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OsteoporosisPrevention and Management

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INTRODUCTIONEPIDEMIOLOGYCLASSIFICATIONPATHOPHYSIOLOGYS/S INVESTIGATIONS BMDBTM DIAGNOSISDD

10.MANAGEMENT11.RECENT ADVANCES12. ORTHOPAEDICIAN)13.COMPLICATIONS 14.CASE PRESENTATION 15.CONCLUSION

Osteoporosis: Nightmare Of Post-menopause/ Old Age

Normal vs Osteoporotic Bone

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It is a disease of aging-Silent disease-fragility fracture/low trauma fracturespontaneous fractureHip fractures-MorbidityQOL

What is Osteoporosis?

Osteoporosis is a systemic skeletal disease characterized 1. low bone density and

2. a micro- architecture deterioration of bone tissue

3. that enhances bone fragility and

4. increases the risk of fracture

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2.Epidemiology

Osteoporosis affects entire skeletonOsteoporosis is responsible for >36.8 million vertebral and non-vertebral fractures per year in USA Spine, hip, and wrist fractures are most common

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Common Sites of fracture

HipVertebral columnWrist

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womenIn women it isThree times more common than men

1.low peak bone mass (PBM) 2.hormonal changes at menopause 3.live longer than men

vertebral #s and wrist #s more common in women

A Retrospective Study Suggests that Vertebral Fractures are Under-Diagnosed934 hospitalised women with a lateral chest x-ray

020406080100120140Patients (n)132652325Fractureidentified by studyradiologistsFracturenoted in radiologyreportFracturenoted inmedical recordReceivedosteoporosistreatmentGehlbach et al.,Osteoporos Int 2000, 11:577

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Hip fracturesHip fractures accounts for most of the morbidity, mortality and cost of the disease

2.Classification

Osteoporosis: ClassificationPrimary Osteoporosis

Type 1- Post menopausal osteoporosisType 2- Senile/Age related osteoporosisSecondary Osteoporosis

Secondary to various causes13

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Post-Menopausal OsteoporosisCaused by a lack of estrogens, which helps to regulate, the incorporation of calcium into bone in women

Lack of estrogen increased bone resorption

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Age Related/Senile OsteoporosisUsually affects people over 70 y.

Results from age-related calcium deficiency

There is decreased bone formation

Patients usually present with fractures of the hip and the vertebrae15

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Secondary OsteoporosisCongenitl Condition Homocystinuria; hemolytic anemia; hypophosphatasia; osteogenesis imperfecta DietCalcium deficiency; malabsorption syndromes; scurvy; starvation DrugsAlcohol; anticonvulsants; cancer chemotherapy; excess thyroid hormone; glucocorticoids; heparin; methotrexate

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Endocrine DisordersCushing's syndrome; growth hormone deficiency; hypercortisolism; hyperparathyroidism; hyperthyroidism; hypogonadism Other Systemic Disorders Diabetes mellitus; leukemia; multiple myeloma; renal tubular acidosisRheumatologic disordersAnkylosing spondylitis, rheumatoid arthritisG.I. diseasesGastrectomy, primary biliary cirrhosis, celiac disease

A.CHILDHOOD-chronic diseasesDuring growth 30 -50y >50 y.Bed rest due to chronic illnessUndernutrition or malnutritionChronic Paediatric disordersGlucocorticoid/growth hormoneAnorexianervosaExercise-associated amenorrhoeaSevere chronic paediatric diseases requiring immunosuppressive agents

B.During late adulthood-endocrine diseasesHypogonadism is a major cause1.Women-menopause-estrgen deficiency-bone marrow of cytokines such as tumour necrosis factors and interleukins that stimulate osteoclastic bone resorption

2.Men declining levels of gonadal hormones-low rates of bone formation

Primary hyperparathyroidsm,,hyperthyroidsm and hypercortisolism

C.Elderly-diet(calcium) Low calcium intake associated with a

reduced endogenous production of vit.D accelerate bone loss

By increasing the secretion of PTH.

