm2.

CONCLUSION: The results of this investigation generallysupport previous studies indicating clinically insigni®cant differ-ences between dominant versus non-dominant proximal femurDXA results. However, dual-femur acquisition may be necessaryin certain patients where signi®cant side-to-side asymmetry mayoccur. Such situations may be encountered in the setting of


severe scoliosis, hemiparesis or hemiparalysis, unilateral arthritisof the hip joint, leg-length discrepancy, and a variety ofcongenital/developmental deformities.

271 (247). RESULTS OF THREE YEARS OF BONE DENSITYTESTING IN SOUTHEASTERN MICHIGAN

L. Scheiber, L. Torregrosa, P. Bereziuk, Henry Ford-WyandotteHospital, Wyandotte, MI,

Objective: The purpose of this study was to analyze three yearsof bone density testing performed in southeastern Michigan.

Methods: Henry Ford-Wyandotte Hospital acquired a HologicQDR 1000 and opened an osteoporosis testing center in April of1996. In the ®rst three years of operation ninety-®ve physiciansreferred 4,147 patients to the center for a central bone densitytest. Of those tested 3,955 were women and 192 were men.

Results: Using NOF/WHO criteria for the diagnosis ofosteoporosis, of the 3,890 consecutive Caucasian women ages19 to 94 yo scanned, 1,696 or 44% were osteoporotic, 1,579 or40% were osteopenic, and 615 or 16% were normal. Of the 1,696Caucasian women that were osteoporotic 333 or 19% were undersixty years of age. Of the 1,579 osteopenic women, 649 or 41%were under sixty years of age. In the group of women seventyyears of age and over 62% were osteoporotic and 32% wereosteopenic, only 6% were normal. One hundred ninety Caucasianmen between the ages of 24 to 92 yo were scanned. Of these, 78or 41% were osteoporotic, 73 or 38% were osteopenic and 39had a normal scan. Fifty-one African Americans were scanned. Ofthe forty-nine African American women tested seventeen or 35%were osteoporotic, twenty-two or 45% were osteopenic and tenhad a normal scan. Two African American men tested, both wereosteopenic. Twelve Hispanic women were tested with three beingosteoporotic, eight being osteopenic and one normal. Four Asianwomen were tested with one osteoporotic, two being osteopenicand one normal.

Conclusion: In our community osteoporosis is clearly not adisease isolated to our Caucasian senior citizens. DXA scanninghas facilitated early identi®cation and treatment of osteoporosisand osteopenia in our community in a variety of races and inindividuals ranging from 19 years old to 94 years of age.

272 (248). IS THERE A NEED FOR FOREARM BMDSTANDARDIZATION? A DIAGNOSTIC COMPARISON OF SIXDENSITOMETERS

J. A. Shepherd, X. G. Cheng, C. F. Njeh, T. Fuerst, M. Grigorian, J.O. Toschke, H. K. Genant, Osteoporosis & Arthritis ResearchGroup, University of California, San Francisco, CA, USA

As part of an effort understand the differences in device-dependent osteoporotic diagnosis, 101 women, aged 20 to 80(ca. 16 per decade) were scanned on six forearm bonedensitometers: the Aloka DCS600EX, the Hologic QDR4500A,the Lunar PIXI, the Osteometer DTX200, the Pronosco X-Posure,and the Norland pDEXA. The scans were analyzed using themanufacturers' suggested methods.

Comparisons were confounded due to large differences in theROI size and placement. The number of ROIs reported for a singlescan by each device varied from one to 12. The magnitude ofBMD change versus age for similar ROIs compared well. Thetable contains the R^2 values for either the only available ROI(radius+ulna), the most distal radius+ulna ROI (QDR4500,pDEXA), or the distal radius (DCS600). Comparative linearregression slopes of the T-scores differed by less than 10% toover 50%. There was no general rule found to predict agreementof T-scores based on ROI or manufacturer most likely due to theinter-relationship of ROI de®nitions and reference populations. Inconclusion, systemic and device-dependent T-score disagree-

ment exists such that standardization is necessary for diagnosticuniformity.

R^2 Values DTX200 PDEXA PIXI QDR4500 X-Posure

DCS600EX 0.77 0.73 0.85 0.82 0.64DTX200 0.61 0.78 0.74 0.57PDEXA 0.82 0.92 0.51PIXI 0.89 0.68QDR4500 0.57

273 (249). PREDICTION OF FRACTURES IN THE EARLYPOSTMENOPAUSAL PERIOD; USE OF DUAL ENERGY X-RAYABSORPTIOMETRY (DXA) AND QUANTITATIVE ULTRASOUND(QUS)

A. Stewart, D. M. Reid, Osteoporosis Research Unit, Dept ofMedicine and Therapeutics, University of Aberdeen, Aberdeen,UK

QUS has been shown to be a predictor of osteoporotic fracturesin the elderly. Studies in younger women are rare. 1000 womenunderwent QUS measurement using a Walker Sonix UBA 575,measuring broadband ultrasound attenuation (BUA) in 1990±1and DXA scan of spine (L2-L4) and hip. Beginning Dec. 1997 thesewomen were asked for a follow-up scan, and completed aquestionnaire with regard any fractures they had sustained sincebaseline. 81 women have a fracture of any site/trauma from a totalof 742 attending for follow-up. Relative risks (RR) (adjusted forage, body mass index and years postmenopause) werecalculated and are as follows (RR with 95% CI for one SD): BUA1.52 (1.17±1.96), L2L4 1.70 (1.28±2.26), Neck 1.47 (1.11±1.94).Combining both DXA and QUS slightly improved the RR's(L2L4*BUA 1.80 (1.36±2.39), Neck*BUA 1.70 (1.28±2.26)). If weexamine the fractures which have occurred only at the site ofwrist, ankle or hip and repeat the adjusted RR we ®nd the valuesare as follows: BUA 1.49 (1.05±2.13), L2L4 1.70 (1.16±2.49), Neck1.47 (1.00±2.15), L2L4*BUA 1.79 (1.21±2.63), Neck*BUA 1.68(1.14±2.49). ROC analysis showed areas under the curve (AUC)ranging from 0.56 To 0.62 but there was no signi®cant differencein the AUC's. In conclusion DXA and BUA can predict those whohave fractures in the early postmenopausal period regardless oftrauma level.

274 (250). THE PREVALENCE OF LOW BONE MINERALDENSITY IN ELDERLY MEN RESIDING IN NURSING HOMES

N. Toofanny, J. Voytas, M. E. Maddens, D. Kowalski, WilliamBeaumont Hospital, Royal Oak, MI, USA

Nursing home residents are at high risk of developing fractures.Little attention has been given to the possibility of low bonemineral density in men. We studied the prevalence of osteopeniaand osteoporosis and evaluated the associated fracture risk inelderly men residing in nursing homes. Ninety three men aged 64to 101 years were recruited from ®ve skilled nursing facilities.Using the Lunar PIXI Bone Densitometer (version 1.43), bonemineral density of the right calcaneus was measured. Charts werereviewed to determine age, current use of medications known toaffect bone density, and history of falls and fractures over theprevious 12 months. Using the Lunar criteria equivalent forosteopenia and osteoporosis (T-score ±0.6 to ±1.6 for osteopeniaand below ±1.6 for osteoporosis), 49 (53%) had osteoporosis and21 (23%) had osteopenia. Of the 37 men (40%) who had a historyof falls, 19 (51%) suffered at least one fracture and of these, 17(89%) were either osteopenic or osteoporotic. Of the 71 men(76%) who were osteopenic or osteoporotic, 11 (16%) were onsome type of bone strengthening agent. In conclusion, this high


prevalence of low bone mineral density in male nursing homeresidents and the associated increased fracture risk calls forfurther studies to delineate proper evaluation and management ofbone loss in elderly male nursing home residents.

275 (251). GLUCOCORTICOID-INDUCED CORTICAL BONEPOROSITY IN POSTMENOPAUSAL PATIENTS WITH ASTHMA

H. Tsugeno, B. Goto, M. Okamoto, S. Harada, T. Mifune, Y.Hosaki, F. Mitsunobu, K. Ashida, Y. Tanizaki, 1Misasa MedBranch, Okayama Univ Med School, Tottori, Japan; 2CalciumResearch Institute, Osaka, Japan

In a previous study, we demonstrated that chronic administrationof systemic glucocorticoids decreases cortical bone mineraldensity (BMD) and induces development of pathologic fracturesin asthmatic patients. To investigate cortical bone porosity, westudied cortical bone volume, BMD, bone strength, and fracturesin patients with asthma in this report.

A total of 82 postmenopausal asthmatic patients were enrolledin the study. Vertebral fractures were diagnosed via plain spinalradiograms. Peripheral quantitative computed tomography(pQCT) was used to measure cortical BMD, relative corticalvolume, and Strength Strain Index (SSI). Multiple regressionanalysis and other statistical analyses were performed.

Lifetime cumulative dose of glucocorticoids was related tocortical BMD, relative cortical volume, SSI, and the number ofvertebral fractures. The cortical volume-density relationshipappeared to remain constant regardless of systemic glucocorti-coid administration. The number of vertebral fractures correlatedhighly with cortical BMD, relative cortical volume, and SSI at theradius.

In conclusion, systemic glucocorticoid administration de-creases cortical bone density, cortical bone volume, and bonestrength. Glucocorticoid administration appears to be respon-sible for the process of cortical bone porosity at both endostealand intracortical sites. Given that both cortical bone density andvolume provide bone strength, cortical bone porosity was seen tocontribute to glucocorticoid-induced bone strength loss andfractures.

276 (252). ASSOCIATION BETWEEN KYPHOSIS AND ACTIVITYOF DAILY LIVING IN JAPANESE ELDERLY WOMEN

I. Tsuritani, R. Honda, F. Sun, Y. Noborisaka, M. Ishizaki, Y.Yamada, Department of Hygiene, Kanazawa Medical University,Uchinada, Ishikawa, Japan

To determine the in¯uence of kyphosis, which could be caused byosteoporosis, on QOL, we investigated the relationships betweenkyphosis and, higher level activity of daily living (ADL) and backpain in elderly women in a community.

Subjects: 128 women, aged 65±88, participating in a physicalfunction survey conducted by the local community.

Methods: Kyphosis index (KI) was calculated as the maximumhorizontal length of the upper back bow divided by the verticalone, using ¯exicurve measurement. Height at age 20 years, use ofwalking aid (including stick) and degree of back pain during lastone year were inquired about by interview. Higher level ADL wasassessed by an Index of Competence developed by TokyoMetropolitan Institute of Gerontology, and the questionnaire wascomposed of questions about ability of 13 kinds of actions in dailylife: 5 for self-maintenance (Am), 4 for intellectual activity (Ai) and4 for social role (As). The answers were counted `1' for ``Yes'' and`0' for ``No'', and the total was calculated as ADL scale (0~13).Statistical analysis was used by ANCOVA.

Results: Mean[SD] of KI was 0.102{0.042] in the subjects. KIincreased signi®cantly with age (r = 0.479, p<0.001). There was asigni®cant correlation between self-reported height loss and KI(r = 0.378, p<0.001). 13 women who used a walking aid, were

signi®cantly older than the others. Neither back pain nor use ofwalking aid was related to KI. Am scale (0~5), Ai scale (0~4), Asscale (0~4) and ADL scale all decreased signi®cantly with age andKI. After adjusting for age and use of walking aid, KI wasassociated negatively and signi®cantly with Am scale, As scaleand ADL scale (p<0.001, p<0.05 and p<0.01).

Conclusion: The present results suggested that progression ofkyphosis was associated with decrease in higher level ADL inelderly women.

277 (253). BONE DENSITOMETRY IN CHILDREN WITHDIFFERENT TECHNIQUES; DISCREPANCIES ANDINTERPRETATION

C. van Kuijk1, R. R. van Rijn2, M. H. Lequin2, I. M. van der Sluis3, S.M.P.F. de Muick Keizer-Schrama3, S. G.F. Robben2, 1Departmentof Radiology, Academic Medical Centre, Amsterdam;2Departments of Pediatric Radiology and PediatricEndocrinology, Academic Children's Hospital, Sophia,Rotterdam, The Netherlands

Introduction: Several different techniques for bone densitometryin children are used in clinical practice. These techniques includeplanar X-ray measurements (DXA); volumetric measurements(QCT and volumetric radiographic absorptiometry (RA); andultrasound measurements (QUS). Questions can be raised withregard to the applicability of these techniques in a pediatricpopulation. We therefore compared several techniques in ahealthy Dutch Caucasian population and compared them withexisting data from our own population and from the literature.

Methods: In our study we have enrolled 278 Dutch Caucasianboys, (range 5.0 to 19.5 years), and 294 Dutch Caucasian girls,(range 5.2 to 19.9 years). Radiographs of the hand were made fordetermination of skeletal age and for volumetric RA. Tibial QUSwas performed in these patients, In a previous study a similarpopulation was used for DXA measurements.

Results: Tibial QUS showed an increase of speed of sound withincreasing age, comparable to DXA ®ndings. However, volumetricRA showed a stable low density until puberty, with a rapidincrease during the pubertal years. The latter ®nding is consistentwith QCT data as reported in the literature as well as data from(calculated) volumetric DXA.

Discussion: True bone density seems to be low and stable untilpuberty; a ®nding that explains the incidence of greenstickfractures in this population. During puberty there is a rapidincrease in true density. Normal values generated by planartechniques (e.g. DXA) and also with tibial QUS show bothchanges in bone density and bone size, which renders thesetechniques dif®cult to interpret in clinical practice.

278 (254). COMPARISON OF QUANTITATIVE ULTRASOUNDPARAMETERS OF THE OS CALCIS BETWEEN YOUNGATHLETES AND AGE-AND SEX-MATCHED NONATHLETHICCONTROLS

B. WuÈ nsche1, K. WuÈ nsche2, H. FaÈ hnrich2, R. Venbrocks1, W.Kaiser2, 1Clinic of Orthopaedics; 2Institute of Radiology,Friedrich-Schiller-University Jena, Germany

Aim: Effective primary preventive treatment of Osteoporosis hasto begin obtaining a higher peak bone mass in childhood andadolescence also by physical activity. The aim of our investigationwas to examine differences between the Ultrasound Boneparameters Broadband Ultrasound Attenuation (BUA) andSpeed of Sound (SOS) in athletes and nonathletic controls.

Method: Parameters of athletes going in for football, wrestling,judo and athletics were compared with those parameters of alarge normal healthy population. The right heel was measuredusing the Bone Sonometer ``SAHARA'' (Hologic).


Results: # p50.05 (Mann-Whitney-U test).

sports / age no. SOS (m/s) BUA (dB/MHz)

football/ 11±16 39 1581.5�22.8 1.7�12.3control-group 857 1562.2�28.7 # 2.9�14.1 #athletics/11±15 17 1588.5�26.8 7.1�17.8control-group 752 1561.0�28.2 # 2.0�13.4 #judo/ 11±16 y. 21 1577.0�18.0 6.3�11.2control-group 680 1560.3�28.0 # 3.2�14.5wrestling/12±17 16 1567.7�21.3 5.7�14.6control-group 770 1561.0�28.5 4.2�15.0

Signi®cant higher values of SOS and BUA were found inathletes of football and athletics, no signi®cant dierence was seenin athletes of judo and wrestling.

Conclusion: High-impact weight-bearing activity like footballand athletics appears bene®cial for bone accretion because ofevaluation of signi®cant higher quantitative bone parameters inthese athletes. This difference is not so well de®ned in morebrawn-intensive physical activity with a high static muscle-load.

279 (255). SEX-RELATED DIFFERENCES OF QUANTITATIVEULTRASOUND PARAMETERS OF THE OS CALCIS INCHILDREN AND ADOLESCENTS

K. WuÈ nsche1, H. FaÈ hnrich1, S. Vogt1, B. WuÈ nsche2, W. A. Kaiser1,1Institute of Radiology; 2Clinic of Orthopaedics, Friedrich-Schiller-University Jena, Germany

Objective: In earlier investigations standard values of BroadbandUltrasound Attenuation (BUA) und Speed of Sound (SOS) inhealthy children and adolescents were evaluated. Are sex relateddifferences in the age range from 6±18 years detectable?

Method: BUA and SOS were measured in 3299 healthy childrenand teenagers (1623 girls and 1676 boys). age range 6±18 years,using the bone densitometer ``SAHARA'' from Hologic. Childrenwith diseases in¯uencing bone metabolism were excluded.

Results: BUA values were signi®cantly higher in 9 and 11 yearsold boys than in girls. Between the age groups 13, 14, 15, 16 and17 years BUA was signi®cantly higher in girls than in boys. SOSwas nearly constant during ageing for both sexes. SOS valueswere signi®cantly higher in 7 years and 13, 14, 15, 16 and 17 yearsold girls than in boys.

Conclusion: The above mentioned differences are probablycaused by the different onset of puberty, the different onset ofgrowth phases and the effects of estrogen or related factors onmuscle-bone relationship. This corresponds to the studies ofRubin et al, [1993] and Ferretti et al, [1998]. The observedsigni®cant sex-related differences in our study support thehypothesis that quantitative ultrasound bone densitometry issensitive to detect small changes of bone mineral density inchildhood and adolescence.

Osteoporosis ± Diagnosis

280 (256). QUANTITATIVE ULTRASOUND (QUS) AT THEFINGER PHALANGES IN PATIENTS WITH CERVICAL ANDTROCHANTERIC HIP FRACTURES

F. E. Alenfeld, U. Baldin, D. Felsenberg, 1Osteoporosis andArthritis Research Group, University Hospital Benjamin Franklin,Germany; 2Free University Berlin, Germany

The purpose of this study was to investigate whether QUSmeasurements at the ®nger phalanges enable to separatepatients with hip fractures from age matched controls andtrochanteric from cervical hip fractures. We measured speed ofsound through the distal metaphysis of the proximal ®nger

phalanges Digit II-V in 43 patients with recent (<3 weeks) hipfracture (21 cases of cervical hip fractures, 22 cases oftrochanteric fractures). The DBM Sonic 1200 (Igea, Italy) wasused, double measurements at the non-dominant hand wereperformed. QUS results of the hip fracture group were comparedto german reference data (Osteop Int 1998 (5)). There was nosigni®cant difference in the compared hip fracture groupsconcerning age, body height, weight and body mass Index.

Table 1: QUS parameters for hip fracture patients and controlsexpressed in Mean � 1SD and in Z-scores of patients comparedwith controls *=p<0.01 vs. controls SOS through the ®ngerphalanges was signi®cant ly lower in patients with hip fracturesthan in controls. SOS did not differ signi®cantly between the twohip fracture groups (T-Test n.s.) however there was a trendtowards lower SOS values in patients with trochanteric hipfractures. We conclude that QUS at the ®nger phalanges is avalid method to diagnose generalized osteoporosis.

Trochanteric Cervical Controls

SOS (m/s) 1778�114* 1790�94* 1905�52Z-Score (SD) ±2.44 ±2.21

281 (257). CALCANEAL ULTRASOUND AND PHALANGEAL DXACOMPARED TO DXA OF THE HIP AND SPINE FOROSTEOPOROSIS DETECTION

D. M. Bachman, P. E. Crewson, Metrowest Medical Center,Framingham, MA, USA

Peripheral screening devices are attractive alternatives to axialdual x-ray absorbtiometry because of portability and lowerexpense. We evaluated the ability of two such devices to detectosteoporosis diagnosed by spine and hip DXA.

453 Caucasian women (mean age 61) consecutively scheduledfor spine and hip DXA on a Lunar DPX-L had heel ultrasound on aLunar Achilles and 180 also had phalangeal DXA measured on aShick Accudexa.

T scores (standard deviation from young adult mean) weredetermined using each device's data base. By either spine, hip orboth, 48% were osteopenic (T ±1.0 to ±2.49) and 26% wereosteoporotic (T less than 2.5). For the osteoporotic group, 43%were less than 2.5 by ultrasound stiffnes index and 24% byphalangeal DXA. If a cutpoint of ±1.0 was used, 55% and 32% ofosteoporotic patients were detected.. On the other hand, 9% ofheel measurements and 8% of digit measurements were at least1.0 S.D. less than the spine and hip measurements. We concludethat while peripheral screening studies will detect some peoplewith osteoporosis, the number is substantially less than thosedetected by axial DXA. We found heel ultrasound more sensitivethan ®nger DXA at all age groups. Sole reliance on theseperipheral devices would identify fewer people as being at riskfor osteoporotic fracture and would be likely to alter treatmentrecommendations for many patients.

282 (258). FRACTAL ANALYSIS OF TRABECULAR BONETEXTURE ON RADIOGRAPHS: EFFECTS OF AGE ONMICROARCHITECTURAL CHANGES

C. L. Benhamou, S. Poupon, L. Pothuaud, R. Niamane, R. Harba,E. Lespessailles, Institut de Prevention et de Recherche surI'Osteoporose, Orleans, France

We have previously developed and validated a fractal analysis oftexture on plain radiographs. Bone alterations are characterizedby a fractal dimension (D) increase. We have studied a populationof 627 control women from 21 to 93 years. Calcaneus x-rays wereperformed following standardized conditions, and radiographic


®lms scanned to obtain texture images. Fractal analysis wasapplied and results expressed by H exponent (H=2-D). Subjectswere classi®ed by range of 10 years, from 20±30 years to 90±100years (Figure). This study suggests that fractal evaluation is ableto characterize age induced changes with an increase in H foryoung subjects followed by a decrease in H after 40 years.

283 (259). PREVALENCE OF OSTEOPOROSIS IN A GENERALPOPULATION

G. K. R. Berntsen1, V. Fùnnebù2, A. J. Sùgaard3, I. Njolstad4, A.Tollan5, J. H. Magnus6, 1Univ of Tromsù, Norway; 2Univ ofTromsù, Norway; 3Univ of Oslo, Norway; 4Univ of Tromsù,Norway; 5Central Hospital, Hamar, Norway; 6Univ of Tromsù,Norway

Our objective was to determine the osteoporosis prevalence bycurrently suggested de®nitions in a general population. Weinvited all men aged 55±74, women aged 50±74 and 5±10%representative samples of remaining age groups aged 25 or moreyears, living in Tromsù to forearm bone densitometry with SXA. Inall 3062 men and 4558 women aged 25±84 years (response rate80.3%) took part. Osteoporosis de®nitions:1) WHO1 BMD <±2.5standard deviations (SD) below female peak BMD. 2) WHO2: BMD<72.5SD below mean pre-menopausal BMD. 3) NHANES: BMD<72.5SD below male peak BMD. 4) Age-speci®c: BMD 5±1 SDbelow the 10 year age- and sex-group BMD mean. 5) UKconsensus: Osteoporosis diagnosis by either NHANES or Age-speci®c criteria. We applied WHO1, WHO2 and Age speci®ccriteria to women, and WHO1, NHANES, Age speci®c and UKconsensus criteria to men. Prevalences were standardised toWHO European standard population. Depending on de®nition,osteoporosis was found in 24%±32% of all women aged 550 andin 2±20% of all men aged 550. The WHO1-de®nition for womenand the UK consensus de®nitions for men yielded the highestprevalences. Of women aged 570 years, 65% were osteoporoticand only 10% had normal BMD (WHO1). Medicalisation of elderlywomen may be an important adverse effect of the WHOosteoporosis de®nition.

285 (261). OSTEOPOROSIS RISK ASSESSMENT USING POINT-OF-CARE TECHNOLOGY

R. Branton1, M Buxton-Thomas, B. Gray, C. Mangion, D.Percival1, C. Moniz, 1King's College Hospital, London, UK;2Provalis Diagnostics, Flintshire, UK

Heel ultrasonography (HUS) performed in a clinic offers a morecost-ef®cient osteoporosis risk assessment compared to DXA,especially in elderly women with bony or calci®cation artefacts.We studied the use of HUS (Achilles, Lunar) and biochemicalmarkers in an Osteoporosis Clinic. 86 elderly women (mean age75yrs, 70±90) were measured prior to consultation. Each provideda second-void, fasting urine sample on which CTx was tested byOsteosalTM (Provalis Diagnostics Ltd) a rapid point of care test. AT-score above +2.5 indicated increased bone resorption. Urinesamples were also measured for CTx using ELISA (CrossLapsTM,

Osteometer BioTech A/S). Using HUS, 47% had a T-score of572.0 (range ±2.0 to ±4.6) and were classi®ed as osteoporotic,34% ranged from ±1.0 to 1.8 and were classi®ed as normal and17% ranged from ±1.0 to ±2.0 and were classi®ed as intermediate.Correlation between Osteosal and ELISA was 0.87 but neithercorrelated with HUS. Those with normal HUS were re-assured andgiven life-style advice but those with Osteosal >2.0 wereprescribed calcium and vitamin D. The osteoporotic group weretreated with bisphosphonates and/or calcium and vitamin D.Osteosal measurements were repeated at 3 months to monitorresponse, 80% showed a signi®cant reduction in value. Theintermediate group were referred for DXA. HUS and Osteosal inthe clinic enables a rapid, relatively cheap and effectiveosteoporosis risk evaluation of elderly patients. Osteosal enablestreatment decisions and monitoring of responses at earlier timepoints. Point of care tests using HUS and bone markers enablesan effective and cost-ef®cient one-stop clinical service.

286 (262). COMPARISON OF THE FEMORAL GEOMETRICVALUES MEASURED BY X RAY RADIOGRAMS AND DEXA INMALE AND FEMALE CASES

H. T. Calis1, M. Eryavuz1, M. Calis2, G. Can3, H. Sayman4,1Physical Therapy and Rehabilitation Departmant, IstanbulUniversity Cerrahpasa Medical Faculty, Istanbul, Turkey;2Physical Therapy and Rehabilitation Departmant, Sisli EtfalEducation and Research Hospital, Istanbul, Turkey; 3PublicHealth Departement, Istanbul University Cerrahpasa MedicalFaculty, Istanbul, Turkey; 4Nucleer Medicine Departement,University Cerrahpasa Medical Faculty, Istanbul, Turkey

Femoral geometric measurements are suggested to be importantin the evaluation of the risk of hip fracture. In this study, femoralgeometric measurements of 34 males and 34 postmenauposalfemales were examined and compared. None of them have hadany hip fracture in their lives and all of them were older than 50ages. In all cases bilateral hip axis length (HAL), femoral neck axislength (FNAL), acetabular width (AW), femoral head width (FHW),femoral neck width (FNW), femoral shaft width (FSW), inter-trochanteric width (ITW), medial femoral neck cortical bonethickness, medial femoral shaft cortical bone thickness, lateralfemoral shaft cortical bone thickness, femoral neck-shaft angle indegrees(N-SA) were measured on AP plain pelvic Xray radio-grams and manual HAL, FNW, FSW, ITW,N-SA on Hologic QDR4500 Dual Energy X-ray Absorbtiometry (DEXA) and automaticHAL values on DEXA were detected.

There was no signi®cant difference between the mean age ofmale (63.08�8.2) and female(63.00�8.01) cases (p = 0.964).Statistically, mean heigth of female (156.23�7.5) cases wassigni®cantly lower than male cases (169.0�86.5) (p<0.05).

Radiographic measurements of HAL, FNAL, AW, FHW, FNW,FSW, ITW and measurements of HAL (manual and automatic),FNW, FSW, ITW on DEXA were signi®cantly lower in females(p<0.001). There was no statistically signi®cant differencebetween the male and female cases in relation to medial femoralneck cortical bone thickness, medial femoral shaft cortical bonethickness, lateral femoral shaft cortical bone thickness and N-SAmeasurements on radiograms and N-SA values on DEXA.

287 (263). QUANTITATIVE ULTRASOUND AND BONETURNOVER IN THE PREDICTION OF VERTEBRAL FRACTURE

C. Cepollaro, S. Gonnelli, B. Rossi, D. Bruni, S. Martini, C.Pondrelli, M. S. Campagna, C. Gennari, Institute of InternalMedicine, University of Siena, Italy

It is well known that bone fracture depends on both bone densityand bone structure. Also bone turnover play a role in theassessment of fracture risk, in fact it has been demonstratedthat high bone turnover independently predicts fracture risk. It


has been shown that Quantitative Ultrasound (QUS) is able topredict femoral and vertebral fracture. Few studies are present inliterature about the relationship between QUS and bone turnover.The aim of this study was to evaluate the ability of QUS and boneturnover alone or in combination in the prediction of vertebralfracture. In 89 postmenopausal women, 38 of those with (61.2�8.7years) and 51 without (62.2�6.2) vertebral fracture we measuredbone density at lumbar spine (BMD-LS) and at femoral neck(BMD-FN) by DXA (Hologic 4500) and broadband ultrasoundattenuation (BUA) at the calcaneus by QUS±2 (Metra Biosysiem).In all patients we also assessed markers of bone turnover: totalalkaline phosphatase (T-ALP) and bone alkaline phosphatase (B-ALP, Hybretech) to evaluate bone formation and urinaryhydroxyproline (HOP/Cr) and a-Cross-Laps (Osteometer Biotech)to evaluate bone resorption. The precision of QUS±2, evaluatedby measuring 5 healthy subjects and 5 osteoporotic women dailyfor 5 days, showed a coef®cient of variation of 1.4% and 1.3%respectively and a standardized coef®cient of variation of 1.8%and 1.7% respectively in healthy subjects and in osteoporoticpatients. All densitometric and ultrasonographic parameters weresigni®cantly lower in postmenopausal women with vertebralfractures with respect to those without vertebral fractures. BUAsigni®cantly correlates with bone density and with markers ofbone turnover. BUA, B-ALP and a-Cross-Laps independentlypredict vertebral fractures; the combination of BUA and B-ALPand of BUA and a-Cross-Laps improves the ability to assessfracture risk. We can conclude that: QUS±2 presents goodcharacteristics of precision and signi®cantly correlates withbone mineral density and markers of bone turnover. Therelationship of markers and BUA in the prediction of fracturerisk are not only independent, but also additive.

288 (264). COMBINATION OF RISK INDICATORS TO ESTIMATEHIP FRACTURE RISK IN WOMEN

C. E. D. H. De Laet, H. A. P. Pols, J. A. Kanis, A. Dawson, O.Johnell, A. Oden, Erasmus University Medical School, Rotterdam,The Netherlands

Although BMD is a well-established risk indicator for hip fracturesit is generally recognised that other risk indicators contributeindependently to hip fracture risk. The purpose of this study wasto provide a framework for their combination based on data fromthe Rotterdam Study.

Based on available evidence we used 4 putative risk indicatorsfor hip fracture risk. To obtain reasonable prevalences for each ofthe 16 combinations of risk indicators we used moderatethreshold values. For low-weight the threshold was set at themedian weight, for tall height this was set at the highest quartile.Other indicators were a previous fracture in the previous 5 yearsand use of a walking aid. The additional risk of having a low BMD(de®ned as a Z score below ±0.5) was assessed and itsprevalence determined in each of the combinations of riskindicators. The analysis was done for both the total populationand also strati®ed by 10-year age groups.

The relative risks (risk indicators adjusted for each other) were1.7 for low weight, 2.4 for tallness, 1.8 for use of a walking aid and1.2 for previous fracture. Prevalence was 14 % for the use of awalking aid and 16 % for a previous fracture. Adding BMD into themodel the relative risk for low BMD was 3.5 and the relative riskfor having a low weight decreased to 1.3. The relative risks for theother indicators remained similar. When the relative risk for hipfracture for individuals having none of the 4 risk indicators wasde®ned as 1, the relative risks for individuals in the 16combinations of risk indicators varied from 1 to 9, and theaverage risk for the total population was 2. Only 25% of thepopulation had a higher than average risk. In the groups with 3 ormore risk indicators the prevalence of low BMD was 60%, muchhigher than the expected 30 %. Several risk indicators, measuringdifferent determinants of hip fracture risk, can be combined in an

easy to use instrument. Further validation is needed to apply thisframework to other populations.

289 (265). VERTEBRAL MORPHOMETRY AND RISK OFVERTEBRAL FRACTURES

D. Diacinti, S. Minisola, E. Tomei, E. D'Erasmo, GF. Mazzuoli,Department of Clinical Sciences, University ``La Sapienza''Rome,Italy

The purpose of this study was to evaluate if a new morphometricindex is to able to predict vertebral fracture risk.

Materials and methods: in 130 postmenopausal women (meanage 65�10; range 46±74 years) who came to our MineralMetabolism Centre lateral spine ®lms were obtained at base lineand after two years. The ®lms were digitized by means of ascanner and then was performed the vertebral morphometry fromT4-L5 using speci®ed software (QR-Verona). The computerautomatically calculated the anterior, middle and posteriorvertebral bodies heights (Ha, Hm, Hp), the ratios of heights ofsingle vertebra (Ha/Hp, Hm/Hp, Hp/Hpp), as well as the sum ofvertebral body heights (AHs, MHs and PHs). At baseline thevertebra was considered fractured if any of the three ratios was<3SD the corrisponding reference ratio of fertile women. A newfracture was de®ned as a reduction of 20% (4mm.), in the heightof any vertebral body between baseline and follow-up. Lumbarbone mineral density (LS-BMD) was measured by dual-energy x-ray absorptiometry using the Hologic QDR±4500 densitometer(Hologic, USA). Osteoporosis was de®ned as a LS-BMD <2.5SDthe mean value in fertile women (WHO).

Results: at base line 35/130 (26.9%) women had AHs <2.5SDthe normal fertile value, 18/35 (51.4%) had vertebral fractures; 48/130 (36.9%) had LS-BMD <2.5SD, 14/48 (29.1%) were fractured.After two years became fractured 8/17 (47%) of the women notfractured at base line but with AHs <2.5SD and 12/34 (35.3%)women with LS-BMD <2.5SD at base line.

Conclusion: vertebral morphometry, detecting minor asympto-matic vertebral deformities, allows to identify women withincreased risk of further fracture.

290 (266). HEARING LOSS AS A COMPLICATION OF PAGET'SDISEASE OF BONE

J. Donath, B. Fornet, M. Krasznai, Gy. Poor, National Institute ofRheumatology and Physiotherapy, Haynal Imre University ofHealth, Oto-Rhyno-Laryngology Clinic, Budapest, Hungary

Background: Hearing loss has long been known to be acomplication of Paget's disease of bone. The aim of this studywas to investigate the hearing loss in Paget's disease and treatingthe patients with pamidronate and tiludronate.

Methods: 65 patients with Paget's disease were examined /30men, 35 women, age range 49±97/. Imaging included radio-graphy/n=65/, bone scintigraphy/n=65/ and QCT scan /n=10/.The quantitative bone scintigraphy/QBS/ was performed in 27cases and the results were expressed as a ratio of the affectedbone and normal uptake of TC99mMDP before and after thetreatment with bisphosphonates.

Results: 28 skull involvements were documented in 65 patientsand 10 had hearing loss. The bone scintigraphy showedincreasing uptake of the petrous pyramids /n=5/. The QCTshowed involvement of the middle ear ossicles /n=5/, ossi®cationof the stapedius tendon /n=1/, narrowing of the external auditorymeatus /n=1/ and involvement of the petrous pyramids /n=5/.After bisphosphonate treatment the patients recognised animprovement in hearing sensitivity. In QBS the activity of petrouspyramids were decreased.

Conclusion: QCT imaging is a well suited for demonstrating thecomplication of the disease.


QBS may be a useful technique for evaluating of the effects ofthe treatment.

Early diagnosis and bisphosphonate treatment may be a way tocontrol hearing loss as a complication of Paget's disease.

291 (267). A SCREENING INSTRUMENT FOR ASSESSINGOSTEOPOROSIS RISK IN ADULTS WITH DEVELOPMENTALDISABILITY

B. Dunford, S. Cottrell, J. Bod®sh, J. McKee, Western CarolinaCenter, Morganton, NC, USA

The prevalence of osteoporosis in individuals with developmentaldisability has not been clearly quanti®ed. Currently availablediagnostic tools such as central or peripheral scans are some-what invasive and expensive to perform. The instrumentdeveloped is an initial attempt to create a non-invasive screeningtool to identify those individuals with developmental disabilitywho are at risk for developing osteoporosis, who may then bereferred for further diagnostic testing, then a treatment plandeveloped to meet the speci®c needs of the individual. Thisscreening instrument accounts for clinical issues speci®c to thepopulation with developmental disability (non-ambulatory statusand exposure to various anti-epileptic drugs). This instrumentwas validated in 360 individuals living in a residential intermediatecare facility for the developmentally disabled (mean age 40.1years, 41% female, 43% nonambulatory). Signi®cant risk factorsidenti®ed were increasing age, history of fractures, history oftreatment with phenytoin and/or phenobarbital, less ambulatoryability, and decreased body weight. The weighting of theindividual questions on the instrument were based on the resultsof a multiple regression analysis from the facility sample tested.This screening instrument has utility for either sex and shouldidentify those at risk for developing osteoporosis allowing forearly intervention to postpone, minimize, or prevent bonedemineralization.

292 (268). CORRELATION BETWEEN KNEE OSTEOARTHRITISAND BONE MINERAL DENSITY OF THE LUMBAR SPINE,PROXIMAL FEMUR AND DISTAL RADIUS

G. Durlanik, F. Sahin, F. Merdol, B. Kuran, Dept. of PhysicalMedicine and Rehabilitation, Sisli Etfal Teaching and ResearchHospital, Istanbul, Turkey

The aim of this study was to determine the possible inverserelation between osteoporosis (OP) and osteoarthritis (OA) byevaluating the association between bone mineral density (BMD)and knee OA. BMD's in proximal femur, lumbar spine and distalradius were measured by LUNAR-DEXA. Knee OA was assessedby a weight bearing anteroposterior radiograph and graded on aseverity scale of 4 according to Kellgren-Lawrence. We comparedthe bone densities of each OA group with those without knee OA.Among a study population of 300 postmenopausal women (agerange 42±86 years) 220 had radiologically diagnosed knee OA.The t scores according to the stages of knee OA were as follows:

Stage 1 Stage 2 Stage 3 Stage 4

No: 21 98 88 13Lumbar t score ±2.52 ±2.45 ±1.77 ±1.62Neck t score ±1.65 ±1.63 ±1.31 ±1.53D. Radius t score ±2.32 ±2.43 ±2.11 ±2.10

This is an on going study. The early ®ndings suggest thatpostmenopausal patients have moderate degrees of knee OA andas the severity of OA increases, the t scores of the lumbar spinedecreases correspondingly.

293 (269). THE DETECTION OF FRACTURE RISK IN PRIMARYCARE

A. Fairney1, M. W. van den Brekel1, A. Keyede2, P. Kyd1, S. Illife2,D. A. Percival3, R. Branton3, 1Metabolic Medicine, ImperialCollege School of Medicine, St. Mary's, UK; 2Lonsdale MedicalCentre London, Flintshire, UK; 3Provalis Diagnostics, Flintshire,UK

Strategies to prevent osteoporotic fractures could be facilitatedby provision of bone density services in the community, togetherwith near patient measurements of bone turnover1.

Patients living in the community were invited to visit the HealthCentre for a forearm bone density measurement (BMD) (DTX 200,Osteometer) and to provide a sample of urine. Urine C-Telopeptide was measured by OsteosalTM immunochromato-graphic test (Provalis Diagnostics Ltd, Flintshire, UK), correctedfor creatinine and results expressed as Osteosal T-scores. Thiswas compared with the urine C-Telopeptide CrossLapsTM

(Osteometer, Denmark CTx).Of 105 subjects, (39M, 66F) mean age 71 years (range 60±89)

33% had normal BMD (N), 40% osteopenia (OPEN), and 27%osteoporosis (OPOR), (WHO criteria). OsteosalTM results corre-lated with laboratory CTx (p<0.0005). Urine CTx, though notOsteosalTM, was higher in OPOR subjects compared to N orOPEN (p<0.0001).

In primary care, the combination of forearm BMD and boneturnover measurements may help to identify those at risk offracture who require preventative treatment. 1Garnero P, et al.Osteoporos Int. 1998;8:563±9.

n BMD T-score OsteosalTM T-score CTX mg/mmol

N 35 0.22 (0.14) 0.86 (0.27) 110 (14)*OPEN 42 ±1.79 (0.06) 0.64 (0.21) 132 (12)*OPOR 28 ±3.42 (0.12) 1.34 (0.29) 252 (26)

Mean (SEM), *p<0.0001 vs. OPOR.

294 (270). THE ABILITY OF AN IMAGING QUANTITATIVEULTRASOUND SYSTEM TO DISCRIMINATE SUBJECTS WITHOSTEOPOROTIC FRACTURE FROM CONTROLS

B. Fan, M. Grigorian, M. Chen, C. F. Njeh, T. Fuerst, I. Saeed, D.Hans, H. K. Genant, Osteoporosis and Arthritis Research Group,University of California, San Francisco, CA,

Quantitative ultrasound (QUS) has emerged as a promising tool inidentifying individuals at risk of sustaining a fragility fracture. Theaim of this study was to assess the ability of an imaging calcanealQUS system (UBIS 5000, DMS, France) to identify women withosteoporotic fracture. The study group consisted of 52 healthywomen (mean age 71�8.14 yr.) with no risk factors associatedwith osteoporosis and 51 women (mean age 76�6.02 yr.) withosteoporotic fracture of spine or hip. All women had calcanealQUS and Hologic 4500 (Hologic, USA) was used for bone mineraldensity (BMD) measurement of the lumbar spine and hip. The t-test was used to calculate the difference between the two groups.Both QUS parameters and BMD of the hip and spine differ-entiated signi®cantly between the fracture and control group(P<0.01). Odds ratios (OR) per standard deviation were computedby using the logistic regression analysis. We also calculated thearea under the curve (AUC) by using CLABROC software. TheOFs, AUC and 95% con®dence intervals (CI) are given in the table.After adjustment for age all the parameters still remain signi®cantexcept BMD of the neck. Our results suggest that the QUSparameters can discriminate the fracture subjects from controlsas well as bone density of the hip and spine.


Parameters Odds ratios (95% CI) AUC(95% CI)

BUA 2.52 (1.54, 4.13) 0.73 (0.63, 0.82)SOS 1.87 (1.21, 2.90) 0.66 (0.56, 0.77)BMD_spine 2.10 (1.32, 3.34) 0.71 (0.61, 0.81)BMD_neck 1.93 (1.21, 3.10) 0.68 (0.58, 0.77)

295 (271). HEEL BMD AND THE NOF CRITERIA PREDICTFRACTURES IN BOTH CAUCASIAN AND NON-CAUCASIANWOMEN

K. G. Faulkner, T. Abbott, D. Furman, J. Panish, E. Siris, P. Miller,E. Barrett-Connor, M. Berger, A. Santora, L. Sherwood,

Participants in NORA are ambulatory, postmenopausal womenwith no prior diagnosis of osteoporosis or BMD test in the pastyear. Heel density data (SXA) and risk assessment data werecollected from 102,101 women at baseline. Women wereclassi®ed into 2 groups: those who met National OsteoporosisFoundation (NOF) treatment guidelines (NOF Tx group: T-score5±2.0 or 5±1.5 with a risk factor) and those who did not (NOFnon-Tx group). For 32,497 of these women, self-reportedprospective fracture data were captured by follow-up surveyscompleted an average 8 months after baseline. The % of womenmeeting treatment criteria varied from 18.05% for AfricanAmericans to 39.46% for Asians. Fracture rates (per 100 personyears) in the Tx group was 2 to 6 times higher than the non-Txgroup, depending on ethnicity. The NOF criteria were particularlystrong predictors of fracture in African American and Asianwomen. We conclude that the NOF criteria based on heel BMDassessments can identify women of various ethnicities atincreased risk for fracture.

Ethnicity African American Caucasian Hispanic Asian

Tx Group: % 18.05 28.51 31.4 39.5Age (Mean) 70.8 69.9 69.6 68.1T-score (Mean) ±2.01 ±2.05 ±2.08 ±2.11Fx Rate 9.7 5.3 4.7 6.4Non-Tx Gp: Fx Rate 1.6 2.7 2.4 1.8Odds Ratio 6.3 2.0 2.1 3.895% CI 2.2, 18.5 1.7, 2.4 0.8, 5.1 1.0, 14.6

296 (272). MISSED OPPORTUNITIES FOR OSTEOPOROSISPREVENTION IN CLINICAL PRACTICE

T. C. Gallagher1, O. Geling2, J. FitzGibbons3, F. Comite4,1University of Illinois, Champaign, IL, USA; 2University of Illinois,Champaign, IL; 3Yale University, New Haven, CT; 4Yale University,New Haven, CT, USA

Adherence to osteoporosis clinical practice guidelines wasassessed in a randomly-selected sample of 1,004 femalemembers (age 40±69) of a network-based managed carearrangement in the Northeastern U.S. Guidelines recommendthat all women receive counseling regarding universal preventivemeasures (calcium, weight-bearing exercise, smoking cessation),those with selected risk factors receive bone mineral densitytesting, and those with identi®ed osteoporosis receive adviceregarding available treatments. Osteoporosis practices werebelow the recommended level. This was true for counselingregarding universal preventive measures (only 49% of the sampleever discussed osteoporosis with a health care provider), BMDscreening (only 18% of women age 65+ advised regarding BMDscreening), and treatment (74% of those with identi®ed osteo-porosis advised of pharmaceutical treatments). Women with

clinical risk factors for osteoporosis were no more likely thanthose with no risk factors to receive clinical preventive services(counseling and screening). In multivariate analyses, those lesslikely to have been counseled about universal preventivemeasures were in their 40s, premenopausal, in good/fair/orpoor health, or had an annual income less than $50 000. Morelikely to have been counseled were women who had visited ahealth care provider for menopausal symptoms. Current osteo-porosis practices appear to be oriented towards management ofidenti®ed osteoporosis, rather than primary or secondaryprevention. Much work remains to be done to fully implementguidelines for primary prevention of osteoporosis, as well as newscreening guidelines.

297 (273). BIOLOGICAL AGE, BALANCE, MUSCLE STRENGTH,VISUAL ACUITY AND BONE MASS IN 75-YEAR-OLD WOMEN

P. Gerdhem, K. Ringsberg, H. Magnusson, K. Akesson, K. Obrant,Department of Orthopaedics, Malmo University Hospital, Malmo,Sweden

The purpose of this investigation was to evaluate a method ofestimating biological age, and to correlate it to known risk factorsfor osteoporotic fractures. Biological age may be an under-estimated factor for fracture risk but lacks de®nition and nomeasurement of it exists. Patients and methods: 993 women, all75 years old. Biological age was assessed as follows: eachwoman was given a subjective fragility score from 1±100 within 15seconds from ®rst sight. 4 investigators took part in the scoring.957 women were scored independently by 2 investigators. Amodi®ed Romberg balance test was performed. Visual acuity (VA)and thigh strength (TS) was measured. Bone mineral density(BMD) of the hip and spine was measured with a Lunar DPX-Lscan. Statistics was calculated with the Pearson product momentcorrelation or the Spearman rank correlation.

Results: Biological age as assessed by two independentobservers had a good correlation (r varying between 0.51 and0.59, p<0.001) The correlation (r-value) between biological ageand balance varied between 0.28 and 0.53 (p = 0.0013- p<0.0001).The r-value between biological age and TS varied between 0.22and 0.30 (p = 0.02- p<0.0001). No correlation existed betweenbiological age and VA or between biological age and BMD.

Conclusion: Biological age, as measured in our study, can quitewell predict balance, an important risk factor for falling andsubsequent fracture, and the correlation between independentobservers is good. It is not possible to anticipate a patients BMDby estimating her biological age.

298 (274). CUT-OFF VALUES FOR VERTEBRAL FRACTURE BYPERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY(PQCT) IN JAPANESE WOMEN

I. Gorai1, K. Nonaka2, H. Kishimoto3, H. Sahata4, Y. Fujii5, T.Fujita5, 1Yokohama City University, Yokohama, Japan; 2NishimotoSangyo Co., Ltd., Tokyo, Japan; 3Sanin Rosai Hospital, Tottori,Japan; 4Nayoro Orthopedic Clinic, Hokkaido, Japan; 5CalciumResearch Institute, Hyogo, Japan

In spite of the bene®ts of bone mass measurement by DXA, theuse of DXA has limitations. It is unable to assess a true geometryof a bone and totally approximate to estimate bone strength. Itcannot discriminate between the trabecular and cortical compo-nents of bone. The purpose of this study is to determine referencevalues of total bone density (BD), trabecular bone density (TBD)and polar strength strain index (pSSI) in Japanese femalepopulation measured by pQCT (XCT±960 Rev. 5.10 or 5.16s,Stratec Medizinteknik GmbH, pforzheim, Germany), and ®nd outcut-off values of BD, TBD and pSSI that could most ef®cientlydifferentiating those subjects with vertebral fractures from thosewithout them. Total of 5,942 healthy Japanese women aged 20 to


89 years entered this study. All the subjects gave informedconsent before the study. Six hundred and twenty-one womenwere extracted from 5,942 subjects for radiographic examinationof the thoracic and lumbar spine at the time of pQCTmeasurement to determine cut-off values of BD, TBD and pSSIfor vertebral fractures. The backgrounds of the extractedpopulation did not differ signi®cantly from those of the wholepopulation. All the subjects were divided into each ®ve-year-agegroup according to their ages. The TBD showed a plateau untilthe ages of 40±44 years, which corresponds to the young adultmean (YAM) values of lumbar spine, femoral neck and radiusBMDs measured by DXA. The TBD decreased signi®cantlythereafter. The pSSI did not change signi®cantly from age groupof 15±19 years to that of 50±54 years, and decreased slightly inage groups of 50±59 and 60±64 years and markedly thereafter.The cut-off values for the discrimination of vertebral fractureswere obtained by the calculation of sensitivities, speci®cities andarea under the curve (AUC) using receiver operating character-istics (ROC) analysis (Table). These ®ndings suggest that differentthresholds are needed among different variables.

Table. YAM and cut-off value for vertebral fractures

n YAM�SD Cut-off value (SD, %YAM)

BD (mg/cm3) 1,298 405.4�61.7 283.8 (±2.0, 70%)TBD (mg/cm3) 1,298 195.8�40.9 117.5 (±1.9, 60%)pSSI (mm3) 928 322.5�69.7 193.5 (±1.9, 60%)

299 (275). QUANTITATIVE BIOMECHANICAL MEASUREMENTOF PROXIMAL FEMUR BY RECONSTRUCTION OF HELICALCOMPUTED TOMOGRAM

B. Goto, J. Maeda, Y. Fujii, T. Nakamura, T. Fujita, CalciumResearch Institute Osaka, Japan

Three-dimensional reconstructiion was carried out on the helicalcomputed tomogram with 3mm slice/ second using GE-Yokogawa Lemage SX-E at 120 kv, 200mA, in the proximalfemur of 17 subjects 67 and 77 years of age, 12 with and 5 withoutosteoporosis by the lumbar BMD. On extraction of cortical bonewith CT number >300, belt-like zones with no detectable corticalbone by this method(Apparent Cortical Defect) were alwaysfound, one surrounding the neck beneath femoral head and theother on the dorsal half of the plane containing the greater and

lesser trochnters. In osteoporotics, the zones of ApparentCortical Defect was de®nitely wider than in non-osteoporotics.Modulus of section (mm3) (Z1s, Z1i, Z2s, Z2i, Z3 and Z4) dividedby distance from the center Z/d indicating mechanical fracturethreshold, was at the minimum in Z1 and Z3. In osteoporotics,Z1s/d1, Z1i/d1 and Z3/d3 were 11.6, 0.8 and 30.9 respectively,always signi®cantly lower in the former than non-osteoporotics(62.2, 18.5, 48.8) (p<0.01). The zones of Apparent Cortical Defectdemonstrated for the ®rst time correspond to the well-knownsites of frequent occurrence of intra-and extracapsular fractures.In control subjects in the 40s, no zones of Apparent CorticalDefect were found.

300 (276). CLINICAL PERFORMANCE OF THE QUS±2: APORTABLE, GEL-COUPLED, SCANNING CALCANEALULTRASONOMETER

S. L. Greenspan1, S. Cheng2, P. D. Miller3, E. S. Orwoll4, the QUS±2 PMA Trial Investigators, 1University of Pittsburgh MedicalCenter, Pittsburgh, PA, USA; 2University of Jyvaskyla, Jyvaskyla,Finland; 3Colorado Center for Bone Research, Lakewood, CO,USA; 4Oregon Health Sciences University, Portland, OR, USA

We recruited Caucasian women 25±84 years of age to evaluatethe clinical performance of the QUS±2 calcaneal ultrasonometer(Metra Biosystems): normative database (n=794), precision(n=79), low bone mass and fracture discrimination (n=528, aged50±84 years). Mean calcaneal BUA was constant in healthywomen from 25±54 years of age and decreased with increasingage thereafter. The mean (SD) BUA in 171 women aged 25±34years was 89.0 (12.4) dB/MHz. Short-term (within day) precision,with and without repositioning of the heel, and long-term (over 16weeks) precision yielded comparable results (BUA SD of 2.1±2.4dB/MHz, CV of 2.5±2.9%). BUA was signi®cantly correlated withBMD of the total hip (TH), femoral neck (FN), and lumbar spine(LS) (r = 0.6±0.7, p<0.0001) in 698 women. Prevalence ofosteoporosis in our population (WHO criteria) was 20%, 17%,21%, and 24% for BUA, TH BMD, FN BMD, and LS BMD,respectively. Age-adjusted values for a 1SD reduction in BUA, THBMD, and FN BMD predicted prevalent clinical fractures (spine,forearm, and hip) with signi®cant (p<0.05) odds ratios of 2.3, 2.0,and 2.1, respectively. Areas under the ROC curves for age-adjusted bone mass values predicting prevalent fracture were0.62 for BUA, 0.59 for TH BMD, 0.60 for FN BMD, and 0.57 for LSBMD; all statistically equivalent. We conclude that the QUS±2calcaneal ultrasonometer exhibits reproducible clinical perfor-mance and is equivalent to BMD of the hip and spine foridentifying women with osteoporosis and fracture discrimination.

301 (277). DOES OSTEOPOROSIS CLASSIFICATION USINGHEEL BMD AGREE ACROSS MANUFACTURERS?

M. Grigorian, J. A. Shepherd, X. G. Cheng, C. F. Njeh, J. O.Toschke, H. K. Genant, Osteoporosis & Arthritis Research Group,University of California San Francisco, San Francisco, CA, USA

In this study, we evaluated the agreement between two heel DXAdevices on BMD and T-scores. A total of 99 healthy females aged21 to 78 years (ca. 16 per decade) had their non-dominant heelBMD measured using the PIXI (Lunar Inc.) and APOLLO (NorlandMedical) DXA machines. The PIXI ROI is the inner 50% area of acircle inscribed on three perimeter markers on the calcaneus. TheAPOLLO ROI is 30 mm long by the calcaneal width starting 6 mmfrom the distal end.

The mean BMD values were 0.492 and 0.607 g/cm2 and themean T-scores were ±0.07 and ±0.25 for the PIXI and APOLLOrespectively. Both the BMD and T-score inter-machine relation-ships were highly correlated but showed signi®cant nonidentityslopes and non-zero offsets.


Furthermore, using Bland-Altman analysis, we found that thedifference in BMD between the two devices tended to increase asBMD decreases (p<0.003). Classifying all patients using the NOFguidelines resulted in an 84% agreement.

Normalizing the reference peaks and SDs using the study's 20±39 aged subjects removed the systematic T-score disagreement.In conclusion, the PIXI and APOLLO are highly correlated.

Differences in BMD values may be solely due to the ROIde®nitions. Additional T-score disagreement highlighted differ-ences in the manufacturers' reference populations and T-scoremethods.

Independent Variable n r2 SE Intercept Slope

PIXI-BMD 99 0.84 0.032 ±0.216 0.81PIXI T-score 99 0.84 0.263 0.208 0.55

302 (278). INTERRELATIONSHIPS BETWEEN SERUM LEVELSOF BONE RESORBING CYTOKINES, BONE MINERAL DENSITYAND BONE TURNOVER IN TYPE I OSTEOPOROTIC PATIENTS

D. Grigorie, E. Neacsu, C. Barbu, M. Dumitrache, M. Grigorie, C.Dumitrache, 1``C.I. Parhon'' Institute of Endocrinology; 2Ana AslanInstitute of Geriatrics and Gerontology, Bucharest, Romania

We measured markers of bone turnover, serum levels ofresorbtive cytokines (IL1alpha, IL1ra and TNF alpha) and serumcalciotropic hormones levels in 50 women in early postmeno-pause. Compared to premenopausal subjects, mean value ofVMD (0.913 g/sqcm) was signi®cantly lower (p<0.001) inpostmenopausal women. Mean levels of serum intact osteocalcin(23.6 pg/ml), crosslaps value (403.9 mcg/mmol creat.) and serumIL1 alpha (5.77 pg/ml) and IL1ra (496 pg/ml) were signi®cantlyhigher (50%, 41%, 32.3%, 44% respective, p<0.05) in post-menopausal women compared with controls. A signi®cantcorrelation was found between VMD and crosslaps values(r = 0.35, p50.05). Serum levels of TNF alpha correlated sig-ni®cantly with serum intact osteocalcin (r = 0.42, p<0.02), serum IL1 alpha (r = 0.33, p<0.05) and IL 1 ra (r = 0.42, p<0.01). Post-menopausal women with very low levels of serum estradiol (<5pg/ml) had a signi®cantly higher mean IL 1 alpha serum levelscompared with postmenopausal subjects with higher serumestradiol levels (> 5 pg/ml). Mean values of serum Ca, serumintact (1±84) PTH, serum (25-OHD) and serum TNF alpha levelsdid not signi®cantly change during menopause. Conclusions: 1) inearly postmenopause, trabecular bone loss is correlated with thelevel of bone resorbtion; 2) our data suggest that the high serumlevels of resorbtive cytokines could be responsible for the highbone turnover and trabecular bone loss in early postmenopause.

303 (279). CAN WE USE THE PIXI DENSITOMETER IN MASSSCREENING FOR OSTEOPOROSIS?: A POPULATION-BASEDSTUDY

D. Hans, C. Perron, G. Conicella, M. Barada, C. Gumy, D. O.Slosman, Nuclear Medicine Div., Geneva University Hospital,Geneva, Switzerland

Some clinicians propose using peripheral densitometry (pDXA)for mass screening. The purposes of this study were toinvestigate the PIXI as a screening tool by checking its ability todiscriminate osteoporotic fractures versus controls.

In the mass-screening environment of the last Geneva fair,more than 400 women were scanned at the calcaneum in lessthan a week using the PIXI densitometer (Lunar Corp., Madison,WI). All volunteers had a detailed questionnaire, using which weextracted 3 sub-groups: 54 young adults (mean age 32�6); 34patients with osteoporotic fracture (mean age 61�9; hip, spine,

wrist fractures); and 102 age-matched controls (mean age60.5�8). All of them were free of any drugs which could affectbone metabolism. The age-adjusted odds-ratio per standarddeviation decrease of calcaneal BMD was calculated to assessthe prediction of osteoporotic fracture. The correlation ofcalcaneal BMD with age was ±0.36 in the combined population.The difference between the peak BMD and that of normal 70-year-old women was 17%, or a T-score of about ±1.0. Fracturecases averaged 12% lower BMD than controls (Z-score ±0.6), andthe odds-ratio was close to 2. Calcaneal BMD predictedosteoporotic fracture comparably to axial BMD in other studies,even though the T-score decrease with age is less than that forspine or femur BMD. This con®rms other reports showing that theWHO de®nition of osteoporosis is not valid for calcaneal BMD.

Calcaneal BMD T-Score ODDS Ratio

Mean SD

Young Adults 0.524 0.09 0 NAControls 0.483 0.1 ±0.5 1.93Osteoporotic 0.424 0.09 ±1.1

304 (280). DIFFERENCE BETWEEN T-SCORE OF LUMBARSPINE AND HIP AS AN INDICATOR FOR PERIMENOPAUSALBONE LOSS


The aim of this study was to examine an index (Im) for thepostmenopausal bone loss comparing the bone mineral densityof the lumbar spine and the hip. The BMD was represented bythe DEXA T-score (Hologic 4500A). The index Im = Scorelumbar

7Scorehip. The investigation included white healthy women,without suspected conditions affecting bone metabolism, dividedinto three groups: premenopausal (PREM) (n = 48, mean age 42.3,range 30±58 years), postmenopausal with Hormone ReplacementTherapy (HRT) (POSTH) (n = 43, 56.5, 46±65) and postmenopausalwithout HRT (POST) (n = 63, 56.5, 39±65). The results show thatthe onset and degree of menopausal bone loss can bedetermined by the Im calculated from the difference betweenthe T-scores of the vertebra with the lowest score (Lmin) and theneck of the femur. We found signi®cant differences betweenmean Im of POST (±1.034�0.826) vs. PREM (0.316�0.704)(P<<0.001) and POST vs. POSTH (0.255�0.588) (P<<0.001).There was no difference between POSTH and PREM. Further-more, we found a strong correlation: with increasing number (x) ofyears since menopause (YSM), the Im in POST was decreasing ina linear mode: Im = ±0.102 x ± 0.274 (SD�0.59) (r = ±0.70). Therewas no similar correlation in the POSTH group (r = 0.17). Weconclude that in healthy perimenopausal women the Im multipliedby ±10 and corrected by ±3 is approximately equal to the numberof years since menopause (±10 Im(TLmin ± Tneck) ± 3 = YSM). Thisnew Im-score allows a dynamic approach to the results of BMDmeasurement even during the ®rst patient visit.

305 (281). EVALUATION OF AN OSTEOPOROSIS SELF-REFERRAL PROGRAM

A. B. Hodsman, N. Platt, S. Baker, L. Nicholson, B. Nicholson,Department of Medicine and the Lawson Research Institute,University of Western Ontario, London, ON, Canada

In an effort to identify women at risk for osteoporosis, anOsteoporosis Self-Referral Program (OSRP) was developed fora fee of $30 Canadian. Clients attended a one hour group classled by a Nurse Practitioner, were informed about risk factors,completed a SCORE1 questionnaire, and underwent calcaneal


ultrasound (U/S). Risk was communicated as low, medium orhigh, based on published tertiles for U/S BUA in women over age65 years (cut-points at 72.5 and 58 ml/sec, Hologic Sahara). Atelephone survey was developed to identify 5 domains ofinformation provided by the OSRP. 517 clients were contacted,at least 6 months post-OSRP, and 271 completed the survey.Ages ranged from <50 yrs (n=72), 50±65 yrs (n=136), to >65 yrs(n=53), of whom 20% were high, 30% medium, and 50% low riskfor osteoporosis.

Results: Over 80% could: de®ne osteoporosis, list >2 signs/symptoms, list >2 risk factors and describe both U/S and DEXABMD tests. Reported diet calcium increased in those withpreviously low intake (p = 0.005). Sedentary clients exercisedmore (p = 0.05). Compared to lower risk groups, high risk clientswere more likely to speak to their doctor about DEXA (p = 0.03).50% of high risk clients vs. only 7% low risk clients had arrangedfor DEXA tests (p<0.001). 60% of high risk clients were either onestrogen or bisphosphonates vs low or medium risk clients, ofwhom 40±50% were already on estrogen.

Conclusion: The unusually high estrogen use suggests a well-motivated client base. However, the OSRP led to effectiveeducation of its clients, and targeted appropriate responses inboth the clients and their primary physicians.

306 (282). AN INTERVENTION STUDY TO EXAMINEKNOWLEDGE AND ATTITUDE TOWARDS CHANGE INOSTEOPOROSIS PREVENTION

J. Im1, D. J. Sartoris1, J. O.F. Reimann2, 1University of CaliforniaSan Diego, San Diego, CA, USA; 2San Diego State University, SanDiego, CA, USA

The purpose of this intervention study was to promoteosteoporosis awareness and prevention among young adultfemales. In this intervention study an osteoporosis lecture and abone mineral density (BMD) measurement were utilized todetermine knowledge and attitude towards change regardingosteoporosis prevention. Twenty-eight Caucasian and Asianwomen ranging from 18 to 29 years of ages were included inthe study.

Each participant completed two question-naires. The twoquestionnaires consisted of knowledge and attitude towardschange concerning osteoporosis. In addition to the two surveys,participants in the intervention group were provided with a bonemineral density (BMD) measurement and an osteoporosis lecture.The Statistical Program for Social Sciences (SPSS) was used fordata analysis. Speci®cally, independent sample t-tests, pairedsample t-tests, and descriptive analyses were performed toconduct data analysis. Results suggest an increase in knowledgeand attitude towards change among individuals who wereprovided with a lecture and a BMD measurement compared tothose who did not receive any intervention. Also, there was asigni®cant difference in knowledge and attitude towards changebetween the pre- and post-test results among individuals whoreceived the intervention.

307 (283). RADIOLOGICAL VERTEBRAL FRACTURE: FACT ORFALLACY?

J.-E. B. Jensen, H. A. Sùrensen, Department of Endocrinologi,H:S Hvidovre Hospital, University Hospital of Copenhagen,Denmark

Vertebral fractures are seriours complications to osteoporosisfound in nearly 25% of all Danish women. A 20% reduction in thevertebral hight is considered dianostic for a vertebral fracture.The purpose of this study was to compare the common clinicalevaluation of X-rays with a semi-automatic digitized measure-ment of vertebral compression.

Material and Methods: 103 consequtively admitted womenaged 69�8.6 years were included in the study and were exposedto a new x-ray of the spine. The x-rays were subsequentlydescriebed by trained radiologists and hence the lateralexposures were digitized to classify the degree of vertebralcompression. The results were compared by calculations ofKappa coef®cients.

Results:

Conclusion: Only a minor fraction of cases could demonstratean agreement between the clinical radiological evaluation ofvertebral fractures and the digitzed parameters of vertebralcompression.

308 (284). A NEUROMUSCULAR TEST BATTERY FOR ADULTS

K. Kerschan-Schindl3, E. Uher3, S. Grampp1, A. Kaider2, V. Fialka-Moser3, E. Preisinger3, 1Dept. of Radiology; 2Dept. of MedicalComputer Sciences; 3Dept. of PM&R, University of Vienna, Austria

The aim of this study was to examine the practicability of a shortneuromuscular test battery in elderly women suffering fromosteoporosis. The number of postmenopausal fractures and thehistory in regard of agility and falls were assessed in 42 womenwith a mean age of 70.0�5.1 years. The women performedneuromuscular tests and bone mineral density (BMD) of the spineand femoral neck were measured. 13.2�1.3 months later, 39women appeared for the follow-up assessment. During theobservation period ®ve women fell once and one woman felltwice; only two vertebral and no non-vertebral fractures occurred.Neuromuscular performance did not change within this observa-tion period. The median changes in BMD between the twoassessments were clinically not relevant. Comparing patientssuffering from established osteoporosis with osteoporoticpatients without a history of postmenopausal fractures showedthat they did not differ in regard of age, neuromuscularperformance, BMD, and fear of falling. This neuromuscular testbattery is a feasible and practicable tool because it is brief andeconomical. However, its ef®cacy as a predictor of fractures hasto be tested in studies with a long-term follow-up.

309 (285). INTERNAL QUALITY CONTROLS OF ULTRASOUNDOF BONE (ACHILLES PLUS) IN THE SEMOF STUDY: THEINFLUENCE OF THE WATERBATH TEMPERATURE

M. A. Krieg, J. Cornuz, L. Sandini, P. Burckhardt, for the SEMOFStudy Group, University Hospital, Lausanne, Switzerland

Background: Stability of the devices should be measured whenusing quantitative ultrasound. During the inclusion phase of theSEMOF study (Swiss Evaluation of the Methods of Measurementof Risk of Osteoporotic Fracture) on 7800 elderly women, 10Achilles+ devices (Lunar), used in 10 centers, were checkedthrough a standardized quality control (QC) program, i.e. byrepeated measurements with a local phantom provided by themanufacture.

Method: QC included measure of: water temperature (wt),water SOS (wSOS), phantom temperature (pt), phantom BUA(pBUA) and phantom SOS (pSOS). It was performed 56 to 98 timein each of the 10 centers.


Results: wSOS was highly correlated with wt (r = 0.87±0.99).The correlation with pt was better for pSOS (r = 0.83±0.99) than forpBUA (r = 0.64±0.94). -In vitro long-term precision of Achilles+before (CV%) and after adjusted by pt (adjCV%), from 10 centers:

CV% range adjCV% range

BUA 1.23 0.69±1.79 0.61 0.40±0.84SOS 0.39 0.28±0.48 0.13 0.05±0.23

Conclusion: wSOS was highly correlated with wt, and pSOSand pBUA with pt. Long-term precision of BUA and SOS wasimproved after correction by temperature. However, speci®cstandardized phantoms have to be developed in order tocompare the different devices used in a multicenter study.

310 (286). OSTEOPOROSIS IN AN INTERNAL MEDICINESERVICE OF A UNIVERSITARY GENERAL HOSPITAL IN SPAIN

J. A. Lopez-Herce, A. Del Castillo, J. Portugal, Hospital GeneralUniversitario Gregorio Maranon, Madrid, Spain

OBJECTIVES To study the incidence, the level of suspicion fordiagnosis and treatment of osteoporosis.

METHODS We have retrospectively reviewed all dischargedcharts of the patients who entered in 1997 in our Internal MedicineService. Men over 55 years old and women over 45 years old. Wehave studied if the patients had been diagnosed or treated ofosteoporosis previously, during their staying in the hospital, orwhen they were discharged.

RESULTS More than 25% of the patients had radiological signsof osteoporosis, but they were not diagnosed nor treated for it.Some of these patients had been receiving yatrogenic treatmentswith corticoids, haparin or thyroxin.

Only 1% of the patients were diagnosed of osteoporosis duringtheir stay in the hospital.

CONCLUSIONS The osteoporosis is a clinical entity under-diagnosed and undertreated.

