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

2. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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 the FDA for the treatment of osteoporosis in men. Cheater!

14. 14 Investigative Findings Lab: normal ionized calcium, PO 4 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. 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. 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. 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. 18 Treatment Tailored to underlying etiology (if other than post-menopause). Bisphosphonates SERMS Calcitonin Vitamin D; Calcium PTH (synthetic analog)

19. 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. 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. 21 Bisphosphonates Alendronate (Fosomax): Take 30” before AM meal with 8 oz H 2 0, remaining upright for 30” minutes to prevent esophagitis. Dose: 70 mg po weekly GI side effects: gastritis, esophagitis Risedronate (Actonel): less GI side effects Single weekly dose: 35mg po before am meal. Similar instructions as above.

22. 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. 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. 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. 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. 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. 27 Calcium and Vitamin D Vit D 2 - 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. 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. 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. 30 Lifestyle Healthy diet Weight bearing exercise Fall precautions, especially in elderly