3.Risk factors

Non-modifiable/Fixed Risk FactorsOlder ageFemale genderEthnic background Small bone structure Family history of osteoporosis or osteoporosis-related fracture in a parent or siblingsPrevious fractureMenopause/hysterectomySome medicines like steroids, anti-epilepticsRheumatoid arthritisReduced levels of gonadal hormones in men

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Modifiable Risk FactorsAlcoholSmokingPoor nutritionVitamin D deficiency/Lack of sunlight exposureInsufficient exerciseLow calcium intake in food

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4.Pathophysiology1.Peak bone mass2.remodling

Determinants Of Peak Bone MassPeak Bone MassPhysical activityGonadal statusNutritional statusGenetic factors

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1.Peak bone mass & OsteoporosisPeak bone mass is the maximum mass of bone achieved by an individual at skeletal maturity, typically between ages 25 and 35

After peak bone mass is attained, both men and women lose bone mass over the remainder of their lifetimes

Because of the subsequent bone loss, peak bone mass is an important factor in the development of osteoporosis 26

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Peak Bone Mass in Women

10 20 30 40 50 60Women achieve lesser peak bone mass than men27

Women

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Stages of Peak Bone Mass in Women

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2.Bone formation takes place throughout life-remodelingBone is a living tissue and is constantly resorbed and formed by the process known as remodeling

Remodelling

Imbalance 1.In Osteoporosis imbalance occurs between bone resorption and bone formation

This imbalance might occur as a result of one or a combination of the following factors:

Increased bone resorptionDecreased bone formation A negative balance occurs and results in a net loss of bone

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5.Signs & Symptoms

Signs & SymptomsIn early stages usually no symptoms therefore also known as silent disease There may be back pain due to spinal compressionFirst sign may be fractures due to slight trauma or even due to bending or lifting or rising-spontaneous or low trauma fractureIf several vertebrae break, an abnormal curvature of spine (a dowager's hump) may develop, causing muscle- strain and sorenessA loss of height by 4 to 8 inches may occur33

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Osteoporosis related bone lossVertebrae, which have a large proportion of trabecular bone, are commonly the first sites to show bone loss in Osteoporosis leadingto spine collapse(upto-4-8 inches)

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Backbone Deformity in OsteoporosisThree generations of women are shown. The elderly women have hunched back which is a sign of vertebral fractures caused by osteoporosis

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6.Differential Diagnoses

Differential Diagnoses Other Problems to Be ConsideredBony metastases Multiple myelomaPrimary hyperparathyroidismSecondary hyperparathyroidismOsteomalaciaRenal osteodystrophyPaget disease of bone

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Osteomalacia/osteoporosisosteomalaciaosteoporosis.h/o persistant skeletal pain of long duration and muscle weaknessh/o gastric surgerySkeletal tendernessA shuffling penguin gaitBiochemistry low ca,ph and increased s.Alka.ph.Reduced 24h urinary ca1.transient episodes of pain usually associated with #s

osteomalaciaosteoporosiX-ray-diminished bone density- marked in the peripheral bone than in the axial Skeletal deformity without #Loosers zoneHistology presence of excess osteoid tissue in undercalcified Treatment is rapidly and consitently successful

7.Diagnosis

BMDDual energy x-ray absorptiometry (DEXA) is the best current test to measure bone density

The ability of the BMD to predict hip # is better than the measurement of BP to predict stroke

BMD 2.5 standard deviation or more below the average for the young healthy female population-osteoporosis

T score for BMD measured at the hip using DEXA is best one

For each standard deviation decrease in BMD, fracture risk increases by approximately 50%.

How is osteoporos is diagnosedDiagnosis is made on the basis ofDetailed medical historyPhysical examinationInvestigations-1.BMD by DEXA or by single energy x-ray absorptiometry 2.BTM

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BMD Tests Other than DEXAQuantitative CT vertebral scanningSingle photon and dual photon absorptiometryPeripheral DEXA

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Bone Mineral Density (BMD)It is a simple test that measures bone thickness/ density at different parts of the body, like spine, hip etcIt employs two x-ray beams of different energy levelsDual energy x-ray absorptiometry (DEXA) is the best current test to measure bone density

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Dual-energy x-ray absorptiometry (DEXA)

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Indications for Bone Density test1.All postmenopausal women 65 yr regardless of additional risk factors

3.Documenting reduced bone density in a patient with a vertebral abnormality or osteopenia on a radiograph

4.Estrogen-deficient women at risk for low bone density, considering use of estrogen or an alternative therapy, if bone density would facilitate the decision