311 (287). SCREENING FOR OSTEOPOROSIS IN LONG-TERMSURVIVORS OF BREAST CANCER

S. M. Mahon, Saint Louis University, St. Louis, MO, USA

Purpose: Improved treatment of breast cancer has created apopulation of survivors who are at risk for osteoporosis due totreatment with chemotherapy, early menopause, and long-termestrogen de®ciency. At least 500 000 women at age 50 are breastcancer survivors with an additional 20 000 women added eachyear. Methods: A mailed survey to a random sample of 668 out-patient oncology nurses (n=320, response rate=48%) wasconducted to determine practices for osteoporosis screening inlong-term survivors. Results: On average, 22.5% report thatpatients with breast cancer have height measured annually. Thisrecommendation is most likely initiated by the physician (n=119,40.5%) or the nurse (n=116, 39.5%). 68.1% of the respondentsreport there is no formal program for bone health education.When this education is done; it is most often initiated by aphysician (n=165, 54.6%) or a nurse (n=89, 29.5%). On average,only 19% have BMD done and is most often initiated by aphysician (n=248, 81.8%). BMD was available at 221 (69.1%) ofthe institutions. Conclusions: These results suggest that educa-tion about risks, means of prevention, and screening forosteoporosis are not routinely discussed or implemented withlong-term survivors of breast cancer. Increased awareness ofosteoporosis and the implementation of protocols to assurescreening and treatment are carried out could ultimately decreasethe morbidity and mortality associated with this treatment anddisease-related complication.

312 (288). COMPARISON OF FRACCIONAL CALCIUMABSORPTION FROM CALCIUM CARBONATE AND CALCIUMCITRATE ON ACHLORHYDRIC PATIENTS

A. Marino, J. R. Talbot, G. Rodriguez, J. R. Zanchetta, E. Roldan,1Metabolic Research Institute; 2School of Medicine; 3Del SalvadorUniversity; 4Dept. Clin. Pharmacology of Gador, Buenos Aires,Argentina

Although the knowledge of calcium absorption performance iscrucial to the understanding of calcium and bone status it hasbeen neglected by most workers on the bone ®eld, regardless ofthe fact that its ef®ciency decreases linearly after 50 years of age.Recently it has been reported that calcium citrate may have abetter bioavailability than other calcium salts probably becausecalcium-citrate complexes can be absorbed by both ionized-transcellular and citrate-induced paracellular mechanisms. Theaim of this study was to compare the calcium absorptionef®ciency from calcium carbonate and citrate salts on patientswith functional achlorhydria induced by atrophic gastritis.

Two fractional calcium absorption tests (a2) were performed toeach of nine 60�4-year-old females. After a 12-h fast, serumsamples were drawn at baseline and one hour after the oraladministration of 20 mg of elemental calcium as carbonate (CBD)or citrate (Mission/Gador) plus 5 uCi of Ca45. Five patients startedthe absorption test taking calcium carbonate ®rst and calciumcitrate two weeks later; the remaining 4 patients started withcalcium citrate and then switched to calcium carbonate.

Fractional calcium citrate absorption was signi®cantly higherthan that of calcium carbonate: (a2�SD = 0.439�0.092 vs0.803�0.062, p<0.001). Our study con®rms that calcium citrateits better absorbed than calcium carbonate in achlorhydricpatients. Since the active calcium absorption decreases in theelderly in favour of the passive mechanism, the higher bioavail-ability of calcium citrate observed in our study, may be explainedby the positive in¯uence of both calcium and citrate ion oncalcium kinetics. Since achlorhydria is also a common disorder inelderly persons, calcium carbonate should not be used as asupplement in individuals with any type of achlorhydria (drug-,disease- or age-related) in the assessed conditions.

313 (289). THE COMPARISON OF DUAL X-RAYABSORPTIOMETRY AND SPINE X-RAYS DATA INPOSTMENOPAUSAL WOMEN

L. A. Martchenkova, A. V. Dreval, N. M. Milov, Moscow RegionalResearch Clinical Institute, Moscow, Russia

The purpose of this study was to evaluate the ef®cacy of axial andperipheral dual X-ray absorptiometry (DXA) in predicting vertebraldeformities in postmenopausal women. The bone mineral density(BMD) measurement and standard thoracic and lumbar spine X-rays were performed at 64 postmenopausal women aged 45±70yrs. BMD at lumbar spine (L1-L4), femoral neck, Ward's triangleand trochanter were assessed utilizing a Lunar DPX absorpti-ometer. Wrist BMD was measured by an Osteometer DTX±200.The positive correlation between BMD (T-score, %) of the lumbarspine and all proximal femur sites were revealed (r = 0.59±0.92,p<0.05), and there was no signi®cant correlation between wristBMD and BMD of the other skeletal sites (r = 0.01±0.37, p>0.05).38% of women with lumbar T-score 52.5 SD had osteoporoticvertebral deformities in the lumbar spine and 76% had ones in thethoracic spine. Nobody of women with normal lumbar BMD hadvertebral deformities in lumbar spine, but 28% of them hadthoracic vertebral fractures. All the women with wrist T-score52.5 SD had vertebral deformities in the thoracic spine.Conclusions: The lumbar spine DXA data objectively assessesonly the risk of fractures in the lumbar spine, but does not predictthoracic vertebral deformities. The wrist DXA data does not giveany information about spinal and proximal femur BMD, never-theless osteoporosis in wrist indirectly testi®es to vertebraldeformities.


314 (290). DECREASED BONE MINERAL DENSITY AFTERBONE MARROW TRANSPLANTATION

G. Massenkeil1, C. Fiene1, O. Rosen1, R. Michael2, W. Reisinger3,R. Arnold1, 1Dept. of Internal Medicine, Div. of Oncology/Hematology; 2Clinic for Nuclear Medicine; 3Institute of Radiology,University Hospital Charite, Berlin, Germany

Purpose of this investigation: To study the changes in bonemetabolism and bone mineral density (BMD) after bone marrowtransplantation (BMT).

Material and Methods: 42 patients were followed prospectivelyafter BMT. Median age 36 years (range 17±58), 24 males, 18females. 38/42 suffered from leukemia (12 ALL, 11 AML, 14 CML,1 MDS), 1 aplastic anemia, 2 NHL, 1 breast cancer. 38 patientsunderwent allogeneic BMT after TBI and chemotherapy, 25/38had a related and 13/38 had an unrelated donor. 4 patientsreceived an autologous transplantation. GvHD prophylaxisconsisted of CSA, MTX and in addition prednisone in MUD.BMD was measured by computerized tomography of the lumbarspine (CT) and sonography of the calcaneus (US) before, 6 and 12months after BMT. Deoxypyridinium (DPD) and pyridinium (PYD)were analysed by ELISA and RIA and vitamine D was measuredby RIA. Serum and urine analyses were performed before BMTand weekly thereafter for six weeks, and 6 and 12 months post-BMT.

Results: BMD Z-scores in CT decreased after BMT from .0.48 to.1.14 after 6 and .1.01 after 12 months. Z-scores in US decreasedfrom .0.03 to .0.89 and .0.77 after 5 and 12 months, respectively.8/42 (19%) patients developed osteoporosis (BMD below .2.5)

Bone metabolism showed pathologically increased DPD andPYD values at baseline: DPD:10.0 nmol/mmol crea (normal 2.5±6.5) and PYD 79.05 nmol/mmol crea 16±37). After BMT valuesnormalized within 2 weeks both rising again to pathologic serumconcentrations with hematopoietic reconstitution. Despite vita-mine D supplementation, the initially normal serum values of 1,25(OH), D3 and 25 (OH)D3 fell to pathologically low values after BMTand did not recover within the ®rst 6 weeks after BMT.

Conclusions: BMT patients frequently have decreased BMDeven before conditioning. Conditioning, BMT and GvHD prophy-laxis add further damage to the bone. Diagnosis, pervention andtherapy of osteoporosis should be included in patients' care afterBMT.

315 (291). COMPARISON OF HEEL BONE MINERAL DENSITYAND QUANTITATIVE ULTRASOUND MEASUREMENTS INDIAGNOSING OSTEOPOROSIS

T. Masud, D. Pearson, D. Jordan, O. Sahota, D. J. Hosking, CityHospital, Nottingham, UK

Bone mineral density (BMD) and quantitative ultrasound (QUS)measurements at peripheral sites are increasingly being used forthe diagnosis of osteoporosis and assessment of fracture risk.The aim of this study was to compare heel QUS with heel BMD indiagnosing osteoporosis using conventional central (hip andspine) dual-energy x-ray absorptiometry (DXA) as the standardmethod.

Women who were consecutively referred for bone densitometryfrom the bone clinic were studied. QUS (stiffness) and BMD of theleft heel were measured by the same trained operator using theAchilles Plus and PIXI (peripheral DXA) [Lunar] machinesrespectively. BMD of the hip and spine were measured usingthe Lunar Expert DXA machine. Receiver operating characteristic(ROC) curves were plotted for QUS and PIXI using EMD at anycentral site (total hip, femoral neck or lumbar spine) as the``standard'' method for diagnosing osteoporosis (employing theWHO T ±2.5 criteria). As the WHO criteria cannot automatically beapplied to all peripheral techniques (because of the occurrence of

``discordance'' in T scores at different skeletal sites), the optimalT-scores for diagnosing osteoporosis were calculated for bothtechniques.

89 women, mean age 69�8, range 33±86 years, were studied.There were signi®cant correlations between QUS and central siteBMDs (total hip r = 0.55, spine r = 0.47), between PIXI and centralsites BMDs (total hip r = 0.56, spine r = 0.61), and between QUSand PIXI (r = 0.66) [p<0.001]. There were no signi®cant differencesbetween areas under the ROC curves for QUS (0.67�0.04) andPIXI (0.72�0.04) [p = 0.4]. The optimal T score cut-offs fordiagnosing osteoporosis were T= ±2.4 for QUS (stiffness) andT= ±1.7 for heel PIXI. These are similar to the T-score equivalentsfor these techniques suggested by the manufacturers, based onequivalent prevalence of osteoporosis using hip BMD as thestandard (T= ±2.5 for Achilles Plus and T= ±1.6 for heel PIXI).Using the calculated optimal cut-offs the sensitivity, speci®city,false positive and negative rates for QUS in diagnosingosteoporosis were 65%, 66%, 16% and 19% respectively, andthose for PIXI were 69%, 68%, 15% and 17% respectively.

In conclusion, QUS (Achilles plus) and BMD (PIXI) measure-ments at the calcaneus site had similar ability in diagnosingosteoporosis. The optimal T-score thresholds for these peripheraldevices, calculated from the ROC curves, were T±2.4 and T±1.7respectively.

316 (292). CONSISTENCY AND CHANGES IN T-SCORECATEGORIES OVER 4 YEARS AMONG EARLYPOSTMENOPAUSAL WOMEN

M. McClung, P. D. Ross, C. Christiansen, D. Hosking, D.Thompson, J. Yates, for the EPIC Research Group, 1OregonOsteoporosis Center, Portland, OR; 2Merck & Co., Inc., Rahway,NJ, USA

Many clinicians use WHO criteria for osteoporosis and low BMD(T-scores 4±2.5 and ±1.0 to ±2.5, respectively). We examinedthe proportions of women who shifted from one category toanother during a 4 yr period, using spine, hip, and total bodyBMD from 373 women ages 45±59 (>6 months postmenopause)in the placebo group of the Early Postmenopausal InterventionalCohort (EPIC) Study, a randomized, controlled trial of alendro-nate. Enrollment of women with osteoporosis was limited bystudy design to <10%, so the proportion with osteoporosis atbaseline may not be representative of the community. Never-theless, this cohort is appropriate for examining changes amongBMD categories over time. The women were given generalrecommendations about calcium intake and exercise for boneloss prevention, but calcium supplements were not provided. Atbaseline, 6.4% of women were classi®ed as osteoporotic, and48.5% had low BMD, based on spine BMD. At the hip and totalbody, 4.3 and 3.8% were osteoporotic, and 41.3 and 50.5% hadlow BMD, respectively. At the end of 4 years, the proportions ofwomen with osteoporosis (T 4±2.5) had increased to 9.4, 5.9,and 7.1%, based on spine, hip, and total body BMD,respectively. Among the 181 women initially classi®ed with lowBMD at the spine, 17 became osteoporotic within thesubsequent 4 years, and 157 remained in the low BMD category.All of the 17 women who became osteoporotic had T-scores4±1.9 at baseline, close to the ±2.5 cutoff. The shift toosteoporosis will accelerate; the proportion of all women withspine T-scores between ±2.5 and ±2.0 increased from 9.7% atbaseline to 15.0% after 4 years. We conclude that the WHOclassi®cations remain relatively stable over 4 years, although theproportion of women with osteoporosis increases substantiallywithin 4 years due to progressive bone loss. The aim ofprevention is therefore to preserve bone mass and therebyminimize the risk of developing osteoporosis.


317 (293). EVALUATION OF HEEL DENSITOMETRY BY PIXIFOR THE DIAGNOSIS OF OSTEOPOROSIS IN PATIENTS WITHAND WITHOUT NON-SPINE FRACTURES

S. Meszaros, E. Csupor, E. Hosszu, K. Bors, E. Toth, C. Horvath,1st Dept Medicine, Semmelweis University, Budapest, Hungary

Precision error and diagnostic utility of the heel bone densito-metry was evaluated in this study. BMD was measured in 106women (28±68 ys) and 44 men (23±72 ys) at heel (PIXI, Lunar), atlumbar spine and hip (DPX-L, Lunar), at radius (NK±364, Gamma).Heel ultrasound (Sahara, Hologic) was also done. Fractures haveoccured in 30 women and 20 men.

In vitro precision error of heel BMD by multiple phantommeasurements was found 0.41% and 0.26%, with or withoutreposition, respectively. In vivo precision error in healthyvolunteers and in patients with spinal osteoporosis was found1.0% and 2.81%, respectively. Heel BMD negatively correlatedwith age in women (r = ±0.348, p50.0001) but not in men. Positivecorrelations were found for BMD between heel and other sites(r = 0.507±0.680) and between heel BMD and heel SOS or BUA(r = 0.546±0.777), in both sexes.

Patients were grouped as normals or osteopenics or osteo-porotics based on T-score at spine or hip or radius. Heel BMD inwomen differentiated normals from patients with osteopenia orosteoporosis, based on any site. In males the normals weredifferentiated from patients with low density but osteopenia wasnot separated from osteoporosis. For heel BMD the differencebetween patients with and without previous non-spine fractureswas signi®cant in female but not in male patients, while heelultrasound resulted in signi®cant difference between the fracturedand non-fractured groups of both sexes.

Our results suggest the heel densitometry to be an effectivetool for the diagnosis of osteoporosis in women with or withoutfractures. However, more investigations seem to be needed forusing this method in osteoporosis of the males.

318 (294). BONE DISEASE AFTER LIVER TRANSPLANTATION(LT). A THREE-YEAR PROSPECTIVE STUDY

A. Monegal, M. Navasa, N. GuanÄ abens, P. Peris, F. Pons, J. M.MartõÂnez de Osaba, J. Ordi, J. Rodes, J. MunÄ oz-GoÂ mez, HospitalClinic, Barcelona, Spain

Aims: To determine the risk factors and the incidence of bonefractures and to assess the evolution of bone mass and turnoverafter LT.

Patients and Methods: Three years prospective study in 45 LTpatients (16m/29f), age 50.8�8 years. The follow-up was 2 years in34 patients and 3 years in 30 patients. For all patients vertebral andfemoral bone mineral density, spinal X-ray (®rst year) and serumlevels of Ca, P, osteocalcin, intact PTH, 25 OH-D and testosterone(men) were evaluated before and 3, 6, 12, 18, 24 and 36 monthsafter LT. Histomorphometric analysis was done in bone biopsiesobtained in 24 patients before and 6 months after LT.

Results: 15 patients (33%)developed fractures after LT. Elderpatients (p<0.05) and those with densitometric criteria ofosteopenia or osteoporosis were more prone to develop fractures(p<0.05). Serum PTH, osteocalcin, 25 OH-D, testosterone andcreatinine levels increased after LT. PTH correlated with creatine(R:0.7, p<0.000) and osteocalcin (R:0.5, p<0.05) values. Bonemass decreased during the ®rst 6 months and reached tobaseline values at the lumbar spine at the second year, withposterior but signi®cant (p<0.05) increase at the femoral neck.Long-term evolution of femoral BMD correlated with PTH levels(R:0.6, p<0.01). Six months after LT bone histomorphometric datashowed an increase in bone formation parameters.

Conclusions: LT patients, specially those with osteopenia orosteoporosis showed a high incidence of fractures. Bone mineraldensity decreased in the short-term period and improved, initiallyat the lumbar spine and later at femur, according to histomorpho-metric evidences of an increase in bone formation. The increase

in creatinine values induces a secondary hyperparathyroidismthat may in¯uence the changes in femoral bone mass.

319 (295). QUANTITATIVE ULTRASOUND AT PHALANXES INTHE DIAGNOSIS OF OSTEOPOROSIS IN MEN

A. Montagnani, S. Gonnelli, C. Cepollaro, M. Mangeri, S. Pacini, L.Gennari, B. Lucani, C. Gennari, Institute of Internal Medicine,University of Siena, Italy

Previous studies in women have shown that Quantitativeultrasound parameters (QUS) could be useful in the diagnosis ofosteoporosis and in discriminating between fractured andunfractured women. Instead, to date few experiences existabout QUS application in the diagnosis of male osteoporosis.

The aim of the present study was to investigate the usefulnessof QUS at phalanxes in male osteoporosis. We studied 88osteoporotic men (59.3�11.0 yrs; 32 with- and 56 withoutosteoporotic fractures) and 120 healthy men (59.8�9.1 yrs). In allsubjects we measured bone mineral density (BMD) at lumbarspine and at femur by DXA (QDR 4500, Hologic, USA) andultrasound parameters at phalanxes by DBM Sonic 1200 (IGEA,Italy). This device gives amplitude-dependent speed of sound(AD-SoS) and other parameters characterising US graphic trace(Fast wave amplitude-FWA, Signal dynamic-SDy, Bone transmis-sion time-BTT and Ultrasound bone pro®le index-UBPI). DBMSonic is characterised by a good precision, i.e. 0.3% for AD-SoS.All QUS parameters were signi®cantly (P<0.001) lower inosteoporotic patients than in healthy subjects, showing amoderate relationship with BMD values at lumbar and femorallevel. As expected, axial and femoral BMD was signi®cantly lowerin fractured group. Among QUS parameters only AD-SoS and BTTshowed a signi®cant difference between fractured and unfrac-tured patients (1938.1�89.9 m/s vs 1995.3�103.8 m/s and 1.4 ms vs1.7 ms, respectively). Moreover, a ROC curves analysis showed agood ability of all QUS parameters in discriminating betweenosteoporotic and healthy subjects, whereas only BTT and AD-SoSshowed a signi®cant, even if moderate, sensitivity in distinguish-ing between osteoporotic patients with or without fracture. Inconclusion our study points out that: in males as well as in womenQUS parameters at phalanxes are able to distinguish betweenosteoporotic and healthy subjects; moreover, BTT and AD-SOScould be useful in discriminating between fractured andunfractured men. Therefore, QUS at phalanxes could be con-sidered a useful tool in the management of male osteoporosis.

320 (296). QUANTITATIVE ULTRASOUND DOES NOT REFLECTMECHANICALLY-INDUCED DAMAGE IN CANCELLOUS BONE

P. H.F. Nicholson, M. L. Bouxsein, Orthopedic BiomechanicsLaboratory, Beth Israel Deaconess Medical Center and HarvardMedical School, Boston, MA, USA

This study assessed the sensitivity of quantitative ultrasound(QUS) to reductions in the elastic modulus (E) of cancellous bonedue to mechanical damage, in the absence of changes inapparent density or architecture. Ultrasonic velocity and attenua-tion were measured using an in-house imaging system in 46cancellous bone cores from the human calcaneus (mean age=82yrs, range=50±99). Cores were tested mechanically to a)determine E prior to damage, b) induce damage by applyingspeci®ed strains in excess of the yield strain, and c) measure Epost-damage. Four groups were used: a control group subjectedto a non-destructive 0.7% maximum strain (em), and three damagegroups subjected to increasing strain levels (em = 1.5%, 3.0%,4.5%). QUS measurements were made before and after mechan-ical testing. At baseline (i.e., before damage was induced), QUSmeasurements were strongly correlated to bone density (r2=0.8570.93, p<0.01) and to E (r2=0.71±0.75, p<0.01). QUS measure-ments were unaffected by mechanically induced damage despite


highly signi®cant reductions in E of up to 72%. These resultsdemonstrate that current QUS measures do not intrinsicallyre¯ect the elastic properties of cancellous bone. This isconsistent with QUS properties being determined by other factors(apparent density and/or architecture) which are normallystrongly associated with elastic properties, but only when boneis mechanically intact. Hence clinical QUS cannot be expected todetect bone fragility in the absence of accompanying changes inbone density or structure.

321 (297). EXCELL, EXCELLplus, REFINEMENTS OF PROVENDXA TECHNOLOGY

J. M. Paucek, L. N. Harrold, Norland MedicalSystems, Inc., FortAtkinson, WI, USA

Norland Medical Systems implemented enhancements to centraldensitometers, to reduce scan times without compromisingprecision or accuracy. A clinical study was undertaken to validatethe performance of these enhancements with respect to previousscanner characteristics. Two Norland scanners, an Eclipse andExcellplus, were used to perform in vitro phantom and in vivohuman scanning. Systems were calibrated according to manu-facturer recommendations. 15 volunteers were recruited. Experi-enced technologists were used for all scanning and analysis.Scan results were as expected, and consistent with previouspublished results, demonstrating the Excell offers signi®cantlyreduced scan times wile retaining continuity with earlier NorlandDXA densitometers.

SCAN SCAN SPEED C.V.

AP SPINE HIGH SPEEDL2-L4 260 mm/SEC 1.1 %HIP HIGH SPEED,FEMORAL NECK 260 mm/SEC 1.4%TROCHANTER 260 mm/SEC 1.5%FOREARM HIGH SPEED,DISTAL RU 20 mm/sec 1.23%Proximal RU 30 mm/sec 0.8%

322 (298). THE UTILITY OF THE ACHILLES STIFFNESSPARAMETER FOR PRE-SCREENING FOR AXIALOSTEOPOROSIS

N. Pocock, N. Culton, G. Gilbert, M. Hoy, R. Babichev, J. Chu, J.Freund, St Vincent's, Liverpool; 2Bankstown Hospitals, Sydney,Australia

Population screening for axial osteoporosis may aid in limiting theincreasing health costs of osteoporotic fractures if it could beprovided on a mass scale. The radiation exposure, and size ofdual energy X-ray absorptiometry (DXA), generally requiring thatscanners be sited within medical centers, limits their utility formass population screening. While quantitative ultrasound (QUS),is radiation free and portable making it ideal for mass screening,previous studies have reached con¯icting conclusions, due oftento the different emphasis placed on the low speci®city of QUS indetecting low axial bone mineral density (BMD), despite itsdemonstrated role as an independent predictor of fracture risk.However even as a screen for low axial BMD, low speci®city maybe acceptable, if high sensitivity can be achieved given the safety,low cost and potential for widespread availability of QUS. Thecurrent study assessed the utility of QUS as a mass pre-screeningtool to stratify the population into a `low risk' group for axialosteoporosis, and an àt risk' group, with a high prevalence ofaxial osteoporosis, who warrant further assessment by DXA. Twohundred females were studied using heel QUS (Lunar Achilles)

and DXA of the lumbar spine and femoral neck (Lunar DPX-IQ orExpert). QUS was `Positive' if the calcaneal Stiffness 470. Usingthese criteria the population was strati®ed into two groups basedon Stiffness. The prevalence of axial osteoporosis, (T4±2.5) ineither the lumbar spine or femoral neck, is shown for the QUSsubgroups for the whole population and for women over 60 yrs.Achilles stiffness 470 identi®es a subgroup in whom furtherassessment by DXA is justi®ed. Pre-screening using Stiffness canstratify the population into `low risk' and àt risk' groups for axialosteoporosis.

Whole Population Women over 60

n Prevalence of axial

osteoporosis (%)

n Prevalence of axial

osteoporosis (%)

US70 74 43 57 53

US>70 126 4 39 8

323 (299). PHALANGEAL OSTEOSONOGRAPHY IN WRISTFRACTURE DISCRIMINATION

R. Rotini1, L.Catamo1, F. Noia1, R. Cadossi2, F. de Terlizzi2, G.Fontanesi1, 1Rizzoli Orthopaedic Institute, 1st Division, Bologna;2IGEA Biophysics Laboratory, Carpi, MO, Italy

In this study we evaluated a group of 50 postmenopausal womenwith low energy forearm fractures and a group of 266 women thatresponded to a public call and that have been measured withultrasound. Measurements were performed at the distal meta-physis of the proximal phalanxes of the hand by the DBM SonicBone Pro®ler using an `àutomatic acquisition mode''.

The reproducibility of the methodology was for AD-SoSCV%=0.64% and for UBPI CV%=2.38. The table shows thecharacteristics of both groups of women and the results of the USmeasurements. We calculated the ROC curves for age-matchedsubgroups of subjects (100 controls and 50 fractured) and theAUC were respectively 0.75�0.04 for AD-SoS and 0.74�0.04 forUBPI.

Our results show that ultrasound investigation at the phalanxesperformed with the `àutomatic acquisition mode'' is reproducibleand ef®ciently discriminates between subjects with wristfractures and a population-based control group. The methodprovides a good reproducibility. The automatic modality of theDBM Sonic Bone Pro®ler is easy to learn and doesn't require askilled operator.

Number Age(yrs)

Age atmenopause(yrs)

AD-SoS(m/s)

UBPI(units)

Control group Avg. and std. 266 60.9 43.0 1915 0.419.1 17.0 111 0.25

Wrist fractured Avg. and std. 50 65.4 47.6 1786 0.176.9 5.7 91 0.13

324 (300). OSTEOPENIC DEGENERATIVE LUMBAR SPINALSTENOSIS IN FEMALE SUBJECTS

H. Sari, U. Akarirmak, C. DoÈ nmez, D. Onel, Cerrahpasa MedicalFaculty, Physical Medicine and Rehabilitation Department,Istanbul University, Istanbul, Turkey

The aim of this study was to investigate the possible role ofosteoporosis in the pathogenesis of Lumbar Spinal CanalStenosis(LSS)


Methods: Bone mineral density was measured by QuantitativeComputerized Tomography(Q-CT) Spinal Canal Stenosis wasdiagnosed by clinical ®ndings and CT measurement. Lumbaraxial shortening was measured on magni®ed lateral topograms.

Results: 32 women with LSS and 72 age matched controls wereincluded in the study. 18 patients were under 50 years of age(56%). 16 patients were premenopausal (50%). Discal bulging in29 patients (90%) and hypertrophy of facet joints were the mustfrequent CT ®ndings

Conclusion: There was a signi®cant decrease in BMC in LSSsubjects compared to controls in the age matched groupespecially in young, menstruating women (n=18.56%). Thus itcould be considered that osteoporosis may be the prime mover insome patients.

325 (301). SEVERE IMMOBILIZING OSTEOPOROSIS ANDCARBAMAZEPINE-INDUCED HYPERCORTISOLISM

H-E Sarnighausen, K Goitom, M Engelbach, T Pohlmann, P Kann,K Lichtwald, J Beyer, Department of Internal Medicine andEndocrinology, University Hospital of Mainz, Germany

The purpose of this investigation was to observe a 77-year-oldmale patient with hypercortisolism of unknown origin andimmobilizing osteoporosis, diagnosed two years ago. A post-operative epilepsia appeared after an operation of a meningiomain 1972. He has not experienced any seizures within the last 6years due to a treatment with carbamazepine. The patient hasbeen diagnosed 6 years ago with carcinoma of the prostate andwas orchidectomized. Methods/Results: AP 304 U/1, g-GT 67 U/1,and an elevated value of cortisol was found in the evening,pathologic overnight dexamethasone suppression test, sup-pressed cortisol in the second half of dexamethasone long testwhich was determined over a period of ®ve days, FSH waselevated, and the testosterone level was low, hyperglycemicsuppressed hGH. No tumor was found in the CT-scan andendosonography of adrenals. Discussion: No sign for adrenal,pituitary or ectopic cortisol production. Lowered ef®cacy of thepituitary feedback of cortisol shown by the elevated cortisol in theevening by carbamazepine [J Clin Endocr Metab 1992;74(2):406±12]. Carbamazepine induces liver-cytochrome-p450-inductionand accelerates the metabolism of dexamethasone [HormMetab Res 1998;30:389±97]. No correlation of bone density andcarbamezepine was found [J Pediatr 1995 Aug; 127(2):256±62]. Inthis case the osteoporosis is probably caused by postoperativehypogonadism.

326 (302). PREGNANCY-ASSOCIATED OSTEOPOROSIS:SEVEN CASES OF PREGNANCY-ASSOCIATEDOSTEOPOROSIS DISCUSSED

T. Sarpel, E. Kozanoglu, R. Guzel, K. Goncu, Dept. of PhysicalMedicine and Reh., Cukurova University, Medicine Faculty,Adana, Turkey

Osteoporosis has been described in pregnant women whodeveloped vertebral and/or hip fractures in their last trimester orshortly after delivery. The etiology of this phenomenon is notknown.

During the last two years we had 7 cases with pregnancyassociated osteoporosis. Osteoporosis was documented withradiographic ®ndings and by bone densitometry test. Also in eachcase other osteoporosis causing factors were eliminated. Thesecases presented with acute low back and/or hip pain. Mean agewas 28.5 (20±35), and 57% of the cases osteoporosis occurredduring the ®rst pregnancy. Vertebral compression fractures wereobserved in all cases, in one patient there was a hip fracture. Allpatients were treated with either bisphosphonates and/or vitaminD metabolites. The response to the treatments will be discussed.

Etiology of the pregnancy-associated osteoporosis is not clear.In our group this is more commonly seen older patients with their®rst pregnancies. We suggest pregnant women with back and/orhip problems during their third trimester or in postpartum periodneeds to be investigated for pregnancy-associated osteoporosis.

327 (303). USE OF PROTON MAGNETIC RESONANCESPECTROSCOPY (1H MRS) FOR ANALYSIS OF LUMBARVERTEBRAE: CORRELATION WITH BONE WEAKENING ANDCOMPARISON WITH DXA

D. Schellinger, C. Lin, J. Lim, A. L. Singer, H. Hatipoglu, D. Fertikh,Georgetown University, Washington, DC, USA

1H MRS is an easy adjunct to spine MRI and may be used to (1)quantify major tissue components of vertebrae and to (2)determine bone strength. The technique can measure the entirevolume of all lumbar vertebrae and will add 1±5 minutes to aroutine MRI. We measured lipid-water-ratios (LWR), percent fatvolumes (PFV), and linewidth. Nomograms for normal subjects(age 15±87; 50 M/46 F) were compiled. In 83 subjects wecorrelated 1H MRS data with MRI signs of bone weakening(fractures, etc.). DXA data of 24 vertebrae (11 subjects) werecompared with 1H MRS data. There was a linear rise of LWR andPFV with age. LWR's of younger subjects (20±39 yrs = LWR 0.31)were markedly lower than those of older people (>80 yrs = LWR1.38). Males showed a higher LWR than females. Subjects withMRI evidence of bone weakening had a higher percent fatvolume. Comparison with DXA showed an inconsistent relation-ship between bone mineral density and percent fat volume. Inconclusion, bone stability is likely determined by multiple factors.1H MRS may provide important additional information about bonestrength.

328 (304). OSTEOPOROSIS PREVENTION COUNSELINGDURING ANNUAL HEALTH MAINTENANCE EXAMS

Sarina Schrager, Department of Family Medicine, University ofWisconsin, Madison, WI, USA

Objective: The purpose of this study was to determine how oftenprimary care providers discussed osteoporosis prevention andadequate calcium intake with healthy women during annual healthmaintenance exams.

Methods and Results: 447 women ages 18±65 were interviewedat eight family practice clinics around the state of Wisconsinimmediately following a health maintenance exam. 46% reporteddiscussing osteoporosis with their provider during the visit and51% reported discussing calcium intake. A total of 61% reporteddiscussing either osteoporosis or calcium intake during the visit.Female providers were signi®cantly more likely to discuss eitherosteoporosis prevention or calcium intake with women. As awoman got older, she was more likely to discuss both of theseissues.

Conclusion: Osteoporosis prevention counseling occursslightly more than half of the time during primary care healthmaintenance exams. Provider education and institutionalchanges may increase the frequency of this counseling.

329 (305). LONGITUDINAL ANALYSIS OF DIAGNOSIS ANDTREATMENT OF OSTEOPOROSIS IN FRACTURE PATIENTS

C. Simonelli, HealthEast Medical Research Institute, St. Paul, MN,USA

The purpose of our study was to determine the rate of diagnosisand treatment of osteoporosis following hospital admission forlow-impact fracture. A chart review and one year follow-up surveyof 301 postmenopausal patients was completed. Retrospective


analysis indicated this population was at high risk for osteoporo-sis and fracture. Despite this, osteoporosis was noted on thehospital chart in only 26% of patients. Calcium and/or vitamin Duse marginally increased from 13.6% on admission to 16.2% ondischarge. Only 39% of women discussed osteoporosis with theirphysician, 10% had BMD testing and only 26% receivedmedication for osteoporosis. Quality of life deteriorated postfracture; 8.4% suffered additional fractures and 77.5% did notreturn to their pre-fracture functionality. The one-year mortalitywas 13%. On the positive side, 86% of those started onosteoporosis treatment remained on therapy for a year.

Conclusion: These patients were at high risk for fracture butmost were not evaluated or treated for osteoporosis. There wasclear deterioration of quality of life post fracture. When physicianschose to intervene and prescribe osteoporosis medication, mostof the women followed their instructions.

330 (306). PERIPHRAL DEXA: AN ECONOMIC ALTERNATIVETO CENTRAL DEXA

Amolak Singh, Houman Kiani, University of Mis souri Hospital,Columbia, MO, USA

Peripheral DEXA (PD) measuring appendicular bone mineraldensity can be helpful in conditions such as hyperparathyroidism.We wondered, if PD can be useful in detecting osteoporosis inpatients who can not afford Central DEXA (spinal and hip DEXA).Limited value of the PD in predicting axial skeletal osteopenia iswell known; however the PD is relatively inexpensive and may beappealing to the under-priviledged population. Four hundred andforty eight (448) patients underwent PD. There were 402 femalesand 46 males. The PD was performed using a low cost devicecalled PIXI (Lunar Corporation). We performed 212 calcaneus and236 forearm (distal radius and ulna) PD studies. Signi®cantosteopenia was de®ned as a T score greater than ±1.2. Theseverity of the osteopenia was graded as mild if T score was morethan ±1.2 but under ±2.0, moderate if T score was more than ±2.0but less than ±3.0, and severe if T score was more than ±3.0.Signi®cant osteopenia was found in 173 of 448 (39%) individualswith age ranging 21±97 years (mean age: 63�13). Of those withosteopenia, the severity was mild in 91 (53%), moderate in 61(35%), and severe in 21 (12%) of patients. The calcaneus andforearm measurements were equally effective in screening. Theosteoporosis was more common in females (39%) than males(33%). The older patients exhibited more severe osteopenia. ThePD may be useful when Central DEXA is cost-prohibitive.

331 (307). RADIUS INDEX: FOREARM BONE DENSITY RATIOAS MARKER FOR TYPE I AND TYPE II OSTEOPOROSIS

Manmohan Singh, University of Illinois at Chicago, IL, USA

PURPOSE of this study is to differentiate Type I (postmenopausal)osteoporosis that results from rapid bone loss after menopauseand affects metabolically active trabecular bone, from type II(age-related) osteoporosis, which affects both cortical, andtrabecular bone tissues.

METHODS involve the use of a Norland 278 SPA densitometerto measure bone density at 5-mm (55% trabecular) bone site indistal radius (DBD), and 2/3rd (95% cortical) bone site in midradius (MBD). DBD/MBD ratio, called radius index (RI), wascalculated to identify women with rapid trabecular bone loss. Twogroups were tested: (1) Normals: 1192 Caucasian women in goodhealth, aged 20±89 years; and (2) Osteoporotics: 186 consecutivepatients in an osteoporosis clinic.

RESULTS indicate that DBD in normal population declinessigni®cantly from 406�54 mg/cm2 (mean�SD) in age group 20±29to 281�48 mg/cm2 in age group 80±89. However, this bone lossdid not signi®cantly change the RI (57�7% in age group 20±29versus 57�9% in age group 80±89) because of balanced

trabecular and cortical bone loss. In osteoporotic patients twodifferent patterns of bone loss were seen (1) Accelerated (type I)trabecular bone loss where low DBD was accompanied by low RI(T-score <±1.0); and (2) Balanced (type II) trabecular and corticalbone loss where DBD was low but RI remained normal.

CONCLUSION of this study is that RI can differentiate type Iosteoporotics with 44% multiple spine fractures from type IIosteoporotics with only 9% multiple fractures.

332 (308). MULTI-SITE ULTRASONOMETRY METHOD FORIMPROVED DIAGNOSTICS IN OSTEOPOROSIS

A. M. Tatarinov1, A. P. Sarvazyan2, 1Riga Technical University,Riga, Latvia; 2Artann Laboratories, Lambertville, NJ, USA

Mono-site QUS usually doesn't discern changes of bone materialand architectural properties. To provide distinctive diagnostics ofosteoporosis of different etiology and manifestation, an ap-proach, utilizing multi-site tests, has been proposed. The idea isto compare changes of ultrasound parameters in differentskeletal area, having prevalence of bulk substance (cortex),spongy tissue and combined spongy and cortical layers. Forthis purpose an experimental set up was built, compiling throughmode and linear array probes, compact controller and mini-PC.Ultrasound velocity and attenuation frequency slope weremeasured in short (heel), ¯at (ilium) and long (ulna, tibia) bones.In phantom studies in¯uence of contributions of mineral content,porosity and thickness of cortex on the said parameters havebeen investigated. First clinical trials involved a limited group offemales with and without osteoporosis symptoms and demon-strated varied combinations of changes of ultrasound velocity inthe sites with compact and spongy bone. Thus, in cases ofchronic renal failure strong lowering was noted in the allmentioned sites. In arthritis patients moderate decrease ofvelocity in heel and ilium was usually accompanied by tends toincrease in cortex of long bones. In the most cases ofpostmenopausal osteoporosis expressed decrease of velocitywas registered in heel and ilium with no marked changes in longbones.

333 (309). DUAL-ENERGY X-RAY ABSORPTIOMETRY (DXA)SCAN INTERPRETATION: LOOKING BEYOND THE NUMBERS

D. J. Theodorou1, S. J. Theodorou1, D. J. Sartoris1, L. J. Deftos2,D. Resnick1, 1Department of Radiology; 2Department of Medicine,Veterans Affairs Medical Center and University of California,School of Medicine, San Diego, CA, USA

Purpose: To investigate DXA scan image ®ndings that deviatefrom anticipated anatomical landmarks and require a sophisti-cated approach to patient positioning, scan analysis, and/or bonemineral density (BMD) determination, with the goal of optimizinginterpretation of computer-generated printouts by clinicians andradiology technologists through radiographic correlation andcritical appraisal of numeric data on DXA scan images.

Patients and Methods: The DXA scan (Lunar DPX, Lunar Corp.,WI) images of 1425 patients referred for 2-site (spine and hip)BMD measurement over a 4-year period were reviewed forvarious artifacts and pathologic processes, and their possiblein¯uence on BMD results.

Results: A wide spectrum of incidental DXA scan image®ndings were identi®ed including degenerative disease of thelumbar spine in 46 (3.2%) cases, fractures in 41 (2.8%) cases,scoliosis in 32 (2.2%) cases, osteoarthritis of the hip in 14 (0.9%)cases, metal artifacts in 13 (0.9%) cases, soft tissue calci®cationin 10 (0.7%) cases, spinal fusion in 8 (0.5%) cases, improperpositioning of regions of interest in 7 (0.4%) cases, metastaticdisease in 5 (0.3%) cases, osteonecrosis of the femoral head in 4(0.2%) cases, and Paget's disease in 2 (0.1%) cases.


Conclusion: DXA provides imaging performance that approx-imates radiographic quality, and may document abnormalitieswhose recognition is critical to optimal interpretation of BMDresults. However, in many cases, the scan quality is insuf®cient toestablish a speci®c diagnosis of ancillary ®ndings; therefore,radiographic or other imaging correlation may be necessary.

334 (310). NORMAL VERTEBRAL DIMENSIONS IN SERIALMEASUREMENTS OF VERTEBRAE: A METHOD USING MRI

E. Thomas, Ph. de Reffye, M. C. Picot, F. Blotman, C. Cyteval,Montpellier, France

Much clinical research on osteoporosis is aimed at documentinga reduction in vertebral fractures rate, but there is disagreementabout de®ning normality. Most methods for measuring vertebralbody dimensions use lateral radiographs. We investigate on thereliability of magnetic resonance imaging (MRI) for normalreferences determination.

A validation study was performed on cadaver by comparingvertebral body volume measured with MRI (sagittal acquisition inT1 weighted sequence) and immersion. The digital data wereconverted to a work station and transfered to a high performancegraphic system (corpus 20001). After manual segmentation,software processing of geometrical measures allows to deter-mine the volume of each vertebral body. MRI was then performedfrom T9 to L5 in a population of 80 women with no vertebralcollapse. All vertebrae measurements were standardized relativeto each other, mean and standard deviation of their volume andmedial area were derived by using a statistical ®tting procedure.

The validation study con®rmes reproducibility and accuracy ofMRI (intraclass correlation coef®cient 0.95). There is a strongcorrelation between volume and medial area of vertebral bodies(Pearson's correlation coef®cient 0.95) and constant relationshipbetween medial area of vertebral bodies for each subject(coef®cient of variation 5.6%).

The notion of normal vertebral body dimensions will allowcomparison with osteoporotic vertebrae and could be useful fortreatments monitoring.

335 (311). HEIGHT LOSS AND VERTEBRAL DEFORMITY INCLINICAL OSTEOPOROSIS

S. E. W. Walsh, S. J. Iqbal, P. R. M. Jones, M. Haddaway, M.Davies, R. Dhingsa, K. Brooke-Wavell, T. Davies, 1From TheLoughborough University, Loughborough, UK; 2Leicester RoyalIn®rmary, Leicester, UK; 3The Robert Jones & Agnes HuntOrthopaedic & District Hospital, Oswestry, UK

Osteoporosis can produce vertebral deformities with total heightloss (THtL) and kyphosis. Can THtL be related to the level ofvertebral deformity? We studied 49 osteoporotics, 43 F, 6 M,mean age 65�12.9, 49 F controls aged 64�10.3. Recalled peakheight (RPkHt) was obtained by a questionnaire and currentheight (CHt) and armspan (ASPN) were measured using a portablestadiometer. Height loss was calculated from: RPkHTt ± CHt =height loss 1 (HtL1) and from ASPN ± CHt = HtL2. Lateral (T4 ± L5)spinal x-rays were used to undertake vertebral morphometry for% wedging, concavity and compression indices using acomputerised image analysis system. Lumbar spinal (L2-L4)bone mineral density (BMD) was measured.

The correlations between: ASPN and RPkHt r = 0.93 p <0.05,and % HtL1 and % HtL2 r = 0.39 p <0.05. HtL2 was signi®cantlydifferent in osteoporotics with vertebral deformity (results inmean�SD) THtL 7.6�4.6 cms to those without vertebral deformityTHtL 3.6�4.1 cm and controls THtL 4.6�3 cms. The BMD wassigni®cantly different in osteoporotics with vertebral deformity(mean SD) 0.78�0.13 g/cm2 and those without vertebral deformity

0.83�0.36 g/cm2 and controls 1.1�0.21 g/cm2. Correlations for %wedging concavity and compression (n = 20) for HtL1 r = 0.31,0.16 and 0.08 respectively and HtL2 r = 0.18, 0.37 and ±0.02respectively. These were not signi®cant. THtL differed inosteoporotics with and without vertebral deformity and withcontrols. THtL was not signi®cantly related to vertebral morpho-metric abnormality in this small sample.

336 (312). FACTOR OF RISK FOR SPINE FRACTURE NORMALCHINESE MEN AND WOMEN IN TAIWAN

Rong-Sen Yang1, Tang-Kue Liu1, Yi-Hsiong Hang1, Poon-UngChieng2, Keh-Sung Tsai3, 1Departments of Orthopaedics;2Radiology; 3Laboratory Medicine, College of Medicine, NationalTaiwan University, Taiwan

INTRODUCTION: To investigate the potential risk of fracture, weassessed the factor of risk (f) of spine fracture in healthy Chinesein Taiwan.

SUBJECTS AND METHODS: 603 females and 223 males aged18±72 years were included in this study. They were divided intoeither young (age <65 years) or old group (age 565 years). Thebone mineral content (BMC) and projection area of lumbar spinewas measured by a Norland XR±26 DXA machine. The estimatedstrength (L) of lumbar spine was calculated from the regressionequation (Carter et al.) and the estimated spinal load (F) for aperson bending over with back horinzontal, either with hand free(F0) or lifting 200N weight (F200), was calculated from forcediagram (William and Lissner). f was de®ned as the quotient of F/L.

RESULTS: The results showed an age-related decrease of BMD(p<0.001) in both genders corrected for weight and height. The ffor F0 and F200 in the old females was signi®cantly larger thanthose of young females, whereas no signi®cant differencebetween the young males and old males. By multiple linearregression analysis, f for F0 and F200 increased signi®cantly withaging corrected for weight and height only in young females(p<0.0001). However, the increment was not signi®cant with agingin both old groups, whereas f for F0 and F200 for the old femaleswere signi®cantly larger than old males (for F0, 0.53�0.10 vs.0.64�0.13, p<0.001, for F200, 0.91�0.16 vs. 1.11�0.22, p<0.0001).

DISCUSSION AND CONCLUSION: This study incorporated thebody status and bone mineral content for estimation of the risk offracture. Such a method may provide a more comprehensiveestimation of fracture risk of spine during daily activities.

Osteoporosis ± Genetics

337 (313). THE RELATIONSHIP BETWEEN DIFFERENTGENOTYPES OF COLLAGEN TYPE I a 1 (COLIA 1) AND BONEMINERAL DENSITY IN POSTMENOPAUSAL WOMEN

Fatma Atalay, Oya Sahin, Volkan Seyrantepe, Gazi UniversityMedical Faculty, Dept Physical Medicine and Rehabilitation,Ankara, Turkey

Objective: This study aimed to investigate the relationshipbetween different genotypes of collagen type I a 1 (COLIA 1)and bone mineral density (BMD) in postmenopausal women.

Material-method: 50 postmenopausal women with no history ofseconder osteoporosis and no usage of any medication that waseffective on bone metabolism except oral calcium replacementwere included to the study. BMD was determined by dual-energyx-ray absorptiometry (DEXA) at lumber spine and right hip. Welooked for presence of signi®cant difference of bone mineraldensity between cases with different genotypes for the bindingsite for the transcription factor Sp1 in COLIA 1 gene.

Result: BMD values, T and Z-scores of the lumbar spine werefound to be the highest in `SS' genotype, they were reduced in


`Ss' genotype and were lower in `ss' homozygotes. However, thedifferences between genotypes were not signi®cant for BMDvalues of the lumbar spine and proximal femur, T and Z-scores ofthe lumbar spine and femoral neck.

Conclusion: We conclude that determination of the genotypeaccording to the polymorphism, de®ned in COLIA 1 gene is notenough for prediction of BMD. Until the studies that are going onmoleculer genetics will result, BMD of the lumbar spine andproximal femur is thought to preserve being the most appropriateway of diagnosing osteoporosis and determining the fracture risk.

338 (314). A FUNCTIONAL POLYMORPHIC VARIANT IN THE IL±6 GENE PROMOTER ASSOCIATED WITH LOW BONERESORPTION IN POSTMENOPAUSAL WOMEN

S. L. Ferrari1, P. Garnero2, Le Ahn-Luong3, H. Montgomery3, S.Humphries3, S. Greenspan,1,4, 1Beth Israel Deaconess MedicalCenter and Harvard Medical School, Boston, MA, USA; 2INSERMUnit 403 and Synarc, Lyon, FR; 3Rayne Institute, Univ. CollegeLondon Medical School, London, UK; 4Univ. of PittsburghMedical Center, Pittsburgh, PA, USA

It has been recently demonstrated that a G±174/C allelic variant inthe Il±6 gene promoter is functional in vitro and in vivo, and thatsubjects with the CC genotype have decreased circulating IL±6levels. The purpose of this study was to investigate the relation-ship between IL±6 gene polymorphisms, markers of boneturnover and bone mineral density (BMD) in postmenopausalwomen. Healthy, community-dwelling women (n=434; >90%Caucasian), older than 65 yrs (mean�SD, 71.7�5.7 yrs), weregenotyped: CC, 68 (16%), GC, 204 (47%) and GG, 162 (37%).Osteocalcin and serum C-telopeptide of type I collagen (CTx)were measured. BMD was evaluated at the proximal femur andwrist by dual-energy X-ray absorptiometry (DXA). Age, height,weight, BMI, and calcium and vitamin D intakes did not differamong genotypes. CTx was signi®cantly lower in CC ascompared to GC and GG subjects: 0.275�0.02, 0.325�0.01 and0.356�0.02 ng/ml, respectively (mean�sem; p = 0.006). The risk ofhaving high bone resorption, i.e. CTx >0.506 ng/ml (the mean+1SD in premenopausal women), decreased with the number of Calleles: odds ratios (95% con®dence interval) 0.65 (0.41±1.0;p = 0.06) and 0.37 (0.18±0.73; p = 0.005) in GC and CC subjects,respectively. In contrast, osteocalcin did not differ among IL±6genotypes. Mean BMD values were 5% higher at the trochanterand Ward's triangle, and 3% higher at the total hip, ultradistalradius and ulna in CC as compared with GG subjects. However,age-adjusted BMD differences approached statistical signi®-cance only at the trochanter (p = 0.09). In conclusion, functionalallelic variants in the IL±6 gene promoter are associated with boneresorption rates in postmenopausal women. Several argumentssupport the reliability of these ®ndings, including the size of eachgenotypic group and the magnitude of CTx differences betweengroups. Nevertheless, there were no statistically signi®cant BMDdifferences among IL±6 genotypes. This might re¯ect the multiplefactors which determine BMD at that age, including the persistingin¯uence of peak bone mass. Further studies will establishwhether IL±6 gene polymorphisms can predict postmenopausalbone loss.

339 (315). BONE LOSS AND BONE TURNOVER IN AGED MEN:HORMONAL AND GENETIC DETERMINANTS

L Gennari1, S. Gonnelli2, L Becherini1, L. Masi1, A. Montagnani2,G. Bargagli2, R. Monaco2, M. B. Franci2, M. L Brandi1, C. Gennari2,1Endocrine Unit, University of Florence, Italy; 2Institute of InternalMedicine, University of Siena, Italy

Predictors of osteoporosis in men are not yet clearly de®ned.Although there are several environmental in¯uences on BMD, a

genetic contribution to the pathogenesis of both female and maleosteoporosis has been recognized. Previous studies examiningthe relationship between candidate gene polymorphisms, such asestrogen receptor (ER) or vitamin D receptor (VDR) genes, andBMD have been performed on women, with con¯icting results.However there are no comparable published data for men. In thisstudy 240 elderly men, recruited by direct mailing (age range 55±88 years) were followed for two years. Femoral and Lumbar BMD(DEXA, Hologic QDR), bone ultrasound parameters at the oscalcis (Lunar Achilles), serum testosterone (T), serum estradiol(E2), sex hormone binding globulin (SHBG), 25OH-vitamin D(25OHD), dehydroepiandrosterone (DHEA), and bone turnovermarkers (a-crosslaps and bone alkaline phosphatase) wereevaluated for each man. Polymorphisms at the ERa (Pvu II, XbaI and TAn repeats), ERb (Alu I), VDR (Fok I) and aromatase (TTTAnrepeats) genes were evaluated after PCR ampli®cation of thepolymorphic sites. No signi®cant relationships of serum T, SHBG,DHEA or E2 levels with bone ultrasound parameters and femoralBMD were observed, even though a serum E2 weakly correlatedwith BMD at the Ward's triangle (r = 0.28, P=0.06). A similarcorrelation was observed between lumbar BMD and serum E2

levels (r = 0.34, P=0.05). Interestingly, the rates of bone loss at thelumbar spine and Ward's triangle resulted signi®cantly higher inmen with a low number of TTTA repeats at the aromatase genethan in those with a higher number of repeats (P=0.01, ANOVA),while the rates of bone loss at the femoral neck were signi®cantlyhigher in men with the ``ff'' VDR genotype than in those with ``Ff''or ``FF'' genotype (P=0.04, ANOVA). Bone alkaline phosphataselevels resulted signi®cantly higher in men with a low number ofTTTA repeats at the aromatase gene than in those with a highernumber of repeats (P=0.03, ANOVA). Taken all together, theseresults con®rm a direct role of estrogens on bone in males andsuggest that different genes may be involved in age-related boneloss at trabecular and cortical bone.

340 (316). EVIDENCE THAT COL1A1 GENOTYPE BUT NOTVITAMIN D RECEPTOR GENOTYPE (VDR) MAY CONTRIBUTETO THE HERITABILITY OF BONE MINERAL DENSITY INPOSTMENOPAUSAL WOMEN (PMW) IN GREECE

E. A. Georgiadis, C. Billi, A. E. Georgiadis, L. Florentin,Osteoporosis Center and Molecular Biology and CytogeneticsCenter of LITO Gynecol Hospital, Athens, Greece

The purpose of this study was to assess whether BMD is relatedto the COL1A1 and VDR genotype in Greek PMW. We havestudied 140 PMW (Mean age 53�6 ys and similar body massindex). 70 of them had osteoporosis at Hip and/or Lumbar spine(LS) (according to WHO criteria) and 70 were normal after BMDmesurements using an Hologic 1000 QDR bone densitometer.Polymorphism of VDR gene was investigated by PCR using TaqIrestriction enzyme and the alleles were characterised (TT, Tt, tt).Polymor®sm of Col1a1 gene was investigated by PCR using BalI restriction enzyme and the alleles were characterised (SS, Ss,ss). The presence of a restriction site was labeled as T or sallele, whereas the absence was labeled as t and S. Our resultsshowed that the proportion of VDR alleles between osteoporoticand normal PMW was approximately the same and the Tgenotype was not found to correlate with low bone mass. Onthe contrary the proportion of the alleles of COL1A1 between thetwo groups (Normals = ss 1% and Osteoporotics = ss 20%)were statistically different (p <0.001) by ANOVA and thepossession of `s' allele was associated with lower BMD at LSand/or hip. Conclusion: There is strong association of COL1A1gene polymorphism and osteoporosis in the Greek PMW andthe `ss' genotype may contribute to the inherited pathologicalcomponent of BMD.


341 (317). ASSOCIATION OF COLLAGEN Ia1 SP1POLYMORPHISM WITH DIFFERENCES IN SPEED OF SOUND INTHE CALCANEUS IN POSTMENOPAUSAL WOMEN

P. Kann,1,3, Y. Fang1, A. P. Bergink2, A. Hofman2, P. L.A. vanDaele1, J. P.T.M. van Leeuwen1, J. Beyer3, A. G. Uitterlinden,1,2, H.A.P. Pols,1,2, 1Dept. of Internal Medicine III; 2Dept. ofEpidemiology and Biostatistics, Erasmus University, Rotterdam,The Netherlands; 3Dept. of Internal Medicine, Endocrinology andMetabolic Diseases, Johannes Gutenberg University, Mainz,Germany

Bone mineral density and fracture risk are under genetic control.An association of the G to T polymorphism of the Sp1 binding siteof the collagen I a 1 gene with the risk for fractures has beenreported previously. This association is only in part explained bydifferences in bone mineral density. Thus, the relationshipbetween the Sp1 collagen I a 1 polymorphism and skeletalfactors other than BMD was analyzed. A parameter characterizingbone material properties and bone stability is the modulus ofelasticity which is a determinator of ultrasound transmissionvelocity (UTV) in bone. In a population based sample of 740women of the age between 55 and 80 years (mean age 64.9�6.5years) we determined collagen I a 1 genotype and UTV in thecalcaneus. UTV in the ``GG'' genotype group was 1522�31 m/s, inthe ``GT'' group 1519�30 m/s, and in the ``TT'' group 1508 m/s(p = .014: ANOVA adjusted for age, height and weight). Calculationof allele-dose-effect showed a mean decrease of UTV 4,312 m/sper each copy of allele ``T'' (p = .016 adjusted for age, height andweight). The differences remained signi®cant after adjustment forbone mineral density measured at the femoral neck. Linearregression analysis showed a progressive negative slope of theregression line of UTV over age from ``GG'' over ``GT'' to ``TT''genotype. These data suggest that collagen I a 1 polymorphism isassociated to the modulus of elasticity of bone as determined invivo by acustical measurement independent of bone mineraldensity.

342 (318). ABSENCE OF THE HIGH RISK `s' ALLELEASSOCIATED WITH OSTEOPOROSIS AT THE INTRONIC SP1BINDING-SITE OF COLLAGEN I a 1 GENE IN SOUTHERNCHINESE

A. W. C. Kung, I. Lambrinoudaki, Dept. of Medicine, University ofHong Kong, Queen Mary Hospital, Hong Kong, PRC

The Sp1 polymorphism in the ®rst intron of the collagen Ia1 genewas recently described to be associated with low bone mineraldensity (BMD) and increased fracture risk in Caucasion popula-tions. The impact of this gene was assessed in a southernChinese population. 181 women, aged 51.1�8.8 years wereevaluated for the Sp1 polymorphism. 22% of the women wereclassi®ed as having osteoporosis on the basis of a T-score at thelumbar spine or the hip below ±2.5 with or without a prevalentfracture. Genotype analysis was performed by PCR ampli®cationand restriction enzyme digestion. Single-strand conformationalpolymorphism analysis (SSCP) was performed in 65 randomlyselected samples to search for any polymorphic site in the PCRampli®ed region. The results showed that no restriction enzymesite could be identi®ed in any of the 181 samples analyzed.Moreover SSCP analysis revealed no polymorphism in the PCRampli®ed region of the ®rst intron of the collagen Ia1 gene. Inconclusion, the `s' allele, associated with low BMD and increasedfracture risk in Caucasians, is non-existent or very rare in thesouthern Chinese population. The absence of this `high risk' allelemay in part account for the reduced fracture risk observed in theChinese in comparison to Western populations.

343 (319). A SYSTEMATIC CANDIDATE-GENE APPROACH FORTHE GENETIC DETERMINANTS OF OSTEOPOROSIS

H. Orimo1, T. Hosoi1, T. Suzuki2, A. Hada3, S. Inoue4, M. Emi5,1Tokyo Metropolitan Geriatric Hospital; 2Tokyo MetropolitanInstitute for Gerontology; 3Asahikawa Medical School; 4Univ. ofTokyo; 5Nippon Medical School, Japan

We have been focusing on candidate-gene approach among thestrategies to investigate the genetic aspects of osteoporosis.Considering the multi-factorial nature of osteoporosis, variousgenes should be considered systematically. We listed a panel ofcandidate genes for osteoporosis, which consists of about 30genes and is being expanded. We used the polymorphic markersin or adjacent to these genes. At ®rst, association studiesbetween BMD and polymorphic markers were conducted in thehealthy un-related postmenopausal women(n=400±500). And thenthe affected sib-pair analysis (approx. 200 pairs) was done usingthe markers which gave positive results in the association study.In additon, single-nucleotide polymorphisms (SNPs) weresearched in the loci of interest. So far, interleukin 6 (IL6) andtransforming growth factor alpha genes gave positive results insib-pair analysis and some novel SNPs were indendi®ed in thepromotor region and exons of IL6 gene. We are elucidating thebiological signi®cance of these polymorphisms in the candidategenes.

344 (320). COLLAGEN TYPE I a 1 GENE POLYMORPHISM INIDIOPATHIC OSTEOPORIS IN MEN

P. Peris, L. Alvarez, J. Oriola, N. GuanÄ abens, A. Monegal, M. J.MartõÂnez de Osaba, J. Jo, F. Pons, A. M. Ballesta, J. Munoz.GoÂ mez, Metabolic Bone Diseases Unit, Hospital Clinic, Universityof Barcelona, Spain

Aims: To analyze the distribution of S/s alleles in collagen 1 a 1 Sppolymorphism (COLIA1) and their relationship with bone meta-bolism parameters and bone turnover in men with idiopathicosteoporosis.

Methods: 35 men (aged 50.4�10.3 yrs) with idiopathicosteoporosis were studied. Serum osteocalcin (BGP), 25-OH-vitamin D and PTH were determined. The COLIA1 Sp1 genotypes(SS, Ss, ss) were assessed by restriction enzyme digestion (Bal 1)of PCR ampli®ed DNA extracted from whole blood. The resultswere compared with a control group of 60 men (aged 47.4�17.6yrs).

Results:

allelic frequency genetic frequency

S s SS Ss ss

Controls (60) 107 (89%) 13 (11%) 48 (80%) 11 (18%) 1 (2%)Patients (35) 50 (71%) 20 (29%) 17 (48%) 16 (46%) 2 (6%)

p = 0.004 p = 0.006

The distribution of genotypes in controls was in HardyWeinberg equilibrium. No dierences were observed betweenSS vs Ss+ss patients or controls in regard to the BGP, PTH and25-OH vitamin D values. Except for allelic and geneticfrequency in COLIA1 polymorphims, no signi®cant dierencesin parameters of bone metabolism were found between patientsand controls.

Conclusion: In men with idiopathic osteoporosis there is a highprevalence of s allele and Ss genotype not related with otherparameters of bone metabolism.


345 (321). LACK OF ASSOCIATION BETWEEN IL±1RA GENEPOLYMORPHISM AND BONE DENSITY IN HUNGARIANPOSTMENOPAUSAL WOMEN

I. Takacs, E. Bajnok, Z. Nagy, G. Speer, M. Kucsera, L. Kiss, Z.Bori, C. Horvath, P. Lakatos, Department of Medicine,Semmelweis University, Budapest, Hungary

Interleukin±1 receptor antagonist protein (IL±1ra) inhibits thebone-resorptive effects of IL±1 and other cytokines. Geneticpolymorphism of IL±1ra gene might have an impact on theeffectiveness of IL±1ra protein, and thus it may in¯uence bonedensity. In this study, we examined whether IL±1ra genepolymorphism is associated with decreased bone mass in 286Hungarian postmenopausal women (age range:40±75). From thiscohort, 98 osteoporotic (OP) patients (mean age: 56.5+7.1) werecompared with 81 (mean age: 54.3+5.5) healthy control (C)women. Bone mineral density (BMD) was measured at thelumbar spine (L2±4) and femoral neck using DEXA method. PCRwas used to amplify polymorphic 86 bp variable number tandemrepeat within intron 2 of the IL±1ra gene. Five alleles wereidenti®ed in the 286 studied subjects. There were three commongenotypes: A1A1 (53.2%), A1A2 (34.9%), A2A2 (8.1%). There wasno signi®cant difference in the allele frequencies of the OP(A1:76.5%, A2:22.4%) and C (A1:69.7%, A2:27.8%) groups. Nosigni®cant effect of IL±1ra genotype on BMD was observed eitherin the whole population or in the subgroups. Our data do notsupport the idea that IL±1ra gene polymorphism have an impacton bone mass in postmenopausal women.

346 (322). DETERMINANTS OF BONE MASS IN CHILDREN 4±6YEARS

M. Willing, J. Torner, T. Burns, J. Warren, K. Janz, S. Levy,University of Iowa, Iowa City, IA, USA

Our work has focused on characterizing biologic variation in bonedevelopment in healthy children, with the goal of understandingthe contribution of genetic, environmental and life-style char-acteristics to bone mass. A cohort of 305 children (145 boys, 160girls, ages 4.3 to 6.5 years; mean 5.2 years) was recruited to thepresent study, which includes bone mineral density (BMD) andcontent (BMC) measurements of the total body, lumbar spine,and femoral neck, as well as genetic studies. We examined allelicvariation at loci for the type I collagen genes (COL1A1, COL1A2),osteocalcin, osteonectin, osteopontin, and the vitamin D (VDR),estrogen and androgen receptors. BMD had a wide distribution(hip 0.409±0.736 g/cm2; spine 0.382±0.685 g/cm2; whole body0.609±0.850 g/cm2). Measurements of body size, including bodymass index (BMI) and height, as well as age and gender hadsigni®cant associations with bone measures. After adjusting forthese factors, preliminary analysis suggests a genetic effect ofboth osteocalcin (C/T promoter polymorphism)and VDR (transla-tion initiation site polymorphism) genotype on hip BMD (p50.05).Data for COL1A1 was suggestive, but did not reach statisticalsigni®cance (p50.10). Our data suggest that genes involved inbone formation and bone matrix structure may be importantdeterminants of bone mass in children. Initial data will bereevaluated when the entire cohort (n=450) becomes available.

347 (323). POSTMENOPAUSAL OSTEOPOROSIS ASSOCIATEDWITH XBAI POLYMORPHIC SITE IN THE ESTROGENRECEPTOR GENE

I. ZÏ ofkovaÂ , K. ZajicÏ kovaÂ , R. Bahbouh, Institute of Endocrinology,Prague, Czech Republic

In this study genes for the vitamin D receptor (VDR), calcitoninreceptor (CTR) and estrogen receptor (ESR) were analyzed inhealthy (n=33) and osteoporotic, but otherwise normal (n=65)Czech postmenopausal women aged 62.3�8.9 years (mean�SD)

for their potential association with postmenopausal osteoporosis.In all subjects the polymorphic variants FokI, ApaI, TaqI and BsmI(for VDR), AluI (for CTR), and XbaI and PvuII (for ESR) weredetermined using a polymerase chain reaction (PCR) andendonuclease digestion. Osteoporosis was diagnozed by dual-energy X-ray absorptiometry (T-score of <±2.5, i.e., more than 2.5SD below the peak bone mass value in the young adult referencepopulation). A signi®cant difference between healthy andosteoporotic women was observed in ESR XbaI polymorphism(Pearson's X2=10.457, p = 0.0054): prevalence of XX homozygoteswas 4.6% in osteoporotic vs 27.3% in healthy women. Nodifferences were, however, found between osteoporotic andhealthy subjects in the remaining investigated genes. This ®ndingsupports the conclusion that ESR gene polymorphism XbaI isassociated with low bone mineral density in postmenopausalwomen. This would contribute to the early detection of the femalepopulation at high risk for postmenopausal osteoporosis, thusallowing application of adequate preventive and therapeutictreatment.

Plenary Session 7: Treatment 1(Saturday, June 17, 0800-1000)

348. HORMONE REPLACEMENT THERAPY (HRT) IMPROVESBOTH ALVEOLAR AND POSTCRANIAL BONE DENSITY

R. Civitelli, T. Pilgram, M. Dotson, J. Muckerman, N.Lewandowski, E. Kardaris, J. Hauser, S. Cohen, M. Vannier, N.Yokoyama-Crothers, C. Hildebolt, Washington University Schoolof Medicine; 2Barnes-Jewish Hospital, St. Louis, Missouri, USA

To test whether the protective effect of HRT on postmenopausalbone loss results in improved oral bone density, we randomized134 postmenopausal women (age 59�6.2; 13.7�11.4 years sincemenopause) to receive either HRT (PremproTM or Premarin1

0.625mg qD) or placebo for 3 years in a prospective, double-blindstudy. All subjects also received daily calcium (1000mg) andvitamin D (800IU) supplements and had yearly dental cleanings.An intention-to-treat analysis was performed at 3 years on allsubjects enrolled (91 completed the study). Bone densityincreased in the HRT group and did not change in the placebogroup at the proximal femur (neck, +2.0�5.5 vs. ±0.2�5.7%; total,+3.6�6.8 vs. +0.2�4.7%, p<0.02). Group differences were notsigni®cant at the spine (+1.0�5.1% vs. +0.2�6.2%; p>0.10),perhaps because of the high prevalence of DJD in thesewomen. Alveolar crest height (ACH) and alveolar bone mass(ABM) were measured from digital images of dental radiographsas indices of alveolar bone loss. Both improved in the two arms ofthe study, suggesting that good dental care and calcium/vitaminD supplementation are very important for oral bone density.However, the increase in ABM was twice as large in the HRT thanin the placebo group (1.8�2.9% vs. 0.9�2.0%; p<0.04), whereas anon-signi®cant trend was observed for ACH (5.0�11.6% vs.3.5�7.3%; p>0.10). Importantly, changes in proximal femur bonedensity were signi®cantly correlated with changes in ABM andACH only in the HRT arm. We propose that improved oral bonedensity constitutes an additional therapeutic bene®t of HRT inpostmenopausal women.

349. NORETHINDRONE ACETATE HAS AN ADDITIVE EFFECTON BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMENTREATED WITH ETHINYL ESTRADIOL

J. P. Symons, N. J. Kempfert, J. A. Simon, J. C. Gallagher, 1Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA; 2Women'sHealth Research Center, Laurel, MD, USA; 3Creighton University,Omaha, NE,

The purpose of this study was to further investigate the additiveeffect of norethindrone acetate (NA) on bone mineral density

Friday/Saturday, June17, 2000 S149

(BMD) in postmenopausal women. It has been previouslydemonstrated that ethinyl estradiol (EE) alone can maintainlumbar spine trabecular BMD. When NA was added to EE therewas an increase in BMD compared to EE alone after 2 years ofcontinuous administration. Signi®cant differences in BMD wereobserved between 5 mcg of EE alone compared to a combinationof 1 mg NA/5 mcg EE suggesting an additive effect of NA whencombined with EE. To further investigate this association 942postmenopausal women were enrolled in a placebo-and positive-controlled clinical trial. All subjects received 100 mg calciumsupplementation daily. Women were randomized to 1 of the 8following treatment groups: placebo, 5 mcg EE, 10 mcg EE, 0.25mg NA/5 mcg EE, 1 mg NA/5 mcg EE, 0.5 mcg NA/10 mcg EE, 1mg NA/10 mcg EE, and 0.625 mg conjugated equine estrogen/2.5mg medroxyprogesterone acetate. Lumbar spine and hip BMDwere measured at baseline and after 6 and 12 months oftreatment. All subjects will have completed the investigation bymid-January 2000 and the data will be available for analysisshortly thereafter. It is hypothesized that the addition of NA willincrease BMD relative to both EE alone or placebo. These resultswill be presented. The relative merits of NA compared with otherprogestins will likewise be established.

