Osteoporosis

1. Osteoporosis Hilary Suzawa Med/Peds August 2005

2. Osteoporosis vs. Osteopenia • National Institutes of Health defined Osteoporosis • A disease of increase skeletal fragility • Low bone mineral density (a T-score below -2.5) • Microarchitectural deterioration • Osteopenia • T-score between -1.0 and -2.5

3. T-score vs. Z-score • T-score: Number of SD the BMD is above or below the mean for young-normal bone density • Z-score: Number of SD the BMD is above or below the mean for an age and sex specific reference group

4. Significance • In the US, there are 1.5 million osteoporotic fragility fractures per year • Fractures occurring after trauma no greater than a fall from a standing height • Half of all post-menopausal women will have an osteoporosis-related fx during their lives • 25% will develop vertebral deformity • 15% will have hip fracture

5. Vertebral Fracture

6. Risks for Fracture • Low bone mass—each decrease of 1 in T-score • Advancing age—each decade after age 50 • Low body weight—less than 126 lb (57 kg) • Recent weight loss of >10 lbs • Delayed menarche—age>15 yrs • Maternal history of osteoporosis or history in a first-degree relative • Smokers • Direction of a fall (worse if fall backward and to one side) • History of a previous fracture—most important risk factor independent of BMD

7. Risk Factors: Medical Conditions • Inflammatory disorders involving musculoskeletal, GI, pulmonary systems • Chronic renal dz • Organ transplantation • Steroids, discontinuation of HRT, LHRH agonists (hypogonadism), sz drugs (Vit D) • Anorexia or “athlete triad” • Immobilization

8. Screening • There are no trials that have evaluated the effectiveness of screening for osteoporosis • A goal for screening is to provide an estimate of the absolute risk of any fragility fx during the next 5-10 years • The absolute 10 year risk of a fragility fx in a post-menopausal woman with T-score <-2.5 and no other risk factors is <5% at age 50 but >20% at age 65

9. Bone Density Tests • Dual energy x-ray absorptiometry (DEXA) is the gold standard • Most extensively validated test against fracture outcomes • Best location is the femoral neck • Best predictor of hip fracture • Comparable to forearm measurements for predicting fx at other site

10. Screening • USPSTF recommends • screening for all women age 65 or older • screening at age 60 for women at increased risk of osteoporotic fractures • Reasons for testing before age 65 • Prior fragility fracture in a pre-menopausal woman or a man • FMH of fracture • Low body weight • Loss of either weight (5% of baseline weight) or height

11. Screening • Reasons for testing before age 65 • Primary hyperPTH • Hyperthyroidism • Hypogonadism • Cushing’s syndrome • Long term steroids (prednisone at 5 mg or more/day for >6 mths)

12. Screening • No studies have evaluated the optimal interval for repeated screening • A minimum of 2 yrs may be needed to reliably measure change • Yield of repeated screening will be higher in older women, those with lower BMD at baseline, and those with other risk factors for fx • No data to determine appropriate age to stop screening

13. Abnormal Z-score • For Z-score below -2.00 • Workup for secondary causes of osteoporosis • Primary hyperparathyroidism • Vitamin D deficiency (low intake, lack of sunlight, malabsorption) • Multiple myeloma

14. Treatment: The Basics • Calcium: 1200-1500 mg per day • Meta-analysis of 15 Ca trials involving healthy women and postmenopausal women with osteoporosis increase of ~2% in spine BMD after 2 years but no reduction in risk of vertebral or non-vertebral fracture • Vitamin D: 400-800 IU per day • Several studies show decreases in hip fracture and other non-vertebral fractures • Decreased risk of falling

15. Treatment: The Basics • Regular physical activity • Weight-bearing and resistance exercise is effective in increasing BMD of the spine and strengthening muscle mass • No trials establish if weight-bearing exercise reduces fracture risk

16. Treatment: Fall Prevention • Muscle strengthening, balance training • Assess home for fall hazards • Withdrawal of medications that increase fall risk • Hip protector

17. Treatment: Pharmacology • Two main classes of drugs • Antiresorptive agents • Block bone resorption by inhibiting osteoclasts • HRT, SERM, bisphosphonates, calcitonin, strontium ranelate • Anabolic agents • Stimulate bone formation by acting on osteoblasts • Sodium fluoride, parathyroid hormone

18. Hormone Replacement Therapy • Estrogen slows bone resorption by blocking cytokine signaling to osteoclast • Reduces incidence of new vertebral fractures by ~50% • In WHI trial, patients who received estrogen had reduction of hip fracture of 33% • Discontinuation of estrogen results in bone loss

19. SERM • Same mechanism as estrogen • Raloxifene decreases risk of vertebral fracture by 40% in women with osteoporosis • Raloxifene has no effect on risk of non-vertebral fracture

20. Bisphosphonates • First line therapy for post-menopausal osteoporosis • Alendronate and risendronate • In women with osteoporosis, reduce the incidence of hip, vertebral, and nonvertebral fx by nearly 50%, esp during 1st year of tx • Alendronate can be safely administered for at least 7 years • Discontinuing long-term (>5 yrs) alendronate results in minimal bone loss over the next 3-5 years

21. Calcitonin • Nasal calcitonin at 200 IU/day has been shown to decrease incidence of vertebral (but not non-vertebral) fx • Only one randomized trial and method has been questioned

22. Strontium ranelate • In post-menopausal women with osteoporosis, reduces the risk of vertebral fracture by 40% • Used in Europe • No currently approved by FDA

23. Anabolic Agents • Synthetic parathyroid hormone • 20 ug of PTH SQ per day increased BMD and reduced vertebral and non-vertebral fx by more than 50% • Black box warning b/c osteosarcoma in rats • No cases of osteosarcoma in humans • PTH limited to patients w/ moderate to severe osteoporosis and duration not to exceed 2 years • Side effect of mild but asymptomatic hyperCa (10.5-11)

24. Clinical Case • 63 yo Asian female presents to clinic for a routine visit. No significant PMH or PSH. She has NKDA and does not take any medications. She is a smoker. Her height is 5 ft and weight 95 lbs. Menarche was at age 13 yrs and menopause at age 51 yrs. Pt’s mother had osteoporosis and had a hip fracture.

25. Clinical Case • What are the patient’s risk factors? • Race—Asian • Post-menopausal • Low body weight—less than 126 lbs • Smoker • FMH of osteoporosis and fracture • Would you screen her for osteoporosis? • Yes, with DEXA of femoral neck

26. Clinical Case • Pt’s T-score is -2.6 and Z-score is -1.7. How would you treat her? • Calcium • Vitamin D • Weight-bearing exercise • Start bisphosphonates • Fall precautions

27. Summary • Screen patients 65 years or older • Screen younger patients with risk factors for osteoporosis, esp. if have h/o fx • DEXA of femoral neck is the best test • Bisphosphonates decrease fx by 40-50% • If the Z-score is abnormal, look for secondary causes of osteoporosis

28. Bibliography • Nelson et al. Screening for Postmenopausal Osteoporosis. Ann of Intern Med. 2002; 137 (6): 529-541. • Raisz, L. Screening for Osteoporosis. NEJM. 2005; 353: 164-71. • Rosen, C. Postemenopausal Osteoporosis. NEJM. 2005; 353: 595-603. • USPSTF. Screening for Osteoporosis in Postmenopausal Women. Ann of Intern Med. 2002; 137 (6): 526-528.