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5.Women who have been on estrogen replacement therapy for prolonged periods or to monitor the efficacy of a therapeutic intervention or interventions for osteoporosis6.Diagnosing low bone mass in glucocorticoid-treated individuals(Prednisolone at 7.5mg daily for 6m.)7. patients with asymptomatic primary or secondary hyperparathyroidism

8.Previous low trauma fragility #9.Premature menopause 1.y.)11.Primary or secondary hypogonadism12.Chronic disorders asso. With osteoporosis13.A meternal h/o hip #14.Alow BMI

BMD Report

WHO Classification: T score1NormalBMD or bone mineral content (BMC) not more than 1 SD below the young adult mean (T-score above -1)2.OsteopeniaBMD or BMC between 1 SD and 2.5 SD below the young adult mean (T-score between -1 to-2.5)3.OsteoporosisBMD or BMC 2.5 SD or more below the young adult mean (T-score at or below -2.5)4.Severe osteoporosis (or established osteoporosis)BMD or BMC 2.5 SD or more below the young adult mean in the presence of one or more fragility fractures

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Bone Turnover Markers(BTM)Biochemical markers of bone turnover are substances in blood and urine that reflect rates of bone resorption or bone formation

they measure the relative activity of osteoclasts and osteoblasts

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Bone resorption markersCurrently available markers of bone resorption include Pyridinoline (PYR)Deoxy pyridinoline (DPD)N-telopeptides of type 1 collagen (NTX)C-telopeptides of type 1 collagen (CTX)

1.Pyridinolines are measured in urine2. telopeptides can be measured in both serum and urine

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Markers of bone formationThe most common markers of bone formation are:Osteocalcin (OC)

Bone specific alkaline phosphatase (bone ALP)

Procollagen type 1 N-terminal propeptide (P1NP)

Procollagen type 1 C-terminal propeptide (P1CP)

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Management of OsteoporosisPrevention & Treatment

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9.Pharmacological management

1.Pharmacological Management OsteoporosisCalciumVitamin DEstrogens/HRTSelective Estrogen Receptor Modulator (SERM)RaloxifeneBisphosphonatesStrontium ranelateCalcitoninPTHTeriparatide

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Normal calcium requirementAgeCalcium/day (mg)Birth-6 months 2106 months-1 year2701-35004-88009-18130019-50100051-701200

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CalciumCalcium citrate may be advantageous for older seniors

Divided 2 to 3 times daily

Vitamin DDoses: 1).400IU per day until 60

2)600-800 IU per day after 60

3.)50,000 IU-D2Every 2-4 weeks

4.)To treat deficiency-50,000 D2IU every week for 2 to 4 m.

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25 hydroxy Vit.D status.30ng-sufficient

20-29ng/ml-insufficiency

3month.2.BMD-T-score below -2.5SD-oral-IV bisphosphonates,calcium,Vit.D

prevention1. prevention of falls2.prevention and treatment of bone fragility3.use of external hip protectors.

1. prevention of falls 1.Impaired balance

2.gait and mobility

3.Poor vision4.reduced muscle strength5.impaired cognition

Other causes for falls-Medication&co-morbid diseasePsychoactive medication-benzodiazepines.antidepressant

Certain co-morbid disease- stroke, Alzheimers dementia and parkinsons diseases

Insufficient Vit.D increases the FallsEssential to maintain muscle function and strengthReduced handgrip strength heaviness in the legsReduced walking distance -Less outdoor activity

Home environment modifications1 removing loose rugs or extension cords2.repairing rickety stairs3.Bathroom ergonomics-adding grab bars4.increasing lighting

Regular physical activity plays a therapeutic role in severe osteoporosis

Hip protectorsSpecialized undergarmentsPoor complianceLatest data-ineffective and should not be recommended alone

13.RECENT ADVANCES

Latest in Osteoporosis Treatment1.Carotenoids, Lycopene Reduce Fracture Risk (Antioxidants)

reactive oxygen intermediates may be involved in the bone-resorptive process and that fruit and vegetable-specific antioxidants, such as carotenoids, are capable of decreasing this oxidative stress. Therefore carotenoids may help in preventing osteoporosis. In particular, an inverse relation of carotenoids and lycopene with biochemical markers of bone turnover has recently been demonstrated.

J Bone Miner Res. 2009 Jun;24(6):1086-94.