350. COST EFFECTIVENESS OF TREATMENTS FOR HIPFRACTURE TARGETTED TO THE GENERAL FEMALEPOPULATION

J. A. Kanis, A. Dawson, A. Oden, O. Johnell, C. De Laet, B.Jonsson, Centre for Metabolic Bone Diseases, University ofShef®eld Medical School, Shef®eld, UK

Current strategies to tackle osteoporosis depend on identifyingindividuals at high risk and thereafter targeting treatments thatare cost effective. From a health economic viewpoint, hipfractures are the dominant complication, the risk of whichincreases exponentially with age. The aim of the present studywas to determine whether age was a suf®cient risk factor suchthat treatments could be targeted effectively to the generalpopulation. We used an established Markov model applied to thefemale population of Sweden using a 5 year intervention thatreduced the risk of hip fracture by 35% during the treatmentperiod, and an effect that reversed to pre-treatment risk duringthe next 5 years.

Cost effectiveness was critically dependent upon the age (i.e.absolute risk) and costs of intervention. Reasonable costeffectiveness ($20±30,000/QALY gained; direct costs only) wasshown even with relatively high intervention costs ($625 perannum) for women at an average risk of hip fracture at the age of85 years or more. For the cheapest interventions ($63 per annum)cost effectiveness could be found from the age of 53 years. Weconclude that segments of the apparently healthy population maybe advantaged by treatment without the necessity for screeningprocedures. Since the identi®cation and treatment of individualsat higher than average risk (e.g. prior fragility fracture) would beeven more cost effective; these data provide a sound basis onwhich to build rational screening strategies, particularly in theelderly.

351. INTRAVENOUS BISPHOSPHONATE THERAPY INCREASESLP (a) AND HDL CHOLESTEROL PLASMA LEVELS

V. Braga, D. Gatti, G. C. Guidi, S. Adami, C. O.C. Valeggio,University of Verona, Italy

Lipoprotein(a) [Lp(a)] is a low density lipoprotein-like particle withathero-thrombotic properties. Lp(a) can be transiently altered bythe acute phase response. Intravenous administration of amino-bisphosphonates are often associated with the appearance of aunique acute phase response. In this study we evaluated the Lp(a)levels, together with other plasma lipids, in 44 women with

postmenopausal osteoporosis given intermittent intravenousNeridronate (50 mg every two months for 12 months). 43women served as controls. In the treated patients bone alkalinephosphatase decreased by 18�22% p<0.0001) within 4 months,remaining unchanged thereafter. Plasma Lp(a) rose progressivelyup to 59�54% (p<0.0001) at the end of the study. A similar trendwas observed for plasma HDL cholesterol (+18�15% p<0.0001 at1 year). Moderate changes were also observed for plasma LDL(75�14% p<0.05), Apo AI (+6�11% p<0.001) and Apo B (±6�14%p<0.05). The serum bone alkaline phosphatase levels werenegatively related to Lp(a) (r = ±0.19 p<0.05). We also studiedthe lipid pro®le in 7 patients after three-monthly Clodronate i.v.infusion (300 mg/day for 5 days) over 6 months. Lp(a) and HDLcholesterol increased by 19�25% (p = 0.09) and by 7�13% (n.s.),respectively. The results of this study show a surprisinginterconnection between bisphosphonate therapy and lipidmetabolism. This interconnection open a new horizon in ourunderstanding of skeletal metabolism. It is somewhat associatedwith the following known ®ndings: 1. Apo(a) [a major componentof Lp(a)] is a member of kringle containing proteins, includingplasminogen activator, which is an osteoblast responsive elementto PTH and other cytokines. 2. The sequence of Apo(a) genecontains several IL6 responsive elements.

352. INTERVENTION STUDY WITH HIP PROTECTORS INORTHOPEDIC PATIENTS WITH HIP FRACTURES

K. Hindsù, J. B. Lauritzen, 1Department of Orthopedic Surgery,Hvidovre Hospital; 2University of Copenhagen, Denmark

Objective To evaluate the effect of hip protectors on risk ofsubsequent hip fractures among elderly orthopedic patientsadmitted with hip fractures.

Design Open prospective case cohort study among elderlyorthopedic patients more than 74 years of age admitted toorthopedics with falls or fractures. A total of 303 patients withfractures at Hvidovre Hospital were offered three sets of hipprotectors (SAFEHIP) and 244 patients at Bispebjerg Hospitalwere controls. Patients were followed from 1 to 1� year. p = 0.05,one alfa.

Results The annual rate of second hip fractures in the controlgroup was 4.6 %. Primary acceptance of hip protectors was 65%. Based on intention to treat analysis the relative risk (RR) was0.83,ns. Based on primary acceptance the RR was 0.73, ns (n 196)and based on continued use referred to still possessing hipprotectors the RR was 0.64, ns (n 110). For those who used hipprotectors regularly or every day the RR was 0.0, p = 0.03 (n 60).

Conclusion Hip protectors demonstrated a signi®cant protec-tive effect against second hip fracture among hip fracture patientswho wore hip protectors on a regular basis and eliminated hipfractures in this subgroup. Based on intention to treat the RR wasreduced by 17%. For those who were registered as having andstill possessed hip protectors the RR for a new hip fracture wasreduced by 36%.

353. SCREENING FOR OSTEOPOROSIS: 5±7 YEAR DATA ONHRT ADHERENCE, BONE LOSS AND FRACTURES RATES

D. J. Torgerson1, A. Stewart2, D. M. Reid2, 1Dept of HealthStudies, York University; 2Osteoporosis Research Unit,Department of Medicine & Therapeutics, University of Aberdeen,UK

Between 1991±3 2051 women aged 45±49, selected at random,were invited to have their BMD measured. The lowest 25% ofBMD at either the hip or spine were encouraged to take HRT toprevent fractures. In 1998/9 the women were recalled to havetheir BMD re-measured and to assess HRT adherence. 1501(73%) were remeasured of whom 538 were current HRT and 334were past users (median length of use for current users 5.0 years).

S150 Saturday,June17, 2000

54% (n=117), 42% (n = 138) and 30% (n = 283) of women with lowBMD at both sites, one site or neither site respectively werecurrent HRT users (p50.001 for trend). 1154 women (77%) hadlost bone at the spine, whilst 347 gained bone or stayed the same.Of current HRT users 39% (n= 212) gained bone or stayed thesame compared with only 14% (n=135) of never or ex-users(p50.001). HRT users with low BMD at baseline lost an average of±0.7% of BMD at the spine compared with ±7.4% of BMD forwomen with low BMD who were not using HRT (p<0.001). 65women out of 645 had suffered a fracture with current HRT usershaving a 30% lower fracture rate compared with all other women(p = 0.21). In conclusion, about seven years after BMD measure-ment about 50% of women with low BMD were still using HRTand this was associated with a 7% difference in BMD, and anonsigni®cant 30% reduction in fracture rates compared with nonHRT users.

Plenary Session 8: Males(Saturday, June 17, 1030-1230)

354. BONE MINERAL DENSITY AND PREDICTION OFMORTALITY IN MEN: THE ROTTERDAM STUDY

M. van der Klift1, C. E.D.H. de Laet1, J. M. Geleijnse2, A. Hofman2,H. A.P. Pols3, 1Institute of Medical Technology Assessment;2Departments of Epidemiology; 3Internal Medicine, ErasmusUniversity Rotterdam, The Netherlands

Recent studies have shown an inverse relationship between bonemineral density (BMD) and mortality. However, most studies onlyinvestigated this relationship in women. Our aim was to model therelation between BMD and all cause mortality in men. In theRotterdam Study, follow-up till 31st March 1997 was complete for2445 men aged 55 and over for whom BMD data were available.During an average follow-up time of 4.7 years, 340 men deceased.We calculated Z-scores from the BMD, which was measured atthe femoral neck. Cox' proportional hazards was used to ®t themodel. An average BMD (Z-score of zero) was used as reference.A cubic model best ®tted the relationship under study, also afteradjusting for age and body mass index. Our model shows that therisk of mortality exponentially increases when BMD is belowaverage. Similar results were found when separate curves weremade for diabetics and non diabetics, smokers (ever or never),and tertiles of BMI. Analysis were repeated excluding subjectswho had suffered hip fractures, adjusting for the number of drugsused and for lower limb disability, respectively, which resulted insimilar risk estimates. Our results suggest that in men a non-linearrelationship between BMD and mortality exists, independent ofcomorbidity and impaired mobility.

355. ANDROGEN RECEPTOR CAG REPEAT POLYMORPHISM:A NOVEL MOLECULAR MARKER OF OSTEOPOROTIC RISK INMEN

J. M. Zmuda1, J. A. Cauley1, L. H. Kuller1, A. B. Newman1, J.Robbins2, T. Harris3, R. E. Ferrell1, 1Universities of Pittsburgh,Pittsburgh, PA; 2California, Davis; 3The National Institute OnAging, Bethesda, MD, USA

Androgenic effects on bone are mediated through the androgenreceptor (AR), a ligand activated transcription factor. The AR genecontains a CAG repeat polymorphism in exon 1 that codes for apolyglutamate sequence of variable length. This polymorphismin¯uences AR trans-activation, with longer CAG repeats con-ferring reduced transcriptional activation of androgen targetgenes. We tested the hypothesis that longer AR CAG repeatsare associated with osteoporotic risk in 508 Caucasian men (age565 yrs) who were participants in the population-basedCardiovascular Health Study. Men with longer CAG repeats(highest tertile) had lower bone mineral density (BMD) at the

femoral neck compared to men with shorter repeats (lowesttertile) (0.736�0.14 vs 0.774�0.13; p<0.05). The prevalence ofosteoporosis (T score 4±2.5) was also greater in the highestcompared with lowest tertile of CAG repeat size (16.1% vs 5.5%;p<0.01), equivalent to an odds ratio (OR) of 3.57 (95% C.I.: 1.54,8.29). This association was attenuated (OR: 2.70; 95% C.I.: 1.14,6.43) after adjusting for the signi®cantly lower body weight of menwith longer repeat size. These results suggest that the AR CAGrepeat polymorphism is a novel molecular marker of osteoporosissusceptibility in older men, and that this effect may be mediatedin part through body weight.

356. BIOAVAILABLE ESTRADIOL MAY BE AN IMPORTANTDETERMINANT OF OSTEOPOROSIS IN MEN. THE MINOSSTUDY

P. Szulc1, F. Munoz1, B. Claustrat2, P. Garnero1, F. Marchand3, F.Duboeuf1, P. D. Delmas1, 1INSERM Research Unit 403, Lyon,France; 2Hopital Neuro-Cardiologique, Lyon, France; 3SSMB,Montceau Les Mines, France

Experimental data suggest that estradiol may play an importantrole in bone metabolism in men, but clinical evidence is limited. Ina cohort of 596 men aged 51 ± 85 yrs, we measured bone mineraldensity (BMD) of the spine, hip, total body (HOLOGIC QDR 1500)and forearm (OSTEOMETER DTX 100), serum levels of sex streoidhormones (total and free testosterone ± fT, total estradiol ± E2 andbioavailable estradiol ± bioE2, androstendione, sex hormonebinding globulin) and levels of markers of bone turnover (serumosteocalcin ± OC, bone alkaline phosphatase ± BAP, N-terminalextension propeptide of type I collagen ± PINP, b-isomerized C-terminal telopeptide of collagen type I ± bCTX as well as urinaryexcretion of bCTX, free and total deoxypyridinoline ± fDPyr,tDPyr). An age-related decrease was found for bio-E2 (r = ±0.16,p = 0.0001) but not for total E2. E2 and bio-E2, bur not otherhormones, were correlated with BMD after adjustment for ageand body weight (e.g.: total hip BMD ± r = 0.16, p<0.001 andr = 0.14, p<0.002 respectively). In age- and body weight-adjustedmodels, bio-E2, but not other hormones, was negativelycorrelated with bone markers (e.g.: OC ± r = ±0.13, p<0.002,serum and urinary bCTX ± r = ±0.18, p = 0.0001 and r = ±0.13,p<0.002, respectively). In the age- and body weight-adjustedmultiple regression models, bio-E2 contributed signi®cantly to theexplanation of the variability of all the markers.

In summary, we have found in a cross-sectional analysis of acohort of men that low levels of bio-E2 are associated with highbone turnover and low BMD. These data suggest that low E2levels may be an important mechanism of osteoporosis in men.

357. GENDER DIFFERENCE IN MORTALITY AFTER HIPFRACTURE

L. E. Wehren, W. Hawkes, J. R. Hebel, S. I. Zimmerman, D. Orwig,J. Magaziner, Univ of MD, Baltimore, MD, USA

Mortality during the 1 to 2 years after hip fracture has been shownto be higher among men than women. Is this due to differences inage, medical comorbidity, functional limitation, metabolic de-rangement, or another factor? We investigated this in a cohort of804 community dwelling men and women in the Baltimore HipStudies who sustained hip fracture and were followed for 2 years.Men were younger (79.5�7.6 yr vs 81.6�7.3 yr), had more baselinecomorbidiy (3.6�2.2 vs 3.2�2.0 conditions), and had longerhospitalization after fracture (17.2�11.3 vs 14.3�8.3 days), buthad no difference in baseline physical or instrumental activities ofdaily living and experienced fewer post-operative complications(1.4�1.4 vs 3.2�2.0) than women. There were no differences intype of fracture or surgical procedure, time to surgery or baselinehemoglobin and hematocrit; however, men had higher ASAscores (2.9�0.6 vs 2.7�0.6) and were more likely to have chest

Saturday,June17, 2000 S151

X-ray abnormalities (47.3% vs 37.3%). Men lived signi®cantlyshorter times (517.2�292.7 vs 624.4�230.0 days); only 57.6% ofmen were alive at 24 months, compared to 76.7% of women. Inlogistic regression modeling, the unadjusted odds ratio (OR) formale survival was 0.428 (95% CI 0.292, 0.628); adjustment for age,comorbidity, complications, ASA score, chest X-ray abnormal-ities, and length of stay produced only a small change in this OR,to 0.492 (95% CI 0.320, 0.755), so that these factors, althoughsigni®cantly associated with survival, do not explain the observedgender difference. The increased vulnerability of men whofracture their hips deserves further careful study.

358. SPINE BONE MINERAL DENSITY PREDICTS VERTEBRALDEFORMITY LESS WELL IN MEN THAN WOMEN: DATA FROMTHE CANADIAN MULTICENTRE OSTEOPOROSIS STUDY(CAMOS)

D. T. Drinkwater1, W. P. Olszynski2, T. M. Murray3, 1University ofSaskatchewan, Saskatoon, SK, Canada; 2Saskatoon Centre ofCaMos; 3University of Toronto, Toronto, ON, Canada

CaMos is a population-based prospective cohort study whichrepresents an age, gender and region speci®c sample of non-institutionalized Canadians. This study allows us to look at theprevalence of vertebral deformities (VDF) and investigate therelationship of VDF to bone mineral density (BMD), especially inolder men. The number, type and severity of VDF for men andwomen, aged 50±96y, were evaluated from spinal X-rays. BMD atthe lumbar spine L1-L4 (LS) and femoral neck (FN) was assessedusing dual-energy X-ray absorptiometry. Of 1745 men and 4383women we found [mean (SD); n, %]:

# LS BMD (g/cm2) FN BMD (g/cm2)VDF Men Women* Men Women*

0 1.041(.173) 0.921(.162) 0.798(.124) 0.702(.117)1374, 78.7% 3363, 76.7% 1374, 78.7% 3363, 76.7%

1 1.037(.176) 0.897(.174) 0.770(.122) 0.665(.113)252, 14.4% 670, 15.3% 252, 14.4% 670, 15.3%

2 0.934(.185) 0.834(.175) 0.717(.121) 0.630(.116)71, 4.1% 204, 4.7% 71, 4.1% 204, 4.7%

3 1.044(.183) 0.835(.180) 0.740(.145) 0.619(.103)27, 1.5% 90, 2.1% 27, 1.5% 90, 2.1%

4 0.937(.194) 0.731(.193) 0.717(.158) 0.546(.100)13, 0.7% 24, 0.5% 13, 0.7% 24, 0.5%

5+ 0.834(.151) 0.738(.195) 0.642(.120) 0.533(.154)8, 0.5% 32, 0.7% 8, 0.5% 32, 0.7%

*p<0.05, women dierent from men at each site

There was a progressive decline in BMD with increasingnumber of VDF for both men (LS: r = ±0.09, FN: r = ±0.17, p<0.01)and women (LS: r = ±0.17, FN: r = ±0.23, p<0.01). At both sites, forthe same number of VDF, BMD values were greater for men thanwomen, although the dierences are less at the FN site. LS BMDwas not as highly correlated with VDF as was FN BMD in bothgroups, possibly the result of trauma or osteophytes. Weconclude that in older men FN BMD appears to be a morereliable predictor of VDF than LS BMD.

359. POLYMORPHISM AT COL1A1, VITAMIN D RECEPTORGENE & RISK OF LOW TRAUMA HIP FRACTURE IN ELDERLYMEN

Ira Pande1, S. H. Ralston2, D. L. Scott3, A. D. Woolf1,1Rheumatology Unit, Truro; 2Dept of Medicine & Therapeutics,Aberdeen; 3Rheumatology Unit, London, UK

Background: BMD is under strong genetic control. Polymorph-isms in the vitamin D receptor (VDR) & the collagen type1a1(COL1A1) gene account for some of the variation in bone

mass in women. There is little data addressing its association withfracture risk in men.

Aim: To analyse the associations & linkage of the Sp1polymorphism in the COL1A1 gene & VDR genotype with BMD& hip fracture risk in elderly men.

Method: 100 men aged over 50 with low trauma hip fracture andequal matched controls were prospectively recruited. Wholeblood for genetic studies was collected at ®rst visit; in cases thiswas within 48 hours of the fracture. BMD was measured by DXA(Hologic QDR±1000) at both the lumbar spine and femur in allcontrols and 62 cases; in cases this was within 1 week of fracture.Col1A1 Sp1 and VDR Bsml genotyping was performed usingstandard techniques.

Result: Fracture cases were older, had lower weight, BMI &BMD compared to controls (p<0.01). Smoking habits, alcoholconsumption, dietary calcium intake and steroid usage weresimilar in the two groups. Cases had signi®cantly more co morbidconditions like Parkinsons, dementia, poor vision and strokereducing mobility (p<0.01).

The frequency distribution of the VDR and Col1a±1genotypeswas similar in cases and controls: (cases Vs controls VDR 15.8%Vs 16% for BB, 48.4% Vs 55% for Bb and 35.8% Vs 29% for bb;Col1a±1 70.2% Vs 64% for SS, 27.7% Vs 32% for Ss and 2.1% Vs4% for ss). Between group comparison by ANOVA showed nodifferences in age, BMI, BMD, vitamin D, parathyroid, androgens(total testosterone, free testosterone, free androgen index,oestrogens (total and free oestradiol), osteocalcin & urinarydeoxypyridinoline among the three VDR and Col1a±1genotypes.

Repeat analysis comparing these variables between menhaving the less favourable allele B (genotypes BB & Bb) withthose without it (homozygous bb) showed no difference. Nodifferences were seen in men with the unfavourable s gene(genotypes ss & Ss) compared to those homozygous for SS.

Conclusion: Our results indicate that VDR and Col1a±1 genepolymorphism is not related to risk of low trauma hip fracture inelderly men. There is no relation to BMD, calciotropic hormones,sex steroids and bone markers.

Osteoporosis ± Pathophysiology

360 (324). MAGNITUDE AND DETERMINANTS OF VITAMIN DINSUFFICIENCY AND DEFICIENCY IN ELDERLY FEMALEOUTPATIENTS: AN ITALIAN MULTICENTER STUDY

S. Adami1, R. Giorgino2, on behalf of the Italian Multicenter StudyGroup, 1Verona, Italy; 2Rome, Italy

Previous studies have shown high prevalence of hypovitaminosisD in elderly Mediterranean people: in Italy, available data arelimited to selected areas. Over a period between Feb. 15th andMarch 15th 1999, an observational study was conducted in 43Italian hospital and university out-patients centers. A medicalhistory and a life-style questionnaire were administered to 799postmenopausal women (age range 60±80 years, median 67) attheir ®rst Osteoporosis work-out. A blood sample was taken forcentralized 25(OH)D and PTH assays. 25(OH) levels 412 ng/mlde®ned Vitamin D insuf®ciency (VDI): 45 ng/ml de®ned a VitaminD de®ciency (VDD) status. Overall, 74% of the patients showed25(OH)D levels 412 ng/ml: 28% of the total patients werede®cient. In 570 years old subgroup, the prevalence of VDI andVDD were respectively 78% and 36%. A signi®cant squarenegative correlation was observed between 25(OH)D and PTHlevels (p = 0.003; r2=0.13). Low sun exposure was mildlyassociated with VDI (p = 0.05): increased PTH levels (p<0.01)were seen in patients with reduced sun exposure. Vitamin Dde®ciency was strongly associated with Activities of Daily Livingimpairment: speci®c ADLs i.e. dif®culty in using stairs (p<0.05),walking at least 400 m (p<0.05), carrying a heavy thing (p<0.001),going in and out of bed (p<0.05), managing ®nances (p<0.05),doing heavy housework (p<0.01) were associated with low


25(OH)D levels. Patients with an history of chronic diseasesshowed an higher prevalence of VDI (76% vs 69%, p<0.05). Moreinterestingly, diabetic patients had a very signi®cantly higherprevalence of VDI (87% vs. 72%, p<0.0001): 39% of diabeticpatients were Vitamin D de®cient. An history of cerebro-vasculardiseases was strongly associated with VDI: 87% and 53% ofthese patients showed 25(OH)D levels respectively 412 and 45ng/ml (both p<0.0001 vs. controls). Twenty-three women (3% ofthe total population) reported an hip fracture: 90% of themshowed 25(OH)D levels 412 ng/ml and 50% were vitamin Dde®cient. In conclusion, this study con®rm the wintertime highprevalence of VDI and VDD in elderly free-living subjects: even ifthis observation is limited to a time of the year corresponding to25(OH)D levels nadir, it seems that hypovitaminosis D affectsoverall QoL beyond its detrimental effects on bone health. Furtherstudies need to be done to explore the potential mechanismbehind the signi®cant association of diabetes and cerebrovas-cular diseases with low 25(OH)D levels.

361 (325). A COMPARISON OF BONE QUALITY IN PAST ANDMODERN POPULATIONS

S. C. Agarwal,1,3, M Dumitriu3, M. D. Grynpas,2,3, 1Department ofAnthropology, Department of Laboratory Medicine andPathobiology, U of Toronto, SLRI of Mount Sinai Hospital,

As osteoporosis has become a growing health concern, there hasbeen steady interest to investigate the prevalence of the diseasein the past. Although a number of studies have shown low bonemass in past populations, few have shown fragility fracture. Inorder to examine age and sex-related changes in bone quality inthe past as compared to modern populations, a study was madeof trabecular bone architecture in a British historic skeletalcollection. X-rays of 5mm thick coronal sections from lumbarvertebrae were taken from 55 adult individuals (m=24, f=31)divided into three age categories (18±29, 30±49, 50+ yrs), andexamined using image analysis to evaluate parameters related totrabecular bone structure and connectivity. A signi®cant age-related loss in the amount (TBV%) and connectivity of bone wasfound between the youngest and the two older age groups, andloss appeared to be greater in males than females. Thesepatterns contrast with those shown in modern populations thatexhibit continuing loss between middle and old age, and greaterloss in females. We speculate that the early age loss may berelated to nutritional de®ciency, while ``lifestyle'' factors such asphysical activity, parity and prolonged periods of lactation mayexplain the low prevalence of fragility fracture and maintenance ofbone connectivity in the oldest age groups.

362 (326). LOW SERUM 25-HYDROXY VITAMIN D ± A POSSIBLECAUSE FOR LOW BMD AT PROXIMAL FEMUR IN HEALTHYINDIANS

V. Arya1, A. Mithal2, 1Department of Endocrinology, Nizam'sInstitute of Medical Sciences, Hyderabad, India; 2IndraprasthaApollo Hospital, New Delhi, India

Osteoporotic fractures are more common amongst Indians andoccur earlier than Caucasian counter part. Subclinical vitamin Dde®ciency is known to increase bone resorption and it isconsidered as a risk factor for osteopenia and fractures. Thereis lack of data regarding the determinant of hip fractures inIndians. Thus, to determine the association between BMD andvitamin D status this prospective study was undertaken.

Material and methods: We studied 75 young healthy volunteers(56 females, 19 males) for daily sun exposure, vitamin D statusand bone mineral density. Sample for serum intact parathormone(iPTH) was collected in 15 volunteers. 25-hydroxy vitamin D

[25(OH)D] estimated by RIA (INCSTAR Inc.) and serum iPTHestimated by two-site binding IRMA assay (DPC Inc.). BMD wasestimated by dual energy X-Ray absorptiometry (DXA) (Hologic-QDR 4500A).

Results: Only 19/75 (25.3%) of the subjects had serum 25 (OH)D concentration above 15 ng/ml. 37/75 (56%) had severe vitaminD de®ciency. Mean of sunlight exposure in our subjects was 11.356.8 minutes per day (range: 5±25 min/day) involving face and armsupto elbow. There was strong correlation between the duration ofsun exposure and 25-hydroxy vitamin D level (r = 0.731, p<0.001).Secondary hyperparathyroidism was found in 7/15 subjects.There was signi®cant linear correlation between serum 25(OH)vitamin D concentration and iPTH. BMD of spine and appendi-cular bone was signi®cantly lower in healthy Indians whencompared with Caucasians normals. There was signi®cantpositive correlation between serum 25-hydroxy vitamin Dconcentration and BMD of ward's triangle and femoral neck(r = 0.50, p = 0.020 and r = 0.46, p = 0.037 respectively).

Conclusions: Despite adequate sunlight throughout the year,hypovitaminosis D is frequent in Indian normals. Low vitamin Dlevels are associated with secondary hyperparathyroidism andlower BMD at femoral neck predisposing Indians at higher risk ofhip fracture.

363 (327). A LARGE ANIMAL MODEL OF OSTEOPOROSIS: THEOVARECTOMIZED AND CORTICOID TREATED SHEEP

P. Augat, C. Gohl, A. Ignatius, S. Iwabu, L. Claes, OrthopedicResearch and Biomechanics, University of Ulm, Germany

To create persisting osteopenic bone in a large animal, 24skelettally mature merino sheep (mean age: 6.1 yrs�0.8 yrs) wererandomly assigned to ovarectomy alone (OVX), ovarectomycombined with glucocorticoid treatment (OVX+GLU) (0.45 mgMethylprednisolon per kg body weight for 6 months), or notreatment (CONTROL). Bone biopsies were harvested 6 monthsafter ovarectomy and onset of treatment from the proximal tibia toassess trabecular bone. The biopsies were scanned for bonemineral density by Quantitative Computed Tomography (XCT960,Stratec) and tested mechanically in uniaxial compression.

The BMD of the bone biopsies was signi®cantly decreased inthe OVX+GLU group (p50.01, Dunnett's test) but not in the OVXgroup (p>0.1; Figure). The elastic modulus decreased by 5% inthe OVX group (p>0.1) and by 53% in the OVX+GLU group (p<0.1).Ovarectomy in combination with glucocorticoid treatment gen-

erates osteopenia of trabecular bone in sheep and may serve as anew large animal model for the study of osteoporosis.

364 (328). B12 DEFICIENCY ± ITS ROLE IN THE DEVELOPMENTOF OSTEOPOROSIS

J. Beynon, C. Murray, S. Vasishta, Dept. of Adult Medicine, St.Woolos Hospital, Newport, UK

Pernicious anaemia (PA) and B12 de®ciency have previouslybeen identi®ed as a risk factor for osteoporosis and itsassociated fractures. The pathophysiologic process is mediatedthrough a suppression of osteoblastic activity due to the


de®ciency in B12. These data highlight that the role of PA andB12 de®ciency as a risk factor for osteoporosis should not beforgotten. To determine the prevalence of B12 de®ciency inpatients with osteoporosis the following study was undertaken.Over a 3-month period the authors reviewed the case notes ofpatients attending the bone clinic. Patients were included in thestudy if they had osteoporosis con®rmed by bone densitymeasurement (BMD). The following data were collected on eachpatient: Basic demographic data, past medical history, fracturehistory, baseline blood count and B12 level, current therapy withB12, BMD measurement. Within this unit normal B12 referencerange is 176±760 ng/l. The data was strati®ed by age, B12 leveland fracture history. 263 patients were included (19 men, 244women). The number of patients in each age range with B12values of 5176ng/l is as follows: 3714 (21.4%) aged 55 years orless, 15/82 (18.2%) aged 56 ± 65,20/110 (18.1%) aged 66 ±75,6/57 (10.5%) aged 76 or above. Of the 44 patients with low B12values 22 had sustained a previous fracture. In only one patientwas another condition identi®ed which would account for thelow B12 value. None of the patients with a low B12 value had ahaemoglobin value below 11g/dl. In this patient population thelevel of previously unidenti®ed B12 de®ciency was in the orderof 16.7%. There have been no large scale studies to show thatB12 replacement improves BMD and reduces fracture risk.However as B12 de®ciency has been shown to suppressosteoblastic activity, enhancing B12 levels should reverse thisaction and consequently lead to an improvement in BMD. Wewould therefore recommend B12 levels be measured as part ofthe diagnostic workup in patients with osteoporosis as it is aneasily treatable.

365 (329). ABSTRACT WITHDRAWN

366 (330). ABSTRACT WITHDRAWN

367 (331). ESTROGEN INCREASES CARTILAGE FORMATIONAND FRACTURE HEALING STRENGTH IN OVX RATS

M. E. Bolander, J. T. Bronk, G. Sarkar, Mayo Clinic and MayoFoundation, Rochester, MN, USA

The protective effect of estrogen (E2) on bone mass in post-menopausal women is well documented; however, the effect ofestrogen depletion on fracture repair has not been evaluated. Wereport that E2 replacement improves fracture healing in OVX rats.

Fractures were made in 120 six-month old rats. Of 90 OVXanimals, 60 were given E2 replacement. Animals were killed attimes representing speci®c stages of fracture healing; specimenswere taken for histology, evaluation of gene expression, andmechanical testing. OVX animals without E2 replacement hadsigni®cantly weaker fracture calluses, and decreased cartilageformation on histology (p<0.05). Evaluation of gene expressionshowed a 13-fold increase in the expression of estrogen receptorduring fracture healing, to a level 70% of that found in the ratuterus. Cartilage-related genes, including type II collagen andaggrecan were expressed at lower levels in the callus from OVXanimals.

Intramembranous bone formation was also decreased in OVXanimals, but histology and evaluation of gene expressionsuggested this was secondary to abnormal endochondralossi®cation. E2 administration normalized cartilage formation,cartilage gene expression, and mechanical properties of thefracture callus. These studies suggest that fracture repair isabnormal in osteoporotic women. Estrogen replacement appearsto normalize the fracture healing process.

368 (332). RELATIONSHIP BETWEEN AWAKENING SALIVARYCORTISOL AND BONE QUALITY IN PREMENOPAUSALWOMEN

K. Brooke-Wavell1, A. Clow2, P. Evans2, S. Ghazi-Noori2, F.Hucklebridge2, 1Dept. Human Sciences, LoughboroughUniversity; 2Psychophysiology and Stress Research Group,University of Westminster,

Cortisol levels show diurnal variation, peaking 30 minutes afterawakening then declining to lower levels for the remainder of theday. Negative associations between 24 hour or basal cortisollevels and bone density have been reported, but the relationshipbetween cortisol levels during the awakening peak and bonedensity has not been studied. We thus examined this relationshipin a group of premenopausal women. Subjects were 40 healthy,eumenorrhoeic, non-smoking women aged mean (SE) 30.7 (1.5) y.Saliva samples were collected on awakening and 30 and 240(n=32) minutes thereafter. Broadband ultrasonic attenuation(BUA) and speed of sound (SOS) were measured at thecalcaneus.

Salivary cortisol concentrations at 0, 30 and 240 minutes afterawakening were 4.7 (0.5), 8.6 (0.8) and 4.3 (1.1) nmol/l. Afteradjustment for body mass, BUA and SOS were positivelycorrelated with awakening cortisol concentrations but not thoselater in the day (r = 0.36*, 0.40* and ±0.09 for BUA and 0.27, 0.36*and 0.05 for SOS at 0, 30 and 240 minutes after wakingrespectively, *P<0.05). In contrast to previous reports that cortisollevels at other times of day are related to poorer bone density, our®ndings suggest that high cortisol levels on awakening areassociated with better bone quality.

369 (333). REDUCING SODIUM INTAKE REDUCES URINARYCALCIUM LOSSES IN THE ELDERLY

F. P. Cappuccio, A. M. Blackwood, G. A. Sagnella, N. D.Markandu, C. Carney, G. A. MacGregor, BPU, Department ofMedicine, St George's Hospital Medical School, London, UK

Background. High salt intake is associated with reduced peakbone mass in young girls and a high rate of bone mineral loss inpostmenopausal women. It is also associated with increasedurinary calcium losses. However, it is not clear whether this is acausative effect and whether it may be quantitatively compatiblewith a negative calcium balance.

Methods. Forty-seven untreated elderly individuals (24 men, 42whites, mean age 66.8�5.3 years, range 60±78) completed a 2-month double-blind randomised placebo-controlled study ofmodest salt restriction with slow sodium and placebo to give asalt intake of either 10g (equivalent to the usual amount for the UKand many western populations) or 5g.

Results. On the higher sodium intake urinary calcium excretionwas 5.19 (SD 2.41) mmol/day with a urinary sodium excretion of177 (49) mmol/day. With modest sodium reduction, urinarycalcium fell to 4.06 (2.12) mmol/day (p<0.001) with a urinarysodium excretion of 94 (50) mmol/day. A reduction in sodiumintake of 83 mmol/day was associated with a reduction in urinarycalcium excretion of 1.13 (95% CI: 0.74±1.52) mmol/day. Urinarysodium excretion was strongly and directly associated withurinary calcium excretion on both the high (r = 0.591; p<0.001)and the reduced (r = 0.475; p<0.001) sodium intake. The changesin urinary calcium per 100 mmol/day changes in sodium excretionwere similar on the high (2.32 [0.64] mmol/day) and on thereduced (2.53 [0.51] mmol/day) sodium intake. The changes incalcium excretion were directly associated with the changes insodium excretion (r = 0.530; p<0.001). It was estimated that achange in 100 mmol/day of sodium excretion would predict 1.19(0.28) mmol/day changes in urinary calcium excretion.

Conclusions. The higher the sodium intake, the higher theurinary calcium losses in an elderly population. A modestreduction in salt intake causes a signi®cant reduction in urinary


calcium losses in older people. This might be equivalent to a bonemineral density loss of 1.5% per year. A high salt intake, at least inthe short term, is directly responsible for inappropriate urinarycalcium losses in older people who are at much greater risk ofdeveloping bone demineralisation. Our results may have im-portant implications for a nutritional approach to the prevention ofosteoporosis and bone fractures in older people.

370 (334). LOW S-ESTRADIOL LEVELS ARE PREVALENT INMALES DIAGNOSED WITH PRIMARY OSTEOPOROSIS

C. G. Carlsen, T. H. Sùrensen, E. F. Eriksen, UniversityDepartment of Endocrinology, Aarhus Amtssygehus, Aarhus,Denmark

Recent studies suggest that estrogens may be more powerfulregulators of bone remodeling in adult males than androgens. Wetherefore investigated estrogen and androgen status in 54 malesdiagnosed with primary osteoporosis in our clinic over a period of3 years. The diagnosis was based on the presence of either lowenergy fractures or a BMD t-score 5±2.5 in the spine or hip.

The subjects underwent extensive clinical examination andbiochemical testing in order to exclude secondary osteoporosis.15 (28%) were classi®ed as secondary osteoporosis (3(5.5%)displayed primary hypogonadism). 39(mean age 58.3 years) wereclassi®ed as primary osteoporosis. 21 exhibited one or morevertebral fractures, 30 a lumbar BMD t-score 5±2.5 and 24 a hipBMD t-score 5±2.5. S-estradiol was assessed using sensitiveassays (detection limits 40 pM). Among the 39 males with primaryosteoporosis, mean S-testosterone was slightly elevated, with amedian value of 19 nM (normal mean for men 50±70 years is 14.6nM (range 8.4±25.4 nM)). Circulating S-estradiol levels were,however, low in a large fraction of the material. 14 of 39 patients(36%) displayed S-estradiol levels below the normal range (48±165 pM; p<0.001).

These results indicate that estrogen de®ciency is much moreprevalent than androgen de®ciency in male osteoporosis.Estrogen de®ciency constitutes a dominating pathogeneticfactor underlying low bone mass in males diagnosed with primaryosteoporosis using currently recommended screening tests.Future screening tests for male osteoporosis should thereforeinclude assessment of S-estradiol.

371 (335). DOES LIFE-LONG INGESTION OF FLUORIDATEDWATER ALTER BONE QUALITY IN HUMANS?

D. Chachra, H. Limeback, A. E. Gross, C. H. Hutchison, D. Zukor,M. Schwartz, M. D. Grynpas, University of Toronto and Mt. SinaiHospital, Toronto, Canada

The purpose of this study is to assess the effects of life-longingestion of subclinical amounts of ¯uoride on the quality ofhuman bone (including chemical composition, mechanical prop-erties, mineralization, and architecture) as a surrogate for itseffect on fracture risk. Femoral heads were obtained during totalhip arthroplasty from 39 patients from Toronto (where municipalwater has been ¯uoridated at 1 ppm for >30 years) and 20 fromMontreal (where water is not ¯uoridated). The F content ofcancellous bone from each specimen was determined by neutronactivation analysis (Toronto mean: 1035(192±2264) ppm F;Montreal mean 643(295±1200) ppm F; p<0.01). Cylinders (6mm6 6mm) of cancellous bone were subjected to compressivemechanical testing, but no relationship was found betweenmechanical properties and F content. The microhardness, whichis related to the mineralization, was measured at a number ofsites; at one of them, it was found to correlate linearly andpositively with the F content (R2=0.304; p<0.001). Image analysisof radiological sections indicated that some connectivity para-

meters decreased with F content (p<0.05); however, this variationwas not observed in histological sections. In conclusion, life-long¯uoride ingestion does not appear to alter the mechanicalproperties of human bone, although there may be a subtleeffect on the architecture and mineralization. Jewish GeneralHospital and McGill University, Montreal, Canada.

372 (336). THE QUEST (QUALITATIVE EFFECTS OF SALMON-CALCITONIN THERAPY) STUDY: AN UPDATE OF THEBASELINE DATA

C. Chesnut1, A. Shields1, P. Schmeer1, S. Majumdar2, D. Newitt2,P. Richardson3, A. Kriegman3, L. Mindeholm3, 1OsteoporosisResearch Group, University of Washington, Seattle, WA; 2UCSF,San Francisco, CA; 3Novartis, East Hanover, NJ/Basel,Switzerland

The QUEST study is a 2 year phase IV double-blind randomizedcontrolled clinical trial designed to de®ne the mechanism ofaction of nasal spray salmon calcitonin vs. placebo in reducingfracture (Chesnut C. et al, 2000), utilizing multiple innovativetechnologies for assessing at multiple skeletal sites the inter-relationship between bone quantity (BQUANT): DXA/US; bonequality (BQUAL): bone biopsy histomorphometry/micro CT/highresolution magnetic resonance imaging (MRI); and bone turnover:serum/urine NTx. Currently under analysis in the enrolled 91postmenopausal osteoporotic (con®rmed fractures by x-ray)women are 1) baseline (BL) assessment of the relationshipbetween BQUANT (DXA/US) and BQUAL (MRI) at the sameanatomical site (os calcis), 2) BL assessment of BQUAL in termsof trabecular bone architecture and structure as measured atmultiple anatomical sites with differing technologies (iliac crest:bone biopsy histomorphometry and micro CT, hip: MRI, os calcis:MRI), and 3) the relationship of BQUANT (DXA/US) and BQUAL(histomorphometry/ micro CT/MRI) to severity of disease in termsof vertebral fracture severity. Our underlying hypotheses in termsof the ongoing BL analyses are that 1) BQUANT and BQUAL arediscordant at the os calcis, 2) BQUAL is concordant in terms oftrabecular structure across multiple sites and techniques, and 3)BQUAL will be a greater determinant of disease severity thanBQUANT. Data currently analyzed will be presented.

373 (337). PULMONARY FUNCTION CHANGES IN SPINALOSTEOPOROTIC PATIENTS

A. CoÈ mlekci2, A. Alacacioglu1, B. Pamuk1, E. Ceylan3, A. Y.Goktay4, A. Akkoclu3, S. Yesil2, 1Dept. of Internal Medicine;2Division of Endocrinology; 3Dept. of Pulmonary Medicine; 4Dept.of Radiology, Inciralti, Dokuz Eylul Univ. Medical School, Izmir,Turkey

Osteoporotic patients may have impaired quality of life for severalreasons. However few data are present on the degree of theseverity of vertebral deformity due to vertebral fractures onpulmonary function. We have investigated the effects of thedegree of vertebral deformity on spirometry and lung volumes on55 osteoporotic patients patients, 51 female, 4 male, mean (�SD)age 62.4�8.2 years). Patients having previous history ofpulmonary disease, smoking and diabetes were not included instudy. Severity of osteoporosis was determined by calculation ofthe spine deformity index (SDI) (SDI-total and SDI-anterior) onlateral radiograph of the spine as described before.

Although there was no signi®cant difference in spirometry andlung volumes between patients having SDI41 and SDI>1, therewere signi®cant negative correlations between SDI and vitalcapacity (VC), FEF25±75, RV/TLC, ERV (p<0.05) in patients withSDI>1.


These data suggest that osteoporotic patients having nopulmonary complaint may have subclinical pulmonary changesdue to the degree of severity of vertebral deformity.

374 (338). CITRATE LEVEL IN OSTEOPOROTIC WOMENTREATED WITH ESTROGEN AND ALENDRONATE

P. D'Amelio1, M. Beccattini2, G. P. Pescarmona2, G. C. Isaia1,1Department of Internal Medicine; 2Department of Genetic,Biology and Biochemistry, University of Turin, Italy

The aim of our work is to investigate the behaviour of plasmacitrate in women with postmenopausal osteoporosis and treatedwith HRT or Alendronate. Basal citrate level was detected in 28women with postmenopausal osteoporosis (T-score 5±2.5 S.D.).16 patients where treated with HRT and 8 with Alendronate andthe citrate level was measured (using a spectrofotometricmethod) at 3 and 6 months of therapy. The citrate were comparedto each other using the Student's T-test. Our results are shown inthe table:

HRT (16) ALENDRONATE (8)

mean S.D. mean S.D.' P

Basal' 127 mmol/L 26 107 mmol/L 26 NS3 months' 102 mmol/L 18 122 mmol/L 296 months' 110mmol/L 27 122 mmol/L 29

The variation of citrate were signi®cant considering the HRTgroup: basal/3 months p = 0.0045, basal/6months p = 0.009, 6months/3months p = NS, wile in the Alendronate group citrate didnot change. Our data show that citrate signi®cantly decrease after3 month of HRT and remains unchanged after 6 months, while it isnot in¯uenced by Alendronate. Citrate level seems to be greatlyin¯uenced by estrogen therapy, these data led us to suppose theimportance of estrogen in determining Krebs cycle and our worksuggests the citrate as a possible ``new marker'' of short termecacy of HRT and of patient's compliance.

375 (339). METABOLIC ACTION ON BONE OFANTICONVULSANT THERAPY IN INSTITUTIONALIZEDPATIENTS SUFFERING FROM EPILEPSY

J. P. Devogelaer, M. Divry, T. De Barsy, Depts Rheumatology andNeurology, St Luc University Hospital, Brussels, and LennoxInstitute, Ottignies, Belgium

Anticonvulsant therapy (ACT) has been for a long time a well-accepted cause of disturbed bone metabolism (BM), mostlyosteomalacia (OM), in patients suffering from epilepsy (E). Wehave assessed the parameters of BM in 30 institutionalizedpatients (A 45.2 (10.4); 16 F, 14 M). BMDs of the lumbar spine (L)and of the hip were measured by DXA using a QDR 4500 (Hologic,Inc.). The results (M � SD) are summarized in the table. There wasan excellent correlation between bone-speci®c alkaline phospha-tase (BAP) and total (T) AP (r2 = 0.58; p50.0001), BAP and urinary(U) NTX/cr (r2 = 0.53; p50.0001) and between TAP and uNTX/cr(r2 = 0.56; p50.0001). Ten percent of patients had a serum Calevel lower than the inferior limit of normal (N) versus 13%, 31%and 35% for P, 25OHD, and 1,25(OH)2D, respectively. Seventypercent of patients had their gGT level higher than the superiorlimit of N, vs 16%, 28%, 3% and 46% for TAP, BAP, iPTH anduNTX/cr, respectively. Z-scores of the BMD of the spine and ofthe total hip amounted to ±0.83 (1.27) and ±1.34 (0.72),respectively. There was a negative correlation between L-BMDand TAP (r2 = 0.33; p50.001), and BAP (r2 = 0.17; p50.05),trochanter and TAP (r2 = ±0.12; p50.05) and BAP (r2 = ±0.11;p = 0.05).

In conclusion, bone turnover is increased in up to 46% ofinstitutionalized patients suffering from E. TAP and to a lesserextent BAP constitute the best predictors of BMD in institutiona-lized patients treated by ACT.

Tot. Ca

mg/dl NV

8.8±10.4

P

mg/dl

2.4±4.4

gG T

IU/l

4±44

TAP

IU/l

65±215

BAP

mg/l

2.9±14.5

25OHD

ng/ml

10±40

1,25(OH)2D

pg/ml

18±45

iPTH

pg/ml

10±60

uNTX/cr

nM/mM

3±65

Mean 9.22 3.15 69 166 12.4 24.3 27.0 27 69

SD 0.32 0.63 53 51 4.6 18.4 15.6 13 41

376 (340). LOW MINERAL BONE DENSITY IN PROFESSIONALSCUBA DIVERS

F. Costa Dias, J. A. Pereira da Silva, J. E. Fonseca, H. CanhaÄ o, C.Resende, M. Viana Queiroz, 1Rheumatology Unit, Santa MariaHospital, Lisbon, Portugal

Scuba diving is associated with a 90 % reduction in effectiveweight and with the loss of a weight bearing effect on joints (dueto a loss of contact with the ground). These conditions are verysimilar to the continuous weightlessness exposure that occurs inspace¯ight, which is clearly associated with signi®cant bonemass loss. In addition to this, the increase in blood CO2, observedfrequently in diving, can also cause an inhibition of osteoblastsand an increase in bone resorption. All these arguments areconsistent with the hypothesis of a bone mass reduction infrequent scuba diving.

Objectives: Evaluate the bone mass and osteoporotic riskfactors in a population of professional scuba divers.

Material and methods: 66 professional scuba divers, working inthe portuguese navy, randomly selected, all male, with a meanage of 33.5�6.5 years and a mean diving time of 31793�19591minutes, during the last ®ve years, were submitted to a bonemineral density (BMD) measurement with DXA and queried aboutosteoporotic risk factors.

Results: The mean vertebral (L1-L4) BMD was 1.07�0.14 g/cm2

(Tscore + 0.17�1.12) and the mean femoral (neck) BMD was0.95�0.12 g/cm2 (Tscore ± 0.29�1.06). 16.7% had a BMD 1 SDbelow the reference population in trabecular bone (L1-L4), 22.8%had a BMD 1 SD below the reference population in cortical bone(femoral neck) and 3% a BMD 2,5 SD below the referencepopulation in cortical bone (25.8% had a BMD 1 SD below thereference population in cortical bone). No signi®cant differenceswere found between the osteopenic and the normal groupsconcerning the amount of alcohol, coffee and calcium consump-tion, age, body mass and diving time. Nevertheless, a signi®cantlyhigher weight bearing physical activity was found in the groupwith normal BMD (p = 0.017, comparing differences in corticalbone). Curiously, a higher tobacco consumption was found in thenormal BMD group (p = 0.006, comparing differences in trabecularbone).

Conclusion: We have found a reduction of BMD in professionalscuba divers, mainly in cortical bone (25.8%) but also intrabecular bone (16.7%). The major additional factor in¯uencingthe BMD was weight bearing physical activity.

377 (341). BONE DENSITY IN PREMENOPAUSAL WOMEN WITHENDOMETRIOSIS AND DURING TREATMENT OFENDOMETRIOSIS

L. Diveky1, M. Hudecova1, P. Payer1, K. Holoman1, M. Krizko1, P.Suska1, 1Dept. Ob/Gyn, Comenius University, Bratislava, Slovakia

OBJECTIVE: To investigate the impact of endometriosis on bonedensity and to evaluate the effect of add-back treatment ofmedrogestone on bone mineral density (BMD) under conditions


of estrogen withdrawal in women with endometriosis who weretreated with Decapeptyl depot.

METHODS: We compared BMD in three groups of 40premenopausal women. The patients were examined for endo-metriosis by laparoscopy or laparotomy because of benigngynecological pathology. Endometriosis was diagnosed in 20patients. They were divided to two groups. A-group (n=10) wastreated by Triptorelin combined with either placebo or 10 mg/dMedrogestone (group-B, n=10) for six months. C-group containedremaining 20 women without endometriosis.

RESULTS: Lumbar spine BMD was measured at 0 and 6 month.Patients in both groups (A and B) had a similar and signi®cantdecrease in BMD after six moths (4.5%, p50.01). Bone density ofthe lumbar spine in month ``0'' were: A-group 0.887�0.335 B-group 0.930�0.34; C-group 0.895�0.29; Statistical analysis wasperformed by means of Student ``t''-test; signi®cance was set upat p<0.05.

CONCLUSION: No signi®cant correlation was observed be-tween any bone density measurement and severity of endome-triosis. Add-back treatment with medrogestone at 10mg/d doesnot prevent lumbar bone density loss in premenopausal womenunder estrogen deprivation. For de®nitive practice conclusions, abigger study is needed.

378 (342). RHEUMATOLOGICAL DISEASES AS RISK FACTORSFOR OSTEOPOROSIS

R. Dreher, G. Lingg, J. Listing, A. Zink, 1Hospital for RheumaticDiseases, Bad Kreuznach; 2Epidemiology Department, GermanRheumatism Research Center, Berlin,

Aims: To compare different rheumtological diseases as riskfactors for osteoporosis. To de®ne patients functional capaclty,severity of the disease, disease duration and in¯ammatoryactivity as risk factors for osteoporosis.

Methods: In cooperation with the National Database of theGerman Cooperative Arthritis Center Berlin, the database of theHospital for Rheumatic Diseases Bad Kreuznach was cross-sectionally evaluated for osteoporosis in women >50 years withvarious underlying rheumatological diseases. Osteoporosis wasde®ned as values for bone mineral density 2.5 SD. or more belowthe young mean in LDXA or SDXA (LUNAR) or below 122 mg HAE(Hydroxy Apatite Equivalent) in lumbar QCT (General Electric 3000single energy scanner). Logistic Regression analysis models withosteoporosis (yes/no) as the dependent variable and variousrheumatological diseases, age, functional capacity FFBH (Hann-over questionnaire score for function), severity of disease(asymptomatic, slight, moderate, severe, very severe) diseaseduration (52 years, 3±10 years, >10 years, ESR (mmW), C-reactive protein (mg/l) and steroid treatment >1 year >7.5mg/d,<7.5mg/d) as covariables were calculated in respect of the risk forosteoporosis (odds ratio) associated with a given number ofindependent variables.

Results:Osteoporosis (number of women with osteoporosis: number of

total women, %) in women >50 years, dependent on theunderlying rheumatological disorder:

Connective Tissue Diseases (17/103, 16.5%), PolymyalgiaRheumatica (54/173, 31.2%), RF pos. Rheumatoid Arthritis (329/953, 34.5%), RF neg. Rheumatoid Arthritis (142/595, 23.9%).Osteoarthritis (141/1158, 12.2%). Ankylosing Spondylitis (12/35,34.3%). Low Back Pain Syndrome (76/408, 18.6%)

Risk factors for osteoporosis calculated as odds ratios (OR) inlogistic regression analysis models adjusted for age Underlyingrheumatological diseases (OR for osteoporosis comparedwith osteoarthritis): 1) Connective Tissue Diseases OR = 1.85,2) Polymyalgia Rheumatica OR = 2.65), 3) RF pos. RheumatoidArthritis OR = 3.45, 4) RF neg. Rheumatoid Arthritis OR = 2.56,5) Ankylosing Spondylitis OR = 5.13.

Functional capaclty (Hannover questionnaire score (FFBH%)for function. OR compared with FFBH = 70±100%): functional

capacity FFBH 0±50% OR = 2.09, functional capacity FFBH 50±70% OR = 1.34 n.s. Severity the disease (OR compared with slightdisease): asymptomatic disease OR = 1.19 n.s., moderate diseaseOR = 2.15, severe disease OR = 3.6, very servere disease OR 7.2Disease duration (OR compared with disease duration 52 years):3±10 years OR = 1.17 n.s., >10 years OR = 1.80 Erythrocytesedimentation rate (OR compared with ESR 530 mmW): ESR 30±50 mmW OR = 1.17 n.s., ESR > 50 mmW OR = 1.30 n.s. C-reactiveProtein (OR compared with CRP 520 mg/l): CRP 20±30 mg/l OR1.34 n.s., CRP >30mg/l OR = 1.14 n.s. Steroid treatment >1 year(OR compared with no steroids) 57.5 mg/l OR = 1.80, >7.5 mg/lOR = 1.83

Conclusion: In¯ammatory rheumatological diseases, severity ofthe disease, disease duration and steroid treatment areassociated with an elevated risk for osteoporosis.

379 (343). EVIDENCE FOR CONTINUED BONE LOSS AFTERCARDIAC TRANSPLANTATION ± A CROSS SECTIONAL STUDYIN 53 PATIENTS

A. Fahrleitner, G. Prenner, D. Kniepeiss, K. H. Tscheliessnigg, L.Stach, C. Piswanger-Solkner, G. Leb, H. Dobnig, Dept. of InternalMedicine, Dept of Surgery, Div. of Endocrinology, Div. ofTransplantation, Karl Franzens University, Graz, Austria, Europe

It is well known that cardiac transplant recipients have a highprevalence of osteoporosis (OPO) before transplantation andusually demonstrate signi®cant bone loss following cardiactranplantation (CTX) with a maximum in the ®rst postoperativeyear. The aim of this study was to evaluate bone mineral ± andfracture status in long-term survivors after CTX. We studied 53patients with an average of 55�5 (SE) mos after CTX. In allpatients a hip DXA, a standardized spinal X-ray and laboratorytests were performed. None of the patients were on osteopro-tective therapy and all received a triple immunosuppressivemedication. WHO-de®ned OPO at the hip was diagnosed in 42%(n=22) of patients, 36% (n=19) had one or more vertebral fractures(3.5#/pat), 74% (n=39) had renal impairment, 62% (n=33) 28 HPTand 30% of all males (n=12) had evidence of primary hypogonad-ism. Patients with vertebral fractures had signi®cantly reduced Z-and T-scores at the hip (±1.14�0.22 vs.±0.40�0.21 and ±2.7�0.22vs.±1.76�0.24, p<0.02) when compared to non-fractured subjects.Fractured patients tended also to have higher creatinine-, PTH-and serum cross laps levels but were comparable in mean timesince CTX to unfractured individuals. To further analyze timeeffects on bone mineral status we grouped patients intocategories A (12±24 mos), B (25±48 mos) and C (49±148 mos)according to time since CTX and could demonstrate a fall in meanz-score (neck) from ±0.43�0.2 to ±0.52�0.3 and ±0.91�0.27 (NS). Inaddition, patients belonging to group C had lower z-scores(trochanter) when compared to group A (±1.0�0.24 vs.±0.26�0.2,p<0.04) and higher creatinine-, PTH-, cross laps- and lowertestosterone values than in the early posttransplantation period.

This cross-sectional study suggests that bone loss extendsover the immediate post-operative period and that additionallong-term complications such as renal impairment, 28 HPT andhypogonadism may contribute to further worsening of bonestatus.

Men

(n=40)

Women

(n=13)

p-value men

vs. women

Normal

range

Age 56.5�0.2 60.2�1.4 NS

Z-score femoral neck ±0.8�0.2 ±0.3�0.2 NS

Z-score trochanter ±0.5�0.2 ±0.4�0.2 NS

T-score femoral neck ±2.2�0.2 ±1.9�0.2 NS

T-score trochanter ±1.1�0.2 ±1.3�0.3 NS

Serum PTH 95�11 136�41 NS 10±65 pg/ml

Serum cross laps 4881�453 6776�1548 NS 1465±4565 pmol/l

Serum osteocalcin 49�5 62�20 NS 10±30 ng/ml

25-OH vitamin D3 20�1.8 15�3.2 NS 9±45 ng/ml


380 (344). LONGITUDINAL CHANGES OF BONE TURNOVERAND BONE LOSS ACCROSS THE MENOPAUSE. THE OFELYSTUDY

P. Garnero,1,2, E. Sornay-Rendul, F. Munoz1, P. D. Delmas1,1INSERM Unit 403, Lyon, France; 2Synarc, Lyon, France

Crossectional studies indicate an increase of both bone formationand bone resorption after the menopause. Whether bone turnoverincreases before menopause is still unclear, because of the lackof longitudinal studies. In this study, a measurements of markersof bone formation [serum osteocalcin (OC) and bone alkalinephosphatase (BAP)] and of bone resorption [urinary C-telopeptideof type I collagen (CTX] and of FSH was performed annually in 257healthy untreated women (mean age, 41.4 yr) followed prospec-tively for a mean (SD) of 5.1 (1.2) yr (range 2±6 yr). At baseline, 186women (w) were classi®ed as premenopausal (FSH levels <16.7UI/l, mean age 39 yr), and 71 as perimenopausal (FSH levels >16.7UI/l with or without irregular menses, mean age 48 yr). Duringfollow-up, 44 premenopausal w. became perimenopausal, 13premenopausal w. became postmenopausal (absence of mensesfor at least 1 yr) and 33 perimenopausal w. became postmeno-pausal.

In the whole population, increased levels of FSH wereassociated with a higher bone turnover (r = 0.27, p = 0.005 andr = 0.22, p = 0.02 for CTX and osteocalcin respectively). Among w.who remained premenopausal, levels of bone formation markersremained unchanged and urinary CTX slightly decreased withtime. In w. who remained perimenopausal during the study (meanfollow-up: 4.3 yr), bone turnover progressively increased withtime (0.76 ng/ml/yr, p = 0.003 and 0.29 ng/ml/yr, p = 0.06, for OCand BAP respectively). In w. who became perimenopausal, levelsof serum OC, BAP and urinary CTX increased and the mean levelswere respectively 17% (p<0.0001), 11% (p<0.0001) and 21%(p = 0.03) higher than the premenopausal values in the samesubjects. Bone turnover markers further increased after estab-lished menopause with values 20±35% higher than perimeno-pausal values in the same subjects (p<0.001). No signi®cantchange of bone mineral density at the mid radius was observed inwomen who remained premenopausal, perimenopausal or whobecame perimenopausal during the study. In contrast womenwho changed from a perimenopausal to a postmenopausal statushad a signi®cant bone loss of 0.4% per year which was correlatedwith increased baseline levels of CTX (r = ±0.41; p<0.03).

In conclusion this longitudinal study indicates that boneturnover begins to increase before the menopause, during theperimenopausal period, and that this increase precedes boneloss

381 (345). LIPOPROTEINS INFLUENCING MENOPAUSAL BONELOSS

R. Gass, E. Bally, ISPM, Epidem., University of Zurich, Zurich,Switzerland

For the prevention of osteoporosis we have to identify causal co-factors.

Methods. In a prospective two-year study the bone mass andloss of 70 healthy women, on average 52 years old and not takinghormones, were measured one to four years after naturalmenopause by peripheral QCT (type Densiscan); additionally, ina cohort study the bone mass in women aged 560 years withseveral years (range 1 to 20) after menopause, the half of these152 measured women being treated with estrogens (HRT).

Results. Regarding the annual change of the pure trabecularbone mass at the ultradistal radius in the two-year study, theprevalence of fast bone-loser women (trabecular bone loss >3.8% per year) is 34 %, the distribution of the bone loss rates beingbimodal. The logistic regression shows: the lower the trabecularbone mass and the higher the ratio of apolipo-proteins B to A1,the greater is the probability that the particular woman has anaccelerated bone loss; moreover, this risk is independently lower

for women with three or more pregnancies, but higher ifnulliparity. For women with pure trabecular bone mass in thethree lower quintiles (<274 mg/cm3), being nulliparous and/orhaving a ratio of apo B to A1 in the top tertile (>0.67), theprevalence of fast bone-loser women is 79 %. The initial values inthe cohort study con®rm these results, the trabecular bone mass(means in mg/cm3) at radius being by non-biased groups:

Apo-ratio >0.72 and/ornulliparous

Apo-ratio 40.72 and one ormore pregnancies

Women N Mean (SEM) N Mean (SEM) P

± without HRT 36 208 (11) 41 236 (8) <.05± with HRT 37 247 (9) 38 256 (10) n.s.P (two-tailed) <.01 =.12

With growing postmenopausal years, only in women withoutHRT trabecular bone masses decrease and the apo-ratiosincrease continuously.

Conclusions. There is good evidence that bone metabolism isin¯uenced by lipid metabolism. With the ending of menstruation,in women with insuf®ciently developped trabecular bone (bonemass 5median) the high ratio of apolipoproteins B to A1 is aspecial risk factor for osteoporosis, suggesting an associationwith atherosclerotic disease.

382 (346). BONE LOSS IN EARLY, ACTIVE RHEUMATOIDARTHRITIS: EFFECTS OF CORTICOSTEROIDS, GENDER ANDMENOPAUSAL STATUS IN THE COBRA TRIAL

P. Geusens,1,2 A. C. Verhoeven2, M. Boers3, J. M. te Koppele4, W.H. van der Laan4, H. M. Markusse5, S. van der Linden1,1Rheumatology Dept, Academic Hospital, Maastricht University,The Netherlands; 2Biomedical Research Institute, LUC,Diepenbeek, Belgium; 3Clinical Epidemiology & Biostatistics, VUUniversity Hospital, Amsterdam; 4TNO Prevention & Health,Vascular and Connective Tissue Research Division, Leiden;5Rheumatology Dept., Zuider Hospital, Rotterdam, TheNetherlands

The degree of bone loss in rheumatoid arthritis (RA) is still amatter of debate. Many clinical studies use mixed patient groupsof men and women with variable disease duration and intensity ofsteroid therapy. In a double blind randomized trial, a group ofpatients with early, active RA was treated with sulfasalazine (SSZ,n=79) or a combination of sulfasalazine + methotrexate +prednisolone (60 mg/d in week 1 tapered to 7.5 mg maintenancedose in week 7) during 6 months, followed by sulfasalazine alone(COMB, n=76) (Lancet 1997; 350: 309±18). All had supplements ofcalcium (500 mg/day) and, if vitamin D de®cient, with vitamin D(400 IU/day). Mean (95% C.I.) lumbar bone density changes over56 weeks were ±1.3% (±2.3, ±0.4) in the COMB group and ±0.3%(71.4, 0.8) in the SSZ group (p = 0.15). In the femoral neck, bonedensity changes over 56 weeks were ±1.9% (±3.1, ±0.7) versus ±1.3% (±2.5, ±0.1) (both p>0.2).

In a multiple regression analysis, including treatment, genderand menopausal status as factors, bone loss was signi®cantlydependent on menopausal status. Premenopausal women (n=33)lost no bone. Postmenopausal women without hormonal replace-ment therapy (HRT) (n=27) lost signi®cant amounts of bone at allsites after 56 weeks, up to ±3.5 (±6.1, ±0.9) after SSZ and ±4.5%(77.9, 71.0) after COMB in the femoral neck. This appearedmore rapidly in the SSZ group but more pronounced in the COMBgroup, although differences between groups were not signi®cant.Women in the COMB group on HRT (n=8) lost little or no boneafter 56 weeks except in the femoral neck [±3.3% (±5.9, ±0.7)].Only men in the COMB group (n=22) lost bone, and only in thespine [after 56 weeks ±2.2% (±4.1, ±0.3)].


We conclude that in women with early active RA, postmeno-pausal status is a risk factor for signi®cant bone loss in the spineand hip, irrespective of antirheumatic treatment regimen. HRTprotected against bone loss, except in the femoral neck. In men,short-term corticosteroid therapy is a risk factor for bone loss inthe spine only.

383 (347). DECREASED PHYSICAL ACTIVITY IS RELATED TOINCREASED BONE RESORPTION IN HEALTHY AMBULATORYELDERLY WOMEN, INDEPENDENT OF VITAMIN D STATUS

P. Geusens,1,2, J. Vanhoof1, K. Declerck1, H. Bischoff3, J. Raus1,Sj van der Linden2, 1Biomedical Research Institute DWI, LimburgUniversity Center, Diepenbeek, Belgium; 2Department ofRheumatology, Academic Hospital, Maastricht University, TheNetherlands; 3Department of Orthopaedics, Rheumatology andGeriatrics, University Basel, Switzerland

Immobility may lead to signi®cant bone loss. Physical activitydecreases with age and after fracture. Increased bone resorptionassociated with lower mobility has been found in institutionalisedelderly, but is not documented in elderly ambulatory women.Physical performance, muscle strength and urinary pyridinolineexcretion (PYR) were measured in 340 healthy elderly ambulatorywomen. Mean PYR was 27% higher in less mobile womencompared to mobile women as evaluated by their ability to risefrom a chair (44 nM/mg creatinine versus 34 nM/mg creatininerespectively, p<0.0001). Mean PYR was 30% higher in womenwith limited daily activities as compared to physically still activewomen (44 nM/mg creatinine versus 34 nM/mg creatinine,p = 0.001). Mean PYR was 15% higher in women with a historyof fracture compared to women without a history of fracture (39nM/mg creatinine versus 34 nM/mg creatinine, p<0.05). PYR wasnot related to vitamin D status. Bone density in the hip wasmodestly related to PYR (r = ±0.114, p<0.05) and to musclestrength (r = 0.174, p<0.05) but not to vitamin D status. Weconclude that, in ambulatory healthy elderly women, decreasedmobility is associated with increased bone resorption that isassociated with low bone density in the hip, independent ofvitamin D status.

384 (348). HIGH LEVELS OF DEPRESSION ARE ASSOCIATEDWITH HIGH LEVELS OF FREE TESTOSTERONE INPOSTMENOPAUSAL WOMEN

M. G. GluÈ er1, A. D. Lazerescu2, H. W. Minne2, B. Begerow2, M.Pfeifer2, T. Schlotthauer2, W. PollaÈ hne2, 1Universitatsklinik CAUzu Kiel; 2Institut fur klinische Osteologie, Bad Pyrmont, Germany

Severity of depression may be in¯uenced by hormones, i.e.estrogen de®ciency in women. We investigated 225 postmeno-pausal osteoporotic women (age 63.38�7.71), assessing hormo-nal status, depression (Hautzinger & Bailer 1992) lumbar spinebone density (BMD, Hologic QDR 2000) and fracture status (SDI,Spine Deformity Index). Hormones included 25-OH-D (NicholsInst., FRG), LH, FSH, SHBG, free testosterone (LIA, ChironDiagnostics, FRG), and 17b-estradiol (measurable in 113 womenonly, FIA, Wallac-ADL, FRG). The sample was subdivided bymedian into groups with high (18.9�6.1) and low (5.9�2.7)depression scores.

Free testosterone was signi®cantly elevated in the group withhigh depression scores (2.0�1.7 pmol/l vs. 1.5�1.3 pmol/l, p<0.01)even when controlled for age and fracture status (p<0.02). SHBG(p<0.087) and SDI (p<0.12) showed somewhat higher levels while25-OH-D (p<0.056) and 17b-estradiol (p<0.23) were somewhatlower. LH, FSH and BMD did not show signi®cant differences.

Results on fracture status agree with previous reports. Theweak association of female hormones may have been caused bysmall sample size and the low levels in elderly women. The strongdifference in free testosterone should be investigated further and,if con®rmed, therapeutic implications should be elucidated.

385 (349).CHOICES FOR BETTER BONE HEALTH: A SELF-MANAGEMENT PROGRAM FOR OSTEOPOROSIS

D. T. Gold, S. L. Silverman, B. E. Miller, 1Duke University MedicalCenter, Durham, NC, USA; 2University of California At LosAngeles, CA, USA; 3Procter and Gamble, Cincinnati, OH, USA

Osteoporosis (OP) has psychosocial as well as physicalconsequences; in addition, poor patient compliance with medica-tion, exercise, and calcium often occur. Traditional patienteducation about OP has focused on a simple transfer ofinformation and has had minimal impact on behavioral change.Based on a needs assessment and focus groups, we havedeveloped a patient self-management course for OP calledCHOICES for Better Bone Health. This course empowerspatients to become active members of their OP healthcareteams. CHOICES is based on the 5 Cs of self-management:Comprehending the problems of OP; Choosing OP managementstrategies; Committing to those management strategies; Com-municating about OP and its management to family, friends, andhealth care providers; and Coping with the challenges of OP.CHOICES is a ®ve-session course, and each class is facilitated bya trained patient (Manager) and allied health care professional(Management Partner). Course content includes backgroundinformation on OP, assessment of bone health, OP medications,management strategies for diet, exercise, calcium/Vitamin Dintake, the psychosocial outcomes of OP, partnering with healthcare providers, and fashion for people with OP. Key messagesinclude, ``It's never too late to begin prevention or treatment ofOP,'' ``You can manage your bone health,'' and ``You have achoice of therapies.'' CHOICES will be available nationally in Fall,2000 and can be modi®ed to meet cultural and regional needs.Evaluation outcomes will include the effect on health-relatedquality of life and adherence to medication/exercise regimens andlife style changes.

