1. IM Grand Rounds Wednesday April 1, 2015

2. Outline Background Recommendations from various groups/organizations Article review (brief)

3. Osteoporosis – a diagnosis for both women and men… (as this photo proves!)

4. Osteoporosis – a diagnosis for both women and men… (as this photo proves!)

5. Osteoporosis in Men Are we missing an opportunity? (to screen, to diagnose, to treat…) Few studies have focused on fragility fractures in the male population There has been higher-than-anticipated rates of fragility fracture among men J Bone Joint Surg Am. 2014;96:1820-7

6. Rationale for looking at this topic Estimate: 2012 → 12 million Americans over age 50 expected to have osteoporosis 50% of postmenopausal women will have an osteoporosis-related fracture during their lifetime -25% of these: vertebral deformity -15% of these: hip fracture Osteoporotic fractures (especially hip fractures) are associated with: chronic pain & disability loss of independence decreased quality of life increased mortality Final Recommendation Statement: Osteoporosis: Screening. U.S. Preventive Services Task Force. October 2014. http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/osteoporosis-screening

7. Some numbers Estimate: 1.5 million individuals suffer a fragility fracture annually (Riggs, 1998) Estimate: 40% of women & 25-33% of men during their lifetime will suffer a hip, spine, or wrist fracture in their lifetime (Binkley, 2006) One year mortality rate of a hip fracture women: 28% men: 35% (U.S. Dept of Health & Human Services, 2004) Riggs BL, O'Fallon WM, Muhs J, et al. Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner Res 1998;13:168-74. Binkley N, Bilezikian JP, Kendler DL, et al. Official positions of the international society for clinical densitometry and executive summary of the 2005 position development conference. J Clin Densitom 2006;9:4-14. U.S. Department of Health and Human Services. In Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004.

8. Some numbers Estimate: 1.5 million individuals suffer a fragility fracture annually (Riggs, 1998) Estimate: 40% of women & 25-33% of men during their lifetime will suffer a hip, spine, or wrist fracture in their lifetime (Binkley, 2006) One year mortality rate of a hip fracture women: 28% men: 35% (U.S. Dept of Health & Human Services, 2004) *Although the fracture risk is highest in cases of osteoporosis, the actual number of fractures is highest in the large group of patients with milder bone loss (osteopenia) (Siris, 2004) Riggs BL, O'Fallon WM, Muhs J, et al. Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner Res 1998;13:168-74. Binkley N, Bilezikian JP, Kendler DL, et al. Official positions of the international society for clinical densitometry and executive summary of the 2005 position development conference. J Clin Densitom 2006;9:4-14. U.S. Department of Health and Human Services. In Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004. Siris ES, Harris ST, Eastell R, et al. Skelatal effects of raloxifene after 8 years: results from the continuing outcomes relevant to evista (CORE) study. J Bone Miner Res 2005;20:1514-24.

9. Some numbers (cont) Cost Estimates: Direct medical care costs of osteoporotic fractures: estimated to be $12.2 to $17.9 billion per year in 2002 *these estimates do not include indirect costs associated with lost productivity of patients and caregivers. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.

10. What is a “Fragility Fracture” →Defined by the World Health Organization (WHO) as a fracture from low-level trauma - a fall from standing height or lower Ann Intern Med. 2008;148:680-684.

11. Definition: Osteopenia Bone Mineral Density (BMD) is classified according to the T- score, which is the number of standard deviations above or below the mean BMD for young healthy adults, as determined by dual-energy x-ray absorptiometry (DEXA or DXA). – A T-score of - 2.5 or less is classified as osteoporosis. – A T-score between - 2.5 and - 1.0 is considered LBD (also known as osteopenia). – A T-score of - 1 or greater is considered normal.