Lycopene is the most common carotenoid found in blood and its levels have correlated with reduced risk of cancer and heart attacks in prior studies. The beneficial effects of lycopene are contributed to its antioxidant activity. In this study the authors concluded that data compiled from the Framingham Study indicated long-term carotenoid (lycopene) intake had beneficial effects on bone density in elderly men and women. In addition, the authors cited several studies that found high serum lycopene to be inversely associated with bone resorption markers such as N-telopeptide (NTX). Tomatoes are a great source of lycopene.

Sahni S et al. Protective effect of total carotenoid and lycopene intake on the risk of hip fracture: a 17-year follow-up from the Framingham Osteoporosis Study. J Bone Miner Res. 2009 Jun;24(6):1086-94.

In vitro and in vivo studies suggest that carotenoids may inhibit bone resorption, yet no previous study has examined individual carotenoid intake (other than beta-carotene) and the risk of fracture.

We evaluated associations of total and individual carotenoid intake (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein + zeaxanthin) with incident hip fracture and nonvertebral osteoporotic fracture.

Three hundred seventy men and 576 women (mean age, 75 +/- 5 yr) from the Framingham Osteoporosis Study completed a food frequency questionnaire (FFQ) in 1988-1989 and were followed for hip fracture until 2005 and nonvertebral fracture until 2003. Tertiles of carotenoid intake were created from estimates obtained using the Willett FFQ adjusting for total energy (residual method). HRs were estimated using Cox-proportional hazards regression, adjusting for sex, age, body mass index, height, total energy, calcium and vitamin D intake, physical activity, alcohol, smoking, multivitamin use, and current estrogen use.

A total of 100 hip fractures occurred over 17 yr of follow-up. Subjects in the highest tertile of total carotenoid intake had lower risk of hip fracture (p = 0.02). Subjects with higher lycopene intake had lower risk of hip fracture (p =0.01) and nonvertebral fracture (p = 0.02). A weak protective trend was observed for total beta-carotene for hip fracture alone, but associations did not reach statistical significance (p = 0.10). No significant associations were observed with alpha-carotene, beta-cryptoxanthin, or lutein + zeaxanthin. These results suggest a protective role of several carotenoids for bone health in older adults.

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2.Omega-3 Fatty Acids Reduce hs-CRP1This study provides evidence that in healthy individuals, plasma n-3 fatty acid concentration is inversely related to hs-CRPHigh sensitivity C-reactive protein (hs-CRP) is a marker of low grade sustained inflammation.Increased hs-CRP by just 1SD increases fracture risk by an amazing 23 percent2.Consider supplementing the diet with omega-3 fatty acids (fish oil). Theyre a great way to help reduce inflammation, hs-CRP, cardiovascular disease, and fractures related to osteoporosis.1. Micallef M A et al., European Journal of Clinical Nutrition, 2009; April 8 [Epub ahead of print].2. Pasco et al. JAMA. 2006;296(11):1353-1355

Omega-3 fatty acids have anti-inflammatory properties and the purpose of this study was to investigate whether their concentration in the blood is related to levels of the inflammatory marker, hs-CRP. Abnormally elevated hs-CRP is correlated to excess production of interleukin-6 (Il-6), a molecule produced in the body during times of chronic inflammation. High levels of hs-CRP are correlated to cardiovascular disease as well as low bone mineral density (BMD) and increased fracture risk.

Reducing hs-CRP by just one point will reduce fracture risk by an amazing 23 percent

An age-stratified sample of 1494 women (99% white), representing 77.1% of eligible participants, was randomly recruited from electoral rolls for the Geelong Osteoporosis Study. The inclusion criterion of age 65 years or older was met by 522 women. Of these, 33 were excluded because serum was unavailable for analysis and 45 were excluded for baseline use of hormone therapy or oral glucocorticoids for at least 6 months, leaving a study populationof 444 women. Baseline assessments were performed from 1994 to 1997, and participants were followed up until fracture, death, migration from the study region, or the end of 2002.

The unadjusted HR for fracture increased by 23% for each SD increase in ln-hsCRP (HR, 1.23; 95% confidence interval, 1.01-1.51). The age-standardized absolute risk of fracture during the study period increased from 16.3% (95% CI, 6.8%-25.8%) for ln-hsCRP less than 1 SD (0.96 mg/L) to 28.9% (95% confidence interval, 17.7%-40.1%) for ln hsCRP greater than +1 SD (6.35 mg/L). Multivariate models consistently included significant contributions from lnhsCRP, prevalent fracture, and BMD. For each SD increase in ln-hsCRP, there was an independent 24% to 32% increase in fracture risk, depending on site-specific BMD used in the model. Fracture risk was independently increased 52% to 79% for each SD decrease in BMD and 52% to 73% by previous fracture.