386 (350). BONE CHANGES DUE TO BISPHOSPHONATETREATMENT IN A MODEL OF ASEPTIC LOOSENING

M. D. Grynpas1, M. Kasra1, R. A. Kandel1, L. White2, A.Binnington3, 1Depts of Lab Medicine and Pathobiology andRadiology, U of Toronto & Mount Sinai Hospital; 2OntarioVeterinary College, University of Guelph,

The aim of this work was to study the bone changes induced bythe bisphosphonate zoledronate (Zln) in a canine model of asepticloosening of hip implant. Between 10 and 20% of hip replace-ments are revisions of failed primary implants. The reason isaseptic loosening caused by polyethylene (PE) and other weardebris leading to in¯ammation and bone resorption. Bispho-sphonates should prevent the bone resorption that leads toimplant loosening. In this study, 30 adult male dogs were given anuncemented titanium femoral prosthesis and a cementedacetabular cup. The femoral components contained multiplehorizontal grooves ®led with micron size PE particles in clottedblood. Each group of 10 dogs received weekely s.c. injections of:vehicle in group 1 (control), 2mg/kg Zln (low dose) in group 2 and10mg/kg (high dose) in group 3. The dogs were allowed fullpostoperative ambulation and were sacri®ced after 26 wks. Theoperated legs were x-rayed preoperatively at 1 day and at 2, 4,and 6 months postoperatively. The membranes surrounding theimplant were harvested and examined histologically. Theyconsisted of hyalinized ®brous tissue with PE fragments andin®ltration by histiocytes and occasional lymphocytes. There wasno histological differences between the 3 groups. There wasdiffuse and localized periosteal new bone formation seenradiographically mainly in the high dose group and to a lesserextent in the low dose group and occasionally in the controlgroup. Mechanical testing was done on 4 longitudinal rectangularstrip of each femur. These 4-point bending tests showedthat elastic modulus and bending stress increased signi®cantlywith increased dose of Zln. These results indicate that Zln


treatment increases the mechanical properties of bone andincreases periosteal new bone formation in this model of asepticloosening.

387 (351). BONE REMODELING UNDER A LOW-DOSE ORALCONTRACEPTIVE

M. Hartard, P. Bottermann, D. Jeschke, M. Schwaiger, WorkingGroup of MusculoSkelatal Interactions, Universities of Munich,Germany

Epidemiological investigations of the Royal College of GeneralPractitioners document a 20% greater risk of bone fracture inwomen who have taken contraceptives (OC) for a long time.These results indicate that further investigations are needed. Theobjective of this exploratory 24-months controlled study was toobserve bone mass and bone metabolism under a low-dose OC(30 mg estradiol and 75 mg gestodene) in women aged from 25±35years. After being off OC for at least 4 months, 24 women decidedto take OC, 25 participated in the control. No differences existedbetween the groups at any time with regard to the anthropo-metric, nutritional and performance data. The groups werecomparable with regard to the data of electrolytes, hormones,bone metabolism and bone mass (DPX: L2±4 and right collum).After two years sign. lower serum levels for alkaline phosphatase(p<0.05), osteocalcin (p<0.0001), pyridinoline (p<0.005) anddeoxypyridinoline (p<0.05) in the OC group, even signi®cantdifferences between the groups (p<0.05) for osteocalcin could beobserved. Both groups did not show any bone mass changes.There is a largely balanced bone remodeling unaffected by OC inthis age group. This brings about suf®ciently quick and extensiverepairs. These observations could be evaluated in terms ofreduced bone remodeling and it cannot be ruled out that low-dose OC's reduce the repair capacity of bone in young women.

388 (352). NO SIGNIFICANT LOSS OF BONE: A TWO YEARFOLLOW-UP OF 173 FEMALE PATIENTS WITH RHEUMATOIDARTHRITIS

G. Haugeberg1, T. K. Kvien1, T. Uhlig1, R. E.Orstavik1, J. A. Falch2,J. I. Halse3, 1Oslo City Dept. of Rheumatology, DiakonhjemmetHospital, Oslo; 2Dept. of Internal Medicine, Aker Hospital, Oslo;3Osteoporosis Clinic, Oslo, Norway

Objective: To examine longitudinal changes in bone mass infemale Caucasian rheumatoid arthritis (RA) patients managed in aregular clinical setting with combined rheumatologist/generalpractitioner care.

Method: A total of 173 female RA patients age 20±70 yrs,recruited from a RA-register (completeness 85%), underwentbone density measurements at baseline and after two years. Allpatients were at baseline adviced about life-style, calcium andvitamin D supplementation, and they received hormone replace-ment therapy or bisphosphonates according to clinical judge-ment. The following baseline characteristics were recorded: meanage 53.6 yrs (SD 11.1), mean disease duration 12.8 yrs (SD 9.6),66.5% post-menopausal, 28.3% current users of estrogen, 54%Waaler positive, mean MHAQ 1.59 (SD 0.42), and 30.8% never,23.1% previous and 46.2% current users of prednisolone. Bonemineral density (BMD) measurements in hip (femoral neck andtotal hip) and spine (L2±4) using DXA (Lunar Expert-XL) wereperformed. The long time phantom coef®cient of variation (CV%)was 0.8% and the in-vivo reproducibility of BMD measurements(assessed from duplicate measurements in 31 healthy females)was 1.5% at the femoral neck, 1.5% at the total hip, and 2.2% atthe lumbar spine (L2±4).

Results: In the two year period a 1.3% reduction in BMD wasfound in femoral neck, 0.8% in total hip and 0.9% in spine L2±4.As shown in the table below no statistically signi®cant BMD(g/cm2) reduction was found over the two year period.

Baseline At 2 yrs BMD reduction (95%CI)

Fem.neck 0.847 (0.159) 0.835 (0.172) ±0.011 (±0.023, 0.002)Total hip 0.871 (0.157) 0.867 (0.159) ±0.007 (±0.016, 0.002)Spine L2±4 1.102 (0.202) 1.092 (0.189) ±0.010 (±0.022, 0.002)

Conclusion: Only minimal bone loss was observed during twoyears in this group of female RA-patients receiving counsellingand prevention/treatment of osteopenia and osteoporosisaccording to clinical judgement.

389 (353). OSTEOPOROSIS PREVENTION AMONG TEENS

Linda L. Hightower, Community Medical Center, Missoula,Montana, USA

The purpose of this investigation was to develop a program toeducate teens about the prevention of osteoporosis. Initially,research was done to understand the future affects of currentteen practices in relation to nutrition and exercise. A presentationwas written based on NOF recommendations about informationteens need and information gathered from some teens them-selves. During presentations in classrooms, a pre- and post-survey was done to evaluate the students' knowledge aboutosteoporosis. An evaluation was done allowing students toanonymously voice suggestions for additions or subtractionsand evaluate how this information might affect their lives. Resultsshowed that most students understand that osteoporosis causesbones to be more fragile but they believe that it only affectselderly women and that there is no prevention or treatment. Theywere very positive about the information and said they wouldrecommend that their friends receive this same information. Inconclusion, teens not only need this information to preventosteoporosis, but they want to hear it.

390 (354). MALDESCENDED TESTIS AND SUBSEQUENTDEVELOPMENT OF OSTEOPOROSIS IN MALES

S. J. Iqbal, M. Quinn, S. Muhlbayer, Dept of Chemical Pathology,Leicester Royal In®rmary, Leicester, UK

In men osteoporosis can by caused by hypogonadism, theactiology of which can be varied. Can maldescent of testis be acause?

Case 1. An Asian, 49 yrs presented with height loss (HtL) of 2 1/2 ins, kyphosis and gynaccomastia. Lateral spinal x-rays (LSPXR)showed mild wedging and spinal bone mineral density (BMD);(L2-L4) was 0.560 g/cm2 (T score ±5.6). PMH included orchido-pexy and later orchidectomies at 31 and 36 yrs. FSH 55 iu/L(1±10), LH 9.5 iu/L (1.0±9.0), testosterone <0.7 nmol/L (10±30),SHBG 5 nmol/L (15 ± 40). He also had severe myopathywith coexisting nutritional osteomalacia. Adjusted calcium 1.75mmol/L, alk phos 803 iu/L, phosphate 0.94 mmol/L, 25(OH)VitD<5 mg/L, PTH 88 pmol/L.

Case 2. A male, 55 yrs, with IgG paraprtoeinaemia developedsevere back pain, kyphosis and HtL 8/9 ins over the past 3 years.PMH included inguinal operations at age of 46 and 49. Results;FSH 28, LH 12, testosterone 3.0, SHBG 71. LSPXR showedmultiple severe wedge fractures. Spinal BMD unmeasurablebecause of kyphosis.

Case 3. An Asian, 48 yrs presented with back pain. PMHincluded R hernia repair at 12 yrs. FSH 5.8, LH 1.7, testosterone5.4, SHBG 15. LSPXR showed no wedging, BMD (L2-L4) 0.948 g/cm2 (T score ± 2.4), pituitary MRI scan NAD.

Case 4. A patient 80 yrs, presented with back pain. LSPXRshowed wedging T9,L1, L3, BMD (L2-L4) 0.805 g/cm2 (T score73.6), FSH 40, LH 97, testosterone 2.8, SHBG 82. Testes were notin the scrotum but in inguinal pouches.


All these men presented with sparse/absent male body hair,with one or both testis which were atrophic or absent and had notfathered any children. They were treated with Testosterone.Males with maldescended testis require monitoring of testoster-one levels, with replacement therapy if necessary, to preventosteoporosis.

391 (355). LACK OF CORTICOSTEROID EFFECT ONTRABECULAR BONE DENSITY OVER 18 MONTHS INSYSTEMIC LUPUS ERYTHEMATOSUS

A. A. Kalla, L. Bewerunge, S. Swanevelder, A. B. Fataar,1Rheumatic Diseases, University of Cape Town; 2NuclearMedicine Department, Medical Research Council, Cape Town,South Africa

Aim: To study the longitudinal effects of corticosteroid therapy inpatients with systemic lupus erythematosus (SLE).

Methods: Patients meeting the ACR criteria for SLE werefollowed up at the Lupus Clinic at Groote Schuur Hospital. Normalvolunteers and patients had dual x-ray absorptiometry (DXA)measurement of the hip and lumbar vertebrae with the HologicQDR 1000 on 2 occasions, approximately 18 months apart.Patients with SLE were monitored with respect to current dailydose and cumulative dose since ®rst DXA measurement. None ofthe subjects were receiving substances that could interfere withbone metabolism. In the SLE group, exclusions were made formale sex, chronic renal failure, dialysis, pregnancy, epilepsy,immobilization and menopause.

Results: There were 56 patients with SLE and 41 normalcontrols. The mean age of the SLE group was 32 (SD7) years andmean disease duration 74 (SD62) months. The mean age of thecontrols was 34 (SD9) years. The 2 groups were comparable forheight and weight. The patients with SLE had lower bone mineraldensity (BMD) than controls at each cross-sectional comparison.However, there was no signi®cant change over 18 months ineither the SLE patients or the normal controls (p>0.50), at any ofthe femoral or lumbar sites of measurement. There were 26patients receiving corticosteroid (CS) therapy at the time of study.The mean daily dose of prednisone was 12 (range 2±45) mg andthe mean cumulative dose over the study period was 7.019 (range1.029±21.973) grams. The mean duration of CS therapy was 32(SD12) months. When the CS-treated subgroup was analyzed forchange in BMD, no signi®cant change was seen at any of the sites(p>0.20). The body mass index increased signi®cantly, suggestingcompliance with therapy.

Conclusions: Bone loss in premenopausal SLE is due to theunderlying disease and is not accelerated by corticosteroidtherapy. Systemic lupus erythematosus may be associated withfactors protecting against CS-induced bone loss. Other potentialmechanisms for bone loss in SLE need to be studied in order toeffectively prevent fractures in later life.

392 (356). ESTROGEN REPLACEMENT THERAPY ANDRECOVERY FROM ANOREXIA NERVOSA: RESTORATION OFAXIAL AND APPENDICULAR BONE SIZE AND DENSITY

K. M. Karlsson, S. Weigall, Y. Duan, E. Seeman, Department ofEndocrinology, University of Melbourne, Melbourne, Australia

The purpose of the study was to evaluate if anorexia nervosa (AN)is associated with reduced bone size and reduced volumetricbone mineral density (BMD) and if estrogen replacement therapy(ERT) or recovery from AN is associated with restoration of sizeand BMD. Using DEXA, we measured bone size and volumetricBMD of the third lumbar vertebral body (VB) and femoral neck(FN) in 77 women with AN, 58 women with AN receiving ERT, 26women recovered from AN, and 205 controls. Results wereexpressed Z scores (mean�sem). In untreated women, de®cits inVB and FN width were ±1.0�0.1 SD and ±0.3�0.1 SD (p50.001

and p50.05), more modest in the ERT treated women at the VB(±0.6�0.1 SD, p50.001) but not at the FN (±0.4�0.2 SD, p50.05).VB and FN width were not signi®cantly reduced in the recoveredwomen (±0.3�0.2 SD, p = 0.1, ±0.3�0.2 SD, p = 0.2 respectively). Inuntreated women, VB and FN volumetric BMD de®cits were±1.6�0.1 SD and ±1.1�0.1 SD (both p50.001), more modest inERT treated women (±1.2�0.2 SD, ±0.6�0.2 SD, both p50.001)and least in recovered women (±0.6�0.1 SD, ±0.5�0.2 SD, bothp50.05). Bone fragility in AN is due to reduced bone size andreduced volumetric BMD. These de®cits may be largely reversedfollowing ERT or recovery from illness.

393 (357). HIGH PREVALENCE OF VERTEBRAL FRACTURES INPATIENTS WITH CROHN'S DISEASE EVALUATED BYQUANTITATIVE MORPHOMETRY

J. Klaus1, J. Bruckel1, M. Steinkamp1, M. Reinshagen1, G. Adler1,A. Rieber2, C. V. Tirpitz1, 1Department of Internal Medicine I,University of Ulm; 2Department of Radiology, University of Ulm,Ulm, Germany

Background and aims: Osteopenia and osteoporosis arefrequent in Crohn's disease (CD). However, there are no datathat show the association of decreased bone mineral density(BMD) and vertebral compression fractures in these patients. Theaim of this study was to examine the prevalence of vertebralfractures in CD patients with decreased BMD.

Methods: 258 CD patients were screened including osteoden-sitometry by dual energy X-ray absorptiometry (DXA) of thelumbar spine (L1-L4) and total upper femur. In 92 CD patients (55female) with osteopenia or osteoporosis at the lumbar spine,both, DXA and X-ray examinations of the thoracic and lumbarspine were available. The assessment of fractures included thevisual reading of the X-rays and the quantitative morphometry(QM) of the vertebral bodies (T4-L4) according to the criteria ofthe European Vertebral Osteoporosis Study (EVOS).

Results: From the 92 CD patients (aged 36,27 years, range 17±67), 29 patients (31,5%) showed osteoporosis (T-score 5±2.5)and 63 (68.5%) osteopenia (T-score 5±1,> ±2.5). 72 CD patientsshowed preclinical osteopenia and osteoporosis with no pre-valent vertebral changes whereas in 20 (21.7%) (13 female) CDpatients the QM revealed one or more vertebral deformities (fxd.)or fractures (fx.). 7 out of the 20 patients only showed fxd., and 13(14.13%) (11 female) patients had criteria of fx. In these 20 CDpatients a total of 25 fx. (14 of the thoracic and 11 of the lumbarspine) and 11 fxd. (8 thoracic and 3 lumbar) were detected. Only in4 patients the fx. were clinically evident (9 fx., two of themconsidered to be caused by minimal inadequate trauma). The fx.in the other 16 patients were clinically undetected. There was nosigni®cant difference considering BMD between the preclinicaland manifest cases (lumbar T-score ±2.09�0,65 vs. ±2.49�0.94,n.s., hip T-score ±1.98�1.18 vs. ±1.80�0.79, n.s., respectively).There was a signi®cant difference regarding BMD at the hipcomparing the 7 patients with fxd. to the 13 patients with fx.(lumbar T-score ±1.95�0.42 vs. ±2.26�1.05, n.s., hip T-score±1.21�0.94 vs. ±2.4�1.09, p<0.05, respectively).

Conclusions: In patients with Crohn's disease (CD) and lowBMD (T <±1) the prevalence of vertebral fractures or deformitiesi.e. manifest osteoporosis was unexpectedly high. By detailedmorphological analysis of X-rays (quantitative morphometry) wewere able to demonstrate 25 fractures and 11 deformities in 20out of 92 (21.7%) mostly asymptomatic patients.

394 (358). COMPARED TRABECULAR BONE ARCHITECTUREIN MEN AND WOMEN

E. Legrand, D. Chappard, I. Degasne, M. F. BasleÂ , M. Audran,Service de Rhumatologie, CHU, Angers, France

We have shown that trabecular bone connectivity is a major andindependant determinant of vertebral fracture in men with mild


osteoporosis (OP) (1). The purpose of the present study was tocompare trabecular bone microarchitecture in osteoporotic menand women.

Methods: spine and hip bone density (BMD) and transilliacbone biopsy were obtained in 31 male patients with idiopathicOP, 10 male patients with hypogonadism induced-OP and 29women with postmenopausal OP. Histomorphometric analysiswas done on a Leica quantimet image processor and thefollowings measures were performed: trabecular bone volume(BV/TV), trabecular thickness (Tb Th) and number (Tb N),Interconnectivity Index (ICI), Star Volume of the bone marrow,Characterization of the trabecular network (node and free-endcount).

Results Women Men

Post menopausaln = 29

Idiopathicn = 31

Hypogonadismn = 10

Age (years) 60.4 49.8 59.5Spine BMD (gr/cm2) 0.64* 0.73 0.70Hip BMD (gr/cm2) 0.63* 0.71 0.70BV/TV (%) 14.1 13.5 12.8Tb Th (mm) 109.8 105.6 118Tb N 1.27 1.3 1.1**ICI 2.6 2.4 4.6**Star Volume (mm3) 17.3 17.9 16.2Free-end (%) 16.0 17.8 29.1**Node (%) 23.9 24.4 18.9

*p<0.05 versus men.

**p<0.05 versus idopathic male OP and versus women.

These results strongly suggest that, despite a higher BMD,architectural changes are equivalent in men with idiopathic OPand post menopausal women. By contrast trabecular bonemicroarchitecture seems to be profoundly altered in men withhypogonadism-induced OP.

(1) E Legrand M Audran. Trabecular bone microarchitecture,bone mineral density and vertebral fractures in male osteo-porosis. J Bone Miner Res 2000; 15(1) in press.

395 (359). DENSITOMETRIC AND BIOMECHANICAL STUDY OFTHE EFFECT OF CHRONIC VENOUS STASIS ON THE RAT TIBIA

G. P. Lyritis1, C. K. Yiannakopoulos1, Th. Karachalios1, K.Kalogera1, M. Katsiri1, A. Galanos1, 1Laboratory for the Researchof the Musculoskeletal System, Athens, Greece

The purpose of our study was to conduct an experiment thatwould elucidate the effects of chronic venous stasis on the ratbone using densitometric and biomechanical methods. Westudied the effect of venous stasis on the rat tibia after ligationof the common femoral vein in 15 adult, 3 month old, male Wistarrats. The bone mineral density (BMD) and the bone mineralcontent (BMC) have been measured in vivo immediately after theoperation and after 8 weeks by dual energy X-ray absorptiometry(DEXA). The special small animal software has been used. Fiveregions of interested have been designed (ROI 1±5). Thecoef®cients of variation was 0.67, 0.89, 1.15, 1.23 and 4.07respectively. The BMD and the BMC exhibited statisticallysigni®cant increase in all regions of interest, except for thedistal tibial epiphysis. The mean percent of BMD increase wasfor the ®ve ROI's 10.23�6%, 17.64�9.47%, 15.97�12.26%,14.69�14.68%, ±5.26�12.13% respectively. The biomechanicalproperties of both tibiae have been examined using a destructivethree point bending test. The biomechanical examinationrevealed statistically signi®cant increase of all the measuredbiomechanical parameters. We conclude that the chronic veousstasis causes signi®cant increase of the bone density in the rat

tibiae, in regions where the cortical bone predominates and inregions with cancellous bone predominance. The increase inbone density is accompanied by an increase of the bone strength.

396 (360). VITAMIN D STATUS IN YOUNG FEMALES DURINGGROWTH

V. Matkovic1, N. E. Badenhop-Stevens1, J. D. Landoll1, E. J. Ha1,S. L. Mobley1, B. Hollis2, L. Nagode1, 1The Ohio State University,Columbus, OH; 2University of South Carolina, Charleston, SC,

The purpose of this study was to evaluate the relationshipbetween vitamin D status and serum parathyroid hormone (PTH)in a group (N=341) of young healthy teenage females from centralOhio (ages 11.8�0.8 y), participants of a long-term study ofskeletal development during puberty. Serum 25(OH)D3 wasmeasured by a radioimmunoassay (RIA) with 125I-labeled tracer(Hollis et al. Clin Chem 39/3,529,1993) and intact PTH wasmeasured using Nichols RIA kits with a method previouslydescribed (Nussbaum et al, Clin Chem 33:1364, 1987). Calciumintake data were established based on the compliance withcalcium supplements and detailed assessment of dietary calciumconsumption utilizing food records. The results indicate a strongseasonal variation in serum vitamin D level with the peak serumconcentration during the month of July with nadir during thewinter season. Serum concentration of PTH was opposite to25(OH)D3 with the highest levels being during winter season andthe lowest during the summer months. Serum PTH was inverselyrelated to circulating 25(OH)D3 (r = ±0.329, p<0.0001) (Figurebelow). When the subjects were separated into a high- (~1500mg/d) and a low (~800 mg/d) -calcium intake groups, theobserved association between PTH and vitamin D was onlypresent in the low-Ca intake group, during both, summer andwinter season. The study suggests that 25(OH)D3 may beimportant for skeletal health during growth particularly when Caintake is low.

397 (361). FRACTURE RISK AND USE OF ORAL STEROIDS

J. W. Meyer, Ingenix Intnl., Eden Praire, MN, USA

Objective To assess the fracture risk associated with oral steroid(OS) exposure.

Methods Data were obtained from claims of subjects, 18±64years, of 8 United Healthcare health plans. OS claims in 1995±96were classi®ed by patterns of use and daily prednisone-equivalent dose. A control group was matched on minimumenrollment duration, age, & gender. Subjects were followed untilage 65, fracture, disenrollment, or up to 3.5 years. Adjustedrelative risks (RR) were estimated using Cox proportional hazardmodels.


Results 36, 271 OS users and 14, 421 controls were included;58% were female, mean age was 42, and mean enrollment was 68and 75 months. Prednisone was the most commonly prescribedOS (69%) and the most common OS conditions were in¯amma-tory skin disorders, arthropathies, and nervous system disorders.Patterns of OS use were 50.7% single OS claims (SNGL), 41.6%intermittent use (INT), and 7.7% continued use (CNTD). Meandaily dose was 8.2 mg/day. Subjects with CNTD and 53 OSclaims had a RR=2.6 for hip and RR=3.0 for vertebral fracturesversus unexposed subjects. SNGL use had a RR=1.9 for hipfractures. Users of 59.5 mg/day OS daily dose had a RR=2.5 forhip and RR=1.7 for vertebral fractures. OS exposure was relatedto other non-vertebral/open fractures (SNGL RR=1.2; INT RR<1.0;CNTD RR=1.5; 3.5±9.5 mg/day OS dose RR=0.9) [All RRs: P<0.05]

Summary Continued and extended OS use had the greatestincrease in risk of hip and vertebral fracture. A separate dosedependent hip and vertebral fracture risk was evident. OSexposure did not increase forearm fracture risk.

398 (362). OSTEOPOROSIS AFTER TRAUMATIC BRAIN INJURY(TBI) COMPLICATED BY TRANSIENT VEGETATIVE STATE (VS)

E. Meys, P. Rigaux, B. Veys, D. Darriet, N. Benabid, B. Sutter, F.Danze, Groupe Hopale, Berck/Mer, France

We have previously shown persistent VS is a risk factor todevelop disuse osteoporosis at the lower limb. We wanted toknow if bone loss was also observed after recovery of transientVS and if the forearm and the heel were affected to the sameextent. We explored 51 TBI male patients (age 32�10 years) whosuffered from transient VS and 51 male controls (33�8 years)using DXA Lunar PIXI device. The time elapsed since injury was39�38 months. At the time of the study all the patients were ableto walk despite paralytic after-effects among 16 of them. Theduration of VS was 1814 weeks but was longer in paralysedpatients (29�14 weeks, p<0.0001). Results are expressed asmean bone loss and T score in comparison with the normativevalues given by the manufacturer. According to the WHO criteria1/3 of the patients are osteopenic and 1/3 are osteoporotic. Thebone loss is mainly observed at the heel, is more severe amongparalysed patients and is strongly correlated with the duration ofVS (r = 0.7 at the heel). The paralysed forearm is also affectedwhich suggests a negative effect on bone of muscle weakness byitself. We conclude TBI patients despite brain recovery may beosteoporotic.

GROUP SITE BONE LOSS T SCORE

Control Forearm ±5 % ±0.5Control Heel 0 0T B I Forearm ±5 % ±0.5T B I Heel ±20 % ±1.4Paralysed T B I Healthy forearm ±1 % ±0.1Paralysed T B I Paralysed forearm ±12 % ±1.2Paralysed T B I Healthy heel ±24 % ±1.7Paralysed T B I Paralysed heel ±35 % ±2.4

399 (363). SERUM CTX PREDICTS THE BONE LOSS AT THEHEEL AFTER SIX MONTHS OF VEGETATIVE STATE (VS)

E. Meys, P. Rigaux, B. Veys, D. Darriet, N. Benabid, F. Bianchi, F.Danze, Groupe Hopale, Berck/Mer, France

Persistent VS after traumatic brain injury (TBI) is a important riskfactor to develop disuse osteoporosis. We have previously shownusing serum CTX the occurence of a high bone resorption rate

among TBI patients. We wanted to know if serum CTX levels atbaseline (T0) were able to predict the extent of the bone loss atthe heel after 6 months (T6) of VS. We explored 36 TBI patients(29M/7F; age 33�12) using ultrasonic Hologic SAHARA device atT0 and T6. Serum CTX was measured by ELISA at T0 (Cis BioOsteometer CROSSLAPS, N<8500 pmol/l). At T0 the time elapsedsince injury was 10.1�4.7 weeks. Glasgow Coma Score at thetime of injury was 5.9�1.6 (48 for all the patients, normal=15) andat T0 was 9.7�2.9. The VS was only transient in 12 patients (groupA) who were able to walk again at T6 while the 24 other patients(group B) were still in VS. Results of ultrasonic parameters at T6are expressed as mean percentage (and standard deviation) ofmeasurements at T0.

QUI T6 BUA T6 SOS T6

WHOLE GROUP 84% (�12) 82% (�12) 98.4% (�1.3)p, T6 vs T0 <0.05 <0.05 <0.05r with CTX ±0.62 ±0.64 ±0.52r2 0.38 0.41 0.27GROUP A 89% (�6) 87% (�9) 99% (�0.7)GROUP B 81% (�13) 80% (�13) 98.2% (�1.4)p, A vs B <0.05 <0.05 <0.05

Serum CTX levels are increased (15299�6672) and are higher ingroup B (17523�6622) than in group A (10852�4105, p<0.0001).We conclude serum CTX at baseline is able to predict the severityof the bone loss measured by ultrasound at the heel after TBIcomplicated by 6 months of VS.

400 (364). THE PSYCHOLOGICAL IMPACT OF A DIAGNOSIS OFOSTEOPOROSIS

C. Murray1, J. Beynon1, J. Board2, 1Dept. of Adult Medicine; 2Deptof Psychology, St. Woolos Hospital, Newport,

Osteoporosis is a chronic condition affecting everyday activities.As well as the physical aspects of the condition one needs toconsider its psychological impact. The emotional implications oflong-term chronic illnesses are well known, the psychologicalimpact of osteoporosis has attracted little attention. A districtgeneral hospital has developed a comprehensive osteoporosisand bone density service tailored to meet individual patientneeds. The following study was undertaken to examine thepsychological impact of a diagnosis of osteoporosis: a) identify-ing the patients' response and feelings at being given a diagnosisof osteoporosis; b) did a prior diagnosis of osteoporosis affectthese feelings; c) were patients' reactions in¯uenced by thepresence of a family member; d) what did patients understand bythe diagnosis of osteoporosis. Patients who attended the onestop shop clinic, in which they have a bone density measurementfollowed immediately by a clinical assessment and nursespecialist interview, were invited to participate in the study. 14consecutive female patients with bone density con®rmedosteoporosis agreed to take part. An independent clinicalpsychologist conducted a questionnaire-based interview lastingone-hour in the patients' home, one to three weeks followingclinic attendance. 7 of the 14 patients expressed distress atreceiving the diagnosis, using emotional language to describetheir feelings ``I was devastated'' ``it hit me like a sledgehammer''. These feelings were not related to whether they hadpreviously been given a diagnosis of osteoporosis. All patientsunderstood the diagnosis of osteoporosis. Patients' reactionswere not in¯uenced by the presence of a family member. Thispreliminary study indicates that the diagnosis of osteoporosis hasa psychological impact on patients. This does not itself in¯uencepatients' ability to absorb and retain information. However thisstudy highlights that osteoporosis services need to offerpsychological as well as physical support to patients.


401 (365). VITAMIN D INSUFFICIENCY AND DECREASED BONEMASS IN JAPANESE FEMALE COLLEGE STUDENTS

K. Nakamura, M. Nashimoto, M. Yamamoto, Niigata UniversitySchool of Medicine, Niigata, Japan

Vitamin D insuf®ciency, a risk factor for osteoporosis, has beenwell investigated in elderly women, but little information has beenavailable in younger ages. The purposes of this study were todetermine serum 25-hydroxyvitamin D levels [25(OH)D, an indexof vitamin D nutritional status] in Japanese young girls, and to testwhether there is an association between 25(OH)D and bone mass.Subjects were 77 Japanese female junior college students aged19±24 years. The investigation was conducted in April in 1998 and1999. Serum 25(OH)D was measured with high-performanceliquid chromatography. Bone mass of the calcaneus wasevaluated with quantitative ultrasound densitometry. The mean25(OH)D concentration was 34.2 nmol/L (SD 12.1). The proportionof subjects with 25(OH)D less than 30 nmol/L, a cut-off value forvitamin D insuf®ciency, was 31/77 (40.3%). Simple linearregression analysis showed that there was a signi®cant linearrelationship between 25(OH)D and bone mass (r2=0.098,p = 0.0069). The association held even after adjusting for weight(partial r2=0.098, p = 0.0023). Body weight was also associatedwith bone mass (partial r2=0.105, p = 0.0034). These resultssuggest that vitamin D insuf®ciency may be prevalent in healthyyoung girls, and that low levels of 25(OH)D in young girls mayadversely affect bone mass.

402 (366). EFFECTIVENESS OF EDUCATION AND/OR NTxRESULTS AS AN MEANS OF ENCOURAGING COMPLIANCE TOALENDRONATE

S. Nattrass, S. Silverman, B. Drinkwater, 1PacMed Clinics,Seattle, WA, USA; 2Osteoporosis Medical Center, Los Angeles,CA, USA

Patient compliance with medication is frequently insuf®cient foroptimal results. This 12 month study was designed to determinewhether an early indication of successful treatment (NTx),intensive patient education, or the combination of the twowould be effective in encouraging patient compliance with anAlendronate prescription. 240 postmenopausal women with aDXA T score <±2.0 of spine or hip were randomly assigned to oneof four groups: 1) NTx (baseline & 3 months), 2) Monthlyosteoporosis educational materials, 3) Combination of 1 & 2, or4) Control. An initial prescription for Alendronate was provided bythe patients' primary care provider. Re®lls were available at 1±3month intervals. Patients returned at 12 months for a DXA and tocomplete a questionnaire. Compliance was measured by numberof months women continued to use the drug. Results: There wereno differences between groups at baseline. 74.4% ®lled theoriginal prescription; 54% took the drug for 12 months. Therewere no differences between groups in compliance. Reasonsfor non-compliance were: chose HRT, 7.9%; adverse effects,9.6%; cost, 4.6; personal reasons, 6.2%. 7.5% were lost to followup.

Table. Number of months on medication (Mean and SE)

Analysis Group 1 Group 2 Group 3 Group 4 p

Intent 7.63 7.70 8.71 7.45 nsdto treat (0.73) (0.69) (0.68) (0.74)On 10±12 11.81 11.73 11.92 11.75 nsdmonths (0.09) (0.15) (0.05) (0.12)

403 (367). BONE MASS DENSITY AND SEX STEROIDS INGREEK HEALTHY MALE INDIVIDUALS

F. G. Papadopoulou1, K. Kalothetou1, G. Koliakos2, Th.Konstantinidis1, E. Nikopoulou1, D. Doukidis1, G. Krassas1, 1Deptof Endocrinology and Metabolism, PANAGIA Hospital,Thessaloniki, Greece; 2Dept of Biological Chemistry, MedicalSchool of the Aristotle University of Thessaloniki, Greece

Osteoporosis is an increasingly recognized disorder in men butpathogenesis of the disease remains obscure. The aim of thisstudy was to investigate the circulating levels of gonadal andadrenal sex steroids in healthy male individuals as well as thepossible correlation of these steroids with bone mass. For thepurpose of this study 363 healthy male individuals were recruitedfrom factory and hospital workers. Mean age was 51.3�8.7yr (30±75) and mean BMI was 27.5�3.7 (18.1±47.9) kg/m2. Bone massdensity (BMD) was evaluated by DEXA at 4 skeletal sites, lumbarspine (LS), femoral neck (FN), trochanter (Tr) and Ward's triangle(WT). Blood samples were taken for the measurement ofdehydroepiandrosterone (DHEA), dihydrotestosterone (DHT),free testosterone (FT) and 17 b estradiol (E2). All measurementswere done by radioimmunoassay. Data were analysed usingKolmogorov Smirnov, student t-test and Spear-man test. Results:Forty four out of 363 (12%) individuals had reduced BMD, with Tscore 4±2.5 in the LS and/or FN. Mean DHEA, DHT, FT and E2

values in the whole group have as follows: 8.8�11.7 (ng/ml),338.9�328.5 (pg/ml), 16.0�5.0 (pg/ml) and 40.6�28.2 (pmol/lt).Serum DHEA was positively related to BMD at LS (r = 0,127,p = 0.027), DHT was positively related to BMD at FN (r = 0.094,p = 0.05), while E2 was negatively related to BMD at 3 sites, i.e. FNr = ±0.329, p = 0.001), Tr (r = ±0.245, p = 0.000) and WT (r = ±0.200,p = 0.03). No association was found between FT and BMD at anysite. In conclusion it seems that testosterone had no relevantin¯uence on BMD, while DHEA, DHT and E2 seem to have ametabolic effect on bone mass.

404 (368). SERUM LEPTIN LEVELS ARE ASSOCIATED WITHBONE MASS IN NON-OBESE WOMEN

J. A. Pasco, M. J. Henry, M. A. Kotowicz, G. R. Collier, M. J. Ball,G. C. Nicholson, Department of Medicine, Geelong Hospital, TheUniversity of Melbourne, Geelong, Victoria, Australia

In vitro studies have demonstrated that leptin directly stimulatesosteoblast differentiation (Endocrinology 1999;140:1630). As bothserum leptin and bone mass are correlated with body fat, ourhypothesis was that circulating leptin may be a regulator of bonemass in vivo.

We investigated 214 healthy, non-obese women (age 20±91 yr;BMI 16±30 kg/m2). Bone mineral content (BMC), projected bonearea and body fat mass were measured by dual energy X-rayabsorptiometry and fasting serum leptin by radioimmunoassay(4.1±8.2% inter-, 5% intra-assay precision). A signi®cant positiveassociation was observed between leptin (natural log) and BMC(adjusted for age, weight, body fat mass and bone area) at thespine (lateral projection), Ward's triangle, the trochanter andwhole body (partial r2=0.019±0.036; all p<0.05). Similar trendswere observed at the femoral neck and PA-spine. With bonemineral density the dependent variable (adjusted for age, weightand body fat mass), the association was signi®cant at the lateralspine (partial r2=0.030; p=0.011), of borderline signi®cance at theproximal femur sites (partial r2=0.012±0.017; p=0.058±0.120) andnot signi®cant at other sites.

The weight and body fat mass adjustments suggest therelationship is independent of mechanical loading and otherhumoral factors asscciated with adipose tissue, supporting thehypothesis that circulating leptin may be a mediator in theregulation of bone mass.


405 (369). VITAMIN D DEFICIENCY IN PATIENTS SUFFERINGFROM CHRONIC PANCREATITIS

J. Payer, Z. Killinger, S. Aleryany, H. Kratochvilova, P. Ondrejka,University Hospital, Bratislava, Slovakia

Chronic pancreatitis is a longlasting in¯ammatory diseasemanifested clinically in the advanced stage by malabsorptionsyndrome. Its manifestations include also changes in the calciummetabolism and the occurrence of osteoporosis and osteomala-cia or their combination. The objective of the study was to assessthe vitamin D3 blood concentration in patients with chronicpancreatitis. The group comprised 15 patients (8 men and 7women), median age 45.0 years. The authors found a signi®cantlyreduced serum concentration of vitamin D3 (p<0.01) in patientswith chronic pancreatitis. They assume that vitamin D de®ciencyis one of the decisive causes of bone complications in prolongedpancreatitis. Supplementation with vitamin D or its metabolites isthen a necessary part of preventive and therapeutic provisions.

406 (370). BONE TURNOVER MARKERS AND SEX HORMONESIN MEN WITH IDIOPATHIC OSTEOPOROSIS

P. Pietschmann, J. Grisar, S. Kudlacek, S. Spitzauer, W.Woloszczuk, R. Willvonseder, M. Peterlik, KrankenhausBarmherzige Bruder, Ludwig Boltzmann Institutes of AgingResearch and Experimental Endocrinology, University of Vienna,Vienna, Austria

In contrast to osteoporosis in postmenopausal women, osteo-porosis in men has received much less attention. Since little isknown about the pathophysiology of osteoporosis in men, wedetermined various biochemical parameters of bone metabolismand sex hormones in 31 men with idiopathic osteoporosis and 35age matched control subjects. In the men with osteoporosis asigni®cantly increased urinary excretion of deoxypyridinoline aswell as increased serum levels of the c-terminal telopeptide oftype I collagen were found. While serum levels of osteocalcin,the bone speci®c isoenzyme of alkaline phosphatase andcarboxyterminal propeptide of type I collagen were not sig-ni®cantly different in the patients and controls, serum bonesialoprotein levels were signi®cantly decreased in the patients.Moreover, in men with idiopathic osteoporosis increased levels ofsex hormone binding globulin and a signi®cant decrease of bothestradiol concentrations and the free androgen index were seen.We conclude that in men with idiopathic osteoporosis boneresorption is increased and exceeds bone formation. Theexcessive bone resorption seen in idiopathic male osteoporosismay be due to decreased estradiol and increased sex hormonebinding globulin levels.

407 (371). THE POST-TRAUMATIC SPINE IN ELDERLYPATIENTS: VARIATIONS OF SAGITTAL CONTOUR ANDCLINICAL-FUNCTIONAL CORRELATIONS

A. Ramieri, O. Moreschini, M. Nocente, Orthopaedic andTraumatology, University ``La Sapienza'', Rome, Italy

In elderly patients vertebral fractures, single or multiple, withspinal deformity are common. Treatment is generally conserva-tive in orthopedic vest but does not guarantee correction ofdeformity. Forty-six cases of single, non-neurological, thoraco-lumbar fracture (D10-L3), were treated by means of 12±16 weeksin a plastic brace: they were aged between 65 and 82 (median 73).Lesions were classi®ed as compression or compression-¯exionwith involvement of the anterior column or both the anterior andmiddle columns as suggested by Denis. Initial and long-termradiographic deformity (range 15±42 months median 33) wasassessed using Farcy's Sagittal Index while long-term clinicalevaluation was based on Knight's classi®cation of pain andfunctional limitation. The majority of patients (60%) had

satisfactory results. Long-term clinical outcome was better inpatients with pure compression fractures, without signi®cantsagittal alterations. In severe deformities consequent to com-pression-¯exion fractures, the sagittal axis appears anteriorlydislocated. A new load balance seems to be achieved by meansof an increase of lumbar-sacral lordosis and patients with mildarthrotic alterations seem to have a higher capacity to adapt.Therefore, clinical-functional recovery in elderly patients withthoracolumbar fractures seems to depend on the ability of thelumbar-sacral spine to adapt to the kyphotic deformity by varyingits lordotic qurvature and establishing a new sagittal load axis.Achievement of this new equilibrium, hindered by spinal stiffnessdue to old-age and arthrosis, is not easy: long-term clinicaloutcome is worse in patients who fail to do so.

408 (372). DIURETICS ALTER THE DIURNAL RHYTHM OFSERUM PTH, CALCIUM, AND PHOSPHATE

L. Rejnmark, P. Vestergaard, L. Heickendorff, F. Andreasen, L.Mosekilde, Aarhus Bone and Mineral Research Group and Centreof Clinical Pharmacology, Aarhus University Hospital, Denmark

Aim: The effect of loop and thiazide diuretic, alone or incombination, on the diurnal rhythm of serum PTH, 1,25-dihydroxyvitamin D, and on serum and urinary calcium andphosphate. Fifty postmenopausal women were randomly allo-cated to 7 days of treatment with either Bendro¯umethiazide(BFMT) 10 mg/day (n=14), Bumetanide (BU) 2 mg/day (n=13),BFMT 10 mg/day plus BU 2 mg/day (n=11), or placebo (n=12). Thediurnal rhythm of each variable was evaluated on the 7th day oftreatment.

Results: In all four groups, all parameters showed a signi®cant(with-in group) diurnal variation. Treatment caused a between-group difference in the diurnal rhythm of S-PTH (p<0.001), S-Ca(p = 0.002), S-Ph (p = 0.001), and urinary calcium (p<0.001). In theBU-group the S-PTH level (8.5�0.9 pmol/l) was signi®cantly abovethe level in the placebo-group (4.4�0.4 pmol/l, p<0.001). From 10a.m. (time of tablet ingestion) to 2 p.m., S-PTH increased 98�16%in the BU-group, whereas the increase in the placebo-group was19�8% (p<0.001).

Conclusion: Treatment with BFMT and/or BU has a majorin¯uence on the diurnal rhythm of parameters of the calcium-phosphate homeostasis. BU may cause secondary hyperpar-athyroidism.

409 (373). HYPERPARATHYROIDISM: NEGATIVE DETECTIONWITH SSBI AND POSITIVE WITH THALLIUM

D. Salica1, E. E. Schulz2, 1Healing Bone and Mineral Institute,Cordoba, Argentina; 2Loma Linda University, Loma Linda, CA,USA

The purpose of this study is to show that Tl201/Tc99 (Tl/Tc)subtraction parathyroid scan (PTS) may be necessary to localizeenlarged parathyroids (PT)in patients clinically hyperparathyroid(HPT), with elevated Ca and PTH, and a negative SSBI PTS, acommon event in osteoporosis.

We are doing almost exclusively SSBI, in the last few years, forsuspected PT adenoma, hyperplasia or carcinoma. Reviewing thecases interpreted by author ES where the ®rst study was SSBI(n=43), we found 7 cases of (-)SSBI but clinically HPT, that had afollow up Tl/Tc scan, excluding those with previous necksurgeries and implants. Six had (+)Tl/Tc (3 had a single areaand 3 had multiple areas) and 1 was negative as the SSBI. Fourout of the six (+)Tl/Tc patients were taken to surgery and all fourhad enlarged PT.

Discussion: It can be argued that our SSBI/PTS technique canbe improved to achieved greater sensitivity using color andsubtraction as we do for Tl/Tc. Most cases however were clearly(-)SSBI and strikingly (+)Tl. We believe that in some cases for


some reason the results between SSBI and Tl can be totallydifferent.

Conclusion: Negative SSBI parathyroid scans with clinicalevidence of HPT probably need a Tl/Tc study to achieve gratersensitivity for presurgical detection of enlarged parathyroids.

410 (374). ARE DEFICITS IN VOLUMETRIC BONE DENSITY INWOMEN WITH FRACTURES DUE TO REDUCED ACCRUAL OREXCESSIVE BONE LOSS?: INSIGHTS FROM THEIRDAUGHTERS

E. Seeman, A. Tabensky, Y. Duan, Austin & Repatriation MedicalCentre, The University of Melbourne, Heidelberg, Vic., Australia

Spine areal bone mineral density (aBMD) is reduced in womenwith spine fractures and their daughters. Femoral neck (FN)aBMD is reduced in women with hip fractures and theirdaughters. About 15±20% of the de®cit in spine aBMD inwomen with spine fractures is explained by smaller bone size(Duan et al, in press). Women with hip fractures have increasedFN volume so that the de®cit is underestimated by ~10% (Duan etal, submitted). The residual de®cit after accounting for reducedbone size, ie the de®cit in volumetric (v)BMD, may be due toreduced accrual and/or excessive bone loss. Any de®cit inpremenopausal daughters must be due to reduced peak accrual.We asked: (i) is BMC and aBMD reduced in daughters afteraccounting for bone size? (ii) is vBMD reduced? (iii) what is thede®cit in vBMD in the mothers?

We studied 45 women with hip fractures (age 76 yrs, range 56±89) and 59 of their daughters (age 47yrs, range 25±70), and 29women with vertebral fractures (age 69 yrs, range 54±90) and 41of their daughters (age 43 yrs, range 24±64). BMC, aBMD weredetermined using dual x-ray absorptiometry (Lunar DPX-L). vBMDwas derived using the Carter method.Results: age, height and weight adjusted Z scores (mean�sem).

Spine Fx

Mothers

(n=29)

Spine Fx

Daughters

(n=41)

Hip Fx

Mothers

(n=45)

Hip Fx

Daughters

(n=59)

FN BMC ±0.25�0.22 ±0.15�0.15 ±0.32�0.16 0.18�0.12

FN aBMD ±0.46�0.20* ±0.04�0.15 ±0.75�0.14{ ±0.02�0.13

FN Volume 0.54�0.32 ±0.15�0.13 1.34�0.28{ 0.42�0.12{

FN vBMD ±0.67�0.21** ±0.04�0.15 ±1.15�0.11{ ±0.31�0.13*

L3 BMC ±0.96�0.15{ ±0.19�0.18 ±0.18�0.15 0.38�0.14**

L3 aBMD ±0.93�0.17{ ±0.28�0.16 ±0.07�0.14 0.26�0.11*

L3 Volume ±0.59�0.14{ 0.03�0.17 ±0.21�0.21 0.36�0.17*

L3 vBMD ±0.99�0.17{ ±0.40�0.15** ±0.13�0.16 0.06�0.12

*p50.05, **p50.01, {p50.001 compared to zero.

Mothers with spine fractures had low bone size, mass andvBMD. Their daughters had low vertebral vBMD, not bone size,suggesting the de®cit in the mother may be the result of reducedpeak accrual in the smaller bone. Women with hip fractures hadincreased FN size (so normal BMC) but low vBMD. Theirdaughters also had increased FN size and reduced vBMD. Weconclude that vBMD and size dier in the fracture types, and lowvBMD may be partly due to low peak since the daughters hadreduced vBMD by 30±50% of the de®cit in the mothers,consistent with the genetic hypothesis.

411 (375). BONE MINERAL DENSITY IN RHEUMATOIDARTHRITIS WITH POSTMENOPAUSE

Y. Sen1, E. Matuyama2, 1Department of Orthopedic Surgery, NaraNational Hospital, Nara City; 2Department of Orthopedic Surgery,Nara Medical University, Kashihara City, Nara, Japan

The purpose of this investigation was to evaluate whether thebone mineral density (BMD) of lumbar spine as determined dual

energy X-ray absorptiometry(DXA) was different between rheu-matoid arthritis(RA) with a mean age of 60.0 years and non-RAwith a mean age of 65.4 years. We measured BMD by DXA in 74patients with RA and 124 patients with non-RA. All patients werepostmenopausal and treated with non-steroidal anti-in¯ammatorydrugs. And we investigate the relation to BMD, age, weight,height, stage, class and disease duration. As a result nosigni®cant differences were found in BMD with RA and non-RA.There were signi®cant correlation between lumber BMD and age(r = ±0.346, p<0.005), weight (r = 0.444, p<0.0001). But there werenon-correlation between BMD and stage, class, disease durationassociated with RA. By Multiple linear regression analysis, ageand weight only were signi®cant predictors of lumber BMD(R=0.550, P<0.01, n=74). In conclusion local bone loss in RA isgeneralized, but general bone loss is likely to be related to loss ofmobility or muscle atrophy associated with RA.

412 (376). GEOMETRIC MEASUREMENTS OF FEMORALDIMENSIONS AND THEIR RELATION TO HIP FRACTURE RISK

Vesile Sepici1, Ercan Dincel2, Oya Sahin1, Ismail Sanli2, BehcetSepici2, 1Department of Physical Medicine and Rehabilitation,Gazi University Medical Faculty; 2Department of I.OrthopaedicSurgery, S.B. Ankara Hospital, Ankara, Turkey

Objective: In this study, we aimed to evaluate whether geometricmeasurements of femoral dimensions were associated withfemoral strength and hip fracture risk.

Subjects and methods: 9 patients (3 men, 6 women, mean age:76�6.16) with fracture of proximal femur related with osteoporosisdue to minor traumas and 10 healthy controls (3 men, 7 women,mean age 73�5.16) were included to the study. The hip axis length(HAL-the distance from below the lateral aspect of the greatertrochanter to the inner pelvic brim), the femoral length (FL-thedistance along the line of the hip axis from the lateral aspect ofthe femur to the line joining the superior and inferior extremes ofthe hip joint) and femoral width (FW-the shortest distance acrossthe femoral neck, at right angles to the line of the hip axis) weremeasured on antero-posterior pelvic radiographs by two differentobservers. Two summary ratios were de®ned as HAL/FW and FL/FW. The differences between patients and controls werecompared.

Results: There was no difference in the mean age of thesubjects. The mean hip axis length was longer in patient group,but the difference was not signi®cant. We also found nosigni®cant association between other femoral dimension mea-surements and the risk of hip fracture (p>0.05).

Conclusion: It was concluded that further controlled studieswith increased number of cases were required to assess theeffects of geometric measurements of femoral dimensions onfemoral strength and hip fracture risk. Increasing the number ofthe cases would also allow to evaluate racial differences infemoral dimensions and risk of hip fracture.

413 (377). BONE DENSITY VS INTERNAL ARCHITECTURE OFHIP (SINGH INDEX) AS PREDICTOR OF BONE STRENGTH

Manmohan Singh, University of Illinois at Chicago, IL, USA

PURPOSE of this in vitro study was to assess the relativeimportance of bone density and bone architecture in determininghip fracture risk.

METHOD involved scanning 65 cadaver femurs, submerged inwater to simulate soft tissues, using Norland 2600 DPA unit tomeasure bone mineral density (BMD). BMD values were obtainedfor total area and nine equal segments of proximal femur. TotalBMD ranged from 352 to 983 mg/cm2 (mean = 658�135 SD). X-rays were donez to obtain Singh index (SI) readings, which rangedfrom 1 to 6 (5.03�1.36 SD). Femurs were then mounted on MTS812 materials testing machine and loaded to failure under axial


compression. Breaking loads ranged from 1967 to 10224 N(5723�1896 SD). Resulting fracture lines consistently simulatedclinical fractures of femoral neck. The head and trochanterfragments were then ashed for mineral content.

RESULTS of regression analysis showed the following correla-tions:

breaking load vs BMD r = 0.58 vs SI r = 0.73

ash density (head) vs BMD r = 0.74 vs SI r = 0.58ash density (troch) vs BMD r = 0.87 vs SI r = 0.60

CONCLUSIONS of the study: (1) bone mineral content (i.e. ashdensity) correlated best with BMD, (r = 0.87); (2) bone strength (i.e.breaking load) correlated better with SI (r = 0.73) than with BMD(r = 0.58), (3) Three segments of femur overlying primary tensiletrabeculae had BMD that correlated best with breaking strength(r = 0.62, 0.51, and 0.56). It was signi®cant to note that SI gradesdepend on changes observed in the same group of trabeculae.

414 (378). BLOOD LEAD CONCENTRATION DURINGPREGNANCY AND BONE LOSS

M. F. Sowers1, T. Scholl2, M. Jannausch3, John Bogden4,1University of Michigan, Ann Arbor, MI, USA; 2University ofMedicine & Dentistry of New Jersey, Stratford, NJ, USA;3University of Michigan, Ann Arbor, MI, USA; 4University ofMedicine & Dentistry of New Jersey, Newark, NJ, USA

Bone is the sink for heavy metals, such as lead, that can beliberated by bone turnover. We evaluated whether bone loss inpregnancy, measured with ultrasound, was associated with anincrease in bone lead concentrations. Bone ultrasound wasmeasured at entry to prenatal care and at seven weekspostpartum in 252 pregnant women, aged 12±34 years. Bloodlead was measured at entry to care, the 28-week prenatal visitand at parturition using atomic absorption spectrometry.Osteocalcin concentrations were also measured using radio-immunoassay in specimens collected in the same time frames.The average blood lead concentrations at entry to care were 1.27mg/dl�0.78. While there was, on average, a 3.6% change inultrasound bone mass in pregnancy, there was no signi®cantchanges in blood lead concentrations. Likewise, there was noassociation between serum osteocalcin concentrations andblood lead concentrations. There are several possible explana-tions. The turnover of bone in pregnancy may be insuf®cient toliberate substantial amounts of sequestered lead or preventionefforts may have reduced the amount of sequestered lead levelsamong women this age.

415 (379). BONE LOSS IN PREGNANT ADOLESCENTS ANDADULT WOMEN

M. F. Sowers1, T. Scholl2, M. Jannausch3, 1University of Michigan,Ann Arbor, MI, USA; 2University of Medicine & Dentistry of NewJersey, Stratford, NJ, USA; 4University of Michigan, Ann Arbor,MI, USA

To determine the amount of bone change in pregnancy, boneultrasound measures were taken at entry to prenatal care and atseven weeks postpartum in 252 pregnant women, aged 12±34years. After adjusting for variation in time at entry to care and timebetween delivery and the postpartum bone measurement, therewas signi®cantly lower bone ultrasound at the postpartum visit(73.6% less, on average, p<0.0001). Women who were nullipar-ous or still-growing adolescents had signi®cantly greater boneloss (p<0.001). Women with higher baseline bone ultrasound also

had more bone change. Weight, weight change during preg-nancy, dietary calcium intake, and less physical activity were notsigni®cantly associated with bone change. This study providesevidence of a non-pathological bone mass loss with pregnancy asmeasured with bone ultrasound. The amount of change would beconsistent with the demands of fetal mineralization as well as thecontinuing mineralization of the maternal skeleton among theyounger primiparas.

416 (380). LONGITUDINAL EVALUATION OF BONE LOSS INELDERLY MEN. THE MINOS STUDY

P. Szulc1, F. Munoz1, F. Marchand2, F. Duboeuf1, P. D. Delmas1,1INSERM Research Unit 403, Lyon, France; 2SSMB, MontceauLes Mines, France

We evaluated bone loss in a cohort of 588 men aged 51±85 yrsfollowed prospectively during 3 years. Bone mineral density(BMD) of spine, hip, total body was measured using HOLOGICQDR 1500 device and BMD of forearm using OSTEOMETER DTX100 device. We found a bone loss at the level of total hip(0.61�1.20 %/yr, p = 0.0001), of the distal and ultradistal sites offorearm (0.55�1.11 and 0.45�1.58 %/yr, p = 0.0001), and of thewhole body BMC (0.44�1.19 %/yr, p = 0.0001). Lumbar spine BMDincreased (0.28�1.66 %/yr, p<0.001) mainly due to an increase ofBMD in the men with osteoarthritis (OA) (0.50�1.73 %/yr, p<0.001)whereas it was stable in men without OA. The rate of bone lossincreased with age at all the skeletal sites. In men more than 70yrs of age, the bone loss rate was higher than before this age(e.g.: distal forearm BMC ±0.52�0.91 vs 0.25�0.82 %/yr, p<0.002;femoral neck BMD ±0.53�1.31 vs 0.17�1.33 %/yr, p<0.01). Therate of bone loss was not related to the current body weight,however, it was correlated with the change of body weight sincethe age of 25 yrs (after adjustment for age) at the level of the hip(r = ±0.11, p = 0.01) and of the whole body (r = ±0.12, p<0.01) andwith the weight change during the follow-up (hip: r = 0.15,p<0.001). Men who gained less than 4 kg of body weight sincethe age of 25 yrs (®rst quartile) had a higher rate of bone loss thanthose who gained more than 4 kg (total hip ±0.79�1.12 vs0.52�0.76 %/yr, p<0.01). In the stepwise regression, the changeof fat mass during the follow-up (and not that of lean body mass)was the major determinant of the rate of bone loss at the level ofthe total hip (r = 0.15, p<0.001) and at the level of lumbar spine inmen without OA.

In summary, we could demonstrate signi®cant bone loss over 3years at various skeletal sites in a cohort of healthy men. Boneloss is more pronounced after the age of 70 yrs and in those whoshow little weight gain especially little gain of fat tissue. Thesedata suggest that peripheral estrogen production in fat tissuemight reduce bone loss in elderly men.

417 (381). CALCIUM LOAD TEST IN OSTEOPOROSIS

R. Tanakol, M. Akyildiz, H. Boztepe, F. AlagoÈ l, Istanbul Faculty ofMedicine, Endocrinology, Turkey

The purpose of this investigation is to detect the value of calciumload test in the differentiation of various causes of hypercalciuriain the pathogenesis of osteoporosis and also the relationshipbetween cAMP suppressibility and BMD. A 2-hr urine sampleafter an overnight fast and after 1 g of calcium by mouth weretested for calcium, PTH, urinary cyclic AMP (UcAMP) andcreatinine. 21 patients (Group I, age: 51�11 yrs) with BMD<72.5 SD T-score and 12 healthy subjects (Group II, 47�9 yrs)with BMD �1SD T-score were studied. Bone formation andresorption parameters were not different between the groups. InGroup I, UcAMP increased from a fasting value of 3.4�1.4 nmol/100 ml GFR to 4.7�5.3 after 1g Ca load, while it decreased from4.2�1.4 to 3.3�1.2 (p = 0.04) in Group II (NS between groups). Ingroup I, urinary Ca increased from a basal fasting level of 0.14


mg/mgCr to 0.22�0.1 after oral Ca load. In Group II, basal fastinglevel of urinary Ca (0.07�0.04 mg/mgCr) was signi®cantly lowerthan group I (p = 0.05) which increased to 0.19�0.0 (NS).Resorptive hypercalciuria was detected in 1 and absorptivehypercalciuria in 11 of the cases. No case with renal hypercalciur-ia was found. Only 3 patients had nonsuppressible PTH levels, as11 patients had nonsuppressible UcAMP after the Ca load. Theresults suggested higher bone resorption in patients withosteoporosis despite the presence intact PTH levels withinnormal ranges. UcAMP may provide a more reliable index ofparathyroid function than intact PTH in Ca loading test.

418 (382). FRACTURE RISK IN PATIENTS TREATED FORHYPERTHYROIDISM

P. Vestergaard1, L. Rejnmark1, J. Weeke2, L. Mosekilde1,1Department of Endocrinology and Metabolism, ArhusAmtssygehus, Aarhus, Denmark; 2Department of Medicine M,Aarhus Kommunehospital, Denmark

Aim: To study fracture risk and risk factors for fractures inpatients with hyperthyroidism.

Material: A total of 864 patients with diffuse toxic goitre or toxicnodular goitre and 1000 randomly selected controls from thebackground population received a standard questionnaire.

Results: Among the patients 621 (72%) and among the controls654 (65%) returned the questionnaire (p<0.01). Within the ®rst ®veyears before the diagnosis the patients had the same fracture riskas the controls (RR=1.1, 95% CI: 0.8±1.5). After the diagnosis,fracture risk was elevated among the patients (RR=1.7, 95 % CI:1.2±2.3), especially in the age group 50 years or older (RR=2.2,95% CI: 1.5±3.3). Fracture risk was elevated for fractures of thespine (RR=5.7, 95% CI: 1.4±23.8) and the forearm (RR=3.1, 95%CI: 1.6±6.2), but not at other skeletal sites. Treatment withradioactive iodine alone was associated with an increasedfracture risk (OR=2.7, 95% CI: 1.2±6.0), a risk that was notpresent in patients who had received methimazole (RR=1.5, 95%CI: 0.7±3.2).

Conclusions: Our study demonstrated an increased fracturerisk in hyperthyroidism, a fracture risk that was present withradioactive iodine treatment alone, but not in subjects that hadreceived both radioactive iodine and methimazole or other typesof antithyroid therapy.

419 (383). FRACTURES IN PATIENTS WITH PRIMARYIDIOPATHIC MYXOEDEMA

P. Vestergaard, J. Weeke, H. C. Hoeck, H. K. Nielsen, J. Rungby,L. Rejnmark, P. Laurberg, L. Mosekilde, Department ofEndocrinology and Metabolism, Aarhus Amtssygehus, Aarhus,Denmark

Aim: To study fracture risk and risk factors for fractures inpatients with primary idiopathic myxoedema.

Material: A self-administered questionnaire was issued to 628patients with primary idiopathic levothyroxine substituted myx-oedema and 1000 randomly selected controls from the back-ground population.

Results: A total of 412 patients (65.6%) and 654 controls(65.4%, p = 0.98) returned the questionnaire. The patients wereolder than the controls (median 57 years, 43 years, 2p<0.01).Overall fracture risk was increased in patients compared tocontrols (Relative risk: RR=1.6, 95% CI: 1.1±2.3). The increasewas temporary and limited to the period within the ®rst two yearsfollowing the diagnosis of myxoedema (RR=2.9, 95% CI: 1.9±4.3).Before the diagnosis and more than two years after the diagnosisthe fracture risk in patients did not deviate from that of thecontrols. The increase in fracture risk was only signi®cant in theage group above 50 years (RR=1.9, 95% CI: 1.2±3.0), and waslimited to the forearms (RR=3.0, 95% CI: 1.4±6.3 for the entire

patient population) while there was a borderline signi®cantincrease in fractures of the feet and toes (RR=2.3, 95% CI: 1.0±5.0).

Conclusions: There was a temporary increase in fracture riskwithin the ®rst two years following diagnosis of primary idiopathicmyxoedema.

420 (384). CAUSES OF OSTEOPENIA IN CHILDHOOD ANDEFFECT OF SUPPLEMENTATION THERAPY ON BONEMINERAL DENSITY

V. VyskocÏ il, J. VarvarÏovskaÂ , E. Benese, Department of BoneDisease IInd Clinic of Internal Medecine, Orthopedic Clinic,University Hospital PLZEN, E. Benese,

Authors present classi®cation of osteopenias and osteoporosis inchildhood according to aetiology. They studied 46 children withspine osteopenia associated with different diseases. The childrensuffering from secondary osteoporosis due to osteogenesisimperfecta, glucocorticoids or other metabolic bone diseaseswere excluded.

46 studied children had base-line Z score values ±1.49 in spine,±1.21 in hip, neck and ±0.61 in distal radius. They receivedappropriate dosis of Calcium (0.5±1.0 g) and Vigantol daily. Aftercompleting 2 years of therapy bone densitometry and markers ofbone resorption were assessed. Subsequently bone densityincrease per year was evaluated. The 18 children without calciumtherapy were assigned as a control group. They had noosteopenia in hip and forearm and their base-line Z score inspine was ±1.58 comparable with the group of treated children.

After a 2-year period of follow-up the intervention group had7.1% of bone density increase in spine (control group 6.3%), inneck 4.1% (control group 0.5%), in distal radius 4.2% (controlgroup 2.24%). The markers of bone resorption showed that theintervention group had signi®cant decrease of parathormone aftertherapy (36 to 18), osteocalcin (122.8 to 83.0) as well as crosslinks(1908 to 243). In the control group there were no signi®cantchanges in markers of bone resorption (parathormone 45.7 to 34,osteocalcin 80.7 to 72.3, crosslinks 917 to 386). No urolithiasis orheterotopic ossi®cations were observed in any child.

The result of the study allow to conclude that the therapymodi®es only bone density in the regions with importantlydecreased bone density but does not raise bone densitysubstantially when compared with the control group. Similarconclusions were drawn in Scandinavian studies.

421 (385). IMPORTANCE OF DENSITOMETRY BEFORE TOTALENDOPROTHESIS APPLICATION AND POSSIBILITIES OFPHARMACOLOGIC PREVENTION OF ENDOPROTHESISLOOSENING

V. Vyskocil1,2, K. Koudela1, O. Topolcan3, 1Department ofOrthopedic Surgery; 2Department of Bone Disease; 3Departmentof Medicine II, Charles University Hospital PLZEN, CzechRepublic

259 patients were examined by means of densitometry beforeapplication of total hip and knee endoprothesis, 212 patientsbefore total hip endoprothesis and 47 patients before knee totalendoprothesis (TEP).

Patients' mean age was 62 years, the youngest patient was 26,the oldest one 82 years old. All BMD measurements wereperformed by using dual-energy x-ray absorptiometry, usingHologic QDR 2000. Measurements were obtained at the poster-oanterior lumbar spine and hip, mostly at the left hip, in cas ofright hip operation ± at the right hip. All patients before operationhad following values of hip BMD expressed in T scorepercentage: left total hip 87%, trochanter 62%, intertrochantericarea 84%, femoral neck 58%, Ward's triangle 83%, right total hip


59%, trochanter 56%, intertrochanteric area 57%, femoral hip62% and Ward's triangle 57%.

WHO classi®cation and its criteria for osteoporosis wereaccomplished in following groups of patients: the left area725% patients for the total hip, 31% for trochanter, 37% forintertrochanteric area, 25% for femoral hip, the right area 730%patients for total hip, trochanter 35%, intertrochanteric area735%, femoral neck 721% patients.

T score values in spine were in¯uenced by severe spondylosiswhich is common in elderly people: L1 90% (range 52±153%), L2area 88.9% (range 54±147%), L3 area 85.3% (range 52±152%), L4area 84.4% (range 56-155%), total L1±4 85.1% (range 57±140%).

Patients accomplishing criteria for osteopenia were treatedwith calcium supplementation, patients with osteoporosis weretreated according to their results of markeers of bone metabolismand risk factors.

Densitometry in all patients was checked up after 1±3 years oftherapy and compared to x-ray ®ndings where the position of TEPwas followed and possible loosening stated.

Authors discussed the possibilities of pharmacologic preven-tion from TEP detachment (loosening).

422 (386). OSTEOPOROSIS TREATMENT AND COMPARISONOF DIFFERENT MEDICAMENTS INFLUENCING BONE MINERALDENSITY AND MARKERS OF BONE METABOLISM

Vaclav Vyskocil, Department of Bone Disease, Charles UniversityHospital PLZEN, Czech Republic

1500 patients treated for osteoporosis in the course of the last 5years (1995±1999) were followed up. Patients suffering fromsecondary osteoporosis and corticosteroid induced osteoporosiswere excluded from the study as well as those ones withspondylosis and spondylarthrotic progression in spine andcoxarthrosis in hip. Patients participating in the study weredivided into 7 main groups according to their treatment: calcium/Ca/ and vitamin D, HRT, alendronate /ALN/, calcitonin /CT/,clodronate, ¯uorides and the last 7th group without therapy.Particular medicaments as ALN and CT were assigned con-formably to used adjuvant substitution in 4 subgroups (calcium,ergocalciferol, cholecalciferol, rocaltrol). The complete group ofpatients was composed of 1306 females and 194 males, theirmean age was 60.8 and mean period of treatment was 15.4months (12±24 months after the applied therapy). Changes ofBMD measured in spine and hip in adults aged 18±65 years werecompared with people older than 65 years or patients sufferingfrom degenerative diseases of spine, forearm and hip. Differencesof BMD in spine were evaluated in L1±4, in hip ± total hip andneck. Initial T score was ±2.05 in spine, ±1.76 in hip and ±2.53 inneck. Structure of study subjects according to their medicationwas as follows: 23% patients without treatment, 14.8% with onlycalcium preparations, 37.4% with ALN, 18.6% with CT, HRT in3.4% patients, ¯uorides 2.2% and clodronate 0.6% patients.Simultaneously changes of bone formation and resorption wereassessed and values of parathormon, osteocalcin, procollagen Iand crosslinks before and after treatment were compared.Percentage changes of spine BMD (compared to baseline value)were at month 12 +2.15% for HRT, 3.69% for ALN, +1.85% for CT,+2.44% for ¯uorieds (but a large dispersion was present), +0.6%for clodronate, ±0.41% for Ca, hydroxiapatite + 1.84%, the lastgroup without therapy decrease of BMD ±2.43%. Total hip BMDshowed increase of + 1.56% in HRT, 1.4% in ALN group, 0.89%for CT, 2.55% for ¯uorieds (but also a wide range of results),clodronate ± nonsigni®cant decrease of ±0.34%, Ca +0.29%,hydroxiapatit +0.84%, the group without treatment decrease71.85%. Neck proved BMD increase +1.32% for HRT, +1.39% forALN, +0.07% for CT, 0.11% for ¯uorides, Ca +0.93%, hydro-xiapatite +1.42%, but signi®cant decrease for clodronate±2.42% and the group without treatment also decrease ±1.5%.The author observed the effectivity of different therapies in

primary osteoporotic patients and dependence of BMD changes,risk of fractures and changes of markers of bone metabolism onthe patients' age.

423 (387). PROTECTION FROM OVARIECTOMY-INDUCEDBONE LOSS BY OSTEOPONTIN DEFICIENCY IS INDEPENDENTOF MOUSE STRAIN

H. Yoshitake1, D. T. Denhardt2, S. R. Rittling2, M. Noda1, 1DeptMolecular Pharmacology, Tokyo Medical and Dental University,Tokyo, Japan; 2Dept Cell Biology and Neuroscience, RutgersUniversity, Piscataway, NJ, USA

Osteopontin is one of the most abundant non-collagenous matrixproteins in bone. It is produced by both osteoblasts andosteoclasts and has been implicated in regulation of boneresorption based on in vitro studies. We have recently observedthat bone loss induced by ovariectomy in mice was reduced inosteopontin-de®cient mice with C57B16/129sv back ground. As itis known that bone metabolism could vary depending on thegenetic background of the mice, we examined whether ovar-iectomy of the mice with pure genetic back ground of 129 couldmake any difference in terms of the effects of osteopontin-de®ciency on ovariectomy-induced bone resorption. Three to fourmonths old female wild or osteopontin-de®cient mice with 129background were either ovariectomized or sham operated. Afterfour weeks of the surgery, uterine weight was signi®cantlyreduced in both wild type and osteopontin-de®cient mice. Bodyweight was not changed during the four weeks in either shamoperated or ovariectomized mice regardless of the geneticbackground. Micro computed tomography analyses indicatedthat the bone volume in the proximal end of the tibiae wassigni®cantly reduced in 129 wild type mice, however, thisreduction in the cancellous bone volume was less in theosteopontin-de®cient 129 mice. These observations are similarto those in mice with C57B16/129sv background and furthercon®rmed that the effects of osteopontin-de®ciency on thereduction of bone loss due to ovariectomy are not restricted inmice with a particular genetic background.

