Osteoporosis

1. Osteoporosis J.B. Handler, M.D. Physician Assistant Program University of New England

2. Abbreviations • BD- bone density • SERM- selective estrogen receptor modulator • PTH- parathyroid hormone • RA- rheumatoid arthritis • SD- standard deviation • S/S- sensitivity/specificity • CC- creatinine clearance • BMD- bone mineral density

3. Osteoporosis • Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. NIH Consensus Development Conference, March 2000

4. Osteoporosis • Most common metabolic bone disease • Decreased bone matrix and mineral “thin bones”. • Women>Men, often asymptomatic early; later, bones fail structurallyfractures. • 20 million cases in USA; 1.5 million fractures annually- spine, hip. • Increased bone resorption, esp. trabecular bone.

5. Bone Density (BD) • Increases dramatically in puberty in response to gonadal steroids. • Peaks in young adults (early 20’s) • Determinants: age, race, genetics, gonadal steroids, timing of puberty, exercise, calcium intake and diet. • Genetics: Female offspring of patients with osteoporosis have lower BD.

6. Physiologic Bone Loss • Begins before menses cease. • Accelerated loss in 1st 5-10 yrs post menopause. • Trabecular (cancellous)> Cortical (compact) bone loss.

7. Bone Structure Images.google.com

8. Physiologic Bone Loss • Net bone loss over 10 years:Trabecular: 25-30%Cortical: 10-15%. • Ongoing bone loss after age 60 is slower. • Theoretically preventable with estrogen, and useful in some subsets (hypogonadism, premature menopause) but not a long term option postmenopause risk of side effects. • Testosterone in men with hypogonadism.

9. Etiologies (increased risk) • Sex hormone deficiency: post menopause; hypogonadism- M&W • Excess glucocorticoids (Cushing’s) • Hyperparathyroidism- PTH • Thyrotoxicosis- bone metabolism • Alcoholism, anorexia nervosa, Vit D deficiency. • Others • RA, Multiple myeloma, leukemias • Genetic disorders (osteogenesis imperfecta), connective tissue diseases

10. Definitions (BD Scores) • Osteopenia: bone mineral density 1-2.5 SD below peak bone density • Osteoporosis: bone mineral density >2.5 SD below peak bone density • Peak bone density = young healthy adult of same gender and race

11. History, Signs and Symptoms • Dietary calcium, Vit D • Delayed puberty, hypogonadism, premature menopause • FH of osteoporosis • Asymptomatic until fracture (often spontaneous) • Back pain, decrease in height, kyphosis deformity

12. Osteoporosis of Spine Images.google.com

13. Men Have Osteoporosis Too! • It has been estimated that 1 out of 5 people with osteoporosis are men. • Lifetime fracture risk in men may be as high as 15-25% (women=50%). • 36% of men with hip fracture die the year following fracture (nearly twice that of women). • Alendronate is approved by theFDA for the treatment of osteoporosis in men. Cheater!

14. Investigative Findings • Lab: normal ionized calcium, PO4 • Vit D levels (25-hydroxy vit D)- test if low bone density proven; may be lacking (diet/sun). • Where indicated: TSH, cortisol, estradiol, testosterone, PTH. • X-rays: spine, femoral head and neck • Bone densitometry: DEXA (dual energy x-ray absorptiometry) is test of choice- High S/S for detecting/ruling out osteopenia/osteoporosis.

15. Bone Densitometry • DEXA typically looks at spinal bone and proximal femur; includes eval of trabecular and cortical bone. • Rapid exam time • OK for F/U changes in BD; response to Rx • Relatively inexpensive • Limited radiation exposure

16. DEXA Scores • T score: number of SD by which patient BD differs from peak BD of young healthy adults of same gender/race. • Z score: number of SD by which patient BD differs from age matched individuals of same gender/race; of limited benefit • Initiate Rx: • Osteoporosis: BMD > 2.5 SD below peak BD of young adults. • Severe osteopenia: BMD of > 2 SD below peak of young adults.

17. Prevention and Treatment • Cannot reverse established osteoporosis; can BD, fractures, halt progression. • Essential to Rx underlying secondary etiologies or predisposing factors if present. • When to screen: All patients at risk for osteoporosis* including postmenopause (see Table in CMDT- Chap 26-10). *+FH, malnourished, alcoholism, renal failure, etc.

