Persistent Osteopenia after Recovery fromAnorexia Nervosa

Anne Ward,* Nigel Brown, and Janet Treasure

Eating Disorders Unit, Institute of Psychiatry, DeCrespigny Park,London SE5 8AF, U.K.

Accepted 5 February 1996

Abstract: Objective: Osteopenia is a known complication of anorexia nervosa. Most studieshave focused on the features of the illness which predict bone complications. The few reportson recovery have been conflicting, with some studies suggesting restoration of normal bonemass with recovery from anorexia nervosa, while others suggest that the improvement mayonly be partial. This is the first report of bone density in a long-term recovered group.Method: We measured bone density in the hip and lumbar spine in 18 recovered women,using dual energy X-ray absorptiometry. Results: We found an unexpectedly high incidenceof osteopenia, with 14 of 18 women affected. Duration of amenorrhea was the best predictorof reduced bone density. An index of the duration of recovery, relating it to the duration ofillness, was also highly correlated with outcome. Discussion: Our findings have implications,both for the individual and for the economic burden to society. We suggest that the use of oralcontraceptives in women recovering from anorexia nervosa needs further investigation. Ad-ditional longitudinal studies are clearly warranted. © 1997 by John Wiley & Sons, Inc. Int JEat Disord 22: 71–75, 1997.

Key words: osteopenia; anorexia nervosa; bone complications

INTRODUCTION

Reduced bone density is a recognized complication of anorexia nervosa (Rigotti, Neer,Skates, Herzog, & Nussbaum, 1991; Szmukler, Brown, Parsons, & Darby, 1985; Treasure,Russell, Fogelman, & Murby, 1987; Seeman, Szmukler, Formica, Tsalamandris, & Mes-trovic, 1992), and can lead to pathological fractures. A major question, given the increas-ing prevalence of anorexia nervosa in young women, is whether or not bone density isrecoverable. Earlier cross-sectional studies supported an optimistic outlook, as subgroupswho had gained weight had improved bone densities (Treasure et al., 1987; Hay et al.,1989; Herzog, Minne, Deter et al., 1993). Short-term prospective studies also demonstrate

*Correspondence to: Anne Ward.Contract grant sponsor: Wellcome Trust.

© 1997 by John Wiley & Sons, Inc. CCC 0276-3478/97/010071–05

Prod. #1195

that weight gain leads to an increase in bone density (Bachrach, Katzman, Litt, Guido, &Marcus, 1991; Klibanski, Biller, Schoenfeld, Herzog, & Saxe, 1995). However, the patientsin these studies were at various stages of recovery from anorexia nervosa, and there havebeen no long-term outcome studies in a group of recovered women. We report such astudy in a group of 18 subjects.

METHODS

Subjects

Eighteen women agreed to take part in the study. The participants had been recruitedfor another study looking at biological vulnerability to anorexia nervosa in a group ofrecovered women (manuscript in preparation). The recovery criteria for that study werea body mass index (BMI) of >18.5 kg/m2 and the resumption of menses for at least 6months. All 18 had a history of anorexia nervosa, as defined in the 3rd rev. ed. of theDiagnostic and statistical manual of mental disorders (DSM-III-R; American Psychiatric As-sociation, 1987).

Bone Densitometry

Bone mineral density was measured using an XR-26 x-ray-based dual photon bonedensitometer (Norland, Wisconsin). Measurements were taken at two sites, the lumbarspine (L2-L4) and the femoral neck. The coefficient of variation on this machine was 1.0%for L2-L4, and 1.2% for the femoral neck. Results were reported as standard deviations ofage-matched means (z-score) and of young adult means (t-scores), thus incorporating acontrol population in the analysis. We followed WHO guidelines, focusing on t- ratherthan z-scores, but giving both to allow comparison with other studies (Kanis, Melton,Christiansen, Johnston, & Khaltaev, 1994).

Statistics

Summary statistics were calculated, using means/standard deviations or medians/ranges as appropriate. The duration of recovery was calculated from the return of menses,rather than the time at which weight had crossed an arbitrary threshold. This criterionwould be less subject to recall bias, given that several subjects had been well for manyyears. Spearman correlation coefficients were calculated between t-scores and the follow-ing clinical variables: (a) the duration of amenorrhea, (b) age of onset, (c) lowest BMI, (d)current BMI, (e) duration of recovery of menses, (f) duration of exposure to the oralcontraceptive pill, (g) cortisol level, and (h) the ratio (duration of recovery of menses/duration of amenorrhea).

RESULTS

Subjects

All of the original volunteers agreed to take part in this present study. All patients werefemale, and the median (range) age was 30.5 (20–46) years. The mean (SD) BMI was 22.0

72 Ward, Brown, and Treasure

(3.0), and the median (range) duration of recovery of menses was 6.0 (1.0–31.0) years. Onepatient with a BMI of <18.5 (18.12) kg/m2 was included, as her periods had returned for11 years. The mean (SD) lowest BMI was 13.3 (1.8), and the median (range) duration ofamenorrhea was 1.5 (0.25–16.0) years.

Bone Densitometry

The median (range) z-scores for hip and spine were −1.42 (−3.12, 0.37) and −1.20 (−2.65,2.08), while the median (range) t-scores for hip and spine were −1.39 (−2.55, 0.16) and−1.30 (−2.69, 2.09), respectively.