424 (388). PREDICTIVE VALUE OF BIOAVAILABLETESTOSTERONE FOR BONE MINERAL DENSITY IN NORMALWOMEN

I. ZÏ ofkovaÂ , R. Bahbouh, M. Hill, Institute of Endocrinology,Prague, Czech Republic

In the cross-sectional study performed on 147 healthy orosteoporotic, but otherwise normal premenopausal womenaged 40.1�9.9 years (n=39) or postmenopausal women aged61.9�8.9 years (n=108) associations between serum ovarial oradrenal sexual steroids and bone mineral density (BMD) wereinvestigated. Serum estradiol, dehydroepiandrosterone (DHEA),DHEA sulphate (DHEAS) and androstenedione and sex hormonebinding globulin (SHBG) correlated positively with BMD at thespine or hip as total testosterone levels with BMD at the spine.However, only SHBG values (but not steroid confounders)correlated with serum cross-linked telopeptide of type I collagenand osteocalcin levels. After adjustment for age, body mass indexand serum estrogen or androgen levels the predictive importanceof bioavailable testosterone (testosterone/SHBG) for BMD at thespine or hip and estradiol for BMD at the spine was demon-strated. The difference in bioavailable testosterone levelsbetween osteoporotic and healthy women were demonstratedin the postmenopausal (but not in the premenopausal) subgroup.The ®ndings document a signi®cant predictive value of bioavail-able testosterone for BMD and outline a possible pathogeneticimportance of this androgen in postmenopausal osteoporosis.


Osteoporosis ± Treatment

425 (389). CYCLIC ADMINISTRATION OF INTRAVENOUSNERIDRONATE INCREASES BONE MASS BOTH IN GROWINGAND ADULT PATIENTS WITH OSTEOGENESIS IMPERFECTA

S. Adami1, D. Gatti1, E. Fracassi1, V. Braga1, F. Corallo1, F.Antoniazzi2, 1Rheumatological Rehabilitation University HospitalValeggio S/M, Italy; 2Pediatric Unit, University of Verona, Italy

In an ongoing clinical trial involving patients affected byOsteogenesis Imperfecta (O.I.) we are administering neridronate2 mg per kg of body weight up to a maximum of 100 mgintravenously every three months. Here we report the densito-metric data in 39 patients who completed the ®rst 12 months oftherapy.

The study group includes 17 males and 22 females. 14 patientswere under 17 years of age (range: 6±16 y.o.) and 25 over 20 yearsold (range 21±68 y.o.). The types of Osteogenesis Imperfectawere: type 1 (n. 26), type 3 (n. 5), type 4 (n. 8).

In the growing patients (aged <17 y.) BMC rose signi®cantly atboth the spine and total hip (+41.2% and 48.6% respectively). Thecorresponding BMD increases were lower (+ 27.9% and 28.8%)for an 10% enlargement of the projected area.

In the patients aged >20 y. BMC and BMD values increasedsigni®cantly both at the spine (2.4% to 3.4%) and at the hip (2.5%to 2.6%).

Intermittent intravenous neridronate induced extraordinaryincreases in bone mass in young growing individuals with O.I.Here we have shown for the ®rst time that I.V. bisphosphonatetherapy increases signi®cantly bone mass also in adultpatients.

426 (390). EFFECTS OF TWO INTERMITTENT ALENDRONATEREGIMENS IN THE TREATMENT OF POSTMENOPAUSALOSTEOPOROSIS

M. Rossini, D. Gatti, V. Braga, G. James, S. Adami, Ospedale diValeggio, University of Verona, Italy

A large proportion of patients have bone mass values for whicha therapeutic intervention is considered necessary but theaccepted aim might be the sole preservation of the actualbone mass. Aim of this study was to investigate effects of twointermittent alendronate regimens in the treatment of non-severeforms postmenopausal osteoporosis. 124 postmenopausalwomen (age range 52±75 years) with a bone mineral density(BMD) at the femoral neck ± 2 SD below the mean values ofyoung healthy individuals, and without a history of previousosteoporotic fracture, were randomly assigned either to calcium/vitamin D supplements alone or associated with 2 differentintermittent oral alendronate regimens: 20 mg once a week(weekly group) or 10 mg daily for one month out of three(cyclical group). After 1 year in both active groups we observeda signi®cant increase of BMD at both the spine (+2.2�2.6 and+2.5�2.9%), and femoral neck (+1.6�4.8 and +1.5�2.2%) forweekly or cyclical regimen, respectively. This was associatedwith a signi®cant diminution of both serum bone-speci®calkaline phosphatase (±25 and ±28%) and urinary NTX (±40and ±30%). In the control group BMD decreased signi®cantly atthe lumbar spine. The compliance to treatment and itstolerability was excellent in both alendronate arms. In conclu-sion, intermittent alendronate at cumulative doses (and costs) 3times lower than those currently recommended for osteoporosistreatment is very well accepted and is able to signi®cantlyincrease BMD at the spine and femoral neck. These regimenscan be clinically useful in the long-term treatment of non severeforms postmenopausal osteoporosis, particularly in women withlow compliance for continuous administration.

427 (391). RISEDRONATE RAPIDLY REDUCES FRACTURERISK IN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS

S. Adami1, O. Sùrensen2, R. Eastell3, E. Sod4, S. Horlait5, N.Watts6, 1Verona, Italy; 2Copenhagen, Denmark; 3Shef®eld, UK;4Cincinnati, OH, USA; 5Staines, UK; 6Atlanta, GA, USA

The primary role of osteoporosis treatment is fracture preven-tion. The effectiveness of risedronate (RIS) in reducing the risk ofvertebral fracture in osteoporotic women was evaluated in 2randomized, double-blind, placebo-controlled trials. VERT-MN(Multinational ± Europe and Australasia) included women with52 vertebral fractures; VERT-NA (North America) included thosewith 1 prevalent vertebral fracture and a T-score 4±2 or 2prevalent vertebral fractures. A total of 3864 women wererandomized to receive RIS (2.5 or 5 mg/d), or placebo for 3years. All received calcium (1 g/d) and those vitamin D de®cientat baseline received 4500 IU/d. Patients were at least 5 yearspostmenopause (mean = 24 years) with a mean age of 69 years.The median number of fractures at baseline was 3 for VERT-MNand 2 for VERT-NA. Quantitative and semi-quantitative methodsof analysis were utilized to determine incident vertebralfractures.

After one year of RIS treatment, a signi®cant reduction wasobserved in new vertebral fracture incidence, ranging from 61%to 65% for RIS 5mg vs. control (p<0.001). The anti-fracture effectwas slightly greater in the more severely osteoporotic group (52prevalent fractures) as the fracture risk reduction ranged from65% to 74% for RIS 5mg vs. control (p<0.001).

These results indicate that risedronate rapidly reduces the riskof vertebral fractures, within the ®rst year of treatment. It isimportant for physicians to treat with a therapy that rapidlyreduces vertebral fracture risk.

428 (392). QUALITY OF LIFE IN OSTEOPOROTIC TURKISHWOMEN TREATED WITH ALENDRONATE

G. AkyuÈ z1, N. Eskiyurt2, D. O¯uoglu1, S. Aki2, O. Kayhan1, A.Oncel2, 1Department of Physical Medicine and Rehabilitation,Marmara University, School of Medicine, Istanbul, Turkey;2Department of Physical Medicine and Rehabilitation, IstanbulUnviersity, School of Medicine, Istanbul, Turkey

Osteoporosis is a metabolic bone disease characterized bydecrease of bone density and increase susceptibility to fracture.The aim of this study is to investigate relationships between painand subjective aspects of quality of life. Sixtyfour patients withosteoporosis were included to our study. Patient's mean agewere 63.6�6.8 (50±74) and menopause duration were 16�8.2years. Their vertebral and femoral bone mineral density weremeasured before and after treatment by Dual X-Ray Absorptio-metry (DXA). Mean vertebral T score were ±3.35�0.7; and meanfemoral neck T score were ±2.2�0.6. All patients were takenalendronate (10 mg/day) plus calcium (1000 mg/day) for 1 year.The assessment was carried out using visual analog scale (VAS),face scale, Mc Master Health Index Questionnaire (MHIQ) andBeck Depression Index (BDI). Differences between before andafter therapy were found statistically signi®cant in all evaluationparameters (p<0.05). As a result, we suggest that alendronatetherapy is effective in patients with osteoporosis to relieve painand increase quality of life.

429 (393). THE EFFECTS OF INDOMETHACIN AND IBUPROFENON HORMONE-DEFICIENT BONE DENSITY LOSS IN ANOVARIECTOMIZED MATURE RAT MODEL

C. G. Ambrose, G. R. Gogola, M. Brennan, University of TexasHealth Science Center, Houston, Texas, USA

The goals of this study were to determine the effect of commonlyavailable NSAIDs in preventing hormone-de®cient bone loss, and


to correlate the mechanical strength of bone after exposure toNSAIDs with the bone mineral density as obtained from DXAmeasurements. Bilateral ovariectomy or sham operations wereperformed on 48 mature female Sprague-Dawley rats. 12 ratswere sacri®ced for baseline measurements. The rest weredivided into three treatment groups and underwent dailygavage for 8 weeks with one of three suspensions: ibuprofen(30 mg/kg/day), indomethacin (2 mg/kg/day), or the suspensionvehicle alone (1ml/day). Bone density of the lumbar spine andthe distal femur was measured on each rat initially and at 8weeks. Bone strength was determined by three-point bending ofthe femoral midshaft, and bending of the femoral neck aftersacri®ce at 8 weeks. In the control group a 10.5% BMD loss wasmeasured in the lumbar spine and a 9.8% loss was measured inthe distal femur. The strength of the femoral neck, but not thefemur mid-shaft, was signi®cantly lower (p = 0.04) in ovariecto-mized animals when compared to sham-operated animals. Theibuprofen-treated animals had a signi®cant loss of BMD in thelumbar spine, but not the distal femur. The femoral neck strengthwas signi®cantly lower in ovariectomized animals when com-pared to sham-operated animals. In the indomethacin treatedanimals, there were no signi®cant differences between theovariectomized and the sham-operated animals in any of themeasured parameters.

430 (394). RALOXIFENE AND HORMONE REPLACEMENTTHERAPY LOWER ATHEROGENIC LIPOPROTEINS TOTHE SAME EXTENT IN HEALTHY POSTMENOPAUSALWOMEN

P. W. Anderson1, D. A. Cox1, A. Sashegyi1, S. Paul1, B. W. Walsh2,S. L. Silfen1, 1Lilly Research Laboratories, Indianapolis, IN;2Brigham and Women's Hospital, Boston, MA,

Background: Non-HDL cholesterol (nonHDL-C) is a measure of allatherogenic, apolipoprotein B-containing lipoproteins in serum,and is predictive of cardiovascular events in women. Raloxifene(RLX) and hormone replacement therapy (HRT) lower LDL-C, buttheir effects on nonHDL-C have not been compared. Objective:To determine the effect of RLX and HRT on nonHDL-C serumlevels in postmenopausal women. Methods: 390 women aged 45±72 years were randomized to either placebo, RLX (60 mg/d or RLX120 mg/d), or continuous combined HRT. Total-C and HDL-Cwere measured in serum at baseline and after 3 and 6 months.NonHDL-C was calculated as Total-C minus HDL-C. Results: Allactive treatments decreased serum nonHDL-C signi®cantlycompared with placebo at both 3 and 6 months (see table). Theeffect of all treatments to lower nonHDL-C compared withplacebo was greatest in women with hypercholesterolemia(Total C >240 mg/dL) at baseline. Conclusion: Raloxifene andHRT lower the serum nonHDL-C concentration, a global measureof atherogenic serum lipoproteins, by the same magnitude inpostmenopausal women, particularly among those with hyperch-olesterolemia.

Median Change from Baseline

3 months 6 months

Placebo ±0.01 (±0.23%) ±0.03 (±0.63%)RLX 60mg/d ±0.39 (±9.2%)* ±0.39 (±10.1%)*RLX 120mg/d ±0.44 (±10.1%)* ±0.43 (±9.1%)*ccHRT ±0.34 (±9.1%)* ±0.40 (9.3%)*

*p<0.001 vs. placebo.

431 (395). BIOMECHANICAL EVALUATION OF ABIORESORBABLE POLYMER FOR THE AUGMENTATION OFSCREW OSTEOSYNTHESIS IN OSTEOPOROTIC CANCELLOUSBONE

P. Augat, A. Ignatius, M. Ohnmacht, P. Pokinskyj, H. J. Kock, L.Claes, 1Institute of Orthopedic Research and Biomechanics,University of Ulm, Germany; 2Merck Biomaterial GmbH,Darmstadt, Germany

The purpose of this study was to assess the ef®cacy of a newresorbable polymer to improve the anchorage of osteosynthesismaterials in cancellous bone. The new resorbable polymer isbased on Alkylen-bis (dilactoyl) methacrylat. Bending strengthand pullout strength of cancellous bone screws were tested in48 bovine and 24 human osteoporotic vertebral bodies.Removal torque was tested in the diaphysis of 8 humanfemora. Strength measurements of bone screws augmentedwith the new polymer cement were compared to non-augmented screws and screws augmented with PMMA.Removal torque of the polymer augmented screw increasedby 77% (p<0.05) compared with non-augmented screws. Inbovine vertebrae augmentation increased the pullout strengthby 88% for the new cement and by 92% for PMMA (p<0.001).Pull-out strength in human osteoporotic vertebrae was in-creased by 118% (p<0.01). Bending strength was increasedafter augmentation in bovine vertebrae (115%, p<0.01; PMMA:90%) and in human osteoporotic vertebrae (114%, p<0.08).Augmentation by the new polymer signi®cantly enhancedanchorage and attachment of bone screws in cancellousbone. While the mechanical properties of the new polymerwere comparable to PMMA, its biodegradable properties maycomprehend some advantages for osteosynthesis applicationsin osteoporotic patients.

432 (396). FEASABILITY OF A TREATMENT WITH HIGHFREQUENCY VIBRATION FOR THE PREVENTION OF BONEAND MUSCLE LOSS IN ELDERLY WOMEN

P. Augat, C. Becker, S. Scheible, U. Lindemann, T. Nikolaus, L.Claes, Institute of Orthopedic Research and Biomechanics andBethesda Geriatric Hospital, University of Ulm, Germany

Cyclic ground based vibration has previously shown to inducebone formation in sheep and increase muscle force in youngathletes. This study was performed to test the feasibility ofapplying ground-based vibration in elderly women.

Fifty-three postmenopausal, healthy women (age 55 yrs to 75yrs, mean age 67 yrs) were enrolled in the study. At studyentrance and at completion functional performance was as-sessed by a functional reach test, a ®ve-chair stand test, andmeasurement of walking velocity. Force and power of the lowerextremity was assessed by isokinetic force measurements(Cybex). All study participants were subjected to 5 minutes ofvertical ground based vibration, oscillating at 30 Hz, two times aweek for a period of 8 weeks.

Forty-three women (81%) completed the study. While 4 womendiscontinued on own request, 6 women (11%) had to cancelbecause of minor problems that might have been associated withthe vibration treatment. Functional reach increased by 11%(p<0.01), time for the ®ve chair test decreased by 19% (p<0.01),walking velocity increased by 2% (n.s.), and isokinetic momentincreased by 10% (p<0.01).

The study showed a high acceptance of vibration treatment ina possible target population for osteoporosis treatment. Itfurthermore suggested its effectiveness in the prevention ofmuscle loss.


433 (397). COMBINED ALENDRONATE AND TIBOLONE ISMORE EFFICACIOUS THAN EITHER MEDICATION ALONEIN THE TREATMENT OF POSTMENOPAUSALOSTEOPOROSIS

A. Avramides, D. G. Goulis, J. Sarris, Ch. Balaris, S. Delaroudis, A.Kiroudi, M. Tzoiti, Department of Endocrinology, HippocrationHospital, Thessaloniki, Greece

The purpose of this study was to evaluate the effectiveness ofalendronate or tibolone as well as their combination (alendrona-te+tibolone) in women with established postmenopausal osteo-porosis.

We carried out a 24-month, randomized, control-matchedstudy of the use of alendronate 10 mg (group A, n=50), tibolone2.5 mg (group B, n=50) or their combination (group C, n=25) in 45to 69 year-old women with postmenopausal osteoporosis. Themean (�SE) bone density of the lumbar spine increased by2.2�1.2 percent and 1.9�1.1 percent in the alendronate andtibolone group respectively (p<0.01 vs. control). It increased by3.8�1.9 percent in the combination group (p<0.01 vs. groups Aand B) whereas it decreased by 0.3�0.3 percent in the controlgroup. Similar changes were found regarding the femoral-neckbone density. There were no differences in adverse effects amongthe three groups.

We conclude that the combined use of alendronate andtibolone results in greater increase in bone density than eithermedication alone in white women with postmenopausal osteo-porosis.

434 (398). USING IN POSTMENOPAUSAL WOMEN WITH BONEMASS LOSS RALOXIFENE AND ALENDRONATE

A. Bazarra1, A. Castro2, M. Suarez, 1Health Sciences andMedicine Dept, University of the Coruna, Spain

Objective: Determining if the combined use of raloxifenehydrocloride and alendronate in¯uences on bone mass loss inpostmenopausal women.

Material and method: We studied for 6 months 21 women whowere 44 to 64 years old at base line, were within 2 and 11 years ofmenopause, and had a bone mineral density at the lumbar spinebetween 145 mg/cc and 50 mg/cc measured by the QBMAPsystem with a spiral CT Picker PQ-S densitometer at L2, L3, L4and L5. Of all the women, 10 were assigned to 60 mg of raloxifenehydrocloride, 800 IU of vitamin D3 and 1 g of calcium carbonatesupplementation. 11 were treated with 10 mg of alendronate, 60mg of raloxifene hydrocloride, 800 IU of vitamin D3 and 1 g ofcalcium carbonate supplementation. The SPSS programme wasused for statiscal analysis.

Results: The characteristics of the women recruited for bothgroups were similar. Mean mineral bone density at the lumbarspine was between 1 and 3 DS below the mean value for 30 yearsold normal premenopausal women. After a treatment of 6 monthsno statistically signi®cant difference was found among bothgroups as for the bone mineral density at the lumbar spine.However, the group with alendronate increased a litle more thebone mineral density.

Conclusions: It is necessary to carry out a wider and longerstudy but it seems that the combination of raloxifene hydroclorideand alendronate contribute advantages to decrease the bonemass loss in postmenopausal women, at least, at lumbar spine.Osteoporosis is a multifactorial disease, maybe its best treate-ment and prevention is combining several drugs and attitudes. Itwould be good to test several adjusted doses to decrease sideeffects.

435 (399). RISEDRONATE THERAPY INCREASES TOTAL HIPBMD IN POSTMENOPAUSAL WOMEN INDEPENDENT OFINITIAL HIP BMD STATUS

C. L. Benhamou1, C. Chesnut2, Ch. Roux3, R. Wasnich4, S.Goemaere5, M. Greenwald6, T. Diamond7, S. Adami8, D. Ethgen9,R. Eastell10, 1Orleans, France; 2Seattle, WA, USA; 3Paris, France;4Honolulu, HI, USA; 5Ghent, Belgium; 6Palm Springs, CA, USA;7Kogarah, NSW, Australia; 8Verona, Italy; 9Mason, OH, USA;10Shef®eld, UK

The risedronate (RIS) osteoporosis clinical program enrolled over15,000 patients with varying osteoporosis severity, based on acombination of low BMD (spine or hip) and/or prevalent vertebralfractures. One large study, the Hip Intervention Program (HIP)enrolled 9331 elderly postmenopausal women at risk for hipfracture. Two other studies (VERT-MN [multinational ± Europe andAustralasia], and VERT-NA [North America]) enrolled 3684patients based on the presence of vertebral fracture status.Patients in all 3 studies received RIS (2.5 or 5 mg) or placebo dailyfor 3 years, 1g calcium daily, and vitamin D supplementation iflevels were 540 nmol/L. Total hip BMD in all 3 studies wasmeasured at those study centers using Hologic densitometers, sodata were available for a subset of patients.

Signi®cant BMD increases for RIS 5mg vs. baseline and controlwere observed at the proximal femur beginning at the earliestmeasurement (6 months) and continued for the duration of thestudy. Consistent increases in total hip BMD were observed forRIS 5mg vs. control across the 3 studies. Total hip BMD increasesat 3 years for all centers were: 3.9%, 5.2%, and 3.1% for RIS 5mgvs. control in the HIP, VERT-MN, and VERT-NA studies,respectively (p<0.001 for the comparison in all 3 studies).

In conclusion, risedronate treatment produces rapid andconsistent increases in total hip BMD compared to controlpatients receiving 1g calcium and vitamin D. These effects areobserved in women independent of their baseline hip BMD status.These consistent increases are sustained over 3 years oftreatment.

436 (400). EVALUATION OF POWER: A MULTISITECOMMUNITY BASED EDUCATIONAL PROGRAM FOR OLDERADULTS WITH OSTEOPOROSIS

L. Bernick1, T. Izukawa1, A. Stephens2, 1Baycrest Centre forGeriatric Care, Toronto, ON, Canada; 2North York GeneralHospital, Toronto, ON, Canada

The evaluation of a six-week, multi-site program aimed toempower older adults with osteoporosis, improve their qualityof life and prevent falls will be presented. The collaborativeprogram is provided by nurses, physicians, physiotherapists anddieticians, from four organizations, and includes culturallysensitive screening, education, nutrition and exercise servicesto community dwelling elders. The formative evaluation includeda review of the program structure and process using the logicmodel and descriptive statistical analysis of data from focusgroups, satisfaction questionnaires, knowledge pre and postt-ests, demographic data and treatment recommendations. Theresults indicated that the majority of the participants (N=187) hadcompleted the program (90%); were female (97%) and a meanage of 73 years; had fallen within the last two years (35.5%); andhad osteoporosis on average for two years. Calcium supplements(46%), Vitamin D (55.8%) and bone resorption-inhibiting drugs(22.4%) were recommended for the participants. They reportedan increase in their calcium intake and daily exercise, life stylechanges and improved knowledge. This program has beenbetween three health care organizations, a pharmaceuticalcompany and public health. This unique collaboration hascontributed to the success of this program.


437 (401). PRETREATMENT BMD AND VERTEBRAL FRACTURESTATUS AS WELL AS CHANGE IN OSTEOCALCIN ARE ALLPREDICTORS FOR THE RISK OF INCIDENT VERTEBRALFRACTURE DURING RALOXIFENE THERAPY

N. H. Bjarnason, C. Christiansen, T. Duong, P. D. Delmas, for theMORE Study Group,

We have previously shown that a short-term change in boneturnover is associated with a long-term decrease in vertebralfracture risk during raloxifene treatment. However, a possiblein¯uence of baseline risk factors such as BMD and vertebralfracture status was not assessed.

The MORE study randomised 7705 osteoporotic women todaily treatment with either placebo, raloxifene 60 mg or 120 mg.Spine X-rays were obtained pre-treatment and after 3 years andwere analysed blinded. In a subset of about 1/3 of theparticipants, a fasting blood sample was collected beforerandomisation and at 6, 12, 24 and 36 months for bone markeranalysis. BMD assessments were performed yearly. Using logisticregression to model the risk of suffering at least 1 vertebralfracture, we performed multi-variable analyses including age,baseline spine BMD, prevalent vertebral fracture status andpercent change at 1 year in osteocalcin for the pooled raloxifenegroups (N=1584). The results are given as odds ratios per 1 stdincrease in each parameter. Results from analyses of additionalbone markers will also be presented.

The strongest predictor for incident vertebral fractures was thepresence of prevalent vertebral fractures, with an odds ratio of3.34 (CI: 2.11±5.31, p<0.0001). Odds ratio for baseline spine BMDwas 0.66 (CI: 0.53±0.83, p = 0.0003) with a std of 0.133 g/cm2 andodds for change in osteocalcin was 0.81 (CI: 0.68±0.96,p = 0.0168) with a std of 28.7%. Thus, if the osteocalcin changeduring raloxifene therapy exceeds 28.7%, the likelihood ofincident vertebral fracture over 3 years decreases with 19%.Age was only borderline signi®cant in the multi-variable analyses.

Our data show that the presence of vertebral fracture and brndare very important risk factors for the development of newfractures, even during treatment. Importantly, the predictive valueof on-treatment change in bone turnover is signi®cant afteradjustment for strong risk factors such as pre-treatmentprevalent vertebral fractures, BMD and age.

438 (402). THE EARLY ANTIFRACTURE EFFICACY OFALENDRONATE IN WOMEN WITH OSTEOPOROSIS: RESULTSFROM FIT

D. Black1, D. Bauer1, D. Thompson2, M. Hochberg3, for the FITResearch Group, 1Univ. of California, San Francisco, CA; 2Merck& Co., Rahway, NJ; 3Univ. of Maryland, Baltimore, MD, USA

We investigated the effect of alendronate (ALN) on fractureincidence in 3658 women from the Fracture Intervention Trial (FIT)with one or more prevalent vertebral fracture (VFx) at baselineand women without a prevalent VFx but with femoral neck T-scores 4±2.5 (WHO threshold for osteoporosis). In this group ofwomen, ALN was effective in reducing the risk of any clinicalfracture (RR = 0.70 (0.59, 0.82)), non-vertebral fracture (RR = 0.73(0.61, 0.87)), symptomatic spine fractures (RR = 0.55 (0.36, 0.82)),hip fracture (RR = 0.47 (0.26, 0.79)) and wrist fracture (RR = 0.70(0.49, 0.98)). The cumulative incidence curves for any clinicalfracture, symptomatic vertebral fracture and hip fracture began todiverge as early as 6 months. For each of these fractures theeffect was consistent (tended to increase) over time. Weobserved a 59% (p = 0.030) reduction in symptomatic spinefracture at 12 months, a 63% (p = 0.014) reduction in hip fractureby 18 months, and a 27% (p = 0.017) reduction in any clinicalfracture at 18 months.

Conclusion: In women with either existing VFx or with femoralneck BMD T-score 4±2.5, alendronate was effective in reducingthe risk of any clinical fracture, non vertebral fractures,symptomatic spine fractures, hip fractures and wrist fracture.The effect of alendronate was evident very early.

439 (403). INCREASING AGE AND FEMALE GENDER AREASSOCIATED WITH DELAYED UNION OF HUMERAL SHAFTFRACTURES

M. E. Bolander, J. T. Bronk, G. Sarkar, D. M. Ilstrup, L. J. MeltonIII, Mayo Clinic and Mayo Foundation, Rochester, MN, USA

Age and gender in¯uence skeletal formation and remodeling, buttheir effects on the time taken for fracture healing are unknown.We report a retrospective analysis of 115 patients with closedfractures of the humeral diaphysis (shaft). The time required forhealing was based on clinical criteria and was analyzed on thebasis of fracture characteristics, patient age, and gender. Forsome analyses patients were divided into four groups: 1) young(15 years or under); 2) adult (16±30); 3) mature (21±55); and 4) old(55 or older). Fractures were transverse in 41% of patients andoblique or spiral in 45%; one third were comminuted. Fracturesoccurred after falls (50%), motor vehicle accidents (30%) or othertrauma (20%). Neither time to healing nor nonunion rate wassigni®cantly affected by the etiology, location, or con®guration ofthe fracture. The time until clinical union increased with age in allpatients (p<0.0001); additionally, fractures in women tooksigni®cantly longer to heal than fractures in men of comparableage (p<0.0001). The incidence of fracture nonunion was increasedin women compared to men (14.0% vs 5.2%, p = 0.066). Olderpatients, especially older females, require increased time forfracture healing than younger patients, and as a result are atpotentially greater risk than younger patients for developingcomplications during fracture healing.

440 (404). RISEDRONATE IS WELL-TOLERATED IN PATIENTSWITH OSTEOPOROSIS INCLUDING THOSE OVER 80 YEARS OFAGE

M. Bolognese1, D. Mclntyre2, I. Fogelman3, W. Olszynski4, H.Beck-Nielsen5, H. Mulder6, I. Barton7, T. Ernst8, A. Chines9,1Gaithersburg, MD, USA; 2South Brisbane, QLD, Australia;3London, UK; 4Saskatoon, SK, Canada; 5Odense, Denmark;6Rotterdam, Netherlands; 7Staines, UK; 8Mason, OH, USA;9Mason, OH, USA

As part of a 15,066 patient clinical program, the tolerability ofrisedronate (RIS) was assessed in placebo-controlled studies ofup to 3 years' duration. Patients were not excluded because ofunderlying medical condition or concomitant medication use


(history of GI disorder or NSAID/aspirin use). Approximately 4000patients were 580 years of age at enrollment, a populationtraditionally excluded from clinical trials. Patients were randomlyassigned to receive RIS 2.5 or 5mg, or placebo, all as ®lm-coatedtablets.

The proportions of patients reporting adverse events (AEs) orupper GI AEs were similar in the RIS 5mg and placebo groups, aswere the percentages of patients discontinuing due to AEs (table).

Age 580 Years Age 580 Years

Placebo

(N=1821)

n (%)

RIS 5 mg

(N=1812)

n (%)

Placebo

(N=1313)

n (%)

RIS 5 mg

(N=1292)

n (%)

Any AEs 1651 (91) 1649 (91) 1154 (88) 1137 (88)

Withdrawals due to AEs 290 (16) 301 (17) 274 (21) 249 (19)

Upper GI (UGI) AEs 419 (23) 416 (23) 265 (20) 241 (19)

Most common UGI AEs

Abdominal pain 189 (10) 174 (9.6) 99 (7.5) 84 (6.5)

Dyspepsia 160 (8.8) 171 (9.4) 94 (7.2) 84 (6.5)

The frequencies of the most common treatment-related GI AEswere also similar between treatment groups and importantly therewas no evidence of increased incidence of clinical adverse eventsor intolerance in patients 580 years of age.

These ®ndings, collected from more than 15,000 patients(approximately 4000 of whom are 580 years of age) across awide range of osteoporosis disease severity, support thatrisedronate is a well-tolerated therapy with a favorable safetypro®le.

441 (405). THE EFFICACY OF CALCITRIOL IN OSTEOPOROTICPATIENTS WITH ASTHMA RECEIVING INHALEDCORTICOSTEROIDS

P. Borman1, Y. G. Kutsal1, F. Kalyoncu2, 1Department of PhysicalMedicine and Rehabilitation; 2Chest Diseases, Samanpazari,University of Hacettepe, Ankara, Turkey

The aim of this study was to evaluate the ef®cacy of calcitriol(Rocaltrol1) in a group of asthmatic women suffering from inhaledcorticosteroid(cs) induced osteoporosis. 21 osteoporotic patientswho were receiving treatment with inhaled cs with a mean dose of1.6�2.31 mg BDP/day, for a mean duration of 4.8�0.92 years,were included to the study. The patients were randomly allocatedinto two groups treated with either 0.25 mg calcitriol (n=11) twicedaily or 1000 mg calcium (n=10) alone for one year. The patientsreceiving calcium had signi®cantly greater bone loss at thelumbar spine (0.82�0.12/0.78�0.11 g/cm2), while the mean valuesof lumbar BMD remained unchanged (0.81�0.13/0.81�0.11 g/cm2)in the patients receiving calcitriol. One new fracture occurred inthe calcium supplement group. No side effects of the drugs wereobserved in the two groups. These results suggest that calcitriolmay be a useful agent to prevent inhaled cs induced osteoporosisin patients suffering from asthma. Long-term studies includingmore patients should follow to con®rm these preliminary ®ndings.

442 (406). INFLUENCE OF EXERCISE ON BONE MINERALDENSITY

S. BrankovicÂ , N. PilipovicÂ , P. Vukojevic, N. VujasinovicÂ -Stupar, D.Palic-ObradovicÂ , Institute of Rheumatology, Belgrade, Yugoslavia

We studied the in¯uence of exercise program on bone mass andthe role of exercise in the prevention and treatment ofosteoporosis. Exercise intervention may provide modest increasin bone mineral density (BMD), but must be sustained for

persistent bone mass improvement. The aim of the study wasto assess the effects of our exercise program (developed inInstitute of Rheumatology) on BMD. The patients with low BMDexercised 3 times a week (for 4 weeks), and after that periodpatients continued regularly exercise at home. BMD wasmeasured by dual x-ray absorptiometry (Lunar DXA system).Group of 24 pts exercised without taking any drugs forosteoporosis, mean age 57.38 (46±73) years and mean BMD0.915�0.12 gr/cm2 with average T score ±2.40�0.98. The ®rstcontrol DXA was done after average period of 10.3 months. BMDwas increased to mean 0.925�0.10 gr/cm2 (1.5%), and T score to±2.28�0.88 (3.7%), (n.s.). Second control DXA was done in sixteenpatients (out of 24) who discontinued exercising at home duringnext year. BMD in this group decreased from 0.923�0.07 gr/cm2

at the end of ®rst year to 0.904�0.06 gr/cm2 (2.1%); (t=2.21;p<0.05), after average period of 11.7 months. Our result suggeststhat exercise have a positive effect on BMD even without anymedicaments. It is necessary to continue exercise because whenpts stoped exercising, BMD decreased signi®cantly to lowervalues compared to values at the beginning.

443 (407). LOW BONE MASS BUT NOT QUANTATIVEULTRASOUND OR BONE MARKERS ARE ASSOCIATED WITHVERTEBRAL FRACTURES IN OLDER MEN

J Cauley, J Zmuda, L Palermo, M Nevitt, Universities of Pittsburghand California, San Fransisco,

To test the hypothesis that bone mineral density (BMD),quantitative ultrasound (QUS), and bone turnover markers areassociated with prevalent vertebral fractures (VFx) in a commu-nity based population of older men, we recruited 306 white men,mean age 73 years. Prevalent VFx were identi®ed withmorphometry. A vertebra was considered fractured if any of thevertebral height ratios were > 3 Standard Deviations (SD) belowthe mean for that vertebral level. BMD was measured using DXA(QDR) and heel ultrasound with Sahara QUS device (Hologic, Inc.,Waltham, MA). Osteocalcin and N-Telopeptides (NTx) weremeasured by Endocrine Science (Calabassas Hills, CA). 14% ofmen (n=43) had a VFx. We calculated the age-adjusted odds ratio(95% Con®dence Interval (CI)) of prevalent fracture for 1 SDdecrease in the parameter using logistic regression. One SDdecrease in BMD was associated with an increased prevalence ofVFx (Table). There was no association with QUS or either bonemarker. We conclude that low BMD is a signi®cant correlate ofVFx in older men.

Skeletal Parameter SD OR (95% CI)

Total Hip (g/cm2) 0.15 1.81 (1.24,2.63)Lumbar Spine (g/cm2) 0.18 1.46 (1.03,2.06)BUA (dB/MHz) 17.1 1.23 (0.86,1.78)SOS (m/s) 32.4 1.14 (0.79,1.64)NTx (nM BCE/mM Cr) 19.4 1.05 (0.74.1.47)Osteocalcin (ng/ml) 3.8 1.10 (0.80,1.51)

444 (408). THE HETEROGENEITY IN BONE MINERAL DENSITYAND BIOCHEMICAL MARKERS OF BONE TURNOVER INRESPONSE TO HORMONE REPLACEMENT

O. Chaki, I. Gorai, H. Yoshikata, R. Kikuchi, F. Hirahara,Yokohama City University, Yokohama, Japan

In order to analyze the heterogeneity in response of lumbar spineand femoral neck bone mineral density(L- and FN-BMD) toestrogen replacement therapy (HRT) and in suppression ofbiochemical markers of bone metabolism and bone-resorbing


cytokines, 31 postmenopausal women, aged 40±63 yrs (meanage, 55.0�5.0 yrs) were treated with continuous combined HRTfor 2 yrs. Six markers of bone formation, bone-speci®c alkalinephosphatase (B-AlP), AlP, intact osteocalcin (I-OC), OC, N-midOC and N-terminal OC (N-OC) and three markers of boneresorption, serum and urinary type I collagen C-telopetidebreakdown products (CTx), and cross-linked N-telopeptides oftype I collagen (NTx) were measured at baseline and 1, 3 andevery 3 months after treatment whereas L- and FN-BMD weredetermined at baseline, and 6, 12, 18, and 24 months after HRT.We divided the whole population into two groups, because of asmall number of the subjects, instead of quartiles, based on yearssince menopause (YSM), baseline L- and FN-BMD and biochem-ical markers at entry, and responsiveness for BMD at 24 months.The percentage changes in L-BMD did not correlate with those inFN-BMD at each treatment period. L-BMD of late postmenopau-sal women with more than 6 YSM increased more than that ofearly postmenopausal women within 5 YSM during 24 months oftreatment. Serum and urinary CTx, B-AlP, N-mid OC and N-OCshowed a nadir at earlier period in late postmenopause than inearly postmenopause. Women with low baseline bone massshowed a signi®cantly higher increase in L-BMD (p<0.05) and asigni®cantly less decrease in FN-BMD (p<0.05) than those withhigh baseline bone mass. With no signi®cant differences inbaseline biochemical markers except for B-AlP between the twogroups, HRT signi®cantly suppressed NTx and N-OC in womenwith low baseline L-BMD (p<0.05) more than in those with highbaseline L-BMD. NTx, I-OC, OC, N-mid OC, N-OC, AlP and B-AlPat nadir (at 6 to 24 months) were signi®cantly suppressed more inwomen with a favorable response in L-BMD (p<0.05) than in thosewith a minimal response, demonstrating that biochemicalmarkers have a variation in treatment period at which eachmarker reached a nadir and in magnitude of suppression of eachmarker. Moreover, N-mid OC at 1 month, and AlP and NTx at 6months in women with a favorable response in L-BMD showed asigni®cant suppression (p<0.05) before they reached a nadircompared to those with a minimal response. We conclude thatthere is a heterogeneity in bone density and in biochemicalmarkers in response to HRT.

445 (409). EFFECTS OF HORMONE REPLACEMENT THERAPYAND HIGH-IMPACT PHYSICAL EXERCISE ON BONE/MUSCLERATIO IN POSTMENOPAUSAL WOMEN

S. Cheng, S. Sipila, J. Puolakka, H. Suominen, Dept. of HealthSciences, University of Jyvaskyla, Jyvaskyla, Finland

The purpose of this one-year intervention trial was to evaluate theeffects of hormone replacement therapy (HRT) and high-impactphysical exercise on bone/muscle ratio in postmenopausalwomen. Eighty healthy women aged 50±57, with <5 years afteronset of the menopause and with no previous HRT were randomlyassigned to one of the four groups: estrogen (Es), exercise (Ex),estrogen + exercise (EsEx) and control (Co). The HRT wasconducted (double-blind) for 1-year using combined estradionor-etisteron acetate (Kliogest). The exercise groups participated in a1-year progressive training program consisting of jumping andbounding activities. Two supervised sessions per week wereperformed with subjects additionally undertaking a series ofexercises at home 4 days/week. A QCT scanner (SiemensSomatom DR) with a program (BonAlyse) was used to calculatebone mineral density (BMD, g/cm3), cross-sectional area (CSA,mm2) and the bone/muscle ratio (BMRT) from the middle region ofthe thigh and lower leg. The percentage (%) changes in BMD,CSA and BMRT after the 1-year period are given in the Table. Ourresults suggest that the alteration of the bone/muscle ratio ismainly due to the contribution of the change in muscle CSA andthe combined effects of HRT and high-impact physical exercisemay exceed the effects of HRT alone.

Ex (n=13) Ex (n=12) EsEx (n=10) Co (n=15)

ThighBMD 0.33 ±0.15 0.61 ±0.21CSAbone 0.92* 0.52 0.94* ±0.27CSAmuscles 4.83** 4.18* 7.40*** 1.45BMRT ±4.23 ±3.62 ±7.19* ±4.01Lower legBMD 1.10* 0.54 2.01** ±0.95CSAbone 0.12 ±0.66 ±0.43 ±0.51CSAmuscles 7.24 4.33 10.46** 4.74BMRT ±7.89 ±5.37 ±12.73** ±5.68

*p<0.05, **p<0.01, ***p<0.001 compared to the control.

446 (410). VAGINAL PREMARIN1 VS. REPLENS1 IN WOMENWITH PRE-EXISTING VAGINAL ATROPHY RECEIVING ORALPLACEBO OR RALOXIFENE: EFFECTS ON SUBJECTIVEENDPOINTS

A. Ciaccia1, L. Nachtigall2, P. Sulak3, R. Basson1, H. Heath1, L.Plouffe1, A. Parsons4, 1Lilly Research Laboratories, Indianapolis,IN; 2New York, NY; 3Scott and White Clinic, Temple, TX;4University of South Florida, Tampa, FL,

Objective: Compare the effects of vaginal Premarin1 andReplens1 vaginal moisturizer on self-reported symptoms inwomen with pre-existing vaginal atrophy who are receivingconcomitant oral placebo or raloxifene. Design: 187 naturallypostmenopausal women with at least 2 signs of genitourinaryatrophy were randomly assigned to receive double-blind oralplacebo or raloxifene 60 mg/day and open-label vaginal Premarin(0.5 g/day; PRM) or Replens (REP). Women described thepresence and severity of vaginal symptoms (including vaginaldryness, itching, painful urination, urinary urgency, vaginalbleeding, and painful intercourse) based on a 4-point scale(1=none, 2=mild, 3=moderate, 4=severe).

Results: Mean age and years postmenopause at entry were 59and 9.5, respectively. There were no treatment group differencesfor any of the symptoms at baseline. After 3 months, almost allmeasurements in each treatment group decreased, indicating anoverall improvement in symptoms. The changes from baseline foritching, painful urination, vaginal bleeding, and painful intercoursewere not signi®cant within each group or across groups. Vaginaldryness rating improved in each group (p<0.043), with nosigni®cant therapy group differences. Urinary urgency wasimproved in the Placebo/PRM and raloxifene/REP groups, butthere were no signi®cant differences between PRM and REP.There were no signi®cant differences between raloxifene andplacebo for any symptom.

Conclusion: PRM and REP treatments are associated withsimilar improvement in vaginal atrophic symptoms. These effectswere not in¯uenced by concomitant RLX therapy.

447 (411). TREATMENT OF POSTMENOPAUSALOSTEOPOROSIS IN PATIENTS WITH IMPAIRED FASTGLUCOSE

Miro Cokolic, Rok Hren, 1Department of Endocrinology andDiabetology, Internal Clinic, General Hospital Maribor, Maribor,Slovenia; 2Institute of Mathematics, Physics, and Mechanics,University of Ljubljana, Ljubljana, Slovenia

Impaired fast glucose (IFG) designates a metabolic stagebetween normal glucose homeostasis and diabetes. The aim ofthis study was to monitor blood glucose level and bone mineraldensity (BMD) in patients with IFG that are treated forpostmenopausal osteoporosis.

Methods: Six women with IFG (serum levels of glucose 6.0 to 7.0mmol/l) and postmenopausal osteoporosis (T-score below ±2.5)


were enrolled in a one-year prospective study. The patients were62 to 71 years old (mean: 68 years) and 9 to 28 years (mean: 18years) after the menopause. They were treated with alendronate(10 mg/d) in combination with 500-mg elemental calcium. TheBMD in the lumbar spine (L2-L4) and left hip were measured in allpatients using dual energy X-ray densitometry (HologicQDR2000+) at the start of the treatment and at 3 months, 6months, and 12 months after the treatment. The serum levels ofglucose, Ca, and creatinine were taken at the same time intervals.

Results: Serum levels of glucose remained relatively unalteredthroughout the treatment, with an average values of 6.3 mmol/l(range 6.0±6.6 mmol/l) in the beginning of the treatment and 6.3mmol/l (range 6.1±6.4 mmol/l) at 12 months after the treatment. In12 months, the BMD increased on average by 2.4% (range 0.0±6.5%) in the lumbar spine (L2-L4) and by 2.4% (range 0.5±4.6%) inthe left hip. Levels of Ca and creatinine remained within normallimits during the treatment. No clinical side effects were observedduring the study.

Conclusions: Our results suggest that alendronate administra-tion can provide clinically relevant bene®ts in postmenopausalwomen with osteoporosis and IFG.

448 (412). EFFECT OF CONTINUOUS TRANSDERMAL-ESTRADIOL AND NORETHISTERONE ACETATE VS ESTRADIOLTRANSDERMAL HRT ON BONE MARKERS INPOSTMENOPAUSAL WOMEN

C. Cooper1, D. F. Archer2, 1Southampton General Hospital,Southampton, UK; 2Department of Obstetrics and Gynecology,Eastern Virginia Medical School, Norfolk, VA, USA

OBJECTIVE: To compare the effects of three doses of continuouscombined transdermal estradiol/norethisterone acetate (E2/NETA) versus E2 alone on bone markers in healthy postmeno-pausal women.

METHODS: A total of 625 postmenopausal women wereenrolled in this 52-week, randomized, double-blind, multicenterstudy. Subjects were assigned to one of four treatment regimens:transdermal E2 50 mg/day or transdermal E2/NETA delivering E250 mg/day and NETA 140, 250 or 400 mg/day. Markers of boneformation (serum bone-speci®c alkaline phosphatase, totalosteocalcin) and bone resorption (urinary N- and C-telopeptide)were obtained at baseline and weeks 24 and 52.

RESULTS: Reductions in bone formation and bone resorptionfor the E2/NETA 50/250 and 50/400 groups were comparable tothose in the E2 group. The decrease in the E2/NETA 50/140 groupwas signi®cantly (P<0.05) less than with the E2 group for C-telopeptide/creatinine ratio, N-telopeptide/creatinine ratio, andosteocalcin. At baseline, bone turnover was higher than thenormal premenopausal range; with E2/NETA and E2, the markersapproached the normal premenopausal range.

CONCLUSIONS: After 1 year of treatment, markers of boneformation and resorption improved with all three doses of E2/NETA. This improvement with transdermal E2/NETA 50/250* and50/400 treatment groups was comparable to that with transder-mal E2.

*trademark: ESTALIS1

449 (413). EFFECT OF ONE YEAR DHEA TREATMENT ORPLACEBO ON BONE MINERAL DENSITY (BMD) AND BONETURNOVER: THE DHEage STUDY

C. Cormier1, J C. Souberbielle2, J. Raison3, C. Kindermans2, F.Forette4, E E. Baulieu5, 1Rhumatologie A, Hopital Cochin;2Physiologie, Hopital Necker; 3Endocrinologie-Nutrition, HopitalHotel Dieu; 4Fondation National De Gerontologie, AP-HP, Paris;5INSERM U444; 6Le Kremlin-Bicetre, France

The secretion and the blood levels of the adrenal steroid DHEAand its sulfate ester (sDHEA) decrease profoundly with age, and

the question is raised whether administration of DHEA counter-acts defects associated with aging. Two hundred and eightyhealthy individuals (70 women±70 men, 60±69 y old, and 70women±70 men 70±79 y old) were given DHEA, 50 mg, or placebo(pl), orally, daily for one year in a double blind, placebo-controlledstudy. We measured hip and forearm BMD before and after 12months (mo) of treatment, and biological markers of boneturnover, serum osteocalcin (Oc) and bone alkaline phosphatase(bAP) for bone formation, and serum Cross-laps (CTx) for boneresorption, before and after 6 and 12 mo of treatment. In men, noeffect of DHEA was recorded, whether on BMD or on biochemicalmarkers, except an increase in bAP (+32%; p<0.05) at 12 mo inthe older DHEA-treated men. However, signi®cant differences inBMD change (data given as median in mg/cm2 [1st;3rd quartiles])between placebo- and DHEA-treated women were observed atseveral sites, the femoral neck (pl:±9 [±16;+18]; DHEA: +13[+1;+13]; p<0.05) and Ward's triangle (pl:±23 [±40;+6]; DHEA:+4 [±19;+25]; p<0.05) in the 60±69 y women and the upper (pl:±10[±19;+5]; DHEA:+4 [±8;+14]; p<0.05) and total radius (pl:±11 [±20;+5]; DHEA:+2 [±5;+10]; p<0.05) in the 70±79 y women. Further-more, serum CTx was decreased by 11% (p<0.05) and 26%(p<0.01) at 6 mo and 12 mo respectively, only in the 70±79 yDHEA-treated women while serum Oc and bAP were unchanged.Considering the 70±79 y women with the serum sDHEA levels inthe lowest quartile at baseline, the decrease of serum CTx waseven larger (±43% at 6 mo and ±35% at 12 mo; p<0.01 in eachcase) and was accompanied by a delayed decrease of serum Oc(±5% at 6 mo, not signi®cant and ±35% at 12 mo, p<0.01). Theseresults suggest that treatment with oral DHEA at a daily dose of50 mg has favourable effects on bone health in women, speciallyin those 70 y old and over, but not in men. Whether or not theseeffects are due to the formation of active estrogen(s) and/orandrogen(s) deserves further studies.

450 (414). PARATHYROID HORMONE IN COMBINATION WITHESTROGEN DRAMATICALLY REDUCES VERTEBRALFRACTURE RISK

F. Cosman, J. Nieves, C. Formica, L. Woelfert, V. Shen, R.Lindsay, Helen Hayes Hospital, West Haverstraw, New York, NY,USA

Our best pharmacological agents for osteoporosis treatmentprevent approximately ®fty percent of osteoporotic fractures.Thus, there is a need for an agent which can further augmentbone mass and reduce fracture risk more substantially. Therefore,we embarked on a trial investigating the utility of PTH incombination with established hormone therapy in women withosteoporosis. Fifty-two women who had been on HRT for at leastone year were enrolled in this trial in which 25 were randomlyassigned to remain on HRT alone and 27 were assigned to remainon HRT and also receive daily subcutaneous PTH (1±34) 400 units(25 mg). Bone mineral density measurements at the spine and hipand biochemical determinations of bone turnover were obtainedevery six months. Lateral thoracic and lumbar spine x-rays wereobtained at baseline and after three years in all patients. Subjectswere also followed for one year after discontinuation of PTH, withbone density measurements and biochemistry obtained at 6 and12 months after discontinuation. In the group receiving HRTalone, bone density and biochemical turnover variables remainedstable throughout the three year treatment trial and one yearfollow up. Subjects in the PTH+HRT group increased bone massby 12.8�1.4% (p<0.001) in the spine, and 4.4�0.6% (p = 0.001) inthe total hip. One year follow-up bone density did not changesigni®cantly at the hip but there was a modest loss at the spine.(1.8% loss at spine p = 0.07; 1.3% loss at total hip p = 0.39).Biochemical variables of bone turnover in the PTH+HRT groupincreased to a peak of 16±50% above baseline by year 1 andremained above baseline for the 3 years. Levels returned tobaseline by 1 year after discontinuation of PTH. There were 12incident fractures in the HRT only group and 2 incident fractures


in the PTH+HRT group using a 15% height reduction cut point(p = 0.001). Using a 20% height reduction cut point, there were 7fractures in the HRT group but 0 in the PTH+HRT group(p = 0.003). 37.5% of women in the HRT group vs 8.3% in thePTH+HRT group had incident fractures using the 15% cut point,and 25% vs 0% had fractures in their respective groups using the20% cut point (both p<0.02). We conclude that the majority of thePTH induced bone mass increment is maintained with continuedHRT 1 year after discontinuation of PTH. Furthermore, para-thyroid hormone in combination with hormone therapy is aneffective means of dramatically increasing bone mass throughoutthe skeleton and speci®cally reducing vertebral fracture occur-rence, dramatically more so than estrogen alone.

451 (415). COMPARISON OF INTRANASAL ANDTRANSDERMAL 17 b-ESTRADIOL ON BONE LOSS IN POST-MENOPAUSAL WOMEN AT 1 YEAR

P. D. Delmas1, C. Ribot2, B. Pornel3, A. Cyganek4, H. S. The5, P.Garnero6, J. Villero-Anuarbe7, 1E. Herriot Hospital, Lyon, France;2Rangueil Hospital, Toulouse, France; 3Brussels MenopauseCenter, Belgium; 4University Medical School, Warsaw, Poland;5Den Helder, The Netherlands; 6Inserm U, Lyon, France; 7HospitalReina So®a, Cordoba, Spain

Objectives: to compare the ef®cacy of intranasal estradiol(S21400: Aerodiol1) and a reference patch on bone turnoverand bone loss.

Design and methods: Multinational study of 56 weeks durationwith a 16-week randomised cross-over treatment period (S21400300mg/d or Estraderm TTS1 50: 2 patches/ week continuously, 12weeks with 2 parallel arms then a 4-week cross-over treatmentperiod), followed by 40 weeks treatment with S21400 or reservoirpatch according to patient's choice. Bone mineral density (BMD)was assessed at spine and hip using a dual X-ray absorptiometry(DXA) at baseline and after 56 weeks. Urinary type I collagen C-telopeptides (CTX), serum osteocalcin (OC) and bone alkalinephosphatase (B-ALP) were assessed at baseline and after 12, 28and 56 weeks of therapy.

Results: 358 postmenopausal women aged 51.5 (4.5) yearswere included. After 12 weeks, mean CTX decreased by 31% and28% in S21400 and patch groups respectively. Groups of longesttreatment duration were compared at week 56. Due to the patientchoice at W16, 232 were assigned to the S21400 group and 126 tothe patch group. BMD increased signi®cantly (P<0.001 vsbaseline in both groups) at the spine and hip. The percentageincrease (mean-SD) was 2.1 (3.0) at the spine in both groups and1.2 (2.4) compared to 1.1 (2.2) at the hip in S21400 and patchgroups respectively. CTX, OC and B-ALP signi®cantly (P<0.001)decreased from baseline to W56 in both groups. At that time bonemetabolism was normalised with a signi®cant decrease frombaseline (P<0.001) of all markers: 56% and 53% for CTX, 24% and25% for OC in S21400 and patch groups respectively.

Conclusion: Pulsed estrogen therapy 300mg/d was as effectivein normalising bone turnover and preventing bone loss after oneyear as a reference reservoir patch delivering 50mg/d.

452 (416). EVIDENCE BASED MEDICINE IN OSTEOPOROSIS: AREVIEW OF SELECTED CLINICAL TRIALS

H. P. Dimai1, S. Sieghart2, K. Klaushofer3, 1University Hospital,Graz, Styria, AUT; 2Kaiserin-Elisabeth Hospital, Vienna, AUT;3Ludwing Boltzmann Institute of Osteology, Vienna, AUT

We conducted a review of several studies to determine theef®cacy of several therapies in preventing boss loss, vertebralfractures and clinical fractures in postmenopausal women withlow BMD and with existing vertebral fractures. Only publishedrandomized studies in which both BMD and fractures areincluded as endpoints are included in the analyses. In general,

the mean age of women in the studies ranged from the mid 60s tothe low 70s. Women in the Chapuy study were much older. Thedropout rates across the studies ranged from a low of 2% in theBlack study to a high of over 45% in the Chapuy study. Except forthe Lufkin and Chapuy studies, the duration of the studies was 2years or more. The table below reports the results from thestudies. A `+' in the BMD column indicates a percent change inBMD less than 5%, a `++' indicates a change of more than 5%. A``Yes in the fracture columns indicates a signi®cant (p<0.05)reduction in fracture risk. In summary, a signi®cant increase inBMD, and a signi®cant reduction in morphometric fractures of thevertebrae has been found for almost all of the therapies includedin our analyses. However, a signi®cant reduction of hip-fracturesand other non-spine fractures has only been shown for Vit-D andalendronate. In addition, alendronate was the only therapy thatalso caused a signi®cant reduction in clinical fractures of thevertebra and the wrist. Thus, in postmenopausal women with lowBMD and existing vertebral fracture, alendronate appears to bethe most effective therapy to prevent osteoporotic fractures atmultiple sites.

Therapy Author BMD* Vertebral Fractures Clinical Fractures

Morphometric Clinical Non Spine Hip Wrist

Etidronate (423) Watts ++ Yes No No No No

Calcitonin (208) Overgaard + Yes No No No No

Vitamin D (213) Dawson + Yes No Yes No No

Vitamin D (3270) Chapuy + No No Yes Yes No

Estrogen (78) Lufkin ++ Yes No No No No

Alendronate (994) Liberman ++ Yes No No No No

Alendronate (2027) Black ++ Yes Yes Yes Yes Yes

453 (417). THREE YEARS PREVENTION OFPOSTMENOPAUSAL OSTEOPENIA WITH ALFACALCIDOL ±DEXA ASSESSMENT OF EFFICACY

A. DimicÂ 1, S. MilenkovicÂ 1, V. RadenkovicÂ 1, R. Filipov1, H.MilovanovicÂ 2, B. SimicÂ 2, 1Institute for Prevention, Treatment andRehabilitation of Rheumatic and Cardiovascular Patients ``NiskaBanja'' In Niska Banja Pharmaceutical Industry, 2``Zdravlje''Leskovac, Yugoslavia

We performed three years prospective study on the effects ofmanagement of postmenopausal osteopenia with active meta-bolite of vitamin D3-alfacalcidol. Hundred postmenopausalwomen aged 50 to 69 years were enrolled in the study. Inclusioncriterion was bone mineral density (BMD) below normal values (Tscore less than ±1, greater than ±2.5) and the absence of thedisease or treatment with medicament negatively in¯uencingBMD. BMD was evaluated using Lunar DPX densitometer beforeentering the study and every six months during the study. Basicparameters of phospho-calcic metabolism (blood and urinarycalcium and phosphorus, alkaline phosphatase) were evaluated inthe same manner. Treated group consisted of 53 women taking0.5 micrograms of alfacal-cidol, and control group (without thetreatment) consisted of 47 women with average age andpostmenopausal status comparable to treated group.

Alfacalcidol showed ef®cacy in controlling postmenopausalosteopenia ± BMD in treated group increased in the ®rst year,stagnated in the second and slightly decreased in the third year,compared to constant BMD loss in the control group. The ef®cacywas greater in older age (60 to 69 years).

During the study only mild adverse events as temporaryhypercalcaemia and renal calculosis were noted in 2% ofpatients.

It can be concluded that alfacalcidol should be used to preventpostmenopausal osteoporosis in women with low BMD, espe-cially in older age.


454 (418). THE EFFECTIVENESS OF OSSIN IN THEPOSTMENOPAUSAL OSTEOPOROSIS

A. V. Dreval1, L. B. Lazebnik2, L. A. Martchenkova1, R. S.Tischenina1, B. I. Minchenko1, C. B. Malitchenko2, L. B. Bondar2,1Moscow Regional Research Clinical Institute; 2Russian MedicalAcademy of Postgraduate Traning, Moscow, Russia

The purpose of this investigation was to compare the clinicalef®cacy of Ossin (GRUNENTHAL) and other methods of therapyof the postmenopausal osteoporosis. 49 females aged 51±68years with postmenopausal osteoporosis received Ossin (sodium¯uoride 34.8 mg/day), or HRT, or combination of intramuscularcalcitonin (50 MU/day) with lalpha-OH-D3 (0.5 mcg/day) for 6month. The bone mineral density (BMD) was measured utilizingDEXA. Intensiveness of the back pane and laboratory follow-up(serum alkaline phosphatase, calcium and phosphorus) were alsoassessed.

Results of treatment:

Ossinn=15

HRTn=22

Calc.+1alpha-OH-D3

n=12

Lumbar BMD, % +7.06* +3.80 +1.61Proximal femur BMD, % +2.40 +1.93 +0.90Serum akaline phosphatase, U/l +15.0* ±29.8* ±23.6Serum calcium, mmol/l ±0.06* ±0.12 ±0.04Serum phosphorus, mmol/l ±0.17** ±0.32* ±0.16*Back pane, units ±2.1* ±0.01 ±1.3*

*p<0.05, **p<0.01.

Conclusion: in postmenopausal osteoporotic patients Ossinsigni®cantly increases spinal BMD, stimulates the bone forma-tion, improves the bone pain, and decreases calcium andphosphorus serum levels.

455 (419). KYPHOPLASTY FOR VERTEBRAL COMPRESSIONFRACTURES

S. Dudeney, I. Lieberman, F. Phillips, 1Cleveland Clinic, Cleveland,OH; 2University of Chicago, Chicago, IL,

PURPOSE: To evaluate the early experience with in¯atableballoon tamp reduction and cement augmentation, ``Kypho-plasty'', in the treatment of osteoporotic vertebral compressionfractures.

BACKGROUND: Kyphoplasty involves the percutaneous pene-tration of the vertebral body with a cannula, followed by insertionof an in¯atable balloon tamp. The tamp restores the vertebralbody back to its original height, while creating a cavity to be ®lledwith bone cement. Cement injection is done under low pressureto reduce leakage.

PATIENTS & METHODS: Forty-Seven consecutive kyphoplastyprocedures were performed in 23 patients. The commonestindication was painful osteoporotic vertebral compressionfractures. Mean duration of symptoms was 3.5 months. Painfullevels were identi®ed by correlating the exam with MRI ®ndings.The levels treated ranged from T7 to L5, the majority at thethoracolumbar junction. Pre and post-operative x-rays werecompared to calculate the percentage height restored. Outcomedata was obtained by comparing preoperative and latest post-operative SF±36 data.

RESULTS: There were no major complications related directlyto use of this technique. The mean percentage height restored bythe procedure was 39%. SF36 bodily pain scores improved from13.6 to 47 (p = 0.004). Physical function improved from 28.7 to55.3 (p = 0.02).

CONCLUSIONS: Kyphoplasty is well tolerated and associatedwith improvement of pain, function, as well as restoration ofvertebral body height.

456 (420). COMPARISON OF ALENDRONATE, CALCITONINAND CALCIUM TREATMENTS IN POST-MENOPAUSALOSTEOPOROSIS

N. Dursun, E. Dursun, S. Yalc, University of Kocaeli, Kocaeli,Turkey

The present study was planned to assess the safety, tolerability,and ef®cacy on bone mineral density (BMD), pain, quality of lifeand fracture risk of alendronate, calcitonin and calcium treat-ments. 84 Post-menopausal women with lumbar spine BMD 2 SDor more below the young adult mean were randomly assigned toone of 3 groups. Twenty-nine patients received oral alendronate10 mg and calcium 1000 mg (alendronate group), 28 patientsnasal salmon calcitonin 100 IU and oral calcium 1000 mg(calcitonin group), 27 patients oral calcium 1000 mg (calciumgroup) daily for one year. BMD was assessed by Dual EnergyX-ray Absorbsiometry, pain by a Visual Analogous Scale (VAS),quality of life by Nottingham Health Pro®le. Both at 6 and 12months mean increases in BMD were signi®cantly (p = 0.02,p<0.001) greater in the alendronate group than those of theother two groups at lumbar spine. No signi®cant difference wasfound between the groups at the femoral neck (p = 0.72, p = 0.72),trochanter (p = 0.44, p = 0.53) and Ward's triangle (p = 0.58,p = 0.78). Both at 6 and 12 months mean decreases in VAS weresigni®cantly (p<0.001, p<0.001) greater both in the alendronateand calcitonin groups than that of the calcium group. Nostatistically signi®cant difference was found in any parametersof quality of life in the calcium group (p<0.05) but in calcitonin andalendronate groups (p>0.05). New vertebral fractures were seen29.4% of the alendronate, 38.3% of the calcitonin, and 41.6% ofthe calcium groups, representing no statistical diference(p = 0.75). No side effects were seen in any of the patientsduring the follow-up.

457 (421). TIBOLONE TREATMENT PREVENTS TRABECULARBONE LOSS IN THE VERTEBRA AND LONG BONES ANDMAINTAINS CORTICAL BONE STRENGTH INOVARIECTOMISED RATS WITH ESTABLISHED BONE LOSS

A. G. H. Ederveen, H. J. Kloosterboer, Department ofPharmacology, N.V. Organon, The Netherlands

Tibolone (Org OD 14) is a tissue speci®c steroid exerting,depending on the tissue, an estrogenic, progestagenic and/orandrogenic effect. In postmenopausal women, tibolone has beenshown to prevent bone loss without stimulating endometriumproliferation. Tibolone has been shown to prevent ovariectomy(OVX)-induced bone loss in the axial and peripheral skeleton ofyoung mature and aged ovariectomised rats. The present studywas designed to examine the effect of a six-month treatment withtibolone in mature rats with an established bone loss.

Three month old rats were ovariectomised and treatment wasstarted at ®ve months after surgery to obtain severe osteopenicrats. After six months of treatment with tibolone, effects ontrabecular bone volume (BV/TV) in the axial and peripheralskeleton, on bone turnover, and on biomechanical properties offemoral cortical bone in a three point bending test wereevaluated.

Five months of estrogen depletion, due to ovariectomy,resulted in rats with osteopenia as indicated by signi®cantdecreases in bone density of the distal femur and BT/TV in theproximal tibia and lumbar vertebrae. A six-month treatment withtibolone prevented further loss of trabecular bone in the proximaltibia and in the lumbar vertebrae L1-L2. With the highest doseeven a 13% increase in BT/TV was found as compared to start oftreatment but this did not reach statistical signi®cance. In theseosteopenic rats, tibolone prevented the signi®cant decrease inmaximum bending stress as compared to the placebo treatedovariectomised control. The effects of tibolone may be mediatedby a reduction in bone tumover as indicated by the decrease in


bone resorption marker (deoxypyridinoline/creatinine) and for-mation (osteocalcin).

We conclude that in ovariectomised rats with an establishedsevere bone loss, tibolone prevents deterioration of the axial andperipheral skeleton by normalising bone turnover resulting inpreservation of cortical bone quality.

458 (422). SECONDARY PREVENTION IN OSTEOPOROSIS

B. J. Edwards1, L. Taft2, 1Northwestern University; 2NorthwesternMemorial Hospital, Chicago, IL, USA

This purpose of this program is to identify and treat osteoporosiswhen fractures motivate a hospital admission. This disease isoften under diagnosed, therefore this population of fracturepatients are at increased risk of subsequent fractures. Baselinedata (1998) demonstrated only 20% of inpatients with osteo-porosis related fractures were treated, while only 10% of thoseseen in the ambulatory setting were treated.

Funding was obtained from the Illinois Department of PublicHealth, and the Northwestern Memorial Foundation. This is theresult of the ®rst six months of program development. Theprogram counts with the participation of the Division of Geriatrics,Endocrinology and Rheumatology, and the Department ofOrthopedics.

Osteoporosis Consults are performed on all patients withfractures, x-ray evidence of osteopenia is gathered and riskfactors assessed. Consultants discuss treatment options with thepatients and the clinical nurse specialist carries out education.Outpatient follow-up is arranged and communication is carriedout with the primary attending. To date over 50 fracture patientshave been evaluated and treated. Fractures patients seen in theoutpatient setting (100) have been hesitant to follow-up with theOsteoporosis Program, this may be due to a lack of awarenessand further public education should be undertaken.

Secondary osteoporosis is very common in this population(25%) chronic renal, pulmonary diseases and steroid use.Patients will have follow-up provided and an outcome analysiswill be performed in the future. This program may serve as amodel to increase awareness and provide secondary preventionin osteoporosis.

Fractures Age Prior Dx Prior Rx Xray osteopenia

Hip fractures 77 20% 10% 80%Extremity 67 25% 20% 42%TJR 62 29% 15% 43%

459 (423). GASTROINTESTINAL SIDE EFFECTS ANDENDOSCOPIC FINDINGS SIMILAR BETWEEN RISEDRONATEAND PLACEBO-TREATED PATIENTS

I. Fogelman1, L. Moreland2, G. Woodson3, D. MellstroÈ m4, E.Boling5, W. Riskin6, D. Strauss7, K. Stevens7, M. Manhart7,1London, UK; 2Birmingham, AL, USA; 3Decatur, GA, USA;4Goteborg, Sweden; 5Rancho Cucamonga, CA, USA; 6Hollywood,FL, USA; 7Mason, OH, USA

As part of the overall clinical program, the tolerability ofrisedronate (RIS) was evaluated by collecting adverse events(AEs) in 15,066 patients (>98% postmenopausal women) rando-mized to risedronate (2.5 or 5mg daily) or placebo daily for up to 3years' duration. Patients were not excluded because of under-lying gastrointestinal (GI) disorders or concomitant use ofmedications, e.g., NSAIDs, aspirin, H2 blockers, or proton pumpinhibitors (PPIs). Endoscopy was performed at the investigator'sdiscretion in 497 patients with GI complaints and was evaluated

by site (esophagus, stomach, duodenum). The table belowindicates the incidence of AEs in these patient subpopulations.

Incidence of Upper GI Adverse Events

Subpopulation N Placebo RIS 5mg

History of Upper GI Disease 3900 29.0% 29.5%NSAID/Aspirin Users 6336 25.0% 25.0%H2/PPI Users 2043 50.0% 51.5%

As shown from the table, in patients with a history of upper GIdisease, use of NSAIDs/aspirin or use of H2 blockers/PPIs theincidence of overall upper GI adverse events was similar betweenthe RIS 5mg group and placebo.

Overall, endoscopy ®ndings were similar in the 3 treatmentgroups among the 497 patients with endoscopy. A `normal'®nding was reported most frequently (58%) at all anatomic sitesin all treatment groups. Gastric ulcers were the next mostcommon observation (24%) and occurred with similar frequencyacross groups.

In summary, risedronate was well-tolerated in patients at risk ofupper GI disease or irritation, and was not associated with anincrease in endoscopically-veri®ed upper GI lesions.

460 (424). ALENDRONATE IN THE TREATMENT OFOSTEOPOROSIS IN MEN: MONITORING BY QUANTITATIVEULTRASOUND SONOGRAPHY (QUS) AND FAN-BEAM X-RAYABSORPTIOMETRY

B. Frediani, A. Allegri, L. Storri, S. Bisogno, P. Falsetti, F. Baldi, C.Ridol®, R. Marcolongo, Institute of Rheumatology, University ofSiena, Italy

Osteoporosis in men is an important clinical condition. Weconducted an open, controlled study of 24 months duration,with the aim of evaluating the effect of Alendronate on BoneMineral Density (BMD) and Stiffness (SI). 60 men, aged 35±79 yr(mean:61 yr), with osteoporosis (femoral neck T-score<±2,5) wereenrolled and received either placebo (PBO, n=30, calcium 500mgper day) or Alendronate (ALN, n=30, 10mg per day). SI wasmeasured by QUS (Lunar-Achilles+); BMD was assessed by fan-beam DXA (Lunar-Expert) of lumbar spine, hip and total-body.Longitudinal precision of BMD and SI has been assessed in PBOgroup. We obtained a normalized coef®cient of variation (nCV)dividing short-term CV by annual decrease of BMD or SI and wecalculated the Lowest Signi®cant Difference (LSD= 3 nCV). In thePBO group SI and BMD decreased signi®cantly; in ALN group SIand BMD increased signi®cantly.