18. Treatment • Tailored to underlying etiology (if other than post-menopause). • Bisphosphonates • SERMS • Calcitonin • Vitamin D; Calcium • PTH (synthetic analog)

19. Estrogen Replacement • Use in patients with hypogonadism or premature menopause for prevention. • Inhibits osteoclastic bone resorption. • Prevents bone loss, fractures. • Problems (dose related): risk breast Ca, risk endometrial cancer (if not coupled with progestins), thromboembolic events, in coronary events (when combined with progesterone). • If used postmenopause (controversial)- low dose topical Rx preferred for short term use only. Consider SERMs for long term use.

20. Bisphosphonates • Inhibit osteoclastic bone resorption; bone density, fractures (vertebral and elsewhere). • Excreted in urine: Requires dose adjustment if CC< 35mL/min- Caution- severe renal insufficiency. • Commonly used as initial Rx.

21. Bisphosphonates • Alendronate (Fosomax): Take 30” before AM meal with 8 oz H20, remaining upright for 30” minutes to prevent esophagitis.Dose: 70 mg po weeklyGI side effects: gastritis, esophagitis • Risedronate (Actonel): less GI side effects • Single weekly dose: 35mg po before am meal. • Similar instructions as above.

22. Bisphosphonates • Ibandronate (new): 150mg po q monthly • IV forms available: Pamidronate (q3mos) and Zoledronic Acid (given 1-2x year- expensive). For patients who cannot tolerate oral forms. • Side effects: muscle, bone, joint pain. Dental concerns: non-healing jaw post tooth extraction. Dental care important for patients on bisphosphonates.

23. SERMS • Selective Estrogen Receptor Modulators- agonist/antagonist effects on estrogen receptors. • Alternative to estrogen in post-menopausal woman with risk of adverse effects; decrease bone loss, bone density (less than estrogen),  vertebral fractures. • For treatment and prevention (woman at risk and osteopenia) of osteoporosis post-menopause.

24. SERMS • Raloxifene (Evista) 60 mgs po/daily: increases bone density but less than estrogen; blocks estrogen effects on breast and uterus. • Does not cause endometrial hyperplasia, cancer or uterine bleeding. • ’s incidence of breast cancer; risk of thromboembolism (like estrogen). • Increases hot flashes

25. Calcitonin • Nasal spray (salmon calcitonin)- inhibits osteoclast action, bone density (2-3% over time): 1 inhalation daily (200 IU).side effects: rhinitis, epistaxis. • Accelerates Ca absorption by bones. • Results: decreases fractures and bone pain. • Parenteral forms available.

26. Calcium and Vitamin D • Diet: Need adequate Ca, protein & Vit D • Intake and GI absorbtion of Ca with age • Vit D levels useful in determining need • Osteoporosis/osteopenia or high risk individuals: supplement Vit D and Ca (replacement doses of Ca if not adequate per diet). • Help arrest bone loss, especially Vit D • Recent concerns in older women (>70).

27. Calcium and Vitamin D • Vit D2- 400-600 IU daily • Calcium: Dietary Ca or supplements to maintain recommended daily amounts (1200 mg/d for men/women 51 y/o & over); ideally via diet- milk/dairy. Ca supplements beyond RDA may increase risk of MI and stroke, especially in women > 70 or with CHD. • Caution: patient on thiazide diuretics or glucocorticoids- hypercalcemia can occur.

28. PTH and Ca Homeostasis • Normal actions: Stimulates osteoclasts and osteoblasts (bone remodeling). Osteoclastic activity predominates physiologicallyCa homeostasis • Paradoxical (anabolic) effects when synthetic PTH given as intermittent (20mcg/d daily) sub-cut injection; results in: • Osteoblastic predominancenew bone formation. • Mechanism of this action not known.

29. Teriparatide • Synthetic analog of PTH (Forteo) • Targets bone formation • For Rx of severe osteoporosis • Administered by daily injection for up to 2 year period. • Significant BD (10-13%), fractures (50-70%, especially of spine);

30. Lifestyle • Healthy diet • Weight bearing exercise • Fall precautions, especially in elderly