Osteoporosis

1. Osteoporosis Rajesh Kataria, D.O. Southern Ohio Rheumatology

2. Disclosures Speaker’s Bureau Novartis Warner Chilcott

3. Objectives State the indications for bone mineral density testing Understand and describe the utility of the FRAX tool List the medications that have proven reduction on nonvertebral fractures

4. Osteoporosis “…is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.” Consensus Development Conference: Diagnosis, Prophylaxis, and Treatment of Osteoporosis, Am J Med 1993;94:646-650. WHO Study Group 1994.

5. Definition of Osteoporosis

6. Bone Health

7. Bone Remodeling (Turnover)

8. Cells in Bone Tissue

9. Bone Remodeling Cycle

10. Bone Remodeling Cycle (cont)

11. Role of Modulators in Bone Remodeling

12. Unbalanced Remodeling in Menopause Leads to Osteoporosis

13. Biochemical Markers of Bone Remodeling

14. Osteoporosis: A Common Problem in the General Population • In the United States, 10 million individuals are estimated to have osteoporosis • 8 million are women • 34 million more are estimated to have low bone mass (osteopenia) • They have an increased risk for developing osteoporosis

15. Estimated Annual Incidence of Osteoporosis-Related Fractures in Women and Men

16. Annual Incidence of Osteoporotic Fractures Higher Than Other Epidemic Diseases

17. Osteoporosis • Fractures • 1 in 2 females over age 50 will fracture • 1 in 4 males over age 50 will fracture

18. Osteoporosis • Fractures • Increased mortality seen after hip and vertebral fractures • 20% mortality in first year after hip fracture • 25% require long-term nursing home care after hip fracture • 80,000 male hip fractures annually (2x mortality with age matched females)

19. Osteoporosis • Cost • Each hip fracture costs $40,000 (2001) • Fractures cost $13 billion per year (2005) • Expected costs to exceed $60 billion by 2030

20. Prior Fracture as a Predictor of Fracture Risk

21. Risk Factors for Osteoporotic Fractures

22. Vertebral Fractures Have Significant Consequences for Patients, Including Dorsal Kyphosis

23. Hip and Other Non-Vertebral Fractures Have Significant Consequences

24. Most Hip Fracture Patients Receive No Pharmacologic Treatment for Osteoporosis

25. Clinical Presentation of Osteoporosis

26. DXA • “Gold-standard” for BMD (Bone Mineral Density) measurement • Measures “central” or “axial” skeletal sites: spine and hip • May measure other sites: total body and forearm • Widely available (about 10,000 DXA machines in USA)

27. Diagnostic Classification WHO Study Group. 1994.

28. Fracture Risk Doubles With Every SD Decrease in BMD Relative Risk for Fracture Bone Density (T-score)

29. 60 50 40 30 20 10 0 NORA: Relationship of BMD with Risk of Fracture in Postmenopausal Women 450 –1.0 to –2.5 ≤–2.5  BMD distribution 400 Fracture rate No. of women with fractures 350 300 250 No. of Women With Fractures Fracture per 1000 Person-Years 200 150 100 50 0 >1.0 0.5 to 0.0 –0.5 to –1.0 –1.5 to –2.0 –2.5*to –3.0 <–3.5 1.0 to 0.5 0.0 to –0.5 –1.0 to –1.5 –2.0 to –2.5 –3.0 to –3.5 BMD T-Scores† *The World Health Organization definesosteoporosis as aT-score ≤ –2.5 †Peripheral devices used to measure T-score Adapted with permission from Siris ES et al. Arch Intern Med. 2004;164:1108-1112.

30. Most Women Who Had a Fracture in the NORA Study Would Not Receive Treatment

31. Indications For Bone Mineral Density (BMD) Testing • Women aged 65 and older • Postmenopausal women under age 65 with risk factors • Men aged 70 and older • Adults with a fragility fracture • Adults with a disease or condition associated with low bone mass or bone loss • Adults taking medications associated with low bone mass or bone loss • Anyone being considered for pharmacologic therapy • Anyone being treated, to monitor treatment effect Women discontinuing estrogen should be considered for bone density testing according to the indications listed above

32. Densitometric Vertebral Fracture Assessment (VFA)

33. Who Should Be Treated?

34. Who Should Be Treated? (cont)

35. Using the FRAX® Tool to Help Determine Fracture Risk in Treatment-Naïve Patients With Low Bone Mass

36. Osteoporosis Treatment: Goals and Strategies

37. Calcium and Vitamin D Supplementation

38. Calcium Purchase Habits in Households With Patients on Bisphosphonates

39. Bisphosphonate and Supplement Intake Habits Survey

40. Pharmacotherapy

41. Pharmacotherapy (cont)

42. Osteoporosis • Calcitonin (Miaclacin, Fortical) • Daily nasal spray • Reduction in vertebral fractures • Short-term analgesic effect

43. Osteoporosis • Raloxifene (Evista) • Selective estrogen receptor modulator (SERM) • Reduction in vertebral fractures • Cholesterol reduction • Increased VTE, hot flushes, leg cramps

44. Osteoporosis • Teriparatide (Forteo) • Anabolic agent (new bone formation) • Daily SQ injection • Reduction in vertebral and non-vertebral fractures • Increased leg cramps

45. Osteoporosis • Denosumab (Prolia) • Antibody to RANKL (osteoclast differentiating factor) • q6 month SQ injection • Reduction in vertebral and non-vertebral fractures • Increased eczema, cellulitis* & flatulence • Hypocalcemia in CKD

46. Alendronate (Fosamax) Calcitonin (Miacalcin, Fortical) Denosumab (Prolia) Ibandronate (Boniva) Raloxifene (Evista) Risedronate (Actonel, Atelvia) Teriparatide (Forteo) Zoledronic acid (Reclast) Proven Reduction on Vertebral Fracture

47. Alendronate (Fosamax) Denosumab (Prolia) Risedronate (Actonel, Atelvia) Teriparatide (Forteo) Zoledronic acid (Reclast) Proven Reduction on Nonvertebral Fracture

49. Osteonecrosis of the Jaws (ONJ) • Bone exposure in the mandible, maxilla, or both • Simulates dental abscesses, “toothaches”, denture sore spots or osteomyelitis

50. Osteonecrosis of the Jaws (ONJ) • 368 reported cases (5/06) • 94% with intravenous bisphosphonate use • (multiple myeloma or bone mets) • 15 cases in patients taking bisphosphonates for osteoporosis • 20 million users for osteoporosis • Risk is < 1/100,000