Mean percent change in BMD (or SI) and mean change in T-score from baseline to 24 months

PBO ALN

BMD-SI T BMD-SI T LSD

Os Calcis ±3.2* ±0.31 6.8*8 0.59 3.5Spine (L2-L4) ±2.8* ±0.20 6.3*8 0.48 3.2

Femur Neck ±3.6* ±0.22 3.4*8 0.28 3.0Total Body ±1.9* ±0.17 2.8*8 0.29 2.9

*p<0.01 vs baseline; 8p<0.01 vs PBO.

Depending on the skeletal regions evaluated, 50 to 70% ofpatients treated with ALN had a densitometric increase greaterthan LSD.


Decreased Unmodi®ed Increased

PBO ALN PBO ALN PBO ALN

Os Calcis 50.0 0 50.0 33.3 0 66.7Spine (L2-L4) 46.7 0 53.3 30.0 0 70.0Femur Neck 66.7 0 33.3 43.3 0 56.7Total Body 33.3 0 66.7 50.0 0 50.0

In conclusion: a) Alendronate (10 mg per day) is eective in maleosteoporosis; b) ultrasonometry of os calcis is as useful formonitoring the eects of therapy as axial X-ray absorptiometry.

461 (425). EFFECTS OF ALENDRONATE ON HEEL STIFFNESSAND AXIAL BMD IN PREVENTION AND THERAPY OFGLUCOCORTICOIDS INDUCED OSTEOPOROSIS

B. Frediani, A. Allegri, L. Storri, S. Bisogno, P. Falsetti, F. Baldi, C.Ridol®, R. Marcolongo, Institute of Rheumatology, University ofSiena, Italy

120 patients, aged 34±72, receiving continuously glucocorticoids(60 women with osteopenia: T-score <-land>±2.5; 60 women withosteoporosis: T-score <±2.5), were enrolled into an open study of24 months duration, with the aim of evaluating the effect onStiffness (SI) and the effect on Bone Mineral Density (BMD) ofAlendronate (ALN: 10 mg per day) or Placebo (PBO: calcium 500mg per day). SI was measured by os calcis ultrasonometry(Lunar-Achilles+); BMD was assessed by fan-beam X-rayabsorptiometry (Lunar-Expert) of lumbar spine, hip and total-body. Longitudinal precision of BMD and Stiffness has beenassessed in PBO group. We obtained a normalized coef®cient ofvariation (nCV) dividing short-term CV by annual decrease of BMDor SI and we calculated the Lowest Signi®cant Difference (LSD= 3nCV). In the PBO groups SI and BMD decreased signi®cantly; inALN groups SI and BMD increased signi®cantly.

Mean percent change (BMD or SI) from baseline to 24 months

Osteopenia Osteoporosis

PBO ALN PBO ALN LSD

Os Calcis ±6.2* 3.3*8 ±5.6* 4.2*8 2.0Spine (L2-L4) ±5.0* 2.2*8 ±4.7* 3.3*8 1.9Femur Neck ±4.8* 1.28 ±4.3* 1.58 2.3Total Body ±4.3* 1.08 ±4.0* 1.88 1.6

*p<0.01 vs baseline; 8p<0.01 vs PBO.

Depending on the skeletal regions evaluated, 30 to 73% ofpatients treated with ALN had a densitometric increase greaterthan LSD.

Decreased Unmodi®ed Increased

PBO ALN PBO ALN PBO ALN

Os Calcis 93.3 0 6.7 26.6 0 73.3Spine (L2-L4) 86.7 0 13.3 30.0 0 70.0Femur Neck 66.6 0 33.3 70.0 0 30.0Total Body 73.3 0 26.6 50.0 0 50.0

Moreover we examined the in¯uence of glucocorticoidcumulative dose (GCD) on the eect of ALN.

ALN increase SI and BMD irrespective of GCD.In conclusion: a) Alendronate (10 mg per day) is effective in

prevention and in therapy of glucocorticoid induced osteoporo-

sis; b) quantitative ultrasound measurement of os calcis is asuseful for monitoring the effects of therapy as axial X-rayabsorptiometry.

462 (426). EFFECT OF HEATED OYSTER SHELL WITH ALGALINGREDIENT (ADVA-CAL) ON OSTEOPOROSIS

T. Fujita, Y. Fujii, B. Goto, A. Miyauchi, T. Takagi, S. Ohgitani,Calcium Research Institute, Osaka and National SanatoriumHyogo Chuo Hospital, Hyogo, Japan

Calcium is better absorbed from Adva-Cal, oyster shell andseaweed Cystophyllum fusiforme heated in vacuo at 800C thanfrom calcium carbonate as shown by the greater increase ofurinary calcium excretion 1~4 hours after oral dose of 1000 mgand the rise of plasma ionized calcium, and more pronouncedPTH suppression after ingestion of 300~600 mg calcium as Adva-Cal than after ingestion of the same amount of calcium from milkor calcium citrate malate. Supplementation with 900 mg/day Caas Adva-Cal increased spinal bone mineral density in anterior-posterior direction measured by DXA in 2 years, in osteoporoticelderly women with a mean age of 80 in a prospective double-blind study over the same amount of calium supplied as calciumcarbonate or placebo. In younger pre-and postmenopausalwomen with osteoporosis or osteopenia, 900 mg/day Ca asAdva-Cal increased distal radial trabecular bone and diaphysealcortical bone desity measured by pQCT in 4 months, whereasplacebo, the same amount of Ca as calcium carbonate or thesame amount as heated oyster shell without algal ingredient hadno effect. The increase of bone mineral density was morepronounced upon administration with etidronate, 200~400 mgdaily for 2 weeks of 2 months. Adva-Cal appears to be effective toincrease BMD in osteoporosis and osteopenia alone and inconjunction with other drugs.

463 (427). MEDICAL CARE COSTS ASSOCIATED WITHPOSTMENOPAUSAL HORMONE REPLACEMENT THERAPY

N. I. Gavin1, R. L. Ohsfeldt2, J. M. Thorp3, J. W. Bray1, 1ResearchTriangle Institute, Research Triangle Park, NC; 2Eli Lilly andCompany, Indianapolis, IN; 3University of North Carolina Schoolof Medicine, Chapel Hill, NC

Objective: This study was conducted to quantify components ofmedical care costs attributable to postmenopausal hormonereplacement therapy (HRT).

Methods: 77,252 patient-years of data over the years 1989±97were obtained from Saskatchewan Health for 5762 women aged55 or older who received HRT during 1990±94 and an equalnumber controls matched on age, residence, and marital status.Medical care costs for a minimum of 3 and maximum of 7 yearsafter the index date for each woman were aggregated intocomponents of annual costs. A regression model was used toestimate the association between the logarithm of annual costsand patterns of HRT use, controlling for prior patient medical carecosts, marital status, rural/urban residence, and year.

Results: compared to never-HRT-users, HRT users had higherannual total and medical management costs. Excess medicalmanagement costs ranged from $200 to $500 per annum (1997Canadian dollars). These excess costs were related to excessrates of uterine and breast-related procedures. Osteoporosis andCHD-related costs were lower among HRT users than never-HRTusers. These cost offsets ranged from $100 to $150 per annum.

Conclusion: postmenopausal HRT appears to generate excessmedical costs associated with its uterine and breast side effects.These medical management costs should be incorporated intofuture analyses of the cost-effectiveness of postmenopausalHRT.


464 (428). WHICH IS THE LEAST EFFECTIVE TRANSDERMALESTRADIOL DAILY DOSE FOR PREVENTING OF BONE LOSSIMMEDIATELY AFTER OOPHORECTOMY? COMPARISON OFHEEL ULTRASONOMETRY AND SPINE DXA DATA FROM A 2-YEAR RANDOMIZED PROSPECTIVE STUDY

R. Giorgino, P. Paparella, D. Lorusso, S. Mancuso, CatholicUniversity, Rome, Italy

The majority of available data on estrogen bone density effects inoophorectomized women are often biased by the lack ofhomogeneity of the populations in terms of time since surgeryand bone turnover rate. Aim was to identify the least effectivedosage of transdermal estradiol to prevent post-oophorectomybone loss in healthy women. Eighty fertile women (age ranging43±53 years, serum FSH and E2 levels within premenopausalrange), underwent hysterectomy and prophylactic oophorectomyfor uterine ®broids. By the ®rst week after surgery, patients wererandomized to receive alternatively 25, 50, 75. 100 mg/daytransdermal estradiol continuously for two years. Duplicatecalcaneus Ultrasonometry was performed on a Lunar Achilles atbaseline and at 6 months intervals: spine BMD was measured byDEXA. Two-year data are available for 10, 15, 13 and 11 patientsrespectively in 25, 50, 75, 100 mg/day treated groups. A signi®cantdecrease of both Stiffness Index and Lumbar Spine BMDwas observed in 25 mg (open circles, *) and 50 mg treatedgroups (open squares, &) in the ®rst year after surgery: nofurther changes were deiected during the following period. In 75mg (closed circles, *) and 100 mg E2 treated groups (closedsquares, &), premenopausal Stiffness Index and Spine BMD weremaintained during the 2 years of observation. In both groups,QUS Stiffness Index changes were signi®cantly greater than spineDXA in magnitude as shown by the AUC comparison (p<0.05 ineach group).

In conclusion, 75 mcg/day transdermal estradiol should beconsidered as the minimum effective dosage to preventtrabecular bone loss at least in the ®rst year after oophorectomy.Moreover, quantitative ultrasonometry is a valid alternative toDEXA spine BMD measurement for monitoring bone changes inthe early period after oophorectomy.

465 (429). TREATMENT WITH ZOLEDRONATE OR SDZ PTS 893RESTORES TRABECULAR ARCHITECTURE IN OVX MICE

M. Glatt, Novartis Pharma AG, Bone Metabolism Unit, Basel,Switzerland

The anti-osteoporotic effects of a highly potent anti-resorptivebisphosphonate and a bone anabolic PTH-derivative were testedin estrogen-de®cient DBA±1 mice.

For this purpose DBA±1 mice were ovariectomized at the age of6 weeks. Six weeks later, treatment was started and continued foranother 4 weeks. 10 mg/kg BW of the bisphos-phonatezoledronate was injected s.c. once weekly, whereas 50 mg/kgBW of the PTH analogue SDZ PTS 893 was injected s.c. 5x/week.At the end of the experiment, animals were sacri®ced and tibiae,femorae and lumbar vertebrae dissected free and stored in 70%ethanol until microtomography was conducted at 9x9x9 mm3

nominal voxel resolution. In an additional experiment SDZ PTS893 treatment was followed by a 4 week recovery period todetermine whether the effects were reversible. Both zoledronateand SDZ PTS 893 signi®cantly increased bone volume fractionand this effect was accompanied by corresponding changes inother parameters such as Tb.N, Tb.Th, Tb.Sp and BS/BV. Themost pronounced effects were found in the tibia, followed indescending order by femur and vertebra. The anabolic effects ofSDZ PTS 893 were partially lost during the recovery periodshowing that in mice the maintenace of PTH-induced new bonewould require continuous treatment.

466 (430). LONG TERM TREATMENT OF POSTMENOPAUSALOSTEOPOROSIS WITH CALCITONIN, ALENDRONATE, ORALPHACALCIDIOL

G. GuÈ ls,en Demirel, N. Paker, H. Yilmaz, Istanbul Physical Medicineand Rehabilitation Centre, Istanbul, Turkey

We compare the effect on the bone mineral density (BMD)measured with DEXA in postmenopausal women treated for threeyears with calcitonin or alendronate or vitamin D.

A group of 378 postmenopausal women with established ordensitometric osteoporosis (2 score <±2.00) were randomlydistributed in three groups. Hundred-thirty patients (mean age56.7�4.6 years) were treated with salmon calcitonin (100 IU dailyby nasal route), 114 patients (mean age 59.5�5.7 years) weretreated with alendronate (5mg/day), 134 patients (mean age61.2�5.3 years) were treated with alphacalcidiol (0.50 mcg/day).Every case received a suplement with 500mg of calcium. Beforetreatment, at one, two, and three years, they were studieddensitometrically with the DEXA method on the level of thelumbar spine, and the proximal femur. Biochemical markers ofbone formation and resorption were measured.

The increase of BMD in lumbar spine was signi®cantly greaterin women treated with alendronate compared to other groups inthe ®rst two years, but not in the third year. The BMD in femurneck showed a statistically signi®cant increase only in the ®rstyear in those treated with alendronate compared to other groups.Salmon calcitonin use is effective in relieving pain and boneresorption compared to other groups.

This is the preliminary report of our ongoing study.

467 (431). ALENDRONATE INCREASES LUMBAR SPINE BONEMINERAL DENSITY IN PATIENTS WITH CROHN'S DISEASE. ADOUBLE BLIND CONTROLLED STUDY

K. V Haderslev1, L. Tjellesen1, H. A. Sùrensen2, M. Staun1,1Rigshospitalet; 2Hvidovre Hospital, Copenhagen, Denmark

Low bone-mineral density is a common complication of Crohn'sdisease and may lead to increased morbidity and mortality due tofractures. We investigated the effect of treatment with the


bisphosphonate alendronate-sodium on bone mass and markersof bone remodeling in patients with Crohn's disease.

A 12-month double blind, randomized, placebo-controlled trialwas performed to study the effect of 10-mg daily of alendronate.A total of 32 patients (9 men, 16 premenopausal and 7 post-menopausal women) with a bone-mass T-score below ± 1 of thehip or lumbar spine were studied. Exclusion criteria includedactive Crohn's disease (Van Hees index >150) and previous smallbowel resections exceeding 100 cm. The main outcome measurewas the difference in the mean percent change in bone mineraldensity of the lumbar spine measured by dual-energy x-rayabsorptiometry. Secondary outcome measures included changesin bone mineral density of the hip and biochemical markers ofbone turnover, i.e., s-osteocalcin, urine pyridinoline and urinedeoxypyridinoline excretion. The mean (�SE) of the lumbar spinebone mineral density showed an increase of 4.6�1.2 percent inthe alendronate group compared with a decrease 0.9�1.0 percentin patients who received placebo (P50.01). Bone mineral densityof the hip increased by 3.3�1.5 percent in patients who receivedalendronate treatment compared with a smaller increase of0.7�1.1 percent in the placebo group (P = 0.08). Biochemicalmarkers of bone turnover decreased signi®cantly in the alen-dronate group (P50.001). Alendronate was well tolerated andthere was no difference in adverse events between treatmentgroups. We conclude that treatment with alendronate 10 mg dailysigni®cantly increased bone mineral density in patients withCrohn's disease and was safe and well tolerated.

468 (432). THE EFFECT OF LONG-TERM HORMONEREPLACEMENT THERAPY ON QUANTITATIVEULTRASONOMETRY

P. Hadji, G. Emons, K.-D. Schulz, Philipps University Marburg,Marburg, Germany

This study was aimed to investigate the impact of a long-termhormone replacement therapy (HRT) on Quantitative Ultrasono-metry.

2006 healthy peri-/post-menopausal women (mean age52.2�10.3 years) were recruited in 5 German centers: 611women (30%) had taken HRT, 1395 (70%) had not. About 90%of the HRT users were current users, the remaining 10% hadrecently stopped HRT (mean 1.5 4 months). Speed of sound,broadband ultra-sound attenuation and the stiffness index werecompared in: (a) all users and non-users of HRT, (b) in HRT usersand non-user controls matched for age, weight, height and bodymass index, and (c) HRT users grouped in relation to the durationof HRT use and their matched controls.

Women taking HRT had signi®cantly higher values (p<0.001)than non-users for all ultrasound variables, even after age, weight,height and body mass index had been controlled for. Women whohad taken HRT for >3 years had signi®cantly higher values(p<0.001) than matched control women for all ultrasonometryvariables, differences increased with the duration of use. Ourresults on a large cohort of healthy women showed thatQuantitative Ultrasonometry differentiates HRT users from non-users even after adjustment for confounding variables. Thesedifferences increased with the duration of HRT use. Therefore,QUS could be useful in both clinical trials and patient manage-ment.

469 (433). ARE WE PRESCRIBING ENOUGH HRT IN PRIMARYCARE?

M. R. Harvey, S. Davidson, Cuck®eld Medical Practice, Cuck®eld,UK

It is suggested that HRT provides adequate prevention for thedevelopment of osteoporosis when taken at least between theages of 50±60. After the age of 60 continuing compliance with

therapy decreases. As part of an evaluation study of screeningwomen between the ages of 50 and 75 for osteoporosis in primarycare, women already on HRT were not excluded. We report the®ndings of those women, with particular emphasis on dosage andcontinuation of therapy after screening. 699 women were invitedto attend the surgery for wrist BMD measurement using anOsteometer DTX 200, and to complete a validated clinical and riskfactor questionnaire. 479 women (68.5%) responded and werescanned. 100 women were already on HRT (20.9%) of whom 66%were below age 60. All women with a T score <±1.5 werereviewed. 27 were on HRT, 9 below age 60 with a predominantrisk factor of an early (before age 45) menopause. Above age 60early menopause and past fragility fracture were equallydominant. 4 women had a T score <±2.5 who were not previouslyknow to have osteoporosis. All the women except two, regardlessof age, have continued on HRT therapy, 5 at an increased dose. 3are taking additional bisphosphonate. The only signi®cant eventhas been a vertebral fracture in a woman of 53 with a previousfragility fracture, who stopped her HRT. Screening for osteo-porosis appears to be a valuable aid to compliance with therapyin the presence of risk factors, particularly over the age of 60when most women stop HRT.

470 (434). EFFECT OF VITAMIN D IN PATIENTS WITHDECLINING VERTEBRAL BONE MINERAL DENSITY DESPITESTABLE BISPHOSPHONATE THERAPY

J. D. Adachi, G. A. Heckman, A. Papaioannou, McMasterUniversity, Hamilton, ON, Canada

Objective: To assess vitamin D supplementation in patients withosteoporosis (OP) not responding to stable bisphosphonatetherapy.

Methods: We analyzed the records of those OP patients beingfollowed at our tertiary care centre who were taking stablebisphosphonate therapy and in whom lumbar spine BMD wasmeasured annually for three years. Patients who took vitamin D1000 IU daily were assigned to the intervention group, whilecontrol group patients did not. We compared the annual rates ofchange of lumbar spine (LS) bone mineral density (BMD) in the 2groups.

Results: In the intervention group, LS BMD declined by 0.99%in the year before vitamin D was started and rose 0.68% in thesubsequent year. The difference of 1.67% was signi®cant(p = 0.008). The control group gained 1.65% the ®rst year and0.88% the second, a change of ±0.77% (p = 0.099). Baselineserum vitamin D levels were similar in both groups.

Conclusion: Vitamin D 1000 IU daily can reverse the decline inLS BMD in patients not responding to stable bisphosphonatetherapy.

471 (435). SIGNIFICANT REDUCTION OF PERIPROSTHETICBONE LOSS BY AN EARLY, SHORT-TERM ALENDRONATETREATMENT


Bone loss around total hip arthroplasty (THA) is well recognizedand occurs with all types of implants whether cemented or un-cemented mainly in the ®rst six months after THA. The aim of ourstudy was to show that a short but very early therapy ofalendronate is ef®cient to prevent this bone loss. We randomized44 subjects (f+m) aged 33±61 with un-cemented THA and alumbar BMD below normal average (T-score <0) but withoutsuspected conditions affecting bone metabolism. A: Treatmentwith 10 mg/d alendronate oral over 10 weeks after the operation(n = 21), C: no treatment as the control-group (n = 23). The primaryef®cacy endpoint was the periprosthetic BMD in the Gruen zones(ROI) measured by DEXA (Hologic, 4500 A) after the 2., 4, 6, and12. month, compared with the value measured in the ®rst week


after surgery. Even after two months there was a signi®cantdifference between the two groups (ROI1±7): A ±2.0% vs. C ±4.2%(p<0.02), which was increasing during the follow up: A ±1.2% vs.C ±5.4% (p<0.01). The ROI 7 (calcar) showed the highest amountof bone loss and the highest difference: A ±4.7%, C ±14.7%(p<0.01), however, during the next months also in the group A thebone loss increased, but the difference remained still signi®cant:A ±16.8% vs C ±26.0% (p<0.029). Alendronate appears to reducesigni®cantly the periprosthetic bone loss due to the initial turn-over of the operative irritation and underloading. The laterremodeling due to stress shielding is not affected adversely bythis mode of therapy.

472 (436). THE EFFECTIVENESS AND TOLERABILITY OFALENDRONATE IN CASE OF POSTMENOPAUSALOSTEOPOROSIS

S. HepguÈ ler, S. Ozvurmaz, C. OztuÈ rk, K. Capaci, R. Aks,it, EgeUniversity Med. Faculty Physical Therapy and Rehab. Dept.,Izmir, Turkey

Aim of this study was to determine the effectiveness andtolerability of alendronate. 68 postmenopausal women with agesbetween 41±77 years (59.19�8.08) were included in the study.According to DEXA, rutine blood, urine, liver functional tests,alkalene phosphotase, urea, creatinine, serum calcium andphoshorus, urine calcium, deoxypyridinoline as bone markerswere investigated for all patients. Alendronate was given once aday with the treatment regimen including elementary calcium dailyand Vit D monthly. At 12th month, signi®cant density increase wasobtained in all patients' lumbar vertebrae, femoral neck andtrochanter. Alkalene phosphotase, deoxypyridinoline valuescomparing to initial changed signi®cantly at 6th 12th months. Atthe end of the ®rst year, the bone mineral densities in lumbarvertebrae, femur neck and trochanter were found to be sig-ni®cantly increased and this increase was at the rate of %4.5 in L1±4 vertebraes, %3.83 in femoral neck, %4.77 in femoral trochanterand %2.22 in wards triangle. Cessation of the treatment was notneeded in cases of gastrointestinal side effects which weredetected in 2 patients. As a result, alendronate is an effectivedrug in the treatment of postmenopausal osteoporosis.

473 (437). THE EFFECTIVENESS OF ALENDRONATE IN THEPREVENTION OF POSTMENOPAUSAL OSTEOPOROSIS

S. HepguÈ ler, H. Toprak, K. Capaci, C. OztuÈ rk, R. Aks,it, EgeUniversity Med. Faculty Physical Therapy and Rehab. Dept.,Izmir, Turkey

The aim of this study was to determine the preventive effect ofalendronate, a spesi®c inhibitor of bone resorbtion, in post-menopausal osteoporosis. Twenty-one postmenopausal osteo-penic women with ages between 31±70 years (mean 56.33�8.82)and whose T scores were found to be between ±1.00 and ±2.50 inDEXA tests were included in the study. Rutine blood, urine, liverfunctional tests, alkalene phosphotase, urea, creatinine, serumcalcium and phoshorus, urine calcium, deoxypyridinoline as bonemarkers were investigated. Alendronate was given every otherday with the treatment regimen including elementary calciumdaily and Vit D monthly. At 12th month, statistically signi®cantdensity increase was obtained in all patients' lumbar vertebrae,femoral neck and trochanter (p<0.05) and this increase was at therate of %10.72 in L1±4 vertebraes, %2.85 in femoral neck, %7.56in femoral trochanter and %2.48 in wards triangle. Alkalenephosphotase, deoxypyridinoline values comparing to initialchanged signi®cantly at 6th 12th months. During the study,because of gastrointestinal side effects two patients and becauseof allergic reactions one patient had to stop the treatment. As aresult, alendronate is an effective drug in the prevention ofpostmenopausal osteoporosis.

474 (438). EFFECT OF CALCITRIOL ON BONE MINERALDENSITY (BMD) IN CHINESE PREMENOPAUSAL WOMEN ONCHRONIC STEROID THERAPY

A. Y. Y. Ho, I. Lambrinoudaki, D. T. M. Chan, C. S. Lau, R. W. S.Wong, S. S. C. Yeung, A. W. C. Kung, Dept. of Medicine,University of Hong Kong, Queen Mary Hospital, Hong Kong, PRC

The effect of chronic steroid therapy on BMD in premenopausalwomen with normal menstrual cycles and its treatment wasevaluated in 81 lupus patients. They were randomly allocated tothree groups: 1: 0.5mg calcitriol and 1200mg calcium daily, 2:1200mg calcium and placebo calcitriol and 3: placebo. BaselineT-score at the lumbar spine was > ±1 in 56.8% and 5±2.5 in 3.7%of the patients. At the end of two years, patients in the calcitriolgroup exhibited a signi®cant increase of 2.1�2.4% in the BMD atthe lumbar spine when compared to baseline value (p<0.05).However this change was not signi®cantly different from therespective change in either the calcium (0.4�2.9%) or the placebogroup (0.3�3.5%). No signi®cant changes were observed in any ofthe treatment groups in the BMD at the hip or at the radius.Alkaline phophatase remained stable in the calcitriol group butincreased in both the calcium and placebo group. In conclusion,the bene®cial effect of calcitriol treatment in these premeno-pausal women was small, at least when it was instituted late in thecourse of steroid therapy.

(This study is partly supported by Roche PharmaceuticalCompany, Hong Kong Ltd.)

475 (439). EFFECT OF CALCIUM AND VITAMIN DSUPPLEMENTATION ON BONE LOSS IN POSTMENOPAUSALCHINESE WOMEN: A COMPARATIVE STUDY

O. R. Huang, J. H. Lu, Q. Zhou, Y. J. Liu, Q. H. Wang, Center ofOsteoporosis Prevention and Treatment, Shanghai Sixth People'sHospital, Shanghai, China

Objective: To determine the effect of calcium and vitamin Dsupplementation on bone turnover and bone loss in postmeno-pausal Chinese women.

Methods: Seventy-nine postmenopausal Chinese women, aged52±69 years, were divided into two groups. Group A: 34 cases,menopause duration 410 years, and group B: 45 cases,menopause duration >10 years. Both groups were administered1.0g calcium and 400 IU vitamin D per day for one year. Atbaseline and at 12 months after treatment, the bone mineraldensity (BMD) of the lumbar spine (L2±4) and proximal femur wasmeasured by dual-energy X-ray absorbtionmetry, and at baselineand at 3, 6, 12 months, serum and urinary markers of calciummetabolism were also examined.

Results: After 12 months, in group B, the percentage changerates of BMD at the sites of femoral neck, trochanter, Ward'striangle and L2±4 were increased 1.58%, 2.10%, 4.26%, 1.33%respectively, P<0.05% for femoral neck, and P<0.001% forothers; while in group A, the percentage change rates of theBMD at intertrochanteric sites were signi®cantly reduced(P<0.05), at other sites were insigni®cantly changed. Ascompared two groups, the percentage change rates of the BMDat trochanter, intertrochanter, Ward's triangle in group B werehigher than those in group A (P<0.05). In both groups, the serumPTH and AKP levels all were signi®cantly decreased frombaseline, there was no signi®cant difference between twogroups at 12 months. U-pyridinoline/creatine (Pyd/Cr) ratioswere changed 42.5% and ±22.6% at 12 months, there wassigni®cant difference between two groups (P<0.01).

Conclusions: By 1.0 g calcium and 400 IU vitamin Dsupplementation, PTH secretion and bone turnover were sig-ni®cantly inhibited, and the BMD of the hip in postmenopausalChinese women with more than 10 years' menopause duration,


but not in whom with not more than 10 years' menopauseduration, were signi®cantly increased.

476 (440). ORAL CALCITONIN PREPARATION WAS NOTPROVED EFFECTIVE IN THE YOUNG JAPANESE MALES. THEPHASE I PILOT STUDY

A. Itabashi1,2, K. Nemoto1,2, M. Tsuboi2, T. Kohno3, M. Koida3, K.Iwamitsu4, 1Saitama Medical School, Saitama; 2NS Clinic, Tokyo;3Setsunan University, Osaka; 4Towa Pharmaceutical Company,Osaka, Japan

Calcitonin is a potent inhibitor of osteoclastic bone resorption andhas been used for the treatment of osteoporosis, Paget's diseaseand hypercalcemia of malignancy. Nasal calcitonin is available inUS and EU countries while only injectable form is approved inJapan. Oral salmon calcitonin manufactured by Cortecs is aunique product. Salmon calcitonin is emulci®ed with phospholi-pids and gelatine-capsulated. It is dissolved in the intestine andabsorbed into lymphatic system. If proved effective, it will be avery useful preparation. We conducted a phase I study in Japan.Forty healthy young Japanese males were recruited afterinformed consent. Each group, consisted of eight candidates,took 200IU, 400IU, 800IU, 1600IU of oral salmon calcitonin orplacebo before breakfast. Plasma salmon calcitonin concentra-tions were serially measured using very high sensitive salmoncalcitonin EIA developed by Kohno. Urinary crosslaps (CTx) anddeoxypyridinoline (DPD) were also measured. Even after theingestion of the highest dose, salmon calcitonin was not detectedin the plasma. Neither urinary CTx nor DPD excretion wassuppressed greater than those in the placebo group as a diurnalvariation. Our assay system has been validated in the case ofnasal salmon or eel calcitonin preparations. These disappointingresults show that oral salmon calcitonin preparation developedby Cortecs has not been proved effective in the short term phase Ipilot study in the Japanese young males.

477 (441). THE POWER PROGRAM: AN EVIDENCE-BASEDSELF-MANAGEMENT PROGRAM FOR OSTEOPOROSIS IN THEELDERLY

T. A. Izukawa1, L. Bernick1, A. Stephens2, 1Baycrest Centre forGeriatric Care, University of Toronto, Toronto, ON, Canada;2North York General Hospital, Toronto, ON, Canada

Osteoporosis as a chronic illness ®ts well into the self-manage-ment concept. We will review the literature on self managementand present a model for a self management program forindividuals living with osteoporosis. The POWER (PromotingOsteoporosis Wellness through Education, exercise and Re-sources/research) program is a short term, community-basedself-management program aimed at Seniors diagnosed withosteoporosis. It is evidence-based, and emphasizes the client'srole in managing their condition, through education, skills andassistance with some areas of personal planning and goal-setting. Aspects of the program that follow the self managementphilosophy include the general education, nutrition education andexercise education components, along with speci®c advice onlifestyle modi®cation and an emphasis on injury preventionplanning. The program is taught by an interdisciplinary team.Evaluation has been built in. Another unique aspect of theprogram has been the partnership between a community hospital,a teaching and complex continuing care hospital, ethnic-basedcommunity health and skilled nursing home facilities and theDept. of Public Health, in conjunction with sponsorship by privatecompanies and government funded agencies. This unique modelmay be an indication of the future direction of health careprovision for seniors with chronic illnesses.

478 (442). EFFECTS OF RALOXIFENE AND ALENDRONATE ONBONE MINERAL DENSITY AND BONE TURNOVER MARKERSIN POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS

O. Johnell1, Y. Lu2, E. Seeman3, J. Reginster4, W. Scheele2,1Universitetssjukhuset MAS, Malmo, Sweden; 2Eli Lilly andCompany, Indianapolis, USA; 3Austin & Repatriation MedicalCentre, Heidelberg, Australia; 4Polycliniques Universitaires L.Brull, Liege, Belgium

Both raloxifene RLX) and alendronate ALN) increase bone mineraldensity (BMD), decrease bone turnover and prevent new vertebralfractures. The purpose of this randomized, double-blind study isto assess the effects of placebo (PL, N=81), RLX 60mg/d (N=82),ALN 10 mg/d (N=83), or RLX+ALN (N=84) in postmenopausalwomen with osteoporosis. BMD and the bone turnover markersN- and C-telopeptide normalized to creatinine (NTx/Cr, CTx/Cr),osteocalcin (OC), and bone-speci®c alkaline phosphatase(BSAP), were assessed at baseline, 6 and 12 months. Overalldifferences among groups and changes within groups wereestimated by ANOVA and t-test respectively. Possible interac-tions in the effects of RLX and ALN were tested by two-wayANOVA. Correlation between BMD and bone markers wasestimated by Spearman's coef®cient. Within-group statisticalsigni®cance at p<.05 is denoted by *. At 12 months, all changes inBMD and bone markers were different between each activetreatment group and PL, and between RLX and RLX+ALN(p<0.05). The increase in femoral neck BMD was greater in theRLX+ALN group compared with ALN (p<0.02). The effects of RLXand ALN are additive, since interaction effects between RLX andALN were not statistically signi®cant at P=0.10. Changes inlumbar spine BMD were correlated with changes in BSAP andCTx/Cr at 6 months in the RLX group, and with OC at both timepoints in the ALN and RLX+ALN groups. RLX+ALN may reducebone turnover more than RLX or ALN alone, resulting in greaterBMD increment. Whether this difference re¯ects better fracturerisk reduction is unknown.

Mean Percentage Change from Baseline to 12-Month Endpoint

PL RLX ALN RLX+ALN

Lumbar Spine BMD 0.06 2.1* 4.3* 5.3*Femoral Neck BMD 0.31 1.7* 2.7* 3.7*NTx/Cr 26.9* ±17.8* ±40.9* ±54.3*CTx/Cr 4.4 ±31.2* ±49.5* ±69.3*OC 5.0 ±25.5* ±38.8* ±48.8*BSAP ±10.6* ±24.4* ±45.3* ±48.4*

479 (443). EFFECT OF ALENDRONATE AND COMBINEDHORMONE REPLACEMENT THERAPY IN TAIWANESEPOSTMENOPAUSAL OSTEOPOROTIC WOMEN

Jung-Fu Chen1, Jao-San Huang2, Jen-Der Lin2, 1Division ofEndocrinology and Metabolism, Chang Gung Memorial Hospital,Kaohsiung; 2Taoyuan, Taiwan, R.O.C.

PURPOSE Osteoporosis becomes to be a serious health problemfor Taiwanese older women and effective treatments are needed.This study is to evaluate the effect of alendronate and combinedhormone replacement on the different site of bone mineral density(BMD).

PATIENTS AND METHOD Seventy-three Taiwanese postme-nopausal women, age (mean�SE, 66�1), with establishedosteoporosis (T 4±2.5) were enrolled. Patients were dividedinto three groups, including the control group (n=25) received 900mg elemental calcium, the alendronate group (n=32) receivedalendronate (10mg) daily and calcium, the combined therapygroup (n=16) received alendronate (10 mg), premarin (0.625 mg),provera (5 mg) and calcium daily. BMD was measured by dual-


energy X-ray absorptiometry (Norland XR36) at the lumber spineand femoral neck before treatment and one year after, comparedfor baseline and percentage changes inbetween.

RESULTS The difference of BMD in the alendronate group whoincreased in the lumber spine by 6.9% and the femoral neck by3.8%. For patients who received combined alendronate andhormone therapy, the increase were 8.8% and 3.8% in lumberspine and femoral neck. The groups with calcium alonedecreased 1.5% and 0.7% in lumber spine and femoral neckrespectively.

The women receiving alendronate had signi®cant BMD increasein lumber spine (p<0.00), and femoral neck (p = 0.36) comparedwith control group, and the women receiving combined therapyhad also signi®cant BMD increase in lumber spine (p<0.00) andfemoral neck (p = 0.39) compared with control group after 1 yearof therapy.

CONCLUSION This study con®rmed alendronate to be anvery effective treatment for Taiwanese postmenopausal osteo-porotic women, and additive effect of combined alendronateand hormone replacement therapy was seen in selectedsubgroups.

480 (444). EFFECT OF COMBINATION THERAPY WITHETIDRONATE AND ALFACALCIDOL AFTER ALFACALCIDOLTHERAPY ALONE ON SPINE, RADIUS AND CALCANEUS BONEMINERAL DENSITY IN POSTMENOPAUSAL OSTEOPOROTICWOMEN

H. Katagri, H. Hagino, R. Teshima, Department of OrthopedicSurgery, Faculty of Medicine, Tottori University, Yonago, Tottori,Japan

Few data are available on the effects of combination therapy forthetreatment of osteoporosis. The aim of this study was toinvestigate the effects of a combination of cyclical etidronate andalfacalcidol on spine, radius and calcaneus bone mineral density(BMD) in postmenopausal osteoporotic women having beentreated with alfacalcidol alone. We examined this therapyamong 13 postmenopausal osteoporotic women having beentreated with alfacalcidol alone for more than 5 years.

Etidronate (200 mg/day) was administered orally for 14 days,beginning 10 to 12 weeks after discontinuation of alfacalcidol.Alfacalcidol (0.5 m g/day) was administered orally for thesubsequent 10 weeks. Treatment cycles were repeated abouteight times for two years. Lumbar spine and distal radius BMDwere measured by DXA three times; two years before starting, atbaseline (just starting) and at one years of this treatment. Themeasurement of calcaneus BMD was performed using SXA.

The mean increase in lumbar spine BMD was 4.4%/yr after thistreatment, which was signi®cantly different from the previousalfacalcidol therapy alone, where there was a ±3.7%/yr change.The distal radius BMD increased 6.3%/yr, which was signi®cantlygreater than the 0.9%/yr increase before this treatment. Thecalcaneus BMD increased 3.7%/yr, while before this treatmentthe BMD decreased 2.6%/yr.

These data indicate that a combination of cyclical etidronateand alfacalcidol is better than alfacalcidol alone in terms ofchanges in BMD at all measurement sites. Further studies areneeded to determine if the combination is more effective thancyclical etidronate alone.

481 (445). SKELETAL EFFECTS OF THE ESTROGEN ANDCALCITONIN IN OVARECTOIZED RATS

V. Kavuncu, S. Sahin, G. Baydas, N. Ilhan, I. Ozercan, A. Yasar, I.Pekkutucu, R. Ozercan, Firat University, Elazig, Turkey

The purpose of this study is to investigate the ef®cacy of salmoncalcitonin and estrogen treatment in a type I osteoporotic modelof rats. Sixty 3-month old female Wistar rats were divided into six

groups in which the ®rst group was the base group, the secondgroup was sham operated, and the other groups were surgicallyovariectomized. After 24 hours of ovariectomy, they were eitheruntreated (ovx) or S.C. injected with 17-b estradiol (E2) 30 mcg/kg/24hours or low-dose calcitonin (LDC) (Miacalcic1amp, byNovartis-Pharma used) 10 IU/kg/48 hours or high-dose calcitonin(HDC) 20 IU/kg/48 hours. At the end of the six-week period, bonedensity was measured by DEXA, and all animals were sacri®ced.Plasma was collected to measure osteocalcin (OC), estrogen,parathormon (PTH), calcium (Ca) and inorganic phosphate (iP)levels. The femurs of the rats were harvested for histomorpho-metric evaluation. While serum estrogen levels were signi®cantlylower in all the groups compared with the base group, the levelsof OC, PTH, and Ca did not differ. ip levels were signi®cantly lowin OVX and E2 groups. BMD of the spine and proximal femur wasfound to be substantially low in OVX group. BMD of the spineseemed to be restored both E2 and LDC and HDC treatments.Although there was also an increase in BMD of proximal femur, itwas not achieved statistical support. Histomorphometric evalua-tion revealed that relative trabecular volume was signi®cantly highin LCT and HCT groups. However, relative and absolute osteoidvolume did not differ as expected. In conclusion, calcitonintreatment restores bone lost in ovariectomized rats, and theseresults in the animal model if estrogen depletion suggest thatcalcitonin provides an important alternative therapy in postme-nopausal osteoporosis.

482 (446). INTRAVENOUS PAMIDRONATE THERAPY INOSTEOPOROSIS

J. Kekow1, W. Flach2, T. Linde1, 1Clinic of Rheumatology,University of Magdeburg, Vogelsang/Magdeburg; 2Department ofLaboratory Medicine, Vogelsang, Germany

Oral bisphosphonates are frequently used to treat osteoporosis.In patients experiencing adverse GI effects from oral administra-tion, parenteral bisphosphonates are recommended. We reporton 25 patients (15 women, 10 men) treated with intravenous (i.v.)pamidronate after failure of ether oral alendronate or etidronatetherapy as de®ned by a lack of BMD increase under oralbisphosphonate therapy for at least 1 year. The group consistedof 17 women with postmenopausal osteoporosis, and 10 patientswith steroid-induced osteoporosis (rheumatoid arthritis: n=4, IBD:n=2, MCTD: n=1, asthma: n=3). The mean age of the patients was63 years (range: 41±86 years).

The patients initially received 60 mg pamidronate i.v. for 4hours, then 30 mg pamidronate i.v. for 2 hours at 3 monthintervals thereafter. Each patient's response was monitored bydetermination of bone marrow density (BMD) (DXA technique,Hologic QDR 1000), measurement of osteocalcin (LUMItestOsteocalcin, Brahms Diagnostica) and crosslaps (CrossLapsserum Elisa, IBL) in sera and of N-telopeptides in urine (ELItestNTX, Brahms Diagnostica). BMD was measured at the lumbarspine (L1-L4) and/or at the femoral neck (FN) if appropriate. Threemonths after the ®rst i.v. pamidronate, the BMD had increased3.6% / 2.5% (L1-L4 / FN), reaching a T-score of ±3.16/±3.53. Threemonths later the BMD had increased 11.6% at L1-L4 (new T-score±2.96), with no further change at the FN versus initial levels. As asign of a reduced bone turnover, osteocalcin showed acorresponding decrease of 40%* (from 7.1 mg/l to 4.2 mg/l,n=23) after 60 mg pamidronate, and of 44%* (from 7.6 mg/l to 4.2mg/l, n=13) after 90 mg pamidronate. The crosslaps decreased by34%* (from 2670 pmol/l to 1769 pmol/l, n=11) and the N-telopeptides decreased by 41%* (from 53.9 nmol/mmol Crea. to31.7 nmol/mmol Crea., n=11) after 60 mg pamidronate, bothchanges indicating a reduction in bone resorption (*p<0.05).Among the adverse effects were fever on the day after infusion(n=5) and transient leukopenia in one patient. Therapy did nothave to be discontinued in any case. Collectively the present datashow that i.v. pamidronate therapy is a therapeutic option forpatients who do not respond to oral bisphosphonates.


483 (447). COMPARISON OF THE EFFICACY OFALENDRONATE IN ELDERLY WITH THE EFFICACY IN EARLYPOSTMENOPAUSAL WOMEN

Y. Kirazli, B. Durmaz, F. Erer, A. On, R. Aks,it, Physical Medicineand Rehabilitation Dept., University of Ege, Izmir, Turkey

This study was planned to evaluate the ef®cacy of treatment withalendronate on bone mineral density (BMD) in women with lowbone mass. There are some published studies with alendronatebeing used in osteoporosis. Early Postmenopausal InterventionCohort Study Group looked for the ef®cacy of treatment inwomen under 60 years of age. On the contrary AlendronateElderly Osteoporosis Study Centers evaluated the ef®cacy inosteoporotic elderly women over 60 but none of the publishedstudies compared the ef®cacy in early postmenopausal periodwith the ef®cacy in elderly.

In this study the ®rst group of patients consisted 40 earlypostmenopausal osteoporotic women under 60 years of age andthe second 40 osteoporotic women over 60. All of the patientswere given 10 mg alendronate plus calcium (500 mg/day). Themain outcome measure was the change in bone mineral densityof the lumbar spine and the hip measured at baseline and afterone year of treatment by dual-energy x-ray absorptiometry. Thewomen in both groups had signi®cantly important importantincreases in BMD at all areas at the end of one year but whenMann-Whitney U-Wilcoxon Rank sum W test was applied to seethe difference between groups it was concluded that the yearlypercentage change in lumbar BMD and femoral neck BMD wassigni®cantly higher in the second group which included womenover 60. The yearly percentage changes in trochanter and Ward'striangle did not show any differences between groups.

484 (448). THE EFFICACY OF ALFACALCIDOL IN THETREATMENT OF OSTEOPOROSIS SECONDARY TO ORALANTICOAGULANTSY. Kirazli, A. Tez, C. OztuÈ rk, A. On, R. Aks,it, Physical Medicineand Rehabilitation Dept., University of Ege, Izmir, Turkey

This study was planned to investigate the effect of active vitaminD in the treatment of osteoporosis (OP) secondary to oralanticoagulant treatment (OACT). 15 of the 30 patients (OP(+),OACT(+)) had alfacalcidol 1 mg / day for one year. The other 15patients formed the control group. All of the patients werefollowed biochemically every two months because of the risk ofhypercalciuria and hypercalcemia. Calcium in the diet was alsorestricted to 800 mg/day. Osteocalcin value increased signi®-cantly in the the group treated with alfacalcidol (p<0.01) whereasit decreased signi®cantly in the control group (p<0.05). The mainoutcome measure was the change in bone mineral density (BMD)of the lumbar spine and the hip measured at baseline and afterone year of treatment by dual-energy x-ray absorbsiometry. Thegroup who had treatment with alfacalcidol showed signi®cantlyimportant increases in BMD values of the lumbar region (p<0.01).The changes in BMD values of the hip were not signi®cant. On theother hand, in the control group, BMD of the trochanter andWard's triangle decreased signi®cantly (p50.05).

It is concluded that appropriate medical treatment is requiredfor the treatment of osteoporosis secondary to oral anticoagulanttreatment.

485 (449). PREVENTION OF BONE LOSS WITH INTRANASALLYADMINISTRATION OF SALMON CALCITONIN DURING EARLYPOSTMENOPAUSAL PERIOD IN HORMONE REPLACEMENTTHERAPY CONTRAINDICATED CASES

S. Koloszar, J. SzoÈ lloÈ si, J. Gellen, L. KovaÂ cs, A. PaÂ l, Departmentof Obstetrics and Gynaecology, Albert Szent-Gyorgyi MedicalUniversity, Szeged, Hungary

The aim of this prospective study was to assess the in¯uence ofsalmon calcitonin therapy given intranasally on bone mineral

density of postmenopausal patients. Thirty ®ve postmenopausalwomen (aged 51.6�2.9 years) with calcipenia within one year aftermenopause were enrolled in the investigation. Indication ofsalmon calcitonin therapy was to prevent of postmenopausalbone loss in such cases when estrogen administration wascontraindicated or the patients refused the hormone replacementtherapy. The investigated group received 200 IU salmoncalcitonin (MiacalcicR, Novartis) intranasally 14 days a monthand 0.5 g calcium daily for one year. The control group (36women, aged 52.1�3.1 years) received 0.5 g calcium daily. In allcases serum calcium, phosphorus and alkaline-phosphataselevels were in the normal range. Bone mineral density wasmeasured in lumbal spine (L2-L4) and femur neck with DXAmethod (LunarR) before and after one year salmon calcitoninadministration. After one year therapy the T-score in the controlgroup (calcium only) decreased in lumbal spine from ±1.67�0.26to ±1.81�0.28 (p<0.01) and in femur neck from ±1.36�0.27 to1.49�0.30 (p<0.01). In the Miacalcic plus calcium treated group T-score in lumbal spine increased from ±1.64�0.29 to ±1.61�0.30(p = N.S.) and in femur neck virtually unchanged ±1.42�0.24 to71.41�0.26 (p = N.S.). On the basis of this one year trial weconcluded that there is evidence that intranasal Miacalcic cancounteract early postmenopausal bone loss by inhibiting boneresorption in such cases when hormone replacement therapy iscontraindicated.

486 (450). THE RESPONSE OF BIOCHEMICAL BONE INDICESAND GEOMETRY OF LONG BONE AFTER 2 YEARS OFCONTINUOUS TREATMENT OF 200 IU INTRANASAL SALMONCALCITONIN ON EARLY POSTMENOPAUSAL WOMEN

I. Ch. Koulouris, I. Paspati, P. Raptou, A. Galanos, G. Trovas, M.Katsiri, G. P. Lyritis, Laboratory for The Research ofMusculoskeletal System, Athens Univ. KAT Hospital, Ki®ssia,Greece

AIM: We studied the response of Salmon Calcitonin (sCT) on thebiochemical bone indices and bone mass-geometry of differentbone envelops in continuous intranasal administration of 200 IUdaily of sCT.

SUBJECT AND METHODS: Fifty early postmenopausal women(1±5 years after menopause), with a mean age of 50�5 yearsincluded in the study ± women taking drugs, or affected bydiseases that interfere with bone metabolism were excluded ±were randomly allocated in two groups and entered in a double ±blinded clinical study. Group A was treated with 200 IU nasal sCTwhereas group B was placebo treated daily for two years period.Both groups received 1000 mg additionally calcium daily. Allwomen included had an initial T-score 42 SD by Dexa and weremeasured 1) serum calcium, phosphorous, alkaline phosphate,osteocalcin fasting urinary Ca/Cr, OHP/Cr, and 2) by peripheralquantitative computed tomography (pQCT, STRATEC XCT 960) at0, 6, 12, 18 and 24 months of treatment. pQCT Measurementswere performed at 4% and 20% of the ulnar length from the distalend. The results were analyzed by student's t-test.

RESULTS: Alkaline phosphate values demonstrated signi®cantdifferences (p = 0.024) at 6 months. At 6 months serum levels ofosteocalcin decreased signi®cantly below baseline in the sCTgroup (±18.9%, p = 0.003) and remained low after that, whereasthe changes in the placebo group were not statisticallysigni®cant. Urinary levels of OHP/Cr decreased signi®cantly inthe sCT group at 6 months (±9.3%, p<0.05), intergroup differenceat the same time between the groups were also signi®cant(p = 0.0046). The changes in the 4% of the trabecular area on thesCT group did not show a statistically signi®cant change on the12 months (6.93%, NS), while in the placebo group the decreasewas statistically signi®cant (±6.5%, p = 0.004) and the intergroupdifference was statistically signi®cant p = 0.008 for the sCT groupand for the same period of treatment. The Trabecular content onthe sCT group signi®cantly increased (+17.07%, p = 0.023) while inthe placebo group dicreased (±5.64%, NS). The intergroup


difference was on the side of the sCT group p = 0.009. Bothgroups presented an augmentation of the subcortical area whichshowed no intergroup signi®cance but was less for sCT group. Nosigni®cance was also found for the subcortical mass, whichnevertheless was smaller in the sCT group.

CONCLUSIONS Treatment with 200 IU of nasal sCT given daily1) Resulted in changes of biochemical bone indices that re¯ect itsparticularly bene®cial effect on bone metabolism at 6 months,whereas it seems that this effect weakens after completion of twoyear of treatment. 2) Affects the subcortical bone in a preservingway (considering that subcortical bone in the area responsible forcortical bone loss,) protects from trabecular loss of mass andarea (volume) compared to the placebo, and achieves itsmaximum action at the ®rst year of treatment although the resultscontinue to persist after 24 months. This is shown from theanalysis of the biochemical bone indices and the pQCTmeasurements.

487 (451). BULGARIAN EDUCATIONAL ``ANTIOSTEOPOROSIS''PROGRAMS FOR ADULTS AND CHILDREN ± IDEAS,STRATEGIES, PRACTICE

R. Kovatcheva, A-M. Borissova, A. Shinkov, R. Shigarminova, N.Mendizova, Medical University, So®a, Bulgaria

Osteoporosis is a major social health problem, also declared assuch by the WHO. In 1997 the Bulgarian League for the Preventionof Osteoporosis (BLPO) launched a Program for the Educationand Prevention of Osteoporotic Patients (PEPOP). The Programtreats the osteoporotic subject as suffering with both bone andpsychoemotional and social problems. The motto of the PEPOPis: `Find time for yourself' and `It is all in your hands'. Theobjectives of the PEPOP are: 1. Clinical; 2. Social; 3. Academic;and 4. Administrative and economic ± development of a NationalStrategy for the Challenging of Osteoporosis and a HealthAuthorities Marketing Program. The practical implementation ofthe PEPOP includes: 1. Weekly lectures; 2. Publication of aneducational book `Let's keep the bones healthy'; 3. Publication ofbooks with physical exercises; and 4. A campaign for free-of-charge bone density measurement, accompanied by lectures anddistribution of educational materials. The enormous cost of theosteoporosis and osteoporotic fractures brings to the front theidea for early prevention. BLPO developed a National educationalprogram ``Let's build healthy bones''. It is directed towards the 6±12 year olds and includes: 1. Educational illustrated book, keywords ± milk, good stature, exercise, healthy bones, healthy child;2. An original song on the topic; 3. Children's show; 4. Video clipfor several TV channels. Conclusion: The BLPO programs areaimed at helping people consider their personal responsibility fortheir own health, good self-esteem and quality of life. This newway of thinking is most easily planted in children.

488 (452). INFLUENCE OF CLODRONATE ON THE BONEDENSITY OF PATIENTS WITH MULTIPLE MYELOMA ± THREE-YEAR FOLLOW-UP OF THE THERAPEUTIC EFFECT

A. Krivanova, Z. Fojtik, Z. Adam, B. Prokes, V. Znojil, R. Hajek, M.Krejei, M. Doubek, J. Vorlieek, IInd Onco-Hemotology Dpt.,University Hospital Brno Bohunice, CZ

Bisphosphonates are used for the treatment of hypercalcaemiaas well as in normocalcaemic patients for the long-term inhibitionof malignant osteolytic bone processes. In patients with multiplemyelomas treated with bisphosphonates in randomized studies areduction of the number of new osteolytic foci was proved andalso improvement of the quality of life was obvious. The objectiveof presented study was the evaluation of the effect of clodronateon the increase of bone density in patients with multiple myeloma.

Since 1994 34 patients (pts) were included in the study. Theresults were evaluated in January 1993. In the 1st year the patients

were given 1000 mg l.v. clodronate (Bonefos ± Leiras) per month,further years 1800 mg per month (Peest et al). Bone marrowdensity (BMD) in the lumbar vertebrae was evalumed by CTdensitometry in six months intervals.

Statistlcal testing of trends of assessed bone density valuesrevealed that not even after three years of the disease astatistically signi®cant reduction of the bone density occurs.

The interesting result was the relationship between changing ofBMD after the administration of clodronate and a type of multiplemyeloma (MM). The BMD had increased after 12 and 18 months inpts with IgA and IgG MM. There were no changes in BMD of ptswith B±1 type. The correlation between the activity of the diseaseand increase of BMD was also interesting. The BMD signi®cantlyincreased in pts in remission, stable disease or partial remission.The BMD of pts with active disease dicreased. Treatment wasvery well tolerated, gastrointestinal problems were an exception.3 pts had symptoms of mild tetany due to hypocalcaemia.

Clodronat stobilizes the amount of bone moss, reduces painand also improves the quality of the patients life. It should beincluded among standard treotment of patients with multiplemyeloma.

Keywords: Bisphosphonates-Clodronat-Multiple myeloma-Densitometry-Therapy.

489 (453). THE EFFECT AND SAFETY OF CALCITRIOLTREATMENT IN STEROID-INDUCED OSTEOPOROSIS INPATIENTS WITH PEMPHIGUS VULGARIS

Y. G. Kutsal, A. Sivri, A. Karaduman, N. Atakan, University ofHacettepe, Ankara, Turkey

The purpose of this study was to evaluate the effect and safety ofcalcitriol treatment in steroid-induced osteoporosis in patientswith pemphigus vulgaris. It has been known for years thatglucocorticoid treatment is the most frequent cause of secondaryosteoporosis, but there are not generally accepted guidelines forprevention and treatment.

In this prospective study, 29 (17 female, 12 male) patientscommencing long-term (mean 53�18 months) corticosteroidtherapy for pemphigus vulgaris were followed up for 6 monthsby biochemical markers and bone mineral density (BMD)measurements of the lumbar spine and femur neck by DEXA.The mean age of the patients was 48.2�5.7 years and the meansteroid dose was 17.2 mg prednisolone/day. We found reducedBMD in all of the patients when compared with age-matchedhealthy controls and treated with Calcitriol (Rocaltrol) 0.5 mg/dayfor 6 months. The results showed statistically signi®cantdifference between the initial and after-treatment lumbar BMDs(p<0.05), but the increase in proximal femur BMD did not reachthe statistically signi®cant values. No complication was detected.As a result, Calcitriol treatment in steroid-induced osteoporosisappeared to be well tolerated and effective.

490 (454). THE EFFECT OF CALCITONIN TREATMENT ONSERUM BETA±2 MICROGLOBULIN LEVELS INPOSTMENOPAUSAL OSTEOPOROSIS

Y. G. Kutsal, A. Sivri, Dept. of PMR, University of Hacettepe,Ankara, Turkey

The aim of this study was to evaluate serum beta±2 microglobulinlevels (b2m), which has a regulatory function in bone metabolismby stimulating osteoclastic activity, in patients with postmeno-pausal osteoporosis and to ®nd out whether salmon calcitoninhas an impact on the serum concentration of b2m.

The study group consisted of 48 women with a mean age of63.7�7.2 years with postmenopausal osteoporosis based on theWHO de®nition. None of the women was receiving pharmacolo-gical treatment. The control group consisted of 20 normal womenof similar age (64.5�8.1 years). Biochemical variables, serum b2m


levels and bone mineral density (BMD) of the lumbar spine andproximal femur by DEXA were measured in baseline conditions inboth groups. Then the patients were evaluated after 3 months oftherapy with salmon calcitonin (100 IU/day nasal spray). At thebeginning of the study, b2m concentration was found to be raisedin women with postmenopausal osteoporosis as compared withthe controls (p<0.05). A signi®cant decrease in serum b2m wasobserved after 3 months of therapy. These ®ndings suggest thatb2m may play an important role as a local regulatory factor in thepathogenesis of postmenopausal osteoporosis.

491 (455). FOUR YEARS INTRAVENOUS INJECTIONS OFIBANDRONATE IN THE TREATMENT OF POSTMENOPAUSALOSTEOPOROSIS

O. Lamy, L. Sandini, J. Burnand, M. A. Krieg, P. Burckhardt,University Hospital, Lausanne, Switzerland

Background: The high potency of Ibandronate (IB) allows iv bolusinjections. Its ef®cacy was tested in postmenopausal OP during a4-year, prospective, controlled study.

Method: 15 postmenopausal women, mean age �67 years,participated ®rst during 1 year at a double-blind, placebocontrolled study. Placebo or IB (4 doses : 0.25 mg, 0.5 mg, 1mg or 2 mg) were injected every 3 months. Then, all received IB 1mg iv every 3 months during 3 years. All got calcium 1g/d andvitamin D 1000 UI/d. BMD was assessed by DEXA (Hologic QDR2000).

Results: BMD change from day 0 (%�SEM). Lumbar spine BMDincreased signi®cantly after 12 months (average dose of IB 0.7mg) and up to 51 months (all on 1 mg). Iv IB was well tolerated. 5symptomatic spontaneous fractures occurred in 4 women: 1trochanter, 1 femoral neck, 2 humerus and 1 vertebral fracture.

Conclusions: 4 years treatment of iv IB together with calciumand vitamin D increased signi®cantly BMD at lumbar spine andprevent bone loss at other sites.

Months 12 27 39 51

Lumbar spine 2.9�1.1* 3.4�1.6** 4.0�1.4* 5.3�2.2*Femoral neck 0.6�0.8 1.8�0.9 2.0�0.9** 1.7�1.1Total hip 1.5�0.9 1.6�1.1 1.1�1.1 1.5�1.4Radius 2.2�1.1 0.4�0.8 0.2�0.8 1.7�0.9

*P50.05, **P= 0.05 (paired t test)

492 (456). TWO YEARS INTRAVENOUS INJECTIONS OFIBANDRONATE IN THE TREATMENT OF OSTEOPOROSIS INMEN

O. Lamy, L. Sandini, J. Burnand, M. A. Krieg, P. Burckhardt,University Hospital, Lausanne, Switzerland

Background: Few drugs are proven effective in the treatment ofosteoporosis (OP) in men. Bisphosphonates are potent drugs, buttolerance to oral treatment is often low. The high potency ofIbandronate (IB) allows iv bolus injections. Its ef®cacy was testedduring a 2 years, prospective, controlled study in men with OP.

Method: 14 men with primary OP, mean age �57 years, meanweight �76 kg, received IB 2 mg iv every 3 months during 2 years.All got calcium 1g/d and vitamin D 1000 UI/d. BMD was assessedby DEXA (Hologic QDR 2000) every 6 months.

Results: BMD change from day 0 (%�SEM). Three patientsreported ¯u-like symptoms: two after the ®rst and second

injections and one after each injection. One patient stopped thestudy after 1 year for reasons not related to IB. One spontaneousfracture occurred.

Conclusions: 2 years treatment of 2 mg iv IB in men with OPincreased continuously signi®cantly BMD at lumbar spine andtrochanter and, together with calcium and vitamin D, preventbone loss at other sites.

Months 6 12 18 24

Lumbar spine 3.7�1.3** 4.9�1.3** 5.2�1.8** 6.7�1.5**

Femoral neck 0.5�0.6 1.1�1.3 2.3�1.0* 1.4�1.1

Trochanter 1.2�0.6* 2.0�0.8** 3.1�0.8** 3.2�0.8**

Total hip 1.5�0.9 1.6�1.1** 1.1�1.1 1.5�1.4

*P50.05, **P50.01 (paired t test)

493 (457). ACCEPTANCE OF A COMMUNITY-BASEDPROGRAMME FOR THE PREVENTION OF FALLS ANDFRACTURES

E. R. Larsen1, L. Mosekilde2, A. Foldspang3, 1Department ofOrthopedic Surgery, Randers Central Hospital, Denmark;2Department of Endocrinology and Metabolism, UniversityHospital of Aarhus; 3Master of Public Health, University of Aarhus,Denmark

Background. Low energy fractures among the elderly may beprevented by reducing the risk of falling or increasing the strengthof the skeleton. Acceptance of these interventions in the targetpopulation is of paramount importance for their success.

Methods. A total of 7,543 community dwelling Danish personsaged 66+years were offered participation in one of threeintervention programmes. Programme I: A home safety inspec-tion, evaluation of prescribed medicine and identi®cation ofpossible health and food problems; Programme II: 1000 mg ofelemental calcium and 400 IU (10mg) of vitamin D3 per day incombination with evaluation of prescribed medicine; ProgrammeIII: A combination of the two programmes. Acceptance wasde®ned as willingness to receive a visit by a nurse.

Results. Overall acceptance of programme I was 50.2%, ofprogramme II 56.2%, and of programme III 46%. Acceptance wasassociated with gender, age and marital status. An importantdeterminant, however, was the effect of the social service centresthat communicated the three programmes.

Conclusions. Acceptance of a fall and fracture preventionprogramme varies with intervention type; with gender, age andmarital status of the target population and with the motivation andattitude of the health workers involved in the implementation ofthe programmes.

494 (458). PREVENTIVE EFFECTS OF A BISPHOSPHONATE(RISEDRONATE) ON BONE MASS IN AN ANIMAL MODEL OFMALE OSTEOPOROSIS (THE ORCHIDECTOMIZED RAT)

H. Libouban, M. F. Moreau, E. Legrand, M. F. BasleÂ , M. Audran, D.Chappard, University and CHU of Angers, France

Preventive effects of an antiresorptive compound (risedronate)were studied in the orchidectomized (ORX) rat using dual energyX-ray absorptiometry (DXA) and scanning electron microscopy(SEM). We have studied four groups of rats (6 animals per group):sham-operated control rats, ORX control rat, ORX treated withrisedronate 2 or 10 mg/kg/day. Risedronate was injected


subcutaneously 5 days per week. Rats were sacri®ced at 2, 4, 8 or16 week post-orx. DXA was performed on an Hologic QDR 2000(with small animal softwares) on the whole body, and proximaltibia region (including the epiphysis and metaphysis).

In the ORX group: the body weight did not differ from the SHAMgroup, even after 16 weeks. However, lean body mass wasreduced over the four periods of study but body fat mass wassigni®cantly increased after 16 weeks. BMD measured on theproximal tibial region became signi®cantly reduced (±7.2% at 8weeks and ±3.8% at 16 weeks).

In the risedronate groups: lean body mass was reduced and alower body fat mass was noted in animals treated for 16 weekswith 10 mg. With the two dosages, BMD was signi®cantly higherthan in the orx group at two weeks. At 4, 8 and 16 weeks, BMDwas signi®cantly higher than in the sham and orx groups(risedronate 2mg: +8.3% at 4 w and +18.4% at 16w). Furthermore,BMD values in the 10mg group were markedly higher than in the2 mg group (risedronate 10mg: +17.4% at 4 w and +24.2% at 16w).SEM observations of the distal femoral region were in agreementwith quantitative results. A bone condensation was observedmainly in the primary spongiosa at 8 and 16 weeks in bothrisedronate groups. Risedronate at a 2mg dosage appears to be apreventive treatment for orchidectomy-induced osteoporosis.

495 (459). MEDICAL TREATMENT OF THE MILD PRIMARYHYPERPARATHYROIDISM

Z. Man, F. Sayegh, A. Otero, TIEMPO Medical Centre, BuenosAires, Argentine

15 patients with a diagnosis of primary hyperparathyroidism(PHPT) were followed for 36 months. 12 were women aged60.45�8.3 years and 3 were men aged 41, 08�20.8 years.Clinically, 8 patients were asymptomatic, 3 of them werediagnosed by means of osteoporosis (OSP) screening and 5had a previous diagnosis of OSP; 7 patients had symptoms, 1with hip fracture and 6 with nephrolithiasis.

The ideal treatment for PHPT is controversial. For patients witha mild degree of it, treatment ranges from observation to surgery.Although some of them had indication for surgery, it wasn'tpossible for different reasons, including patient's refusal to it. Wetried medical treatment with these patients, seeking biochemicalcontrol of the disease. We administered alendronates with thepurpose of normalizing serum calcium. Three months later weadded low doses of calcitriol, with the aim of reaching normalvalues of PTH. If the urine calcium kept high, thiazides wereadded to the treatment.

The results were:

Time Serum

calcium

(mg/dl)

Ionized

calcium

(mg/dl)

PTH (*) Calcium/

creatinine

Serum

phosphorus

(mg/dl)

Alkaline

phosphatase(*)

Baseline 10.7�0.5 5.1�0.2 1.7�0.8 0.32�0.21 2.8�0.5 0.78�0.3

1 month 10.0�0.7 5.1�0.1 0.7�1.0 0.32�0.22 2.4�0.9 0.91�0.3

3 months 10.2�0.4 5.1�0.3 1.6�1.2 0.29�0.15 2.6�0.3 1.06�0.4

6 months 10.1�0.6 4.8�0.5 0.8�0.6 0.20�0.01 2.8�0.5 0.73�0.1

12 months 10.3�0.6 4.8�0.1 1.1�0.1 0.25�0.12 3.2�0.9 0.71�0.2

18 months 10.0�0.3 4.7�0.3 0.7�0.2 0.17�0.07 2.9�1.0 0.57�0.2

24 months 10.3�0.5 5.3�0.3 1.0�0.1 0.30�0.15 3.3�0.7 0.61�0.2

30 months 10,2�0.7 4.5�0.5 0.7�0.5 0.12�0.37 3.2�0.5 0.57�0.1

36 months 9.6�0.6 4.5�0.6 0.7�0.5 2.7�0.1 0.54�0.05

(*): ratio: value obtained/superior normal value.

Medical treatment controls biochemical indices of hyperpar-athyroidism. It is an alternative when surgery is not advisable,mainly in mild cases.

496 (460). COMPARATIVE STUDY ON THE EFFECT OFANTIRESORPTIVE THERAPY WITH NASAL CALCITONIN (NC)AND SODIUM ALENDRONATE (SA) ON BONE MINERALDENSITY (BMD) AND FORMATION MARKERS (FM) IN AGEDWOMEN

A. Mantakas, T. Drossos, H. Vlahou, A. Hadjilouka, Dept. ofNuclear Medicine, Osteporosis Unit Pammakaristos GeneralHospital, Athens, Greece

Objective: To compare the effect of antiresorptive cyclic therapywith NC and continuous therapy with SA for at least 6 months withcontrols over a period of 12 months

Materials and method: BMD was measured in all women beforethe trial and after 12 months in LS and hip with DEXA (HologicQDR 1000). Formation markers, osteocalcin (BGP) and boneskeletal alkaline phosphatase (sALP) were measured withimmunoradiometric assays every six months.

Patients: Thirty-seven (37) women with established osteoporo-sis were randomized to cyclic therapy with NC 100IU/ alternateday and 1 g/day Ca for 12 months. 36 women to continuoustherapy with SA 10mg/day and 500 mg/day Ca for at least 6months. The control group was 20 women in comparable age.

Results: After one year, signi®cant difference was observedbetween treatment groups and untreated controls in % change inBMD and in BFM. NC group BMD: LS slightly increased, in Ward'striangle signi®cantly (p<0.05). BFM: BGP and sALP increases overbase line (p>0.05). SE group: BMD: alendronate induces asigni®cant gain in bone mass p<0.05 and smaller in throchanter.BFM: SA leads to a great suppression of bone turnover especiallyin sALP after 6 months.

Conclusion: Treatment with NC in comparison with untreatedwomen increases slightly the BMD in LS but signi®cantly inWard's triangle (p<0.05). The BFM are increased (p>0.05). SAincreases BMD in LS (p<0.05) and in trochanter. SE reducesmarkedly the BFM after six months and remains in low levels after12 months.

