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. WHO Study Group. 1994. 27 Diagnostic Classification ClassificationT-score Normal-1 or greater OsteopeniaBetween -1 and -2.5 Osteoporosis-2.5 or less Severe Osteoporosis -2.5 or less and fragility fracture

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

29. Fracture rate 60 50 40 30 20 10 0 Fracture per 1000 Person-Years *The World Health Organization defines osteoporosis as a T-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. BMD distribution BMD T-Scores † >1.0 1.0 to 0.5 0.5 to 0.0 0.0 to –0.5 –0.5 to –1.0 –1.0 to –1.5 –1.5 to –2.0 –2.0 to –2.5 –2.5* to –3.0 –3.0 to –3.5 <–3.5 No. of women with fractures 450 350 300 250 200 100 0 150 50 400 No. of Women With Fractures NORA: Relationship of BMD with Risk of Fracture in Postmenopausal Women ≤ –2.5–1.0 to –2.5

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

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

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

51. AAOMS, ADA & ASBMR Recommendations Route dental exams & promotion of good oral hygiene Dental exam is not necessary prior to bisphosphonate therapy No alteration or delay in planned surgery is necessary Discuss benefits/risks of treatment

52. Safety Topics in the Media Atrial Fibrillation No cause and effect relationship

53. Safety Topics in the Media Atypical subtrochanteric femur fracture FDA (3/10): data have not shown a clear connection with bisphosphonate use Similar number of these fractures in those not on bisphosphonates

54. Safety Topics in the Media Typical femur fracture Atypical femur fracture Associated with fall (95%) No fall No prodrome Prodromal thigh pain 30-50% reduction with effective bisphosphonate Often associated with bisphosphonate/steroid use Located at or above trochanter Below intertrochanteric line General unilateral Uni or bilateral No cortical thickness change Increased femoral cortical thickness Generally spiral Transverse with medial spike

55. Safety Topics in the Media Esophageal Cancer 2 large studies in the UK with conflicting results FDA has not concluded that taking an oral bisphosphonate increases the risk of esophageal cancer Would avoid bisphosphonates in patients with Barrett’s esophagus

56. Drug Holiday: FDA “ In light of all the risk-benefit challenges with the bisphosphonate class, these data suggest that bisphosphonate therapy could be safely discontinued from an efficacy standpoint. However, additional long- term data would be needed to further define an appropriate duration of drug cessation and to determine if interim monitoring is appropriate on an individual basis.” “There are no substantial data available to inform decision regarding the initiation or duration of a drug holiday.” FDA Advisory Committee (9/9/11)