So supplementing the diet with omega-3 fatty acids (fish oil) should be considered. Theyre a great way to help reduce inflammation, hs-CRP, cardiovascular disease, and fractures related to osteoporosis.

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3.Vitamin K Improves Bone Strength and Reduces FracturesReview of RCTs showed that vitamin K(1) and vitamin K(2) supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption.

Iwamoto J et al., Nutrition Research, 2009; 29(4): 221-228.

Despite the lack of a significant change or the occurrence of.Despite the lack of significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K1 and vitamin K2 supplementation improved indices of bone strength in the femoral neck and reduced the incidence of

In a review of the literature to assess the effects of vitamin K supplementation on bone in postmenopausal women, the authors of this study found that high-dose vitamin K improves bone strength in the hip and reduces fracture. This reduction in fracture appears to be more from changes to the quality of bone rather than quantity, as only 7 randomized controlled trials found (modest) increases in bone mineral density.

There was only a modest increase in bone mineral density, but high-dose vitamin K(1) and vitamin K(2) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures

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4.Atypical femoral fractures due to bisphosphonates Atypical femoral fractures with bisphosphonate treatment

Experience in two large United Kingdom teaching hospitals

14. Case study

Case 1. Sitaratnam 85y.Severe osteoporoti, Known diabetic ,HTN and hemiplegic pt. presented with 1.y.post operative non union troch.# with PFN

Cemented bipolar

Excised the femoral head from fracture site

reconstucted the femoral neck taking bone graft from femoral head and cement

Replaced with bipolar porstesis And put her on bisphosponates,calcium and vit.D

Pt.was followed up for 2years-pt.is walking without any support and refractures

Operative procedure more difficult than conventional arthroplastyReduced length of hospital stayIndications for primary prosthetic replacement are remain ill definedProspective randomized trails are needed to determine the role for acute prosthetic replacement for treatment of IT #s

Case no 2.Secondary osteoporosis

Pallavi,31/f,on Antiepileptic drugs since 6m. age

Ref. from Apolo hospitalSecunderabad9053725362,9700178806D0A-27-4-12,4-5-12She presented with fracture shaft femur due to slip &fall in bath room on 9-4-12First -.treated with pop cast for 3 weeks by an orthopaedic surgeon subsequantly they went to APOLO hospital from there she was referred to GANDHI hospital

3rd x-ray on 18 -5- 12

Investigations Low s.calcium and phosphorus

25 hydroxy vit.D- Insufficient -20Ng/ml

PTH,,Alk.phosphatase-normal

DEXA-severe osteoporosis

Calcium-7.5 (8.5-11mg%) insufficiency

25 hydroxy Vit.D-20Ng/ml insufficiency(6-20ng/ml)

BMD tasted by DEXA

DEXA-OSTEOPOROSIS-severe osteoporosisLT.FEMUR3.8

RT.FEMUR3.2

SPINE4.1

Now pt. is on 1.)Calcium-1g/d

2.)Vit.D 6o ooo/w

3)high protien diet

4.)Teriparatide-25microgram/day

BONISTA/FORTEO1)BONISTA-ORTHOLANDS RANBAXY

2)FORTEO-Eli LILLY

Iatrogenic fracture Epilepsy has been diagnosed at the age of 6m.in NIMSSince then she is on antiepileptic drugs for 30y.Though she was suffured from multiple fractures, attended big hospitals,and treated by qualified doctors. No one has suspected this problem and adviced her BMD test and prescribed simple calcium& vit.D

Had it diagnosed at early age this fracture would have been prevented

BONISTA-Rs 18.000/mounth-2y.

Had it diagnosed at early stage and treated with simple calcium and vit.D it would have been prevented both fracture, as well as this costly treatment (teriparatide)This amounts to a iatrogenic fracture

15.CONCLUSION

Education -Ignorance about osteoporosis is still common among Health professionals Patients and Public, - So that the education of all of these groups is necessary.

So ,Our aim should be1. increase knowledge of bone physiology and osteoporosis

2.raise the awareness of major risk factors and 3.provide information on possibilities of primary and secondary prevention and management of the disease

Thank you

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