497 (461). SINGLE INFUSION OF NERIDRONATE INRHEUMATOID ARTHRITIS PATIENTS: EFFECTS ON DISEASEACTIVITY AND BONE RESORPTION MARKERS

M. Mazzantini1, M. R. Metelli2, M. Bulleri1, R. Giordani2, A. DelleSedie1, G. Pasero1, O. Di Munno1, 1Rheumatology Unit,Department of Internal Medicine; 2Laboratory Unit, Department ofExperimental Pathology and Biotechnology, University of Pisa,Pisa, Italy

Bisphosphonates, which are strong inhibitors of bone resorption,have been also shown to reduce the in¯ammatory response in theadjuvant arthritis model and to inhibit lymphocyte proliferationand prostaglandin synthesis in vitro. In this view, pamidronate 40mg was given in single infusion to rheumatoid arthritis (RA)patients (pts) and induced a signi®cant reduction of erythrocytesedimentation rate (ESR), C-reactive protein (CRP), n8 of swollenjoints and Ritchie's articular index (RI) (J Rheumatol 1994). Aim ofthe present study is to assess whether also neridronate (N), 6-amino-hydroxylidene±1,1-bisphosphonate, can exert similar anti-in¯ammatory effects in RA pts. Forty-®ve pts (10 m, 35 f) withactive RA were randomized to receive, on a double-blind basis, asingle infusion of either N 50 mg, N 25 mg, or placebo in 500 ml0.9% saline over 3 h. At baseline, 7 and 21 days the followingparameters were evaluated: ESR, CRP, RI, as indices of RAactivity; urinary excretion of free deoxypyridinoline (Dpyr, ELISA),N-telopeptide of type I collagen (NTx, ELISA), and hydroxyproline(OHP, colorimetric method) ± corrected for creatininuria ± asindices of bone resorption. Statistical analysis (repeated mea-sures ANOVA) of the data regarding DPyr, NTx, and OHP wasperformed comparing mean percentage variations vs baselinevalues, whereas that of the data regarding ESR, CRP and IR wasperformed comparing mean variations vs baseline values. At day7, in the N 25 mg group a signi®cant decrease of ESR was


observed vs the N 50 mg group (p = 0.003), and a signi®cantdecrease of CRP was observed vs both the placebo (p = 0.012)and N 50 mg groups (p = 0.017). At day 7, in the N 25 mg and N 50mg groups signi®cant decreases of NTx and OHP excretions wereobserved vs the placebo group (p = 0.001 and p = 0.002, respec-tively, for NTX; p = 0.001 and p = 0.004, respectively, for OHP). Atday 21, in the N 50 mg group the difference of OHP excretion vsthe placebo group was still signi®cant (p = 0.014). Therefore, wecan conclude that in pts with active RA a single infusion of N: 1.exerts at the dose of 25 mg a transient anti-in¯ammatory effect,as shown by the signi®cant reduction at day 7 of ESR and CRP; 2.exerts a signi®cant inhibition of bone resorption; 3. reducespreferentially the urinary excretion of NTx with respect to DPyr.Repeated single infusions of N (e.g. every 3 weeks) may helpcontrol disease and prevent generalized osteoporosis in RApatients.

498 (462). THE CLINICAL UTILITY OF NNT TO REDUCEFRACTURES

M. R. McClung, D. E. Thompson, 1Oregon Osteoporosis Center,Portland, OR; 2Merck Research Laboratories, Rahway, NJ, USA

NNT is a popular expression of the effectiveness of therapeuticinterventions. NNT is the number of patients that must be treatedfor a de®ned interval to prevent the occurrence of a singlediscreet clinical event such as fracture. Appropriate use of NNTrequires an understanding of its determinants ± the incidence ofevents in the control group (%) and the relative risk (RR) of theevent with therapy, expressed as follows: NNT=1/ (% x (1 ± RR)).NNT is signi®cantly in¯uenced by both the effectiveness of thedrug (RR reduction) and the fracture incidence in the patientstreated. When the reduction in RR is similar, NNT is determinedsolely by the risk attributes of the population treated such asBMD, age and presence of fractures (data in table). The sameNNT (40) can be achieved in a relatively low risk population (%=5)with a very effective therapy (RR=0.5) or with a less effectivetreatment (RR=0.9) in a higher risk population (%=25). Thus, NNTcan be used to compare the effectiveness of treatments only ingroups of patients in whom risk is identical. The cost-effective-ness of treatment for osteoporosis can be calculated and speci®cgroups of patients can be selected for therapy if NNT is usedappropriately.

Reduction in Vertebral Fracture Risk

% control % treated RR NNT

FIT Vert fx arm 15 8 .53 15FIT Clin fx arm 3.8 2 .56 60

499 (463). ESTRADIOL MATRIX TRANSDERMAL SYSTEM(VIVELLE) IN THE PREVENTION OF POSTMENOPAUSAL BONELOSS

C. D. McKeever, The Novartis Menopause Study Group , HealthAdvance Institute, Houston, TX, USA

The purpose of this multicenter, randomized, modi®ed double-blind, placebo-controlled, parallel-group study was to evaluatethe safety and ef®cacy of the estradiol matrix transdermaltherapeutic system (Vivelle1) in the prevention of postmenopau-sal bone loss.

Methods. 261 postmenopausal women were randomized toapply the estradiol matrix transdermal system (Vivelle1) (0.025mg/d, 0.0375 mg/d, 0.05 mg/d, or 0.1 mg/d) or matching placebotwice a week for 2 years.

Results. Following 2 years of treatment, all doses of Vivelle1

produced a signi®cant difference at 0.05 signi®cance level when

compared to placebo with respect to percent change frombaseline in bone mineral density of the L1-L4 AP lumbar spine (0.1mg/d and 0.05 mg/d, P<.001; 0.0375 mg/d, P=.024; 0.025 mg/d,P=.002). Percent changes from baseline in bone mineral densityof the femoral neck and total body bone mineral content following2 years of treatment also consistently supported the ef®cacy ofthe estradiol matrix transdermal system when compared toplacebo (All P<.044). The estradiol matrix transdermal systemwas well tolerated. The most common drug-related adverseevents were vaginal bleeding and breast pain.

Conclusion. The estradiol matrix transdermal system (Vivelle1)at doses 0.025 to 0.1 mg/day effectively prevents postmenopau-sal bone loss, and has a safety pro®le consistent with the knowneffects of estrogen/progestin.

500 (464). PAMIDRONATE IS EFFECTIVE IN THE TREATMENTOF OSTEOPOROSIS IN MEN DUE TO SYSTEMICMASTOCYTOSIS: A PROSPECTIVE, CONTROLLED STUDY

H. W. Minne1, A. D. Lazarescu1, M. Pfeifer1, D. Lazarescu2, G.Delling3, 1Clinic ``DER FUERSTENHOF'' Bad Pyrmont; 2TechnicalUniversity of Berlin, Berlin, Germany; 3University of Hamburg,Hamburg, Germany

A severe osteoporosis (OPO) with multiple spontaneous vertebralfractures and severe bone pain are often the only manifestation ofa mast cell in®ltration in the bone marrow. Previous data showthat the prevalence of mastocytosis (MASTO) is quite low, but itscorrect diagnosis could be crucial for at least 1% of all patientwith OPO. Bone turnover in MASTO is not always increased,urinary excretion of histamine metabolites could be elevated.Urticaria pigmentosa is not usual. We diagnosed MASTO in 6 menwith severe OPO using transiliac bone biopsy and skin biopsy.They were treated with 60 mg pamidronate intravenously everythree months over 3 years and 1000 mg of calcium and 1000 I.Uvitamin D per day. Bone mineral density (BMD) was measuredbefore and after treatment (QDR 2000, Hologic, USA).

Results are presented in Table 1:

Mean age at diagnosis (years): 48.57�8.18Time between diagnosis of OPO and MAST (years): 2.43�2.23Mean loss of height (cm): 5.67�1.97Presence of urticaria pigmentosa (%): 28.57BMD spine at diagnosis of MASTO (g Ca/cm2): 0.71�0.11BMD spine after pamidronate therapy (g Ca/cm2): 0.75�0.19*BMD femoral neck at diagnosis of MASTO (g Ca/cm2): 0.71�0.11BMD femoral neck after pamidronate therapy (g Ca/cm2): 0.74�0.16*Vertebral fractures at diagnosis of MASTO (no.): 7.43�1.72Vertebral fractures after pamidronate therapy (no.): 7.52�1.78

(*p<0.01 signi®cantly dierent before and after treatment)

In middle aged patients with severe OPO a transiliac bonebiopsy should be performed to exclude MASTO. Three years oftreatment with intravenous pamidronate increase BMD at thelumbar spine and femoral neck and stops fracture progression inpatients with severe OPO due to MASTO.

501 (465). ANTIFRACTURE EFFECT OF HORMONEREPLACEMENT THERAPY ± A 5 YEAR COMPREHENSIVECOHORT STUDY IN 2,000 PERIMENOPAUSAL WOMEN

L. Mosekilde, P. Vestergaard, H. B. Nielsen, S. P. Nielsen, O. H.Sùrensen, The Danish Osteoporosis Prevention Study Group,Aarhus University Hospital, Aarhus, Denmark

Background: We aimed at studying the fracture reducingpotential of hormonal replacement therapy (HRT) in recentpostmenopausal women in a primary preventive scenario.


Methods: Prospective controlled comprehensive cohort trial.2,016 healthy women aged 45±58 years from 3 to 24 months pastlast menstrual bleeding were recruited from a random sample ofthe background population. Mean age was 50.8�2.8 years, andthe number of person years followed was 9,335.3. There were twomain study arms: a randomised arm (randomised to HRT [n=502]or not [n=504]) and a non-randomised arm (on HRT [n=221] or not[n=789] by own choice). First line HRT was oral sequentialoestradiol/norethisterone in women with intact uterus and oralcontinuous oestradiol in hysterectomised women.

Results: After ®ve years, a total of 156 fractures were sustainedby 140 women. There were 51 forearm fractures in 51 women. Byintention to treat analysis, overall fracture risk was borderlinestatistically signi®cantly reduced (RR=0.73, 95% CI: 0.50±1.05),and forearm fracture risk was signi®cantly reduced (RR=0.45,95% CI: 0.22±0.90) with HRT. Restricting the analysis to womenwho had adhered to their initial allocation of either HRT (n=395) orno HRT (n=977) showed a signi®cant reduction in both the overallfracture risk (RR=0.61, 95% CI: 0.39±0.97) and the risk of forearmfractures (RR=0.24, 95% CI: 0.09±0.69). Compliance with HRTwas 65% after ®ve years.

Conclusion: It is possible to reduce the number of forearmfractures and possibly the total number of fractures in recentpostmenopausal women by use of HRT as primary prevention.

502 (466). MODULATION OF SKELETAL AND CALCIUMMETABOLISM IN ELDERLY WOMEN ADMINISTEREDALFACALCIDOL

K. Nakatsuka, S. Saito, H. Naka, T. Miki, Y. Nishizawa, H. Morii,Osaka City University, Osaka, Japan

Although administration of active forms of vitamin D3 amelioratePTH-mediated bone resorption and modulate bone turnover inthe elderly, little is known on its actions on skeletal metabolismassessed by bone-speci®c biochemical markers. Enrolled were in16 elderly women receiving orally 1 mg of alfacalcidol (1 a (OH)D3:AlfarolTM, Chugai, Tokyo) a day. Blood and urine samples wereobtained at baseline and 1, 4, 12 and 24 week following theinitiation of 1 a (OH)D3 administration for biochemical measure-ments. Serum 1,25 (OH)2D were signi®cantly increased by 44.9%at 1 Week and returned to the values at baseline. Serum intact-PTH levels decreased by 13.2% and 27.8% at 1 Week and 12Week respectively. Although bone formation markers includingosteocalcin and bone-speci®c ALP had a tendency to increasefrom baseline values at 1 Week and decrease afterwards. Urinarydeoxy-pyridinoline and type I collagen c-telopeptide, weredecreased signi®cantly by 11.7% and 12.5%, respectively, at 12Week compared to the baseline levels and were signi®cantlycorrelated with the changes in intact-PTH levels at 12 Week. Bothserum Ca levels and urinary Ca excretion were found signi®cantlyelevated but remained within reference ranges over time. Inconclusion, 1 a (OH)D3 directly activate bone metabolismtransiently in vivo as seen in vitro. Long-term use of 1 a (OH)D3attenuates bone formation and improves high bone resorptionthrough suppression of parathyroid function in the elderly.

503 (467). EFFECTS OF RALOXIFENE ON COGNITIVEFUNCTION IN POSTMENOPAUSAL WOMEN WITHOUTDEMENTIA

T. Nickelsen1, K. Yaffe2, K. A. Krueger1, S. Sarkar1, D. A. Cox1,1Lilly Research Laboratories, Indianapolis, In; 2UCSF, SanFrancisco, CA

Background: Raloxifene (RLX) is a selective estrogen receptormodulator (SERM) for prevention and treatment of postmeno-pausal osteoporosis. Several studies suggest that estrogen mayimprove cognition in postmenopausal women, but it is unclearhow SERMs impact cognitive function. We assessed the effect of

RLX on cognition in older women. Design: 7705 osteoporoticpostmenopausal women (mean age, 67 years) enrolled in theMultiple Outcomes of Raloxifene Evaluation study, were rando-mized to placebo or RLX (60 mg or 120 mg) daily for 3 years. Sixcognitive tests were administered at baseline, 6, 12, 24, and 36months. Cognitive decline was de®ned as present in womenwhose 3-year change in score was in the worst 10th percentile.Results: Baseline characteristics did not differ between treatmentgroups. Mean cognitive scores did not worsen over the 3 yearsand were similar between treatment groups. There were fewerwomen on RLX than on placebo who developed cognitive declineon Trails A (8.2% vs 9.4%, P=0.09) and on Word List Recall (4.5%vs 5.9%, P=0.05); no differences were observed for the othertests. Among women at greater risk for cognitive decline (age >70years), those assigned to RLX performed better compared toplacebo after 3 years on Trails A (52 vs 54 sec; P=0.009) and onWord List Recall (7.6 vs 7.4; P=0.016). No treatment differences inscores were noted among women 470 years. Reporting of hot¯ushes did not in¯uence the effect of treatment on testperformance (P50.3). Conclusion: RLX for 3 years does notaffect overall cognitive scores in osteoporotic but otherwisehealthy postmenopausal women. RLX may lower the risk ofdecline in attention and memory, and may improve attention andverbal memory performance in women >70 years old.

504 (468). EFFECTS OF BLACK COHOSH ON URINARY BONEMARKERS AND FEMORAL DENSITY IN AN OVX-RAT MODEL

T. Nisslein, J. Freudenstein, Schaper & Bruemmer, Salzgitter,Germany

The purpose of this study was to investigate potential bene®cialeffects of a herbal preparation traditionally used for alleviatinggynecological disorders on osteoporosis-like changes observedin a gonadectomy rat model. 3 groups of 10 ovariectomized(ovx) female Sprague Dawley rats were used, the ®rst of whichreceived a standardized isopropanolic extract of rhizomacimicifugae racemosae (iCR). The animals of the second groupwere treated intragastrically with raloxifene (RAL), whereas thoseof the third group received no treatment at all. Weekly 24h-urinesamples were collected for HPLC-quanti®cation of parametersof bone metabolism pyridinoline (PYR) and deoxypyridinoline(DPD). At necropsy femoral density was calculated frompycnometer measurements according to Archimedes' principle.In the untreated animals, PYR and DPD excretion declined byapprox. 30% until 5 weeks after ovx but remained stablethereafter. In the RAL treated animals PYR and DPD dropped by>50% within two weeks. After 3 weeks iCR treatment urinaryPYR and DPD levels were comparable to those of RAL treatedanimals and for a time also signi®cantly (Student's t-test,p<0.05) lower than those of untreated control animals. Meanfemoral density in the control group was reduced whencompared to the RAL (statistically signi®cant) or the iCR(statistically not signi®cant) treated animals. The results pre-sented here clearly demonstrate that iCR has an inhibitorypotential on hormone regulated bone resorption. The traditionaluse of this preparation against hormone-de®ciency symptoma-tology lets one speculate whether this effect might be mediatedvia SERM pathways.

505 (469). THE EFFECT OF ALENDRONATE TREATMENT ONURINARY CALCIUM EXRETION IN WOMEN WITHPOSTMENOPAUSAL OSTEOPOROSIS

M. OchodnickyÂ 1, E. OchodnickaÂ 2, P. Galajda1, L. VlaÂ dar1, M.MokaÂ nÄ 1, 1Jessenius Faculty of Medicine, Department of InternalMedicine 1, 2Department of Histology and Embryology, ComeniusUniversity, Martin, Slovak Republic

The ef®cacy of aminobisphosphonate alendronate sodium in thetreatment of postmenopausal osteoporosis is well documented.


Much less attention has been devoted to changes in calciummetabolism during alendronate treatment.

A group of postmenopausal women (aged 50±70 years, at least5 years postmenopausal with BMD [Osteometer 200] T-scoregreater than 2.5 SD below the mean) was enrolled in this study.

During the treatment period 10 mg of alendronate sodium wasadministered orally. All patients received 1 250-1500 mg ofelemental calcium and 800 I.U. of cholecalciferol daily.

The urinary calcium excretion was assessed before treatmentand after 4 months and 1 year treatment with alendronate sodium.

No signi®cant changes in serum calcium and immunoreactivePTH were noted during the treatment.

There was statistically signi®cant decrease in urinary calcium/creatinine ratio (Nordin's index) and calcium excretion/GFR afterone year treatment with alendronate as compared with pretreat-ment values. This signi®cant decrease in urinary calciumexcretion occurred despite the supplementation of calcium andcholecalciferol.

506 (470). SMALL LOCAL DENSITY CHANGES INCREASE THEFAILURE LOAD OF OSTEOPENIC AND OSTEOPOROTICFEMURS

Z. M. Oden, W. Wang, D. M. Selvitelli, M. L. Bouxsein, 1Univ. ofTX-Houston Med. School, Houston, TX, USA; 2Beth IsraelDeaconess Medical Center, Boston, MA

The approved therapies for are pharmacologic agents that actsystemically. In this study, we evaluated the feasibility ofpreventing hip fractures with a local rather than systemic therapy.Our hypothesis is that a local therapy that increases bone densitymay be as effective at reducing fracture risk as a systemictherapy. The goal of this investigation was to use ®nite elementanalyses to study the effect of a local increase in bone density onthe human femur. Two models were generated to representosteoporotic and osteopenic femurs (t=±3.1 and ±1.6). The loadsrequired to break a femur in a fall to the side were predicted afterincreasing the bone density within small regions in the proximalfemurs. In the osteoporotic bone, increasing the density by 25%relative to the baseline values in a small region (0.86 cm3) of thefemoral neck increased the failure load by 6.2%. The samedensity increase in a much larger region (4.92 cm3) increased thefailure load by 15%. In comparison, a global 5% density increaseincreased the failure load by 5.2%. The in¯uence of augmentationon the failure load was less dramatic in the osteopenic bone.Augmenting a small (~0.81 cm3) region by 25% resulted in a 2.3%increase in failure load. The maximum failure load increase (4.7%)was with the large (~5cm3) region of augmentation. These®ndings suggest that agents capable of inducing increasedbone density in small, localized regions of the proximal femurhave the potential to reduce hip fracture risk. The bene®t of alocal bone-forming agent to protect the femur against fractureappears to be more potent in more severely osteoporotic femurs.

507 (471). EFFECTS OF THE SELECTIVE ESTROGENRECEPTOR MODULATOR, RALOXIFENE ON CALCIUM-PTHHOMEOSTASIS

A. Oleksik1, T. Duong2, C. Popp-Snijders1, N. Pliester1, G. Asma1,P. Lips1, 1Academic Hospital, Vrije Universiteit, Amsterdam, NL;2UCSF, San Francisco, USA

Estrogen and the selective estrogen receptor modulator (SERM),raloxifene may maintain bone mass by interacting with calcio-tropic hormones. We studied effects of raloxifene on calcium-PTH homeostasis. This was done in the third year of the MORE(Multiple Outcomes of Raloxifene Evaluation) trial, a double-blind,placebo (PBO) controlled study in postmenopausal women withosteoporosis. After an overnight fast, calcium glubionate (5 mg/kgBW*hour) was given intravenously, and 2� hour later, Na3EDTA(40 mg/kgBW*hour) was infused. The duration of infusions was

based on baseline total calcium, the target calcium (2.60 and 1.95mmol/l), and calcium change (0.010 mmol/l*min). Blood sampleswere taken at 0 and every 5 min of both infusions. Parathyroidfunction was ®tted into inversed sigmoidal relation betweencalcium and PTH. Differences were tested using linear regressionadjusted for age and BMI. Raloxifene (RLX) was associated withlower serum albumin (Alb), total calcium at baseline (Ca) and at50% of PTH maximal secretion (SP=set-point), and lower non-suppressible PTH (Pmin, pmol/l). After correction for Alb, thedifferences in Ca and SP were no longer signi®cant. In contrast,Pmin may play a role in the bone-protective action of raloxifeneby increasing the effectiveness of calcium supplements.

(N) PBO (9) RLX60 (13) RLx120 (10) p

Alb,g/l 40.7�1.8 38.0�2.0 38.5�2.3 0.01Ca,mmol/l 2.28�0.07 2.24�0.07 2.21�0.07 0.03SP,mmol/l 2.23�0.06 2.18�0.07 2.16�0.08 0.06Pmin 0.85�0.19 0.75�0.10 0.74�0.05 0.02

508 (472). EFFECTS OF THE SELECTIVE ESTROGENRECEPTOR MODULATOR ± RALOXIFENE ON IGF1-GH ANDINSULIN-GLUCOSE HOMEOSTASIS

A. Oleksik1, T. Duong2, N. Pliester1, G. Asma1, C. Popp-Snijders1,P. Lips1, 1Academic Hospital Vrije Universiteit, Amsterdam, NL;2UCSF, San Francisco, USA

Besides a direct action on bone, the selective estrogen receptormodulator (SERM), raloxifene may act via changes in hormonalhomeostasis. We investigated effects of raloxifene on the GH-IGF1, and insulin-glucose homeostasis during the third year of theMORE (Multiple Outcomes of Raloxifene Evaluation) trial, adouble blind, placebo controlled study in postmenopausalwomen with osteoporosis. This additional protocol was per-formed in 32 participants without diabetes mellitus, aged 67�7years. A fasting blood sample was obtained (7:30 to 9:00 a.m.)and women received a subcutaneous injection of human GH(Humatrope, 0.05 mg/kgBW). The second blood sample wasobtained 24 hours later. The differences were tested using linearregression after adjustment for age and BMI. In comparison towomen treated with placebo (PBO), patients using raloxifene(RLX) had higher BMI (kg/m2; p = 0.03), but lower baseline andGH-stimulated IGF1/IGFBP±3 ratio (mU/mmol; p<0.01) andinsulin/glucose ratio (pmol/mmol; p = 0.04 and 0.07). Baselineand GH-stimulated glucose, GH and IGFBP±3 were similar. Inconclusion, raloxifene use is associated with decreased serumIGF levels without compensatory increase in serum GH levels.Raloxifene may improve glucose metabolism.

(N) PBO (N=7) RLX60 (N=16) RLX120 (N=9)

BMI 24.7�1.7 25.0�3.1 28.8�5.8IGF/IGFBP±3 (0) 4.3�0.7 2.9�0.7 3.0�0.7IGF/IGFBP±3 (24) 8.1�1.5 5.5�1.1 6.0�1.3Ins/glc (0) 13.7�5.2 11.9�5.9 9.5�2.3Ins/glc (24) 23.9�15.1 19.5�14.6 15.5�4.5

509 (473). BONE HISTOMORPHOMETRIC RESULTS OF A 2YEAR RANDOMIZED, PLACEBO CONTROLLED TRIAL OFRALOXIFENE IN POSTMENOPAUSAL WOMEN

S. Ott1, A. Oleksik2, Y. Lu3, K. Harper3, P. Lips2, 1University ofWashington, Seattle, WA; 2Vrije Universiteit, Amsterdam, TheNetherlands; 3Eli Lilly & Co, Indianapolis, IN,

Raloxifene (RLX) is a selective estrogen receptor modulator thatincreases bone density. The purpose of this study was to examine


the effects of RLX on bone histomorphometry and histologicsafety parameters. Data were analyzed from 65 postmenopausalwomen with osteoporosis from 2 European (n=26) and 2 US(n=39) sites in the double-blind, randomized MORE trial. Womenwere treated with placebo (PL) or RLX at 60 or 120mg/d, andthose who consented to a tetracycline-labeled bone biopsy wereincluded. Standard histomorphometric parameters were mea-sured in transiliac crest bone biopsies taken at baseline and at 2years. At baseline, there were no differences between treatmentgroups in age (range 51±79 years), percentage of prevalentfractures (~29%), or bone density. At least 94% of this subset ofwomen have taken 80% of the study medications. Wall andtrabecular thickness and mineralizing surface were differentbetween European and US sites and results shown for thosevalues are from the US. Bone formation rate (BFR) was decreased21% in PL, 28% in RLX60 and 62% in RLX120 (p = .03, PL vsRLX120). Similar percent decreases were seen in activationfrequency. Bone cells appeared normal and no ®brosis,osteomalacia, or other toxic effects were noted.

Median Change from Baseline

PL RLX60 RLX120

Bone volume/Tissue volume (%) ±0.39 ±0.79 ±1.83Trabecular thickness (mm){ 7.2 12.9 7.6Osteoclast number 0.17* 0.08 ±0.05Osteoid thickness (mm) 0.75* 1.03 0.34Osteoid surface/Bone surface (%) 1.1 ±0.3 ±2.5Wall thickness (mm){ 1.9 7.1 0.3Mineralizing surface/Bone surface (%) ±0.87 ±0.22 ±3.27*BFR/Tissue volume (%/yr) ±4.9 ±7.4* ±18.0*

*p<.05 from baseline; {Data from US sites only

510 (474). THE COMPARISON OF THE EFFECTS OFBISPHOSPHONATES AND CALCITONINE WITH DEXA INOSTEOPOROSIS

C. OztuÈ rk, S. HepguÈ ler, S. Eyigor, K. Capaci, H. Toprak, R. Aks,it,Ege University Medical Faculty Physical Therapy and Rehab.Dept., Izmir, Turkey

Aim of this study was to determine and to compare the effects ofalendronate, etidronate, calcitonine 50IU and 100IU in osteo-porosis. 138 patients with ages between 40±75 years wereincluded in the study. A questionnaire about patients' specialitieswas given. According to DEXA, rutine blood, urine, liver functionaltests, alkalene phosphotase, urea, creatinine, serum calcium andphosphorus, urine calcium, deoxypyridinoline as bone markerswere investigated for all patients with the diagnosis ofosteoporosis. To 68 patients alendronate 10 mg, to 25 patientsdidronate 400 mg, to 25 patients calcitonine 100IU and to 23patients calcitonine 50IU were given. In DEXA tests at 12th month,signi®cant density increase was obtained in lumbar vertebrae,femoral neck and trochanter of alendronate group, in lumbarvertebrae, femoral trochanter and wards triangle of didronategroup and in only lumbar vertebraes of calcitonine 50IU group.There was found to be no density change in any area incalcitonine 100IU group. There was no statistically meaningfuldifference in all groups in regards of percentage change in bonemineral density per year except the calcitonine 100IU group.

511 (475). EFFECT OF PAMIDRONATE, TESTOSTERONE,VITAMIN D AND CA IN A PATIENT WITH KALLMANNSYNDROMEG. M. A. Palmieri, P. Whittle, D. McCommon, The West andCampbell Clinics, Memphis, TN, USA

Kallmann syndrome (absence of Gn RH, anosmia or hypo-osmia)may be associated with bone loss (Taylor H, Obstet Gynecol,

1996). A 64-year-old African American male fractured the rightfemur, left tibia and right humerus in a car accident. Duringsurgery reduced consistency of the bones was noticed. Themedical history revealed arterial hypertension and anosmia but noprior fractures. Serum ionized Ca 4.79 mg/dl (4.5±5.3); bonealkaline phosphatase (BA) 66.1 mg/L (5.9±22.9) total (t) and free (f)testosterone (T) 39 ng/ml (200±700) and 1.1 pg/ml (9±31)respectively; prolactin 5.3 ng/ml (3±20); FSH <0.4 mlU/ml (1±10);LH <0.5 mlU/ml (2±9); Calcidiol (D) 12.9 ng/ml (10±55). Urinary Ca(UCa) 46 mg/24h (100±300). X-rays showed compression of mostend plates of dorsal and lumbar vertebrae. DEXA T scores:Femoral neck (FN) ±2.8, Total femur (TF) ±3.5, Lumbar spine (LS)74.1. After 1 y treatment with pamidronate 60 mg iv every 6 mo.,Depo-Testosterone 200 mg im every 3 weeks, vitamin D 50 000 Uonce a week and Ca 1500 mg/d, the patient felt better andstronger. Serum BA was 34.1 mg/L; D 42 ng/ml; t T 180 ng/dl, f T5.9 pg/ml; UCa 81 mg/24h. DEXA per cent changes at 6 and 12mo were: FN +24, +25; TF +25, +33; LS +32, +48. This observationsuggests that the combination of pamidronate + testosterone +vitamin D + Ca was effective in spite of only partial correction ofhypogonadism. The dramatic DEXA improvement could suggesta component of osteomalacia in addition to osteoporosis in thispatient.

512 (476). FOSAMAX IN TREATMENT OF POSTMENOPAUSALOSTEOPOROSIS AND ITS COMPLICATIONS

V. V. Povoroznyuk1, P. I. Nykonenko1, F. Atarchuk2, 1Institute ofGerontology, S Ukraine; 2Institute of Pediatrics, Obstetrics andGynecology, S Ukraine

Bisphosphonates is a new class of medicaments having apronounced antiresorptive effect on bone tissue. Fosamax(alendronate sodium, trademark of MSD) is an amino-bispho-sphonate acting as a powerful and speci®c inhibitor of osteoclast-induced resorption of bone tissue. To study the ef®cacy ofFosamax in the treatment of post-menopausal osteoporosis andits complications (vertebrae fractures) 25 women aged 56±75years (mean age ±63.6�1.2 years) were examined. Osteoporosisand its complications was diagnosed by means of ultrasound androentgenography of thoracic and lumbar spine. 11 patients(44.0%) had vertebrae fracrures of a clinoid deformity type andcompression. To evaluate structural-functional state of bonetissue ultrasound densitometer «Achilles+» (Lunar Corp., Madi-son, WI) was used. Speed of ultrasound spreading (SOS, m/sec),broadband ultrasound attenuation (BUA, dB/MHz) and Stiffnessindex of bone tissue (SI, %) were determined. Fosamax wasprescribed in a dose of 10 mg, in the morning, on an emptystomach, 1/2 hour before the meal. Ultrasonometry, evaluation ofpain syndrom's promouncement were carried out in 1, 3, 6, 12months from the beginning of treatment 25 patients (I group) weretaking the drug for 3 months, 17 patients (II group) were taking itfor 6 months, 11 patients (III group) were taking it for 1 year.Patients ceased taking drug because of ®nancial dif®culties andnot because of absence of effect or side effect. 9 women takingFosamax for 1 year were examined in 12 months after the end oftreatment (they were included in the IV group). Fosamaxconsiderably reduced the pronouncement of pain syndrome andgreatly improved structural-functional state of bone tissue: Igroup ± SOS (before treatment ±1513�4 m/sec; in 3 months71514 m/sec); BUA (before treatment ±91.0�2.1 dB/MHz; in 3months ±93.4�2.2 dB/MHz); SI (before treatment ±64.5�2.1%; in 3months ±66.5�2.3%); II group ± SOS (before treatment ±1512�6m/sec; in 6 months ±1514�6 m/sec); BUA (before treatment790.4�2.5 dB/MHz; in 6 months ±96.8�3.2 dB/MHz; p = 0.019); SI(before treatment ±64.0�3.0%; in 6 months ±68.7�2.9%;p = 0.012); III group ± SOS (before treatment ±1516�7 m/sec; in12 months ±1518�6 m/sec); BUA (before treatment ±91.9�2.5 dB/MHz; in 12 months ±99.5�2.8 dB/MHz; p = 0.030); SI (beforetreatment ±66.2�3.1%; in 12 months ±71.2�2.7%; p = 0.036); IVgroup ± SOS (before treatment ±1522�8 m/sec; in 12 months


71525�8 m/sec; in a year after the end of treatment ±1516�10 m/sec); BUA (before treatment ±90.0�2.2 dB/MHz; in 12 months799.4�2.9 dB/MHz; in a year after the end of treatment ±97.6�4.5dB/MHz; p<0.05 compared to the parameter before treatment); SI(before treatment ±66.8�3.2%; in 12 months ±73.1�2.6%; in a yearafter the end of treatment ±69.6�4.3%).

Results of our studies show Fosamax's ef®cacy in treatment ofpostmenopausal osteoporosis and its complications. The druginoreases bone mineral density, improves its solid characteristicswhich is followed by a considerable decrease of a painsymdrome's pronouncement and increase in functional abilitiesof patients.

513 (477). POSTURAL STABILITY OF POSTMENOPAUSALWOMEN ACCORDING TO HABITUAL PHYSICAL ACTIVITY ANDMENOPAUSAL HORMONE REPLACEMENT THERAPY USE

G. M. Prelevic1, K. Brooke-Wavell2, C. Bakridan3, J. Ginsburg1,1Dept Medicine, Royal Free & University College London MedicalSchools, UK; 2Dept Human Sciences, Loughborough University,UK; 3School of Biosciences, University of Westminster, UK

This study examined whether body sway and muscular strengthdiffered according to physical activity or menopausal hormonereplacement therapy (HRT) use in postmenopausal women.Subjects were 70 women had been on HRT for >5y, (42 ontibolone and 28 on transdermal oestrogens) and 45 women whohad not taken HRT. Physical activity duration was estimated from3 day accelerometer recordings and subjects divided into highand low physical activity groups by median split. Postural stabilitywas assessed using a simple swaymeter. Maximal isometric knee¯exor strength was determined in 23 tibolone, 26 transdermal and12 no therapy subjects.

Body sway was lower in more physically active women (p<0.05)and this effect persisted after inclusion of age as a covariate.Muscular strength did not differ signi®cantly according tophysical activity participation. Body sway tended to be lowerand muscular strength higher in groups receiving HRT, althoughthese differences were not statistically signi®cant. More physi-cally active postmenopausal women had signi®cantly betterpostural stability, whilst HRT did not have signi®cant effect.Physical activity might thus reduce risk of fractures by reducingfall risk.

514 (478). THE UV b LIGHT EXPOSURE FROM FLUORESCENTLAMP TO HYPOESTROGENIC MACACA FASCICULARIS FORBONE REMODELING

I. A. Rachman, Immuno-endocrinology Reproduction Sub-division, Department of Obstetrics and Gynaecology Faculty ofMedicine, University of Indonesia/Cipto Mangunkusumo Hospital,Jakarta, Indonesia

ABSTRACT: The need of UV b (ultraviolet Beta) light exposurefrom sun for vitamin D3 skin production and calcitriol productionfrom kidney has already known. Limited of UV b sun exposuremean low calcitriol and low bone mineralisation. If it happened toreproductive woman till premenopause woman will induce theosteopenia and osteoporosis sooner. The UV b light exposurefrom ¯uorescent lamp with emanates UV b rays equivalent to theUV b rays of the sun (290 ± 390 nm) has already been use asphototherapy againt psoriasis by using the vitamin D3 producedfrom skin. Would the exposure to UV b rays from ¯uorescentlamps apart from increasing the production of vitamin D3 by theskin also increase the calcitriol content and induce osteoblastactivity? We prepare 3 group of Macaca fascicularis, group I (E0)with normal estrogen, group II (E1) with beginning low estrogenand group III (E2) with beginning very low estrogen. All group wedevided to two sub group, the ®rst subgroup we expose the UV blight from ¯uorescent lamp, and the second subgroup no UV b

light expose. After six month of UV b exposure from the ®rstsubgroup of Macaca fascicularis with normal estrogen, lowestrogen and very low estrogen wefound calcitriol, osteocalcinand DPD still or normal level. But for the other subgroup ofMacaca fascicularis with no UV b exposure calcitriol level,osteocalcin level become low (out of the lowest normal range) itmean to that the osteoblast activity (bone formation) became lowand DPD still in normal level it mean the osteoclast activity (boneresorption) still normal, in this condition osteopenia will happen tothe bone while estrogen level still normal and menstruation stillhappen. In UV b exposure group from Macaca fascicularis withnormal estrogen level, beginning low estrogen level andbeginning very low estrogen level the activity of osteoblast(bone formation) and activity of osteoclast (bone resorption) stillin normal range. So UV b exposure from ¯uorescent lamp canprotect bone from low osteoblast activity (low bone formation)specialy in beginning low and very low estrogen level (same withpremenopausal stage). This inform that estrogen hormonecombine with calcitriol hormon still need in postmenopauseosteoporosis therapy.

515 (479). N TELOPEPTIDE AND BONE ALKALINEPHOSPHATASE DURING ONE YEAR TREATMENT WITHTIBOLONE

G. Riera-Espinoza, J. Ramos, R. Carvajal, E. Belzares, G.Stanbury, R. FariaÂ s, G. Riera GonzaÂ lez, Universidad deCarabolso, Hospital Universitario Angel Larralde, Valencia,Venezuela

Inhibition of bone resoprtion is the goal of any osteoporosistreatment in the early post menopausal period. There are a fewreports about the value of N-telopeptide and Bone AlkalinePhosphatase during tibolone therapy, ad this is the objective ofthis study.

A total of 36 women with more than a year of menopause wereenrolled to receive tibolone (Livial) 2.5 mg/day on a continuosbasis. Exclusion criteria included: patient exceeding 30% of ideal


weight, previous fractures from minor trauma, use in the last 12months of anabolic steroids, glucocorticoids, calcitonin, vitaminD, biphosphonates, thyroid hormones, antiepileptic drugs or HRT.Patients with diseases known to affect mineral metabolism,alcohol or smoking habits.

Bone markers Total Alkaline Phosphatase (UI/L.TAP. Labtest),Bone-speci®c Alkaline Phosphatase (UI/L. BAP. Enzyme Inmu-noassay. Alkphase-B, Metra Biosystems. USA). Tartrate ResistantAcid Phosphatase (UI/L. TRAP Paranitrophenylphosphate hydro-lysis at 4.8 pH) and N-telopeptide (nmolBCE/mmolCreat. EnzymeInmunoassay. NTx. Osteomark. Ostex. USA.) were measured atbaseline, 3, 6 and 12 months.

NTx values diminished progressively during 12 month periodfrom 74.39�30.7 to 36.1�2.7 (p50.001 vs. basal) as BAP from36.67�15.7 to 22.7�1.5 (p50.001 vs. basal). On the contrary TAPdidn't change (TAP: 37.7�13.8 vs 31.4�2.3, p = ns vs. basal). TRAPdiminished just at 12 months: 9.8�0.4 vs 8.2�0.4 (p<0.01 vs.basal)

The use of tibolone 2.5 mg/day progressively inhibit boneturnover expressed by decrease in speci®cs formation andresorption markers like Bone Alkaline Phosphatase (Alkphase-B)and N-telopeptide (NTx). Progresive change were ±32.3%,742.6% and ±51.5% for NTx and ±25.5%, ±28.2% and ±37.8%for BAP at 3, 6 and 12 months respectively.

516 (480). LOW TURNOVER TYPE I POST MENOPAUSALOSTEOPOROSIS TREATED WITH NANDROLONE DECANOATE25 MG IM/ EVERY 3 WEEKS FOR TWO YEARS

G. Riera-GonzaÂ lez, T. Ortega, R. Peralta, M. Manzo, G. Riera-Espinoza, J. Ramos, J. Molina, Universidad de Carabolso,Hospital Universitario Angel Larralde, Valencia, Venezuela

Anabolic steroids have been used for osteoporosis treatment.Nandrolone Decanoate (ND) does not have the androgenic effectsas testosterone does. Side effects include lipid problems, hoarsevoice, virilazing signs and hirsutism. The aim of the study was toevaluate the effect of 25 mg IM/ every 3 weeks ND on LowTurnover Type I Osteoporosis.

39 patients, age 61.2�6.9 year, age of menopause 45.5�6.2year, with Type I Osteoporosis whose bone markers were withinthe normal range (mean�1SD) received ND 25 mg IM/ every 3weeks for 2 consecutive years. Exclusion criteria included: patientexceeding 30% of ideal weight, use in the last 12 months ofglucocorticoids, calcitonin, vitamin D, biphosphonates, thyroidhormones or antiepileptic drugs. Patients with diseases known toaffect mineral metabolism, alcohol or smoking habits. BMD wasmeasured by DEXA (LUNAR. DPX) basal, 1 and 2 years. Bonemarkers Total Alkaline Phosphatase (UI/L.TAP. Labtest), TartrateResistant Acid Phosphatase (UI/L. TRAP. Paranitrophenylpho-sphate hydrolysis at 4.8 pH) and N-telopeptide (nmolBCE/mmolCreat. Enzyme Inmunoassay. NTx. Osteomark. Ostex.USA.) were measured at baseline, 3, 6, 12 and 24 months.Trabecular bone estimated at lumbar spine (L2-L4 BMD)improved progressively in 36 out of 39 patients: 0.929�0.01,0.954�0.02, 0.974�0.02 (p<0.01) at 1 and 2 years, T-scorechanged from ±2.26�0.13 to ±2.02�0.21 and ±1.79�0.4 at 1 and2 years (p<0.001 for both vs. basal). Cortical bone measured atfemoral neck also improved specially at 1 year with no furtherincrease at the 2nd year: 0.781�0.01 basal, 0.799�0.02 and0.789�0.02 (p<0.01 for both vs basal). T-score values basal, 1and 2 years at femoral neck were ±2.26�0.13, ±2.02�0.21 and71.79�0.4 (p<0.001 for both vs basal).

As these patients had low bone turnover we did not expectedchanges in bone markers. In generally bone markers did notchange, however there was a discrete decreased in TRAP at 6and 12 months and in TAP at 6 months (p<0.05 for both markersvs basal). We did not observed signi®cant side effects at thisdose.

In conclusion the use of 25 mg IM/every 3 weeks in postmenopausal patients with Low Turnover Type I Osteoporosisimproved progressively Bone Mineral Density in 92.3% of themduring a two year treatment period without signi®cant sideeffects.

517 (481). ALENDRONATE TREATMENT OF ESTABLISHEDPRIMARY OSTEOPOROSIS IN MEN: TWO YEAR RESULTS OF APROSPECTIVE COMPARATIVE TWO-ARM STUDY

J. D. Ringe, A. Coster, A. Dorst, R. Umbach, Medizin. Klinik 4,Klinikum Leverkusen, Univ. of Cologne, Germany

Male patients with osteoporosis have been neglected in the pastand so far only few therapeutic trials have been performed insolely male patient groups. Especially with bisphosphonatesthere is little therapeutic experience documented in literature.

In a prospective controlled two arm trial we are studying theeffect of alendronate in comparison to alfacalcidol in men withestablished primary osteoporosis. 134 males (average T-scorelumbar spine BMD ±3.38; 72 with, 62 without vertebral fractures)are treated either in group A (n=68, mean age 52.7 years) with10mg alendronate plus 500mg calcium or in group B (n=66, meanage 53.3 years) with 1mg alfacalcidol plus 500mg calcium. Ingroup A the initial T-score value of lumbar spine BMD was ±3.42and at the femoral neck ±2.53. The corresponding values in groupB were ±3.35 and ±2.56 respectively.

During the two years of observation both regimens were welltolerated without major side effects or drug-related drop outs. Inboth groups a signi®cant decrease in back pain was observedover the 24 months of follow up. The average increases of lumbarspine BMD after 24 months amounted to +10.1% in group A and+2.8% in group B; the respective mean increases at the femoralneck were +5.2 and +2.2 (group A vs. B at both sites p = 0.0001).We observed in group A 5 and in group B 14 new vertebralfractures (p = 0.0460). The rates of patients with new vertebralfractures were 5 and 12 resp. (p = 0.0712). The resp. incidencerates of non-vertebral fractures were 8 and 9 (n.s.).

From this two year results of our ongoing trial we conclude thatalendronate is well tolerated by men with primary osteoporosisand that it is superior to alfacalcidol in terms of restoring BMD atthe spine and femoral neck and in reducing the risk of vertebralfractures. Based on these data and results from a randomizedplacebo-controlled multi-center study on 241 men we suggestthat alendronate therapy may prove to be at least as effective inmales as it was documented for postmenopausal osteoporosis inthe large well-known studies.

518 (482). A COMPREHENSIVE REVIEW OF TREATMENTS FOROSTEOPOROSIS

R. Rizzoli1, H. Hauselmann2, 1Cantonal University Hospital,Geneva, Switzerland; 2Zentrum fur Rheuma-und, Zurich,Switzerland

Purpose: To assess the relative ef®cacy of treatments forosteoporosis in women with low bone mass or with an existingvertebral fracture.

Methods: We searched the literature for studies (randomized,double blind, placebo controlled and prospective) that reportedon drugs registered in Europe or North America. All subjects hadlow bone mineral density or an existing vertebral fracture. Weincluded 39 reports on 12 agents: alendronate, calcitonin,calcitriol, calcium (alone), calcium & vitamin D, etidronate, ¯uoride(slow release), hormone replacement therapy, pamidronate,raloxifene, risedronate and vitamin D (alone). To assess theintra-consistency of the studies for each drug, we plotted thepercent change in BMD for the control group on the vertical axis


and the percent change in BMD for the treated group on thehorizontal axis. We used methods of cluster analysis to determineintra-consistency. For each agent we summarized the relative riskfor vertebral and for hip fractures.

Results: Duration of the studies ranged from 1 to 4.3 years.Patients who discontinued treatment ranged from 0 to 46 percent.Most of the studies reported on change in BMD. 22 (10 drugs)studies provided data on new vertebral fractures and 8 (5 drugs)on hip fractures. The largest increases in spine BMD (relative toplacebo) were seen in the studies with ¯uoride. Increases in BMDwith bisphosphonates were greater than those seen theremaining treatments. Generally, for each agent, the changes inBMD (relative to placebo) for each agent were consistent amongthe studies. The exceptions were calcitriol and calcitonin forchanges in BMD of the spine and of the femoral neck. Onlyalendronate, risedronate and raloxifene showed signi®cantreductions in the risk of vertebral fractures. Only alendronateand the combination of Calcium plus Vitamin D had a signi®canteffect on the risk of hip fracture.

Conclusion: Most therapies are effective in increasing BMD, fewdecrease the risk of vertebral fracture. For hip fracture, alen-dronate reduced the risk in women with osteoporosis and calciumand vitamin D reduced the risk in institutionalized patients.

519 (483). ALENDRONATE REDUCES VERTEBRAL FRACTUREINCIDENCE AND PREVENTS HEIGHT LOSS IN MEN

R. Rizzoli1, S. Adami2, R. Lorenc3, D. Felsenberg4, P.Pietschmann5, E. Orwoll6, M. Ettinger7, S. Weiss8, P. Miller9, D.Kendler10, J. Graham11, R. Harning12, K. Vandormael12, A.Lombardi12, 1University Hospital, Geneva, Switzerland;2University of Verona, Italy; 3Memorial Hospital, Warsaw, Poland;4University of Berlin, Germany; 5University of Vienna, Austria;6Oregon Health Sciences University, Portland, OR; 7ClinicalResearch Center of So Florida, Stuart, FL; 8San Diego EndocrineClinic, San Diego, CA; 9Colorado Center for Bone Research,Lakewood, CO; 10Vancouver Hospital and Health Science Centre,Canada; 11Ashford Hospital, Australia; 12Merck & Co, Rahway, NJ

Background: Despite the large number of men with osteoporosis,the disease has been largely under-diagnosed and inadequatelystudied. This is of particular concern given that osteoporoticfractures in men are associated with a marked degree ofmorbidity and mortality, even exceeding that of women.

Methods: In this ®rst large, randomized, multicenter study everconducted on male osteoporosis, 241 men aged 31±87 years withosteoporosis (femoral neck T-score <±2 SDs/history of osteo-porotic fractures) were randomized to placebo (PBO, n=95) oralendronate (ALN, n=146) 10 mg/day for 2 years. 36% had lowfree testosterone and 50% had prevalent vertebral fractures atbaseline. Incident vertebral fractures were assessed semiquanti-tatively (SQ) and by quantitative digitization of x-rays, the goldstandard for vertebral fracture assessment.

Results: The key results are shown below. ALN was welltolerated in this study. Adverse experiences, including upper GIevents, occurred in similar proportions of men in both groups.

Conclusion: ALN signi®cantly increased spine and hip BMD,reduced vertebral fractures, prevented height loss, and was welltolerated.

BMD changes (%) PBO ALN ALN vs. PBO (p)

Lumbar spine 1.8 7.1 40.001Total hip 0.6 3.1 40.001FracturesNon-vertebral 5.3 4.1 NSVertebral (digitized) 7.1 0.8 0.017Vertebral (SQ) 8.1 3.1 0.12Stature change (mm) ±2.4 ±0.6 0.02

520 (484). NUTRITION COMPONENT OF THE POWERPROGRAM FOR COMMUNITY DWELLING SENIORS LIVINGWITH OSTEOPOROSIS

C. Robertson1, S. Logan2, 1Baycrest Centre for Geriatric Care,Toronto, ON, Canada; 2North York General Hospital, Seniors'Health Centre, Toronto, ON, Canada

Osteoporosis is a common disease in older adults, with anestimated 1 in 4 women and 1 in 8 men over 50 years of ageaffected. POWER is a six week culturally sensitive multi-siteprogram, created to empower older adults with a diagnosis ofosteoporosis to improve their quality of life, prevent falls and selfmanage their disease process. This paper focuses on the nutritioncomponent of the program which communicates practicalknowledge of dietary factors affecting bone. It's goal is todevelop interest, ability and motivation to put this knowledgeinto practice in day-to-day meal planning and food intake, oftenwithin the context of other dietary interventions for diabetes,weight loss or gain, hyperlipidemia milk allergies or intolerances,and others. Emphasis is placed on the role of other less wellknown micronutrients in maintaining optimal bone density, theimportance of consuming a diet that includes a variety of foodsfrom all of the food groups within currently recommended dailyintakes. Key content areas, facilitative strategies, and pre andpost tests of knowledge and practice will be discussed in thecontext of the effectiveness, future direction and improvement ofthe nutrition component and the program as a whole.

521 (485). CORRECTION OF STRESS-SHIELDING FOR THEPREVENTION OF THE IMPLANT INSTABILITY IN PATIENTSWITH OSTEOPOROSIS

S. Rodionova, T. Popova, A. Balberkin, A. Morozov, A. Kolondaev,Central Institute of Traumatology and Orthopaedics, Moscow,Russia

According to our data (Rodionova S. et al, 1999) in 47% patientsafter total hip replacement for the articular degenerative-dystrophic changes the osteoporosis is diagnosed and it is thehigh risk factor for implant loosening. The aim of the study was toassess the ef®cacy of miacalcic in the decrease of bone massloss around the implant. There were 25 patients (mean age 67)after total hip replacement for coxarthrosis. In all patientsosteoporosis was diagnosed by DEXA method. Fifteen patientsreceived 100 IU miacalcic every day during 1 month. Completetreatment consisted of 3 courses with 2 weeks interval betweeneach course. Ten patients were the controls. They received Capreparations during the total period of six months. Bone massaround the implant stem was evaluated at points A, B, C, D by``Orthopedic Program Lunar'' immediately after operation, 2 and 6months later. Two months after operation in patients on miacalcicregimen the mean bone tissue loss at point A was 15%, at point B±22%, at points C and D ±25%. Six months later in miacalcicgroup the mean bone loss at points A and B was completelysmoothed, but in points C and D it was 10% and 13%,respectively. In control group the mean bone loss at all pointswas signi®cantly more. Thus, the use of miacalcic during the ®rstmonths after total hip replacement allows to prevent the loss ofbone mass around the implant stem.

522 (486). PARATHYROID HORMONE (HPTH 1±34) ANDESTROGEN DRAMATICALLY INCREASES BONE DENSITY INPOSTMENOPAUSAL OSTEOPOROSIS: A PLACEBO-CONTROLLED RANDOMIZED TRIAL

E. B. Roe1, C. F. Cann1, S. D. Sanchez1, P. Bachetti1, D. Black1, C.D. Arnaud, 1University of California-San Francisco, San Francisco,CA

We determined the bone-building ef®cacy of daily, self-adminis-tered, subcutaneous hPTH 1±34 (400 IU/day) plus oral estrogen in


a 2-year, randomized, double blind, placebo controlled trial inwomen, at least 5-years postmenopausal, with osteoporosis[spine or hip bone mineral density (BMD) >2.5 SD below the meanfor young normal women (YNW)]. They all had taken estrogen forat least one year immediately prior to study entry. 74 womenreceived conjugated estrogens 0.625mg/d, medroxyprogester-one, if needed, vitamin D 800 IU/d, and calcium supplements toensure a total daily intake of 1500 mg. Secondary endpointsincluded biochemical markers of bone turnover and spine x-rays.60 subjects (81%) completed the treatment phase. The tableshows median BMD changes as measured by DXA.

Lumbar Spine Femoral Neck

Months Placebo PTH Placebo PTH

6 0.7% 9.2%* 0.2% 0.1%12 0.7% 20.6%* 0.0% 4.0%**18 0.6% 23.6%* 0.1% 7.3%*24 0.9% 29.2%* 0.2% 11.0%*

*p50.0001, **p = 0.002** when compared with baseline

89% of those receiving PTH 1±34 increased lumbar spine BMDgreater than 2 population SD and 64% achieved BMD values thatwere within the reference range for YNW. These ®ndings showthat hPTH 1±34 plus estrogen therapy can restore osteoporoticbone in postmenopausal women at the lumbar spine and femoralneck to osteopenic or normal levels.

523 (487). CHANGES IN BONE TURNOVER MARKERS AFTERONE YEAR OF ALENDRONATE TREATMENT INOSTEOPOROSIS

J. A. Roman, C. FernaÂ ndez, J. MillaÂ n, A. Fuertes, L. Abad, J. Pons,M. Blasco, I. Calvo, Hospital Universitario Dr. Peset, Valencia,Spain

PURPOSE: To evaluate the effects of Alendronate on biochemicalmarkers of bone turnover as predictors of treatment response inpatients with osteoporosis.

METHODS: Thirty-one patients with osteoporosis (age range32±76) were evaluated at baseline and after one year of treatmentin a twelve-month study of 10 mg. of Alendronate. The diagnosisof osteoporosis was made on the basis of criteria proposed byHMO. The primary end points were the differences in the meanpercent of change in serum Bone Alkaline Phosphatase (BAP) andOsteocalcin (OC) from baseline to one year. Student's paired tTest was used to compare values. P values<0.05 were consideredsigni®cant.

RESULTS: The mean (�SE?) BSAP and OC values decreased by52,8 percent and 28,8 percent respectively. Serum BSAP andserum OC were signi®cantly decreased, respect to baselinevalues, after 12 months of Alendronate treatment. (p = 0.004 andp = 0.001 respectively).

Serummeasurement

Baseline(n=31)

12 months(n=31)

Mean percentof change (%)

pvalue

BSAP 65.91�41,93 31.11�22.80 52.8 0.004Osteocalcin 4.36�1,51 6.12�1.51 28.8 0.001

CONCLUSION: Alendronate decreases biochemical markers ofbone turnover, so BSAP and OC may be used for the evolutiveevaluation in patients with osteoporosis.

524 (488). TREATMENT OF OSTEOPOROSIS INPOSTMENOPAUSAL WOMEN: ALENDRONATE VSINTRANASAL CALCITONIN

C. J. Rosen1, S. L. Bonnick2, P. D. Miller3, J. Palmisano4, 1St.Joseph Hospital, Bangor, ME, USA; 2Texas Woman's Univ.,Denton, TX, USA; 3Colorado Center for Bone Res., Lakewood,CO, USA; 4Merck & Co., Inc., West Point, PA, USA

Alendronate (ALN) and intranasal calcitonin (CT) are commonlyprescribed treatments for osteoporosis in postmenopausalwomen. This randomized study enrolled 275 postmenopausalwomen with osteoporosis (T-score ±2.0 or below at lumbar spine(LS) or femoral neck (FN) AND T-score ±1.0 or below at other site)and was designed to compare the ef®cacy of daily ALN to CT for aperiod of 2 years. During YR±1, subjects were randomized toreceive either ALN 10 mg/d, CT 200 IU/d or ALN placebo (2:2:1ratio). All patients received vitamin D 400 IU/d and calcium 51gm/d. YR±1 results demonstrated that at 6 and 12 months,treatment with ALN 10 mg/d vs. CT 200 IU/d, ALN producedsigni®cantly greater increases in BMD at the trochanter and LS(p<0.001) and at 12 months at FN (p = 0.003). BMD changes withCT were not different from PBO at hip or spine. During YR±2, alltreatments were open label; the placebo group crossed over toALN 10 mg/d; the other two groups remained unchanged.Ef®cacy endpoints were BMD of LS, FN and hip trochantermeasured by DXA at baseline, 6, 12, and 24 months. Boneturnover was assessed by biochemical markers of boneresorption (urine NTx) and bone formation (BSAP) at baseline, 6,12 and 24 months. Safety and tolerability were assessed byreporting of clinical adverse experiences (AEs) and withdrawalsdue to AEs. The YR±2 data will be available April 2000. These datawill help guide treatment decisions for postmenopausal womenwith osteoporosis.

525 (489). RISEDRONATE RAPIDLY AND CONSISTENTLYREDUCES VERTEBRAL FRACTURE RISK IN ELDERLYPOSTMENOPAUSAL WOMEN

Ch. Roux1, R. Wasnich2, J. Adachi3, H. Zippel4, K. Bos5, I.Fogelman6, 1Paris, France; 2Honolulu, HI, USA; 3Hamilton, ONT,Canada; 4Berlin, Germany; 5Mason, OH, USA; 6London, UK

As part of the risedronate (RIS) clinical program, the HipIntervention Program (HIP) was the ®rst to investigate hip fracturerisk reduction as a primary outcome. The study consisted of 9331elderly postmenopausal women (age 570 years) with low FNBMD and/or at least 1 additional clinical risk factor for hipfracture. In addition to hip fracture ef®cacy, vertebral fractureef®cacy was also determined. Patients received risedronate (2.5or 5mg) or placebo daily for 3 years, in addition to 1g calciumdaily and vitamin D supplementation if baseline levels were 540nmol/L. Prevalent and incident vertebral fractures were deter-mined radiographically via a combination of qualitative andquantitative methodology. Lumbar spine BMD was assessed atbaseline and then at 6 month intervals in a subset of patients. Themean age was 78 and patients were on average 32 yearspostmenopausal. The table below shows the results of theanalyses. Overall, RIS 5mg signi®cantly reduced new vertebralfracture risk by 55% vs. control at 1 year of treatment. Thesigni®cant treatment effect was also observed at 1 year insubpopulations at risk for vertebral fracture. Effects on vertebralfracture continued through the duration of the study.

These results con®rm previously reported studies that rise-dronate rapidly and consistently reduces the risk of vertebralfracture in elderly postmenopausal women.


1 Year Vertebral Fracture Risk Reduction ± RIS 5mg vs. Control

Population Risk Reduction P N* No. vert fx*

Overall 55% <0.001 3146 11052 prevalent vert. fx 67% <0.001 656 55LS T-score 4±2.5 93% 0.013 432 14

*RIS 5mg + control

526 (490). PREVENTION OF BONE LOSS INPOSTMENOPAUSAL WOMEN WITH CALCIUM AND VITAMIND3

L. Rozhinskaya, L. Dzeranova, E. Marova, N. Sazonova, T.Chernova, National Research Center for Endocrinology, Moscow,Russia

The bene®ts of calcium and vitamin D supplementation in elderlyinstitutionalized women is well documented. But the results ofsuch therapy for prevention osteoporosis in postmenopausalwoven are controversial. To determinate the effect of 1-yeartreatment by 100 mg calcium and 400 ED vitamin D3 on bonemineral density (BMD) and parameters of Ca-P homeostasis 62women aged 52±73 years were studied. They were divided in 2groups: treated group ± 28 women, who had received 2 tabletsCaD3 Nycomed daily (1000 mg Ca and 400 ED vitamin D3); controlgroup ± 34 women did not take any medicine for 1 year. BMD wasmeasured in lumbar spine (L2-L4) and proximal femur using``Expert XL'' Lunar densitometer. Current Ca intake without Casupplement was calculated in both groups. Data are presented inTable 1 and Table 2.

Table 1. Baseline data of both groups

Age

years

Menopause

years

Ca

intake

L2-L4

T-score

Neck

T-score

T.hip

T-score

Treat 61.2 12,1 652�79 ±1.8�0.45 ±1.17�0.28 ±1.2�0.31

Cont 59.8 10,75 638�94 ±1.65�0.26 ±1.3�0.37 ±1.25�0.33

Table 2. Changes in BMD (in %) after 1 year

L2-L4 Neck Ward Trochanter Total hip

Treat ±1.12�0.45 +0.1�0.22 ±0.9�0.3 +0.15�0.23 ±0.28�0.19

Cont ±1.47�0.39 ±0.73�0.21 ±1.4�0.27 ±0.65�0.18 ±0.87�0.22

P >0.1 <0.02 >0.1 <0.02 <0.05

There was no signi®cant dierence between groups andbetween baseline and after 1 year in each group in Ca, P, alkalinephosphatase and PTH. The table 2 shows: BMD did not changesigni®cantly from baseline in both groups. But we revealeddierence in femoral BMD between control and treated group after1 year.

Conclusion. Calcium and vitamin D supplement prevents boneloss in proximal femur in postmenopausal women, but does notin¯uence BMD in lumbar spine.

527 (491). COMPARISON OF THE EFFECTS OF ALENDRONATEAND CALCITONIN ON POSTMENOPAUSAL OSTEOPOROSIS

F. Sahin, G. Durlanik, D. Parlar, M. Palanci, F. Merdol, B. Kuran,Dept. of Phys. Med. & Rehab., Sisli Etfal Teaching and ResearchHospital, Istanbul, Turkey

OBJECTIVES: To compare the effects of alendronate and salmoncalcitonin (Sct) on Type 1 osteoporosis.

METHOD: Of the 93 osteporotic patients 63 cases were givenalendronate (10mg/day) and oral calcium (1000 mg/day) (Groupl),33 cases were treated with Sct nasal spray (200IU/day) and oralcalcium (1000mg/day) (Group 2). Assessment by bone densito-metry (LUNAR-DEXA) in 3 body regions (lumbar spine, proximalfemur and forearm) was made at the beginning and end of thetherapy period (12 months). Annual differences in bone densitywere evaluated both by the changes in BMD (gr/cm2) and tscores. Student's t test and paired student's t test were used forthe statistical analysis.

RESULTS: Average age of group 1 patients was 64.1�6.4 andgroup 2 patients was 60�9.5 years (p<0.01). In Group 1, theincrements in BMD values were statistically signi®cant in lumbarspine (BMD p<0.0002, t score p<0.0001) and in femoral neck BMDp<0.001, t score p <0.0003). In group 2 only femorak neckdensities increased signi®cantly (BMD p<0.05, t score p<0.01).

CONCLUSION: While alendronate teatment was effective inboth spine and femur, calcitonin was mainly effective on femoralneck regiom. None of these drugs were able to increase theforearm densities in our study.

528 (492). CHARACTERISTICS ASSOCIATED WITH THE USE OFHORMONE REPLACEMENT THERAPY IN 657 ELDERLYWOMEN OF THE SEMOF COHORT

L. Sandini, J. Cornuz, M A. Krieg, P. Burckhardt, the SEMOFStudy Group, University Hospital, Lausanne, Switzerland

INTRODUCTION: The use of hormone replacement therapy (HRT)is associated with a decrease of bone loss and of osteoporoticfracture risk. However, few studies have focused on the socio-demographic and clinical variables associated with HRT useamong elderly women.

METHODS: Between December 1997 and September 1999,7800 women aged 68±82 were enrolled in the SEMOF Study(Swiss Evaluation of the Methods of Measurement of Risk ofOsteoporotic Fracture). Initial evaluation included a clinicalevaluation and a validated questionnaire concerning sociodemo-graphic data, current medication and lifestyle characteristics. Amultivariate analysis was performed to assess the independantvariables associated with HRT use among the 6250 women forwhom data were available.

RESULTS: 657 patients reported the use of HRT (10.5%) with amedian duration of 8.3 years. Age 575 (Odds ratio [OR] 2.4, 95%Con®dence Interval [95%CI] 2.1±2.9), Calcium supplementation(OR 1.5, 95%CI 1.2±1.9), Vitamin D supplementation (OR 1.3,95%CI 1.0±1.7) and a Body Mass Index inferior to the median(25.4kg/m2) (OR 1.5, 95%CI 1.2±1.9) were associated with HRTuse. Women not living alone (OR 1.3, 95%CI 1.1±1.5), havingworked either as quali®ed worker or in liberal professions (OR 1.5,95%CI 1.2±1.9) reported HRT use more frequently than the non-users. Tobacco use, educational level, and past fractures werenot associated with the use of HRT.

CONCLUSION: In this prospective study of 6250 elderlywomen, current users of HRT were more likely to have a ``healthconscious'' pro®le (younger, thinner, more likelyto have Calciumand Vitamin D supplements, and having worked in a higherprofessional level) than the non-users.

529 (493). RELATIONSHIPS BETWEEN CHANGES IN BONEMINERAL DENSITY AND THE RISK OF NEW VERTEBRALFRACTURES WITH RALOXIFENE TREATMENT

S. Sarkar1, K. D. Harper1, M. Wong1, S. R. Cummings2, D. M.Black2, 1Eli Lilly and Company, Indianapolis, IN, USA; 2Universityof San Francisco, San Francisco, CA, USA

This study examines the relationships between changes in bonemineral density (BMD) from baseline and the relative risk for newvertebral fractures (VFx) with raloxifene (RLX) at 3 years. In the


Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705postmenopausal women with osteoporosis were randomized toplacebo or RLX (60 or 120 mg/day). Femoral neck and lumbarspine BMD were assessed by DXA at baseline and annuallythereafter. Vertebral fractures were assessed with a combinationof morphometry and semiquantitative reading of spine x-raysobtained at baseline and 3 years. The relationships betweenchanges in BMD from baseline and the risk of 51 new VFx weredetermined using logistic regression analyses with treatment,changes in BMD from baseline, and treatment-by-percentagechange interaction in the model. RLX patients had a statisticallysigni®cantly greater decrease in VFx risk than did placebopatients for any percentage change in lumbar spine or femoralneck BMD. There was no statistically signi®cant treatment-by-percentage change interaction in femoral neck BMD. Thus, fromthe model, RLX patients with any change in femoral neck BMDhad a 36% lower risk of VFx compared with placebo. Thetreatment-by percentage change interaction in lumbar spine BMDwas signi®cant (p = 0.016). RLX patients who had 0.3% to 6.1%increases (25th to 75th percentiles) in lumbar spine BMD had a39% to 52% lower risk of VFx than placebo patients. From thelogistic regression model, the percentage change in BMDaccounts for a small proportion of the total VFx risk reductionwith RLX treatment.

530 (494). TREATMENT OF MALE OSTEOPOROSIS WITHALENDRONATE OR FLUORIDE

M. Sarli, A. L. Negri, J. R. Zanchetta, Metabolic Research Institute,Buenos Aires, Argentina

Few studies have evaluated treatment response in males withosteoporosis. We reviewed the medical records of 24 malepatients with osteoporosis (T score 5±2, 5 at L2-L4 and/orfemoral neck) treated at our institute. Half of these patients havebeen treated with alendronate 10 mg/day (AL) and the other halfhave been treated with sodium mono¯uorphosphate (15±26 mg F-per day). The patients had a follow up of at least two years. All ofthe patients received 1000 mg clacium as citrate or carbonatesalts. Bone mineral density (BMD) was measured at the lumbarspine (LS) and at the femoral neck (FN) every 12 months with aNorland XR 26 densitometer with dynamic ®ltration. Both groupswere comparable at baseline in age, height, weight, LSBMD andFNBMD as well as in the number and type of vertebral fractures.Patients with AL had an increase in LSBMD of 6.2% 1st year and2.98% 2nd year while patients with ¯uoride had a similar increasein both years: 4.62% and 4.42% respectively. In the AL groupFNBMD increased 5.35% in two years and 0.92% in the F group.Two patients treated with AL had upper gastrointestinaldisconfort. Two patients with F had artralgias and three hadabdominal disconfort. We conclude that treatment response inmales is very similar to that in females and, because of the lack ofeffect on FNBMD, ¯uoride should be restricted to vertebralosteoporosis.

531 (495). ONCE-WEEKLY ALENDRONATE: UPPER GI SAFETYPROFILE

T. Schnitzer1, R. Emkey2, I. Smith3, J. Foldes4, M. Ettinger5, I.Reid6, J. Orloff7, A. Santora7, A. Kaur7, D. Freedholm7, For TheAlendronate Once-Weekly Study Group , 1NorthwesternUniversity, Chicago, IL, USA; 2Radiant Research, Wyomissing,PA; 3Wrightington Hospital, Wiligan Lancs, UK; 4HadassahUniversity Hospital, Jerusalem, Israel; 5CRC of So. Florida, Stuart,FL; 6University of Auckland, Auckland, New Zealand; 7MerckResearch Labs, Rahway, NJ,

Background: Daily oral alendronate (ALN) increases BMD,reduces vertebral and non-vertebral (including hip) fracture, andis generally well tolerated. Animal data suggest that the potential

for esophageal irritation, seen with daily oral bisphosphonates,may be substantially reduced with once-weekly dosing, whilemaintaining ef®cacy. This dosing regimen would provide patientswith increased convenience and may enhance patient compli-ance.

Methods: The ef®cacy and safety of treatment with ALN 70 mgOW (n=519) and ALN 10 mg D (n=370) were examined in a one-year, double-blind, multicenter study of postmenopausal women(age 40 to 90) with osteoporosis. The therapeutic equivalence ofALN 70 mg once-weekly (OW) and ALN 10 mg daily (D) has beenreported previously. We now report the results of special upper GIsafety analyses from this study. Adverse experiences (AEs) wereanalyzed using Fisher's exact test, life-table methods andgeneralized linear models where appropriate. Upper GI AEswere examined by grouped categories, onset with regard to thelarger OW unit dose, and risk factors for upper GI AEs (patientswith prior upper GI disease; those using NSAIDs).

Results: A similar incidence of overall upper GI AEs (includingesophageal) was observed for each treatment regimen (23.5% Dvs 22.4% OW, respectively). The incidences of esophageal AEsand gastro-duodenal AEs (1.9% D vs. 0.8% OW, and 1.9% D vs0.6% OW, respectively) were lower (p = NS) in the OW group.Serious upper GI AEs (whether or not considered drug related)were less common in the OW vs. the D group (0.0% vs 1.4%;p = 0.01). Relative to the D group, which received a OW placebo,upper GI AEs were not increased within 48 hours of taking the 70-mg OW dose. The incidence of upper GI events was not differentbetween groups in those patients with a history of upper GIdisease or during periods of concurrent NSAID use.