The median (range) absolute bone density at the hip was 0.78 (0.60–1.03) g/cm2, and atthe spine 0.96 (0.78–1.40) g/cm2. Duration of amenorrhea was negatively and highlysignificantly correlated with t-score hip (r = −.81, p < 0.001) and with t-score spine (r =−.68, p = .002). The ratio (duration of recovery of menses/duration of amenorrhea) wasalso significantly correlated to t-score hip (r = 0.62, p = .006) and t-score spine (r = .50, p= .03). Other correlations were not significant at the 5% level, but are included for interest.The age of onset was not associated with current bone density (t-score hip: r = .09, p = .71;t-score spine: r = .29, p = .24). Subject’s lowest BMI was not significantly correlated witht-score hip (r = .16, p = .52) or with t-score spine (r = .26, p = .30). Neither was current BMIsignificantly associated with t-score hip (r = .42, p = .09) or t-score spine (r = .28, p = .26).The duration of exposure to the contraceptive pill was not correlated to either t-score hip(r = .42, p = .09) or t-score spine (r = .21, p = .41).

Cortisol Levels

Cortisol levels were available for 17 of the 18 subjects, whose median (range) age was29 (20–46) years, and mean (SD) BMI was 22.1 (3.0) kg/m2. The median (range) age for the18 controls was 25 (20–48) years, and the mean (SD) BMI was 22.4 (3.1) kg/m2. Therecovered subjects’ median (range) 9 a.m. cortisol was 368 (187–1,001) nmol/l. The controlgroup had median (range) values of 440 (121–889) nmol/l. Control values were notstatistically different from recovered subject values. There was no significant correlationbetween cortisol levels and bone density (t-score hip: r = −.39, p = .12; t-score spine: r =−.23, p = .38).

DISCUSSION

This is the first report of bone density in a long-term recovered group. Previous reportson recovery have been conflicting, with some studies suggesting restoration of normalbone mass with recovery from anorexia nervosa (Treasure et al., 1987; Klibanski et al.,1995), while others suggest that the improvement in bone density may only be partial(Herzog et al., 1993; Bachrach et al., 1991). In Klibanski et al.’s study (1995), the group thatrecovered from anorexia nervosa and regained normal bone mass had been less ill initially(>70% ideal body weight), and it is possible that the recovered patients in other studiesmay have had clinical features which independently predicted a higher bone mass. Nev-ertheless, the trend from previous studies suggested that recovery over time was possiblefor some, if not all, patients. Our results then are somewhat surprising, and a cause forconcern.

Four of our 18 subjects had bone densities in the normal range for both hip and lumbar

Osteopenia and Anorexia 73

spine. One of these four was African, and as the ‘normal’ reference range in our laboratoryis based on a Caucasian population, her t-and z-scores may be inappropriately high. Twosubjects had been very overweight at different stages of their lives, which may have hada protective effect. The fourth subject was atypical in that she had her first episode ofillness at the age of 31 years. All other subjects were at increased risk for fractures, wherefracture risk increases 1.5–3-fold or more for each standard deviation decrease in bonemineral density (Kanis et al., 1994). Twelve subjects had t-scores between −1 and −2.5,defined as osteopenia by the WHO, and 2 subjects had osteoporosis, defined as values lessthan this. This represents a considerable morbidity, with both physical and economicimplications.

In keeping with other studies (Salisbury & Mitchell, 1991), we found that the durationof amenorrhea was a powerful predictor of bone density. A related index, the ratio of theduration of the recovery of menses to the duration of amenorrhea, was also highly cor-related to current bone density. From this analysis, it does not appear that a simple‘catching-up’ phase is all that is required for the restoration of bone density. Some sub-ject’s recoveries far outlasted their illnesses, but bone density was still reduced. However,the cross-sectional nature of this study limits the analysis, and longitudinal studies areneeded for a more accurate assessment. Age of onset was not significantly correlated tocurrent bone density. This was somewhat surprising, as the median (range) of onset was16 (13–31) years, with 13 patients becoming ill in their teens. Our numbers were too smallto attempt a regression analysis, and it may be that with larger numbers, an influence ofage of onset would become apparent. It is also possible that early onset is confounded byshort duration of illness, with recovery at a stage when bone is still being rapidly formed.A larger analysis could also address this possibility. Dietary calcium intake and level ofphysical activity were not assessed in this study, as we felt that recall over such a longperiod would not produce an accurate picture. We did note a period of veganism in onesubject’s history, which may have contributed to her reduction in bone density. Serumcortisol levels were not related to bone density in our study, although it is possible thata more representative 24-hr urinary measurement may have given a different picture.

It has been shown that estrogen replacement alone cannot prevent progressive osteo-penia in women with anorexia nervosa (Klibanski et al., 1995). In our study, 13 of 17subjects had a history of oral contraceptive use, but there was no correlation between theduration of use and indices of bone density. Nor was there a difference in bone densitybetween those who had or had not used the pill, although the latter group only containedfour subjects. It may be that the balance between bone absorption and remodeling isdifferent at different stages of recovery, such that the antiresorptive properties of estrogenare more or less effective. In Klibanski et al.’s study, the authors suggested that the naturalcycle of estrogen/progesterone may be important in bone recovery, raising questionsabout the use of oral contraceptives in patients recovering from anorexia nervosa.

In summary, this is the first study to look at predictors of bone mineral density in agroup of long-term recovered anorexic women. We found an unexpectedly high incidenceof osteopenia, with 14 of 18 women affected. Duration of amenorrhea was the best pre-dictor of reduced bone density. An index of the duration of recovery, relating it to theduration of illness, was also highly correlated with outcome. We suggest that the use oforal contraceptives in recovering women needs further study. Further research in the formof longitudinal studies and into the mechanisms of osteoporosis in this condition is clearlywarranted.

74 Ward, Brown, and Treasure

We acknowledge statistical advice from Dr. Graham Dunn, Department of Biostatistics, Institute ofPsychiatry. Anne Ward and Nigel Brown were funded by the Wellcome Trust.

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