Conclusion: Once-Weekly ALN 70 mg was well tolerated andtherapeutically equivalent to ALN 10 mg daily, providing patientswith greater dosing convenience. The trend for a lower incidenceof serious upper GI and esophageal adverse events suggests thepotential for improved upper GI tolerability with Once-Weeklyalendronate.

532 (496). EFFECTIVENESS OF ETIDRONATE ANDALENDRONATE IN THE TREATMENT OF OSTEOPOROSIS INMALES: A PROSPECTIVE OBSERVATIONAL STUDY

R. J. Sebaldt, J. D. Adachi, A. Tenenhouse, J. Caminis, A. Petrie,G. Ioannidis, C. H. Goldsmith, The CANDOO Project, McMasterUniversity and McGill University, Canada

Optimal treatment for osteoporosis (OP) in males remainsuncertain. Etidronate (E) and alendronate (A) are two bispho-sphonates available in most countries for the treatment ofosteoporosis (OP). From CANDOO, our prospective observationaldatabase of patients with OP or osteopenia who are beingfollowed at our academic tertiary care centre, we extracted therecords of males who had had an initial BMD determination(immediately prior to any bisphosphonate therapy) and a follow-up BMD after 1 yr. Males treated with calcitonin, ¯uoride oranother bisphosphonate were excluded. We divided them into 4groups: E users for at least 1 yr (n=91), A users for at least 1 yr(n=33), switchers (users of E for at least 2 yr followed by switch toA for at least 1 yr) (S, n=18), and control (calcium or vitamin Donly, n=97). At baseline, lumbar spine (LS) and femoral neck (FN)BMD t-scores in the 3 treatment groups did not differ signi®cantly(except for LS t-scores in S vs A and S vs E) but were allsigni®cantly lower than in the control group. At 1 yr, LS BMDincreased signi®cantly within the A, E and S groups (3.9�0.6±6.6�1.3%). Femoral neck (FN) BMD increased in the A group andincreased slightly in the E group. All increases were signi®cantlygreater than the changes in the control group (p<0.005). Theincreases in LS BMD and FN BMD in the A group were alsostatistically signi®cantly greater than in the E group (p<0.05). Weconclude that both A and E can increase BMD in males with OP orosteopenia. In this study, A was associated with a slightly greatermean increase in BMD than E.


533 (497). PATIENT COMPLIANCE WITH BISPHOSPHONATETHERAPY

R. J. Sebaldt, J. D. Adachi, W. Olszynski, J. Brown, D. Hanley, A.Tenenhouse, J. Caminis, A. Petrie, C. Yuen, G. Stephenson, C. H.Goldsmith, The Multicentre CANDOO Project, Canada

To assess compliance with bisphosphonate (B) therapy, eitheretidronate (E) or alendronate (A), initiated in patients withosteoporosis (OP), we analyzed CANDOO, our prospectiveobservational database of OP and osteopenia patients seen atour Canadian tertiary care sites. All patients in CANDOO initiallyseen in Jan/95 or later, who started E or A on or after their initialclinic visit and who were seen at least once in clinic after initiatingB were included. There were 1176 patients (1037 women) in the Egroup and 1003 (855 women) in the A group. Patients in the Egroup were slightly older than those in the A group (65 vs 61,p = 2.67e±13) and were a little more likely to have had a vertebralfracture prior to the start of B (23% vs 20%). There was nosigni®cant difference between the lumbar spine bone mineraldensity tscores in the two groups (±2.46 vs ±2.48) at the start of B.At 6, 9 and 12 months after start of B therapy, 94%, 91% and 88%of patients in the E group and 86%, 83% and 80% of patients inthe A group were still continuing therapy. The differences of about8% between the E and A groups at each time point arestatistically signi®cant, although the rate of discontinuationbeyond 6 months after initiation of B (1% of the initial cohortper month) is the same in both groups. The causes of drugdiscontinuation were not assessed and may have included cost(A = 4 x E), reimbursement (E but not A is covered for seniors bythe provincial plan) or side effects. We conclude that compliancewith longer-term B therapy is very good, at least in a tertiary caresetting, and is notably higher than compliance reportedhistorically with hormone replacement therapy.

534 (498). VERTEBRAL FRACTURES AND QUALITY OF LIFE

R. J. Sebaldt, J. D. Adachi, W. Olszynski, J. Brown, D. Hanley, A.Tenenhouse, J. Caminis, A. Petrie, C. Yuen, G. Ioannidis, C. H.Goldsmith, The Multicentre CANDOO Project, Canada

We analyzed CANDOO, our prospective observational databaseof osteoporosis and osteopenia patients seen at our Canadiantertiary care sites, to determine the effect of vertebral fractures onquality of life (QoL). All postmenopausal patients in CANDOOaged 50 or over and who had answered a validated osteoporosis-related quality of life questionnaire (mini-OQOL) on at least twoclinic visits were included. The mini-OQOL addresses ®vedomains (symptoms, physical function, emotional function,activities of daily living, leisure) with 2 questions for each.Responses are on a Likert scale from 1 (low QoL) to 7 (highQoL), so that total scores range from 2 to 14 (each domain) and 10to 70 (complete questionnaire). In patients who had vertebralfractures (VF) during follow-up (VF group, n=47), the pair of mini-OQOL scores before and after the VF were compared. In patientswithout fractures during follow-up (control (C) group, n=1813), thepair of scores closest to those in the VF group in their follow-uptimes from initial consultation were compared. At the time ofthe earlier mini-OQOL questionnaire, patients in the VF groupwere somewhat older (72�9 vs 65�9) and had lower LS BMD t-scores (±2.6�1.1 vs ±2.0�1.2), more previous fractures and lowerQoL scores (43�18 vs 55�14). In patients with new VF, the totalmini-OQOL score decreased (±7.4, p = 0.007) as did the 5individual domain scores (±0.9 to ±2.1, p = 0.00003 to 0.045). Inthe C group, none of these scores changed (p>0.12). Weconclude that the complete mini-OQOL questionnaire, as wellas each of its 5 component domains individually, are able tomeasure a signi®cant reduction in QoL in patients who sustain aVF.

535 (499). THE EFFECT OF HRT+EHDP IN NON-RESPONDERSTO HRT

M. Shintani, K. Beppu, Y. Hara, Nara Prefectural Mimuro Hospital,Nara, Japan

In a previous study we have shown that approximately 20% ofpostmenopausal women in Japan are BMD non-responders toHRT, ie bone density decreases during HRT administration. Thisis a higher rate than observed by Hassager (1994) et al. In thisstudy, HRT and etidronate (EHDP) were concomitatly adminis-tered to HRT non-responders to study the effect on LBMD.While climacteric disorders and vaginal dryness due to estrogende®ciency improved, some patients were ``fast losers'', LBMDdecreased more than 1.5% in 6 months. We chose such 25patients for this study. Their mean age was 57.1�7.0 yrs, theirmean years postmenopause was 9.3�4.9 yrs, and their serum E2level at the time HRT+EHDP administration was started was62.4�28.6 pg/ml. HRT was administered without change, and200mg EHDP was administered concomitantly for 2 weeks,followed by 600 mg calcium aspartate for 10 weeks. Two ormore courses of EHDP were adminstered. LBMD was measuredevery 6 months using DPX-L (a DXA method). LBMD at thetime HRT administration was started was 0.892�0.097(mean�SD) g/cm2. After 6 months of HRT, LBMD decreased to0.868�0.095 g/cm2 LBMD increased to 0.906�0.094 g/cm2 after6 months of HRT+EHDP, and to 0.916�0.093 g/cm2 after 12months, and to 0.916�0.100 g/cm2 after 18 months. Duringcombination therapy LBMD decreased for only one patient. Nochange was observed in serum E2, serum ALP, serum Ca, orurine Ca/Cr ratio. We therefore propose that HRT+EHDP therapyis an effective treatment for non-responders to HRT. It isnecessary to identify non-responders to HRT as early aspossible but the method to identify such individuals is currencyunder investigation.

536 (500). EFFECTS OF LOW DOSE HRT AND VITAMIN DCOMBINATION THERAPY ON LBMD IN POSTMENOPAUSALWOMEN: COMPARISON WITH NORMAL DOSE HRT ANDVITAMIN D IN COMBINATION

M. Shintani, K. Beppu, Y. Hara, Nara Prefectural Mimuro Hospital,Nara, Japan

In this prospective 2 year study, we administered a combinationof 0.3mg/day of CEE and 2.5mg/day of MPA, and 1mg/day of 1-avitamin D3 to 30 postmenopausal women with decreased BMD(YAM±1.5SD) (low HRT group). For the comparison group weselected 60 subjects who had received a combination of0.625mg/day of CEE and 2.5mg/day of MPA, and 1mg/day of 1-avitamin D3 for 2 years (HRT group). Using DPX-L (a DXAmethod), we measured the LBMD values from the 2nd to the 4thlumbar vertebra approximately every 6 months. There were nosigni®cant baseline differences between the two groups for age,age at menopause, number of years since menopause, weight,height, BMI, or LBMD (unpaired t-test). The change from baselinein LBMD in the low HRT group and HRT group were, respectively,4.5% and 7.9% after 1 year; and 6.4% and 10.3% after 2 years.The increse in LBMD from baseline was signi®cant for bothgroups at both time points (ANOVA p<0.0001). The change frombaseline in LBMD in the HRT group was signi®cantly higher thanthat of low dose HRT group (ANOVA p<0.05). Thus, low dose HRTand vitamin D in combination is a possible treatment regimen forpostmenopausal women with decreased BMD who are averse tovaginal bleeding and breast pain.


537 (501). IS THE SKELETAL RESPONSE TO ETIDRONATE THESAME IN MEN AND WOMEN?

T. H. Sùrensen, C. G. Carlsen, E. F. Eriksen, UniversityDepartment of Endocrinology and Metabolism, AarhusAmtssygehus, Aarhus, Denmark

Bisphosphonates are used extensively for the treatment ofosteoporosis in both males and females. Little is, however,known about eventual sex-differences in skeletal responsivenessto these drugs in men and women. We therefore comparedchanges in BMD over time in a group of 21 osteoporotic men (age56.9�11 years (meanSD)) and 19 osteoporotic women (age60.5�12 years) (NS) treated with cyclical etidronate in ourdepartment. 66% of the males had primary osteoporosis and33% secondary osteoporosis. Among the women, 84% werediagnosed with primary osteoporosis and 16% with secondaryosteoporosis. At baseline vertebral fracture prevalence in menwas 3.5�2.7 fractures/person and in women 3.6�3.1 fractures/person (NS). Baseline DEXA-scans revealed no differences inlumbar spine T-score between women and men (±2.9�2.1 vs73.6�1.1) (NS). All patients received 1000 mg Calcium and 400IUvitamin D daily. To measure the effect of treatment we comparedbaseline lumbar spine and hip BMD with the latest spine and hipBMD measurements performed in each patient. The meantreatment duration for men was 3.59�1.7 years and for women2.7�1.2 years (NS). Lumbar DBMD/year in men versus womenwas 0.013�0.02 g/cm2 vs. 0.012�0.02 g/cm2 (NS). Hip DBMD/yearin men versus women was 0.01�0.03 g/cm2 vs ±0.002�0.02 g/cm2

(NS). In women DBMD/year in the lumbar spine was higher than inthe hip (p = 0.04). In men no such difference was demonstrable. Inconclusion this study showed no difference in the response totreatment with etidronate between men and women.

538 (502). HORMONE REPLACEMENT THERAPY ANDFRACTURES IN A PROSPECTIVE STUDY OF WOMEN: THEOFELY COHORT

Elisabeth Sornay-Rendul, Patrick Garnero, Francoise Munoz,Francois Duboeuf, Pierre D. Delmas, INSERM Unit 403, Lyon,France

The longterm effects of hormone replacement therapy (HRT) onfractures, bone mineral density (BMD) and bone markers levelshave not been assessed simultaneoulsy in a prospective study.We have assessed prospectively incident fragility fractures duringa 6.2�0.7 yr follow-up in 478 postmenopausal women taken fromthe OFELY cohort, by an annual questionnaire for non vertebralfractures (con®rmed by radiographs) and by lateral spine radio-graphs for vertebral fractures at baseline and after 3.9�0.3 yr.Only 5 incident fractures occurred among the 121 women whohad been taking HRT at baseline (for an average of 3yr at entry)whereas 69 incident fractures occurred in the 357 women whohave never taken HRT (22 vertebral, 47 peripheral). Afteradjustment for age, BMI, physical activity, prevalent fracturesand follow-up duration, the risk to sustain a fracture in the HRTgroup was reduced by 66% (RR (95%CI): 0.34(0.12±0.92)).

After controlling for age and BMI, bone loss over 4yrs at thedistal radius was lower in the HRT group compared to untreatedwomen (±0.17�3% versus ±2.6�3.8%, p<0.0001). Levels of bonemarkers (serum osteocalcin and bone alkaline phosphatase,urinary and serum CTX, urinary NTX) measured annualy werelower (p<0.0001) in the HRT group and did not increase over time.In the HRT group, incident fractures were not associated withlower BMD values, faster forearm bone loss nor higher bonemarkers levels. The duration of treatment was the only factorassociated with incident fractures with a relative risk reduced by0.60 for each additional year of treatment (0.40±0.90), afterajustement for age and prevalent fractures. In conclusion, thislarge prospective study con®rms the bene®cial effect of HRT onfractures, BMD, bone loss, and bone turnover. The mechanism bywhich some treated women sustain fractures remain unknown.

539 (503). OSTEOPOROSIS AND FALLS PREVENTION: AMULTIDISCIPLINARY COMMUNITY BASED PROGRAM FOROLDER ADULTS

A. Stephens1, R. Bentley2, L. Bernick2, T. Izukawa2, 1North YorkGeneral Hospital, ON, Canada; 2Baycrest Centre for GeriatricCare, ON, Canada

Osteoporosis and associated fragility fractures affects more than25 million people in the United States and an estimated 1.5 millionCanadians. More than 90% of all hip fractures are suffered bypeople over the age of 70 resulting in decreased quality of life,hospitalization, and billions of dollars per annum spent onassociated health care costs. The POWER program (PromotingOsteoporosis Wellness through Education, Exercise and Re-sources) is a multidisciplinary, multisite, collaborative programmodel designed to reduce fracture risk and improve quality of life.This innovative health care model combines medical screening ofolder adults who have fracture risk and osteoporosis with acomprehensive education, exercise and nutrition program. Thisprogram model, derived from evidenced based literature,combines current guidelines with culturally sensitive corecomponents that empower the older adult to participate in selfmanagement. Screening processes, key content areas, facilitativestrategies, evaluative data and future directions of this successfulprogram model will be presented.

540 (504). ARTHROPLASTIES IN HIP JOINTS AFFECTED BYOSTEOPOROSIS

W. Thomas, F. Bove, Clinica Quisisana, Rome, Italy

Because of the continuous increase of the average life expecta-tion, political econimy and health policy of necessity had to turntheir main interests to the problem of osteoporosis which is oneof the major complication of postmenopausal women (Melton etal. 1992; Hans et al. 1996). The obviously most crucial skeletalpart with respect to the development of an osteoporosis processis the proximal femur extremity. Orthopaedic surgeons areconfronted with this problem for the following two aspects:

1. the necessity of treating pathological femur neck fracturesdue to osteoporosis and,

2. the endoprosthetic treatment of degenerative alterations ofthe hip affected by severe osteoporosis of proximal femurbones.

If in such cases an indication for the application of anendoprosthesis is undoubtedly set, many surgeons adopt theconcept of using bone cement for the ®xation of endoprostheses.We consider such a procedure as questionable particularly in thepresence of an osteoporosis and want to present our ownconsiderations in this regard as well as our concept of cementless®xation.

541 (505). RISEDRONATE HAS SIGNIFICANTLY LOWERINCIDENCE OF GASTRIC ULCERS COMPARED TOALENDRONATE

A. B. R. Thomson1, R. H. Hunt2, F. L. Lanza3, J. M. Provenza4, M.Blank5, for the Risedronate Endoscopy Study Group, 1Edmonton,ALB, Canada; 2Hamilton, ONT, Canada; 3Houston, TX, USA;4Shreveport, LA, USA; 5Mason, OH, USA

Bisphosphonates (BPs) are effective treatments for osteoporosis,but some have been associated with injury of the upper GI tract.We compared the incidence of gastric ulcers after treatment withrisedronate (RIS), a pyridinyl BP, and alendronate (ALN), a primaryamino BP, in a randomized study. Healthy, postmenopausalwomen received RIS 5 mg (N = 255) or ALN 10 mg (N = 260) for 2weeks. Endoscopic assessment of the mucosa was performed atbaseline and on Days 8 and 15. The study was powered (90%) todetect a 7% absolute difference between groups. The number


and incidence of gastric ulcers was signi®cantly lower in the RISgroup compared to ALN (table).

NUMBER (n) and INCIDENCE (%) OF GASTRIC ULCERS

ALN RIS

Visit n % n %

Overall 30 13.2 9 4.1*Day 8 21 8.7 9 3.9+

Day 15 20 8.7 8 3.5+

*p<0.001; +p<0.04

Mean gastric erosion scores were lower in the RIS group(p<0.001). Mean esophageal and duodenal erosion scores weresimilar in the 2 groups. Esophageal ulcers were noted in 3evaluable ALN subjects and no RIS subjects. Duodenal ulcerswere noted in 1 evaluable ALN subject and 2 RIS subjects.

In conclusion, when evaluated at doses used in the treatment ofosteoporosis, risedronate was associated with a signi®cantlylower incidence of gastric ulcers than alendronate, con®rmingthat BPs differ in their potential to damage upper GI mucosa.

542 (506). THERAPY OF OSTEOPENIA AND OSTEOPOROSIS INCROHN'S DISEASE PATIENTS WITH IBANDRONATE VS.SODIUM FLUORIDE IN ADDITION TO A VITAMIN D/CALCIUMSUBSTITUTION

C. v. Tirpitz C, J. Klaus, M. Steinkamp, G. Adler, M. Reinshagen,1Department of Medicine I, University of Ulm

Background and aims: Osteoporosis is a frequent complicationin Crohn's disease. Aim of the present study was to compare anosteoanabolic and an anti-resorptive drug regimen in patientswith Crohn's disease and reduced bone density.

Methods: 58 patients were investigated prospectively. A bonemineral densitometry (DEXA) of lumbar spine and femoral neckand X-ray examination of the thoracal and lumbar spine wasperformed at baseline and after one year. 28 patients withosteopenia (T-score 5±1) were randomly assigned to receiveeither 800 mg calcium and 1000 IE vitamin D daily, or additionally50 mg sodium ¯uoride daily or infusion of 1mg lbandronate everythree months. 30 patients with osteoporosis were randomized toreceive either sodium ¯uoride or lbandronate in addition tocalcium and vitamin D.

Results: A total of n=50 patients completed the one-year study.No new vertebral fracture or worsening of preexisting fracturesoccured in any group. Lumbar and femoral bone density did notchange in the 9 patients of the calcium/vitamin D group. In the 21¯uoride patients the lumbar bone density increased signi®cantlyfrom ±2.0�0.74 to ±1.64�0.87 (Z-score �SD, p50,05) whilefemoral bone density was unchanged during the study period.In the group of 20 patients who were treated with lbandronate,lumbar bone density increased from ±2.30�0.66 to ±1.89�0.80,p50,05). Femoral bone density tended to decreased from71.43�0.92 to ±1.61�0.58 (n.s.).

Conclusions: Treatment with sodium ¯uoride or lbandronate isef®cacy in regard to lumbar bone density in Crohn s diseasepatients with osteopenia and osteoporosis, while there was noeffect to the femoral bone density. Supplementation of calciumand vitamin D was able to prevent further bone loss, both inlumbar spine and femoral neck. No differences of new vertebralfractures could be seen between the treatment groups asexpected. As this should be the main endpoint of treatmentstudies in osteoporosis, a long-term multicenter study is nowperformed in these patients.

543 (507). LONG-TERM (SEVEN-YEAR) EFFICACY AND SAFETYOF ALENDRONATE IN THE TREATMENT OF OSTEOPOROSISIN POSTMENOPAUSAL WOMEN

R. P. Tonino, P. J. Meunier, R. D. Emkey, J. A. Rodriguez-Portales, C. J. Menkes, R. D. Wasnich, H. G. Bone, A. C. Santora,M. Wu, R. Desai, P. D. Ross, for the Phase III OsteoporosisTreatment Study Group, 1University of Vermont, Burlington, VT;2Inserm U 403, Hopital Edouard Herriot, Lyon, France; 3BoneResearch Center, Reading, PA; 4Catholic University, Santiago,Chile; 5Hopital Cochin, Paris, France; 6Hawaii OsteoporosisCenter, Honolulu, HI; 7Michigan Bone and Mineral Clinic, Detroit,MI; 8Merck Research Labs., Rahway, NJ, USA

Alendronate sodium (ALN), a speci®c inhibitor of osteoclasticbone resorption, reduced the risk of vertebral fractures andproduced progressive increases in BMD over ®ve-years in a studyoriginally enrolling 994 postmenopausal osteoporotic women. Wereport the results from 350 women consenting to a double-blind2-yr extension after 5-years of continuous alendronate treatment.During yrs 6±7, patients in the ALN 5 mg/d and 10 mg/d groupscontinued those treatments, and patients in the ALN 20/5 mggroup (20 mg for 2 yr then 5 mg for 3 yr) received placebo (Pbo).The total increases in lumbar spine BMD were 11.4% for the 10-mg and 8.4% for the 5-mg groups over 7 yrs of ALN daily. In yrs 6±7, lumbar spine BMD increased signi®cantly by 1.6% with 10 mgand 1.5% with 5 mg. After the initial 18 months, each additional yrof treatment increased spine BMD by 0.8% for the 10 mg doseand 0.6% for the 5 mg dose. Prior increases in BMD at otherskeletal sites and decreases in biochemical markers of boneturnover remained stable during yrs 6±7. Among womenpreviously taking alendronate who were switched to Pbo, therewas no signi®cant decline in BMD at the spine or hip, whereassmall but signi®cant decreases in BMD at the forearm and totalbody, and moderate increases in biochemical markers wereobserved during the 2-yr extension. The safety and tolerabilitypro®les of ALN 5 and 10 mg were similar to Pbo. We conclude thatalendronate treatment is effective for 7 yrs, and is generally well-tolerated. Increases in spinal BMD continue for at least 7 yrs, andother skeletal bene®ts are maintained. Discontinuation does notlead to accelerated bone loss, but continuous treatment yieldsthe optimum skeletal bene®t.

544 (508). SUBCUTANEOUS COLLAGEN THICKNESS ANDDENSITY AS POSTMENOPAUSAL OSTEOPOROSIS RISKFACTOR: INFLUENCE OF THERAPIES

M. Valente, N. Buscemi, M. E. Re, C. Dettori, I Insitute of Obstetricand Gynecology, University of Rome ``La Sapienza'', Rome, Italy

Objective: The aim of this prospective study was to evaluate thereduction of subcutaneous collagen in postmenopausal osteo-porosis and possibilities of diagnosis and prevention.

Material and methods: Hundred postmenopausal women wereenrolled in our outpatient Prevention of Postmenopausal DiseaseClinic. An informed consent was obtained from all patients. Weevaluated the subcutaneous collagen decrease using an ultra-sound technique through Osteoson DCIII. According to the majoror minor collagen reduction the women were divided in twogroups (Group A and B).

Women who showed a major collagen reduction (Group A) weretreated by Ca+Vit D3 while the other (Group B) received oral HRT.Both therapies have been administered once a day, for one year.After six months there was a cross-over between the two differenttherapies.

Results: The collagen thickness has been evaluated at the sixthmonth and at the end of the study. In both groups there was anincrease of collagen thickness. All the oral HRT treated subjetsshowed during the six months a major increase than the othergroup, but not very signi®cative.


Conclusion: The follow-up we performed 60 days after therapydiscontinuity demonstrated that the effects of both therapieswere persistent.

545 (509). THE EFFECT OF ALENDRONATE TREATMENT INMEN WITH PRIMARY AND STEROID-INDUCEDOSTEOPOROSIS

V. Vyskocil1,2, J. Vyskocilova3, O. Topolcan2, K. Koudela1,1Department of Orthopedic Surgery; 2Department of BoneDisease; 3Department of Medicine II; 4Department ofTuberculosis and Respiratory Disease, Charles UniversityHospital PLZEN, Czech Republic

A total of 90 men were enrolled in the study. 90 men were treatedwith daily dose of 10 mg alendronate, 500 mg calcium and 1200IU of cholecalciferol for 12 months. Of those, 45 (mean age 48.7years) suffered from steroid induced osteoporosis due to theglucocorticoid therapy of pulmonary disorders and the remaining45 men (mean age 65.5) were diagnosed with idiopathicosteoporosis. The control group consisted of 18 men (diagnosismean age 46.5) treated with daily doses of 500 mg calcium and400 IU vitamin D for 12 months.

Both the BMD (measured by DEXA at spine, hip and femoralneck) and markers of bone turnover (S-PTH, osteocalcin, PICP, U-DPyr) were assessed at the baseline and after 12 months oftherapy. In the lumbar spine, the base-line BMD T-score was72,06 in the alendronate-steroid-treated patients and ±1,94 in thealendronate-idiopathic osteoporosis patients, while in the hipthe T-scores were ±1.2 and ±1.37; and in the femoral neck ±1.89and ±2.21 respectively. In the control group these values werespine ± 0.99, hip ±1.17 and neck ±0.6 T score.

After 12 months of treatment, there was a drop in S-PTH in bothalendronate-steroid treated and calcium-vitamin D -only treatedpatients, while in the non-steroid alendronate-treated group therewas a non-signi®cant increase in S-PTH. There was a drop in S-osteocalcin, PICP and U-DPyr in the alendronate-treated group.In the control group was decrease in all markers of boneresorption.

In the patients treated with alendronate, the BMD changes inthe spine were +3.79% in the steroid treated ones and +2.8% inthe non-steroid treated ones. Regarding the hip, the increase was+.058%, neck +2.05% in the steroid treated patients and +1.55%in hip and +2.17% neck in those not treated with steroids. In thecalcium and vitamin D group there were following changes inBMD: spine +1.28, hip ±1,38% and femoral neck ±0,74%respectively.

Alendronate is an effective antiresorptive drug in patients withboth steroid-induced and idiopathic osteoporosis. However, acombination of calcium and vitamin D remains an effectivetherapeutic tool in osteoporotic patients who never receivedcorticosteroids.

546 (510). BMD CHANGE EXPLAINS ONLY A FRACTION OFTHE OBSERVED FRACTURE RISK REDUCTION INRISEDRONATE-TREATED PATIENTS

N. Watts1, R. Bockman2, C. Smith3, Z. Li4, R. Eastell5, S. Pack6, R.Lindsay7, 1Atlanta, GA, USA; 2New York, NY, USA; 3Minneapolis,MN, USA; 4Mason, OH, USA; 5Shef®eld, UK; 6Mason, OH, USA;7West Haverstraw, NY, USA

The objective of this analysis was to establish and quantify therelationship between changes in lumbar spine BMD and vertebralfracture risk in a population of postmenopausal osteoporoticwomen taking risedronate. Patients with prevalent vertebralfractures were enrolled into 2 vertebral fracture studies (VERT-NA [North America] and VERT-MN [Multinational ± Europe andAustralasia]) and randomized (N=2457) to receive either placeboor risedronate (RIS) 5mg daily, in addition to 1g calcium daily and

vitamin D supplementation if baseline levels were 540 nmol/L. ACox proportional hazards model was used to examine therelationship between time-to-®rst vertebral fracture and lumbarspine BMD change.

In the ®gure, a positive association is observed between lumbarspine BMD increase and reduction in vertebral fracture risk inrisedronate-treated patients. The overall slope of the curveindicates that for large increases in spinal BMD (5±9%), thecorrelation between BMD increases and vertebral fracture riskreduction is weak. In contrast to the observed vertebral fracturereduction of 41±49% in the VERT trials at 3 years, the modelpredicts only a 17% reduction in vertebral fracture risk.

In summary, BMD increases explain only a portion of theobserved fracture reduction, suggesting that factors other thanbone density in¯uence the fracture reduction ef®cacy ofrisedronate.

547 (511). THE EFFICACY OF ALPHA TOCOPHERAL INPREVENTION OF OVARIECTOMY-INDUCED BONE LOSS INRAT

S. J. Wimalawansa, S. Surendran, C. Thota, A. Recinos,Department of Internal Medicine, The University of Texas MedicalBranch At Galveston, Texas, USA

Numerous studies have been conducted in order to develop andoptimize prevention and treatments of osteoporosis, but thus farthe only major class of drugs that have evolved are those thathave anti-osteoclastic bone resorption activities. Drugs that areef®cacious in promoting bone formation and also cost-effectiveare presently still unavailable. Since free radicals of oxygen areknown to accentuate bone resorption and vitamin E (D1-alpha-tocopherol) is a well-established, cost-effective antioxidant, wehave examined the ef®cacy of this compound in prevention ofovariectomized (OVX)-induced bone loss in rats. Results of eight-week treatments with a-tocopherol were compared to those withestrogen, or both of the two drugs in a combination treatment.

Ovariectomy-induce loss of bone mineral density was pre-vented by treatment with estrogen (estradiol cypionate, 100 mg/kg, once per week) as well as by tocopherol (50 IU per kg, onceper week), or by the combination treatment (p<0.01). Femurweight was signi®cantly higher in a-tocopherol-treated versusplacebo-treated OVX rats (p<0.05), and there was no difference inthese weights between a-tocopherol-treated OVX animals andsham-operated placebo-treated animals. These data suggest thata-tocopherol counteracts bone loss associated with estrogende®ciency and at appropriate doses, may be used as an effective


alternative therapy to counteract the estrogen de®ciency-inducedbone loss.

548 (512). NITRIC OXIDE DONOR, NITROGLYCERIN, IS HIGHLYEFFECTIVE IN PREVENTION AS WELL AS TREATMENT OFOVARIECTOMY-INDUCED BONE LOSS

S. J. Wimalawansa1, C Yallampalli2, 1Department of InternalMedicine; 2OB/GYN, The University of Texas Medical Branch AtGalveston, Texas, USA

Nitric oxide (NO) is known to inhibit osteoclastic bone resorption.We have demonstrated that the NO donor, nitroglycerin (NG),prevents both ovariectomy- as well as corticosteroid-inducedbone loss, as assessed by bone mineral density, bone weight,and bone histomorphometry in rats. Furthermore, using the NOsynthase inhibitors, we have shown that at least part of thebene®cial effects of estrogen on bone is mediated through NO.

In animal studies using ovariectomized (OVX) female Sprague-Dawley rats, 24±52 weeks of age, we examined the effects oftopical application of NG (Fougera, NY 2% ointment) on bonemetabolism [i.e., bone mineral density (BMD)], biochemicalmarkers of bone turnover, and bone histomorphometry and bonestrength in several studies. In these experiments we used 17b-estradiol as a positive control and compared its effects with NG.

It was demonstrated that the effects of NG are equivalent toestrogen in preventing, as well as in treating, OVX-induced boneloss. However, although applications of NG once daily (0.2 mg/kg)was highly effective in the prevention of OVX-induced bone loss,multiple applications of the same dose were ineffective. We alsoshowed that the bene®cial effects of NG are biphasic andmaximal between 0.2 and 0.5 mg/kg/day, NG applied in the AMwas more ef®cacious than that applied in the PM; and, NG wassuperior to all other NO donors we examined. Finally, wedemonstrated that effects of the combination of NG with vitaminD, calcitonin, or in particular bisphosphonates are additive inprotecting bones. However, no such additive effects are seenwhen NG was co-administered with any sex-steroid hormones(i.e., estrogen, progesterone or testosterone). These resultsindicate that at appropriate doses. NG has marked bene®cialeffects on bone metabolism.

549 (513). PREVENTION OF POSTMENOPAUSAL BONE LOSSWITH NITRIC OXIDE

S. J. Wimalawansa, Department of Internal Medicine, TheUniversity of Texas Medical Branch, Galveston, Texas, USA

Nitric oxide (NO) has been reported to inhibit osteoclastic boneresorption and possibly osteoblast stimulation. Following ourpostulation of the roles of nitric oxide (NO) in affecting osteoclasts/ osteoblasts in 1988, we have demonstrated that the NO donor,nitroglycerin (NG), prevented ovariectomy-, as well as corticos-teroid-induced bone losses as determined by changes in bonemineral density (BMD), bone weight, bone strength, and bonehistomorphometry in rats. Furthermore, using the NO synthaseinhibitor, L-NAME, we have shown that at least part of thebene®cial effects of estrogen on bone is mediated through NO.

Base on our animal studies, then we designed a one-year pilothuman clinical study (16 patients) (dose of NG=0.2 mg/kg/day) toassess the ef®cacy of NG ointment, in comparison with oralestrogen (0.625 mg/day premarin), using BMD and biochemicalmarkers as primary and secondary end points. Data from thisstudy showed that both agents prevented the expected oophor-ectomy-induced bone loss in these women (i.e., early post-menopausal bone loss). The ef®cacy of NG therapy was similar tothat of estrogen (premarin) in maintaining BMD. Biochemicalvariables showed a ~30% reduction in urinary NTx levels withboth estrogen and NG. However, the women treated with NG hada 53% increase of serum osteocalcin, and 27% increase of bone-speci®c alkaline phosphatase levels, suggesting a positive effect

on the bone homeostasis. This, prospective, randomized, controlclinical study demonstrates for the ®rst time that NG can be usedin postmenopausal women as an alternative therapy to estrogenin postmenopausal women for the prevention of estrogende®ciency-associated bone loss. However, a larger study isnecessary to con®rm these ®ndings.

550 (514). ONCE WEEKLY RISEDRONATE THERAPY

Grattan Woodson, Atlanta Research Center, Decatur, GA

Introduction: Once weekly therapy of osteoporosis with a potentbisphosphonate drug is an attractive option for several reasons.First, the mechanism of action of this class suggests that onceweekly treatment should be effective. Second, reducing thenumber of times the patient has to take a tablet is likely toimprove compliance. Lastly, less frequent exposure of the GI tractto these agents is likely to improve their tolerability.

Methods: 13 Caucasian women with postmenopausal osteo-porosis who were intolerant of other FDA approved therapies forthis disease were treated with risedronate (P&G P, Cincinnati, OH)30 mg po once weekly on an empty stomach ®rst thing in themorning for 12 months. BMD was measured by DXA in the PAlumbar spine, the femoral neck, and the total hip sites with aHologic 4500A (Hologic Inc, Bedford, MA).

Results: All patients tolerated the therapy well. The patient'saverage age at the beginning of therapy was 64 years. The meaninitial T-scores for the PA lumbar spine, the femoral neck, and thetotal hip sites were ±2.21, ±2.02, and ±1.63 respectively.

Summary: Once weekly therapy with the bisphosphonate,risedronate, appears to be an effective and well-toleratedosteoporosis therapy in this small group of osteoporosis patients.

551 (515). BONE MINERAL DENSITY (BMD) AND FRACTURERISK REDUCTION WITH ALENDRONATE

J. Yates, K. Faulkner, P. J. Meunier, 1Merck Research Labs,Rahway, NJ; 2Synarc, Inc., Portland, OR; 3Dept. Rheum. and BoneDiseases, Edouard Herriot Hospital, Lyon, France

Most of the variability in bone strength is related to BMD, and inepidemiological studies, each SD (approximately 10±15%)difference in spine BMD is associated with around a 1.5-folddifference in vertebral fracture incidence. Alendronate increasesspine BMD vs. placebo by about 9% after 3 years. If the quality ofalendronate-treated bone was unchanged and the distribution ofrestored bone was equivalent to that in untreated subjects withthe same spine BMD, such an increase would be expected toresult in a 20±30% decrease in vertebral fracture incidence,whereas the observed effect is close to 50%. This differencecould be accounted for by at least three possible mechanisms,which are not mutually exclusive:

1) More favorable distribution of bone at a macroscopic level.BMD increases far more at cancellous sites (important forvertebral body strength) vs. cortical sites, but may be under-estimated by DXA, which measures composite bone mass whichconsists predominantly of cortical bone.


2) More favorable distribution of bone at a microscopic level.High turnover results in microarchitectural deterioration and moreactive resorption sites, which compromise the strength ofindividual trabeculae. Decreasing turnover ameliorates or re-verses these effects.

3) More favorable degree of mineralization of bone. Highturnover is also associated with hypomineralization of bone, sincemuch of the bone is immature because time for secondarymineralization is shortened. New data for alendronate, obtainedfrom quantitative microradiography and presented at this meeting(Boivin et al.), show that much of the observed increase in BMDwith alendronate is related to improved degree of mineralization.

These factors collectively appear to adequately account for thesubstantial fracture risk reduction seen with alendronate and thecontribution of any extraskeletal effects of alendronate seemsimplausible, due to its speci®city for bone. Further research isrequired to elucidate the relative contributions of these mechan-isms.

552 (516). RALOXIFENE IN POSTMENOPAUSAL OSTEOPENICWOMEN WITH MILD ASYMPTOMATIC PRIMARYHYPERPARATHYROIDISM

J. R. Zanchetta, C. E. Bogado, 1Instituto de InvestigacionesMetabolicas; 2USAL University School of Medicine, Buenos Aires,Argentina

Currently, a signi®cant decline in bone mass in patients withprimary hyperparathyroidism is considered an indication forsurgical intervention. Since skeletal status has such an importantin¯uence on the management of patients with primary hyperpar-athyroidism, there is a clear need to assess the ef®cacy of potentialtherapies for preventing bone loss. We report here the effects of 12months treatment with raloxifene on BMD and biochemicalparameters in 3 postmenopausal osteopenic women (mean age64, range 59±67 years; mean baseline lumbar spine T score ±1.92)with mild, asymptomatic primary hyperparathyroidism.

During the study, intact parathyroid hormone levels did notchange (baseline = 73�14.5, 12 months = 75.7�19.6 pg/ml;p = 0.799). There was a trend for decrease in both total andionized calcium levels, but did not reach statistical signi®cance.Serum phosphate levels decreased signi®cantly (baseline =3.1�0.5, 12 months = 2.8�0.3; p = 0.042). Urinary markers ofbone resorption decreased signi®cantly with treatment. Deox-ypyridinoline excretion had decreased by 44% after 6 months(p<0.01 compared with baseline) and by 49% after 12 months(p<0.01); fasting calcium excretion was 47% lower at 6 months(p<0.05) and 52% lower at 12 months (p<0.05). On the other hand,serum total alkaline phosphatase did not change signi®cantly.Bone mineral densities increased by 3.8% at lumbar spine and by3.3% at femur neck after 12 months of treatment.

Our results suggest that raloxifene may be an alternativetreatment for preventing bone loss in postmenopausal osteope-nic women with mild, asymptomatic primary hyperparathyroid-ism. Larger, controlled studies are needed to con®rm the ef®cacyof raloxifene treatment in this group of patients.

553 (517). EFFECT OF FRACTURE ON HEALTH CAREUTILIZATION OF NURSING HOME RESIDENTS

S. I. Zimmerman1, J. M. Chandler2, W. Hawkes3, P. D. Sloane4, J.R. Hebel5, J. Magaziner6, A. R. Martin7, C. J. Girman8, 1Universityof North Carolina, Chapel Hill, USA; 2Merck ResearchLaboratories, Blue Bell, PA, USA; 3University of Maryland,Baltimore, USA; 4University of North Carolina; 5University ofMaryland; 6University of Maryland; 7Merck ResearchLaboratories; 8Merck Research Laboratories,

Purpose: Medical care after fracture is not known for nursinghome residents, whose fracture rates are markedly higher than

community-dwellers. Knowing the degree of care followingfracture can help determine the effect of prevention on utilizationand costs.

Procedures: A prospective cohort study, with 18 months offollow-up, of 1427 randomly-selected white female residentsages 65+ from 47 randomly selected nursing homes in Maryland,USA.

Findings: Nursing home residents who fractured were hospita-lized more than six times as often as those who did within sixmonths of fracture (RR: 6.30, 95% CI: 4.05±9.81); rates ofemergency department use, contacts with physicians, andtherapy were also increased. Those who fractured were receivingmore PT/OT before their fracture, and less therapy by six monthspost-fracture.

Conclusions: Higher utilization rates continued beyond the ®rstsix months following fracture, and the pattern of utilizationchanged for hospitalization (for hip fracture) and therapy (for allfractures). Efforts to lessen residual utilization and to maximizefracture prevention are worthwhile.

Plenary Session 9: Treatment 2(Saturday, June 17, 1500±1700)

554. EFFECTS OF ``FREQUENCY-SPECIFIC'' IMPACT LOADINGON BONE MASS OF THE HIP: A PRELIMINARY REPORT

D. Hans1, L. Genton1, M Drezner2, R. Paci®ci3, L Avioli3, P JMeunier4, 1Geneva University Hospital, Switzerland; 2DukeUniversity, USA; 3Washington University, USA; 4Lyon University,France

Over a century ago, Wolff hypothesized that the skeletaladaptation to its physical environment is a function of both themagnitude and direction of the applied external force, resulting inoptimizing the response to local stress. While it has beenrecognized that weight-bearing physical activity and mechanicalstress upon bones may help prevent bone loss, the optimum formof exercise essential to initiate and maximize a skeletal responseis still to be determined. It also illustrates the likelihood thatadditional factors may play a primary role in the formation of newbone. Based on Bassett's prior work, the aim of the current studywas to further test the hypothesis that an impactive mechanicalsignal of speci®c frequency and adequate amplitude is pre-dictably appropriate for the reduction of bone loss and rebuildingof bone mass in the hip.

The study was a 24 month, multi-center, randomized, prospec-tive study. 157 women aged from 60±85 years were enrolled atthree different centers. A total of 99 active patients used theOsteocare1 device to perform precise axial signal stimulationdaily (active group). 32 controls performed the same motion on theunit but without triggering a signal stimulation (sham group) and26 control patients did no prescribed exercise (control group). HipDXA was performed at regular intervals. To evaluate theeffectiveness of any weightbearing program to strengthen the


hip, Wolff's law must be taken into account. As a consequence,speci®c de®nitions had to be developed to classify patientresponse as ``gainer'', ``maintainer'' or ``loser''. These criteriawere set up prior to beginning the trials after extensivediscussions between the major investigators and statisticians. Inconclusion, over 75% of the active signal patients responded bymaintaining or increasing site speci®c BMD over the 2 year trials.

555. OSTEOPROTEGERIN (OPG) AND PARATHYROIDHORMONE HAVE ADDITIVE EFFECTS ON BONE MASS INAGED OVARIECTOMIZED RATS

P. J. Kostenuik, C. Capparelli, S. Morony, D. Lacey, C. Dunstan,Amgen Inc., Thousand Oaks, CA, USA

Osteoprotegerin (OPG) is a novel and naturally occurringantiresorptive protein which inhibits osteoclast formation, func-tion, and survival. Recombinant OPG (rOPG) prevents osteopeniain the acute ovariectomized (OVX) rat. Established osteopenia inaged rats presents a signi®cant challenge to anti-resorptivetherapy. We tested the effects of rOPG, alone or with intermittentPTH-(1±34), in an aged OVX rat model of established osteopenia.SD rats, 18 months old and 15 months post-OVX, were treatedthree times/week for 5.5 months with vehicle (VEH), rOPG (10 mg/kg SC), PTH (0.08 mg/kg, SC), or rOPG + PTH. OVX resulted in asigni®cant decrease in bone mineral density (BMD, by DEXA) inthe lumbar vertebrae (LV) and in the distal femur (FEM). Asmonotherapies, both OPG and PTH signi®cantly increased BMDin the LV and FEM, compared to VEH. These effects were morepronounced with PTH than with OPG. In combination, rOPG +PTH caused signi®cantly greater increases in BMD at both sites,compared to each monotherapy. Histologically, PTH aloneincreased osteoclast (Oc) surface in the LV by 50%, while rOPGalone decreased Oc surface by 99%. Oc surface in the PTH +rOPG rats was reduced by 94% and 96% compared to VEH orPTH monotherapy, respectively. Osteoblast surface was similar inall treatment and control groups. In conclusion, these dataindicate that, 1) bone resorption is not required for the anaboliceffect of PTH; 2) in aged and severely osteopenic OVX'd rats, bothrOPG and PTH are effective monotherapies for increasing bonemass; 3) rOPG + PTH is more effective than rOPG or PTH alone inincreasing bone mass, which suggests that this combination mayhave clinical utility in reversing post-menopausal osteoporosis.

556. DOES TREATMENT WITH PARATHYROID HORMONEINCREASE VERTEBRAL SIZE?

R. Lindsay, F. Cosman, J. Nieves, L. Woelfert, 1Helen HayesHospital, W. Haverstraw, NY, USA

Parathyroid hormone promises to be an exciting agent for thetreatment of osteoporosis. Unlike currently available treatmentsPTH stimulates bone formation. The effect is most clearly seenin cancellous bone presumably because of its greater surface tovolume ratio. Increased bone formation in the cortical boneenvelope has also been reported, but increased remodeling alsoproduces cortical tunneling, which potentially could weakencortical bone. This could be offset by increases in the overallwidth of the bone, which would have a much greater positiveeffect on bone strength. To examine whether there is evidenceof increased bone size, we have evaluated DXA data from our 3year randomized study of 1±34hPTH in 52 postmenopausalwomen with osteoporosis, already established on HRT. PTH wasgiven (n=27) by daily subcutaneous injection in a dose of 25mcgfor 3 years. Bone mineral density was performed at 6 monthlyintervals by DXA using a Hologic QDR 1500. Radiographs of thedorso-lumbar spine were obtained annually throughout thestudy. Bone mineral content in lumbar spine increased by

18.9% (p<0.001) over the three years of treatment in the PTH +HRT group, with a 3% increase in the HRT alone group. Thearea of the lumbar vertebrae increased also by 5.5% (p<0.01)during three years of treatment with PTH. With HRT the areaincreased 2% (n.s.), signi®cantly less than in the PTH group.Fifty percent of the area increase was seen during the ®rst yearof treatment, with the remainder occurring linearly during the®nal 2 years. Area increase correlated with the increase in BMC,but in the PTH + HRT group the change in area accounted foronly 36% of the variance in BMC (vs 64% in HRT group). Nosigni®cant changes in area were found on radiographs. Fracturerisk is related to both BMC and bone size. If the increase invertebral size observed here represents new periosteal boneformation such bone growth could contribute signi®cantly tofracture prevention with PTH.

557. PRELIMINARY OUTCOMES OF THE FIRST 226CONSECUTIVE KYPHOPLASTIES FOR THE FIXATION OFPAINFUL OSTEOPOROTIC VERTEBRAL COMPRESSIONFRACTURES

J. M. Lane1, F. Girardi2, H. Parvataneni3, S. N. Khan4, M. A.Reiley5, I. H. Lieberman6, S. R. Gar®n7, H. A. Yuan8, 1Hospital forSpecial Surgery, NY; 2HSS, NY; 3HSS, NY; 4HSS, NY; 5Berkely,CA; 6Cleveland Clinic, Cleveland, OH; 7UCSD, San Diego, CA;8SUNY, Syracuse, NY

Purpose: A prospective multicenter investigation was performedto determine the ef®cacy and safety of minimally invasivereduction and ®xation of painful osteoporotic vertebral bodycompression fractures, utilizing percutaneous In¯atable BoneTamps.

Methods: The ®rst 226 consecutive kyphoplasties (121patients) were evaluated. The average age was 73.7 years(range 40±90) with 71% female. 1.6 levels were performed pereach procedure with an average of 1.16 procedures performedper patient. 1.87 vertebral fractures were treated per patient witha maximum of 7 levels in 1 patient. 44% of the fractures werethoracic and 56% were lumbar. Diagnosis included primaryosteoporosis (69%) secondary osteoporosis (21%) and multiplemyeloma (5%) and other (6%). All patients had failed conservativemedical management.

Results: The ®rst 30 patients demonstrated a 45% restorationof body height anteriorly, 71% mid-line, and 54% posteriorly. Theaverage reduction in kyphosis was 17%. 75 patients wereevaluated for functional relief and in that group 1 patient wasworse, 2 patients had no change, and 72 patients had good toexcellent pain relief. Of the 226 kyphoplasties there was 1 incidentof epidural bleed requiring decompression (full recovery), 1incomplete spinal cord injury, and 1 case of transient ARDS. Noepisodes of infection, PE, or myocardial disease were reported.

Conclusion: Kyphoplasty offers a highly successful method toprovide marked rapid pain relief in (96%) patients with compres-sion fractures that have failed medical management. There is lessthan a 1% complication rate per kyphoplasty which comparesfavorably with a 6% complication rate for vertebroplasty.Kyphoplasty acutely reduces the fracture and kyphosis in afresh fracture and is able to deliver methylmethacrylate in acontrolled and predictable fashion. Kyphoplasty therefore offers asolution for pain and deformity and rapid rehabilitation of thepatient while awaiting the later bene®ts of medical intervention.

558. EARLY APPLICATION PEMF OF IN OSTEOPOROTICVERTEBRAL FRACTURES: CLINICAL ADVANTAGES

O. Moreschini, A. Ramieri, M. Nocente, Orthopaedic andTraumatology, University ``La Sapienza''Rome, Italy

In treatment of osteoporotic vertebral fractures, application ofpulsed electromagnetical ®elds (PEMF) may alleviate acute pain,


reduce assumption of pain-killers and immobilization times whileimproving tolerance of the orthopedic vest. In this study 107 post-menopausal, osteoporotic females with single thoracic or lumbarfractures without neurological involvement were considered. Onthe basis of standard X-ray ®lms, they were divided according toMagerl's classi®cation into A1, A2 or A3.1 fractures. Fifty-sevencases (group A, median age 68.4 yrs) were treated using PEMF for49�25 days with applications lasting 6.4�2.8 hrs per day. Theother 50 cases (group B, median age 65.9 yrs) were not treated byPEMF and represented the control group. PEMF application wasbegun 2 days after trauma (range 1±4). Both groups were treatedconservatively (bed-rest, pain-killers and/or muscle relaxants,orthopedic vest). X-ray ®lms were performed after trauma andthen 15, 30, 60, 90 and 120 days later to evaluate evolution of thefracture and any compression of other bodies. Data regardingpain Prolo's classi®cation), medication and orthopedic vestcompliance were compared in the 2 groups for the ®rst 3±6months. Application of PEMF during the acute phase in patientswith osteoporotic vertebral fractures helped to reduce adminis-tration times of pain-killers (group A; average 18 days, group Baverage 24.7 days). In group A, painful symptoms improved morerapidly, compliance was superior and patients regained the abilityto walk earlier. The better clinical results obtained using PEMFseem to suggest that they favour the consolidation process andreduce the risks connected with necrosis of the fragments.

559. RISEDRONATE REDUCES HIP FRACTURE RISK INELDERLY WOMEN WITH OSTEOPOROSIS

M. McClung1, R. Eastell2, W. Bensen3, C. L. Benhamou4, C.Chesnut5, S. Adami6, J. DiGennaro7, D. Axelrod8, J-Y. Reginster9,1Portland, OR, USA; 2Shef®eld, UK; 3Hamilton, Ontario, Canada;4Orleans, France; 5Seattle, WA, USA; 6Verona, Italy; 7Mason, OH,USA; 8Mason, OH, USA; 9Liege, Belgium

The Hip Intervention Program (HIP) is the ®rst to investigate abisphosphonate with hip fracture ef®cacy as a primary outcome.A total of 9331 patients were classi®ed as the intent-to-treatpopulation: Group 1 patients (N=5445) were less than 80 years oldand were required to have low FN BMD (T-score 5±3) and at leastone additional clinical risk factor for hip fracture. Group 2 patients(N=3886) were at least 80 years old and required to have at least 1clinical risk factor for hip fracture or FN T-score 5±4. Fifty-eightpercent of patients in Group 2 were enrolled on the basis ofdif®culty standing, poor tandem gait, and fall-related injuries inthe previous 12 months. Group 2 BMD status was known in 31%of patients. Patients received risedronate (RIS 2.5 or 5mg) orplacebo daily for 3 years, and 1g calcium daily, and vitamin D iflevels were low (less than 40 nmol/L).

Overall in Group 1, RIS reduced the risk of hip fracture by 39%over 3 years in women with low FN BMD compared to control(p = 0.02). In Group 1 women with both low FN BMD and at leastone prevalent vertebral fracture, the risk of hip fracture wasreduced by 58% vs. control (p = 0.004; NNT=28). No effect on hipfracture risk was observed in Group 2. In Group 2 control patients,hip fracture incidence in those with FN T-score > ±2.5 (2.8%) wassimilar to the incidence in those without BMD assessment (3.4%).Compared to those with FN T-score 4±2.5 (10.7%), theimplication is that Group 2 patients were generally notosteoporotic.

In summary, risedronate treatment signi®cantly reduced therisk of hip fractures in women with osteoporosis as con®rmed bylow FN BMD. The ®ndings in Group 2 suggest that clinical riskfactors alone may not predict response to antiresorptive therapy.This ®nding stresses the need to properly identify patients at riskwho will bene®t from an anti-resorptive therapy to prevent hipfracture.

Plenary Session 10: Treatment 3(Sunday, June 18, 0800±0930)

560. EFFECTS OF RALOXIFENE AND HORMONEREPLACEMENT THERAPY ON MARKERS OF INFLAMMATIONIN HEALTHY POSTMENOPAUSAL WOMEN

D. A. Cox1, A. Sashegyi1, S. Paul1, R. A. Dean1, R. P. Tracy2, B. W.Walsh3, P. W. Anderson1, 1Lilly Research Laboratories,Indianapolis, IN; 2University of Vermont, Burlington, VT; 3Brighamand Women's Hospital, Boston, MA

Background: In¯ammatory cytokines may play a role in post-menopausal osteoporosis and atherosclerosis. Hormone replace-ment therapy (HRT) and raloxifene (RLX) inhibit postmenopausalbone loss and improve certain markers of cardiovascular disease.Their effects on in¯ammatory markers remain unclear.

Objective: To determine the effects of HRT or RLX on TNFa, IL±6, and C-reactive protein (CRP) serum levels in postmenopausalwomen.

Methods: 390 healthy postmenopausal women (45±72 years)randomly received continuous combined HRT, RLX (60 mg/d or120 mg/d), or placebo for 6 months. A subset of baseline andendpoint sera samples (N=187) were assayed for TNFa, IL±6 andCRP. Baseline to endpoint changes were compared. Results:HRT and both doses of RLX signi®cantly decreased serum TNFa.Neither treatment signi®cantly affected serum IL±6 levelscompared with placebo, although IL±6 tended to increase withHRT. HRT, but not RLX, signi®cantly increased serum CRP levels.

Conclusions: Serum levels of TNFa, a mediator of bone lossinduced by estrogen de®ciency, is decreased signi®cantly byboth HRT and RLX in postmenopausal women. HRT and RLXhave opposite effects on CRP, an independent risk factor forcardiovascular events. Changes in IL±6 with treatment tended toparallel those of CRP, although no signi®cant changes comparedwith placebo were observed. Assessing the clinical conse-quences of these effects requires further study.

Median Baseline to Endpoint Change

Placebo HRT RLX 60 RLX 120(n=47) (n=39) (n=51) (n=50)

TNFa +0.04 ±0.29 ±0.46 ±0.30(pg/ml) (+1.6%) (±9.3%)* (±3.5%)* (±10.8%)#IL±6 ±0.05 +0.07 ±0.05 ±0.02(pg/ml) (±3.6%) (+6.9%) (±3.1%) (±1.3%)CRP +0.01 +0.72 ±0.03 ±0.01(mg/L) (+2.1%) (+82.6%)* (±1.9%) (±1.9%)

*p<0.001 vs. placebo; #p = 0.003 vs. placebo.

561. EFFECT OF THREE YEARS RALOXIFENE THERAPY ONFALLS AND NEUROMOTOR FUNCTION IN OSTEOPOROTICPOSTMENOPAUSAL WOMEN

S. Sarkar1, K. Yaffe2, K. A. Krueger1, D. A. Cox1, M. H. Fisher1,1Lilly Research Laboratories, Indianapolis, IN; 2UCSF, SanFrancisco, CA

We studied the effect of raloxifene (RLX), a selective estrogenreceptor modulator used for the prevention and treatment ofpostmenopausal osteoporosis, on risk of falls and neuromotorfunction in older women. 7705 osteoporotic postmenopausalwomen (mean age, 67 years), enrolled in the Multiple Outcomes ofRaloxifene Evaluation study, were randomly assigned to placeboor RLX (60 mg or 120 mg) daily for 3 years. Neuromotor functiontests assessing static balance (3 stances), lower extremity musclestrength (time to stand/sit 5x), and gait (# steps to walk 13 feet)were administered at baseline and 6, 12, 24, 36 months. Reports

Saturday/Sunday,June18, 2000 S207

of falls and near-falls were collected at each visit. There were nodifferences among placebo, RLX 60, and RLX 120 groups in thepercentage of women reporting at least one fall (56%, 55%, and56%, respectively; P=0.91) or near-fall (35%, 37%, 35%; P=0.32)during the study. There were no overall treatment groupdifferences in mean changes from baseline on the neuromotortest scores (Table). Among potentially frail women (those in thelowest decile of body mass index), baseline-adjusted lowerextremity muscle strength after 3 years was better in womenassigned to RLX compared with placebo (12.8 vs. 13.4 sec;P=0.01). RLX treatment for 3 years does not affect the risk of fallsor neuromotor function in osteoporotic postmenopausal women.RLX may improve lower extremity muscle strength in women withlow body mass index.

Mean 3-Year Percent Change from Baseline

Test PLN = 2230

RLX 60N = 2194

RLX 120N = 2194

P-value

Static Balance (:=better) 1.5�0.7 1.6�0.5 0.9�0.5 0.61Muscle Strength (;=better) 4.6�0.9 2.6�0.8 2.6�0.8 0.13Gait (;=better) 3.9�0.4 3.7�0.4 4.1�0.4 0.74

562. HIP PROTECTOR TRIAL IN JAPANESE NURSING HOMES

A. Harada, M. Mizuno, M. Takemura, National Chubu Hospital,Obu, Japan

The purpose of our study is to investigate the effect of the hipprotector on prevention of hip fractures in Japanese nursinghomes. We performed the hip protector trial from July, 1996, toSeptember, 1999. One hundred sixty-four elderly female residentswith ADL above wheelchair level agreed to participate in thisstudy, among these 88 were randomly selected to wear a hipprotector and 76 controls did not. All falls and resulting injurieswere recorded daily. In the anthropometric measurement andultrasonic evaluation of calcaneal bone, no signi®cant differenceswere noticed between the two groups, except height. Twenty-three wearers and 8 non-wearers dropped out within six months.During an average of 1.3 years during which the remaining 65wearers and 68 non-wearers continued the trial, they fell a total of123 times, and 89 times, respectively. Among the wearers, therewere two non-hip fractures and one hip fracture, so the annual hipfracture rate was calculated at 1.2%, against 8 hip fracturesamong the wearers, or 9.1% per year. The frequency of hipfractures was signi®cantly lower among the wearers than non-wearers (Fisher's exact p = 0.03), while the incidence of falls andthe frequency of fallers remained the same. It is supposed thatthe hip protector is a bene®cial method for the prevention of hipfractures.

563. CAN ALENDRONATE BE TAKEN BEFORE LUNCH ORDINNER? A RANDOMIZED TRIAL IN OSTEOPOROTICWOMEN

P. P. Delmas, E. Confavreux, G. Genolet, P. Gamero1, B. Gibelin2

C. Folens2. J. Yates3. From Inserm Research Unit 403 and Cl.Bernard University, Lyon, France, 1Synarc, Lyon, 2M.S.D., Paris,France and 3MRL Rahway, USA

The current mode of administration of alendronate (FOSAMAX1)is very strict and experienced as constraining by some patients.In order to test the ef®cacy of other dosing schedule, werandomized 139 postmenopausal women (67�5 year old) withosteoporosis (mean spine T score ±2.8) to 3 dosing regimensofalendronate, 10 mg/day, in an open label design: � hour beforebreakfast, 1 hour before lunch, or 1 hour before dinner. Allpatients had been fasting for at least 4 hr before takingalendronate. The primary objective is to analyze the effects of

the 3 dosing regimens on the 6 month decrease of thefollowing markers: serum osteocalcin (OC) measured by IRMA(Elsa OsteoTM, Cis), serum bone alkaline phosphatase (BAPAlkphaseTM, Metra), serum and urinary type I collagen Ctelopeptide (CTX, crosslapsTM, Osteometer) measured byELISA. The decrease in bone turnover of the ®rst 84 patientsthat completed 3 months of treatment was highly signi®cant(p<0.001 for all markers in each group) and did not differsigni®cantly between the 3 dosing groups.

% decrease (SE) at 3 months of

Patient groups n OC BAP sCTX uCTX

1 before breakfast 31 ±32 (1.6) ±28 (2.4) ±54 (7.5) ±69 (5.9)

2 before lunch 26 ±31 (2.9) ±24 (3.9) ±58 (5.5) ±72 (4.7)

3 before dinner 27 ±25 (2.7) ±26 (3.0) ±48 (5.8) ±65 (4.2)

In addition, the percentage of responders was not differentbetween groups. For example, the % of patients of groups 1, 2and 3 who showed a 540% decrease of urinary CTX was 87%,92% and 93% respectively. In conclusion, this interim analysissuggests that alendronate 10 mg daily given either I hour beforelunch or dinner in patients fasting for 4 hours, has the sameef®cacy in decreasing bone turnover as alendronate given fasting� hour before breakfast.

Plenary Session 11: Treatment 4(Sunday, June 18)

564. RISEDRONATE RAPIDLY REDUCES VERTEBRALFRACTURE RISK IN PATIENTS WITH VARYING DEGREES OFOSTEOPOROTIC SEVERITY

R. Eastell1, J. Prendergast2, M. Molloy3, J. Adachi4, P. Miller5, S.Pack6, N. Watts7, 1Shef®eld, UK; 2Atherton, CA, USA; 3Cork, UK;4Hamilton, ONT, Canada; 5Lakewood, CO, USA; 6Mason, OH;7Atlanta, GA, USA

In 5 studies from the risedronate (RIS) clinical program, wedetermined vertebral fracture ef®cacy at 1 year in patientsenrolled across a range of risk factors for vertebral fracture.Two studies enrolled 3684 postmenopausal osteoporotic womenat risk for vertebral fracture, in either North America (VERT-NA) orin Europe and Australasia (VERT-MN [multinational]). The HipIntervention Program (HIP) enrolled 9331 postmenopausalwomen at risk for hip fracture. Two studies enrolled 518 menand women either initiating (study RCP) or continuing (study RCT)oral corticosteroids. Patients in the VERT and HIP studiesreceived RIS 2.5 or 5mg, or placebo, daily for up to 3 years,and 1g calcium (Ca) daily and vitamin D supplementation ifnecessary. Patients in RCP and RCT took RIS 2.5 or 5mg, orplacebo, daily for 1 year; RCP patients took 500mg Ca daily, RCTpatients took 1g Ca and 400 IU vitamin D daily.

In the table below, a consistent reduction in vertebral fracturerisk is observed at 1 year for RIS 5mg vs. control across allstudies re¯ecting patients with varying degrees of osteoporoticseverity and vertebral fracture risk. Number of patients needed totreat (NNT) to prevent a fracture in one year is also correspond-ingly favorable.

1 Year Vertebral Fracture Risk Reduction ± RIS 5mg vs. Control

Study Risk Reduction CI, % p NNT

VERT-NA 65% 38±81 <0.001 25VERT-MN 61% 32±78 <0.001 14HIP 55% 33±70 <0.001 38RCT + RCP 70% 26±89 0.01 10

S208 Sunday,June18, 2000

In conclusion, risedronate consistently demonstrated a rapidantifracture bene®t in patients with various risk factors forosteoporosis. An antiresorptive therapy that provides this rapidbene®t is important in treating patients at risk for vertebralfracture.

565. A NEW TREATMENT PARADIGM: QUARTERLYINJECTIONS OF IBANDRONATE REDUCE THE RISK OFFRACTURES IN WOMEN WITH POSTMENOPAUSALOSTEOPOROSIS (PMO): RESULTS OF A 3-YEAR TRIAL

R. R. Recker1, J. A. Stakkestad2, D. Felsenberg3, C. H. ChesnutIII4, C. Christiansen5, M. P. Ettinger6, A. Nordby7, S. R. Weiss8, H.Huss8, T. Von Stein10, D. B. Karpf11, for the Ibandronate I.V. StudyGroup, 1Creighton U., Omaha, NE, USA; 2CECOR AS, Haugesund,Norway; 3U. Benjamin Franklin, Berlin, Germany; 4U. Washington,Seattle, WA, USA; 5CCBR, Ballerup, Denmark; 6CRCSF, Stuart,FL, USA; 7Central Radiol. Inst. AS, Trondheim, Norway; 8Del Mar,CA, USA; 9Roche, Mannheim, Germany; 10Roche, Palo Alto, CA,USA; 11Roche, Palo Alto, CA, USA

The nitrogen-containing bisphosphonates (N-BPs) have demon-strated substantial ef®cacy in the treatment of PMO, but havedrawbacks in terms of poor oral absorption, rigid dosingrequirements and GI side effects. Due to its very high potency,Ibandronate (IBN) is a N-BP under development for treatment andprevention of PMO both as an oral formulation (daily or weekly),and as an i.v. injection administered 4 times per year over as littleas 10 seconds. This mode of administration provides 100%bioavailability, avoids food/drug interactions and the known riskof GI irritation, and thus should enhance longterm patientcompliance.

Methods: In 1995±1996, 2,862 postmenopausal women from 11countries in North America and Europe with spine bone mineraldensity (BMD) T-score 4±2 and at least 1 vertebral fracture wererandomized to receive double-blind placebo or IBN 0.5 or 1.0 mgby i.v. injection every 3 months for 3 years. All patients received500 mg/d of calcium and 400IU vitamin D.

Results: Final results for the primary endpoint of vertebralfractures, as well as for BMD, bone turnover, and safety will bepresented.

566. THERAPEUTIC EQUIVALENCE OF ALENDRONATE (ALN)35-MG ONCE WEEKLY (OW) AND 5-MG DAILY (D) IN THEPREVENTION OF POSTMENOPAUSAL OSTEOPOROSIS

M. Luckey1, K. Insogna2, N. Gilchrist3, H. Bone4, M. Davie5, T. DeVilliers6, J. Orloff7, A. Santora7, M. Wu7, J. Yates7, 1OsteoporosisCenter, Livingston, NJ; 2Yale U., New Haven, CT; 3PrincessMargaret Hospital, Christchurch, New Zealand; 4Michigan Bone &Mineral Clinic, Detroit, MI; 5Jones & Hunt Orthopedic Hospital,Shropshire, UK; 6Capetown, South Africa; 7Merck Research Labs,Rahway, NJ, USA

Background: Dosing convenience is a key element in the long-term management of osteoporosis. Animal data support therationale that OW dosing with ALN 35 mg (7 x daily oral preventiondose) should prevent bone loss as effectively as ALN 5 mg D, andmay reduce the potential for esophageal irritation. This dosingregimen would provide patients with greater convenience andmay enhance patient compliance.

Methods: We compared the ef®cacy and safety of treatmentwith ALN 35 mg OW (n=362) and ALN 5 mg D (n=361) in a one-year, double-blind, multicenter study of postmenopausal women(56 months) aged 40 to 70 years with lumbar spine [LS] andfemoral neck BMD T-scores above ±2.5 (mean baseline LS T-score = ±0.9). The primary ef®cacy endpoint was the compar-ability of LS BMD increases de®ned by strict prespeci®ed criteria.

Results: Mean increases in LS BMD at 12 months wereequivalent (see ®gure). BMD increases at other skeletal sitesand effects on bone turnover were also virtually identical for thetwo dosing regimens. All treatment regimens were well toleratedwith no increased frequency of upper GI adverse events with thelarger weekly unit dose.

Conclusion: OW alendronate 35 mg is therapeutically equiva-lent to alendronate 5 mg D, providing patients with the provenef®cacy of ALN, good tolerability and greater dosing conve-nience.

567. IN POST-MENOPAUSAL OSTEOPOROTIC WOMEN,ALENDRONATE AUGMENTS BONE STRENGTH BYINCREASING THE DEGREE OF MINERALIZATION OF BONETISSUE

G. Boivin1, A. C. Santora2, J. Yates2, P. J. Meunier1, 1INSERMUnite 403, Faculte Medecine R. Laennec, Lyon, France; 2MerckResearch Laboratories, Rahway, NJ, USA

The mean degree of mineralization of bone (MDMB) wasmeasured by quantitative microradiography on transiliac bonebiopsies taken from 53 postmenopausal osteoporotic womenwho had been treated with alendronate (ALN, 10 mg/day) for 2 (9patients) or 3 years (16 patients) or with placebo (PLA, 15 and 13patients, respectively). In the same patients, bone mineral density(BMD) values were obtained by DXA on lumbar spine at thebeginning and end of treatment. Histomorphometric parameterswere also measured on the iliac biopsies. After 2 years of ALN,MDMB in compact bone was 9.3% (p = 0.0035) and in cancellousbone was 7.3% (p = 0.0009) higher versus PLA, respectively. After3 years of ALN, MDMB in compact bone was 11.6% (p = 0.0002)and in cancellous bone was 11.4% (p = 0.0001) higher versus PLA,respectively. After 2 and 3 years of ALN, the distribution of thedegrees of mineralization in compact and cancellous bone clearlyshowed a shift towards the higher mineralization values and adecrease of the basic structure units (BSUs) having low values ofmineralization. The between group differences in MDMB werecompared to those in lumbar spine BMD (+8.7% and +9.6% after2 and 3 years, respectively), and to the histomorphometric results(no detectable change in cancellous bone volume, trabecularthickness or other microstructure parameters, marked reductionof activation frequency). Present results suggest that a major partof the increase in BMD induced by ALN is explained by the MDMBaugmentation. They support the hypothesis that the reduction inthe activation frequency caused by the antiresorptive effect ofALN is followed by a prolonged secondary mineralization whichincreases the percentage of BSUs having higher degrees ofsecondary mineralization and, through this mechanism, MDMB.That these effects contribute to improved bone strength isdemonstrated by the reduction in fracture incidence previouslydemonstrated in these patients.

Sunday,June18, 2000 S209

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