12. DXA Testing Previous studies evaluating the accuracy of DXA for predicting fractures have focused mainly on women; studies have only recently assessed the predictive ability of DXA in men. A large prospective cohort study in the Netherlands that included men and women older than 55 years reported the incidence of vertebral and non-vertebral fractures approximately 6 years after patients obtained baseline DXA measurements of the femoral neck. For each SD reduction in BMD at the femoral neck, the hazard ratio for vertebral and non-vertebral fractures increased to a similar degree in both men and women Kanis JA, Oden A, Johnell O, Johansson H, De Laet C, Brown J, et al. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int. 2007;18:1033-46.

13. In table format… National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

14. FRAX tool – predicting risk for fracture National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

15. FRAX tool National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Baseline risk case: 65 year-old woman*; 10 year risk of ANY osteoporotic fracture - 9.3%

16. Risk Factors for Osteoporosis (1 of 2)  Increasing age  Female sex  Postmenopause for women  Hypogonadism or premature ovarian failure  Ethnic background (risk is greater for whites)  Low body weight  Previous fracture due to minimal trauma  Parental history of hip fracture  Rheumatoid arthritis  Low BMD  Current smoking  Alcohol intake (3 or more drinks per day)  Vitamin D deficiency  Low calcium intake  Hyperkyphosis  Falling  Immobilization  Risk factors include (but are not limited to): National Osteoporosis Foundation. Clinician’s Guide To Prevention and Treatment of Osteoporosis. Available at www.nof.org/sites/default/files/pdfs/NOF_ClinicianGuide2009_v7.pdf. Newberry SJ, Crandall CC, Gellad WG, et al. Comparative Effectiveness Review No. 53. Available at www.effectivehealthcare.ahrq.gov/lbd.cfm.

17.  Risk is also increased with the chronic use of some medications, including, but not limited to:  Glucocorticoids  Anticoagulants  Anticonvulsants  Aromatase inhibitors  Cancer chemotherapeutic drugs  Gonadotropin-releasing hormone agonists Risk Factors for Osteoporosis (2 of 2) National Osteoporosis Foundation. Clinician’s Guide To Prevention and Treatment of Osteoporosis. Available at www.nof.org/sites/default/files/pdfs/NOF_ClinicianGuide2009_v7.pdf. Newberry SJ, Crandall CC, Gellad WG, et al. Comparative Effectiveness Review No. 53. Available at www.effectivehealthcare.ahrq.gov/lbd.cfm.

26. Review: Screening Recommendations from various organizations

29. Screening recommended: All men at age 70 Men aged 50-69 if additional risk factors J Clin Endocrinol Metab, June 2012, 97(6):1802–1822

30. Screening recommended: All men at age 70 Men aged 50-69 if additional risk factors Risk Factors: History of fracture after age 50Glucocorticoid use (prednisone 7.5mg/day) Hx of delayed pubertyGnRH agonists HypogonadismSmoking HyperparathyroidismAlcohol Use Hyperthyroidism COPD J Clin Endocrinol Metab, June 2012, 97(6):1802–1822

31. Screening recommended: All men at age 70 Men aged 50-69 if additional risk factors Risk Factors: History of fracture after age 50Glucocorticoid use (prednisone 7.5mg/day) Hx of delayed pubertyGnRH agonists HypogonadismSmoking HyperparathyroidismAlcohol Use Hyperthyroidism COPD Treatment: alendronate, risedronate, zolendronic acid, teriparatide; Denosumab for men receiving ADT for prostate cancer therapy J Clin Endocrinol Metab, June 2012, 97(6):1802–1822

32. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

33. Screening National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

34. Screening Tools DXA testing Vertebral Imaging National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

35. Treatment Who should be considered for treatment: Post-menopausal women and men age ≥ 50y with 1.A hip or vertebral fracture 2.T-score ≤ -2.5 (at femoral neck, hip, L-spine) 3.Low bone mass (T-score btwn -1.0 and -2.5) and a 10-year probability of hip fracture ≥ 3% 4.Low bone mass and 10-year probability of any major osteoporosis- related fracture ≥ 20% National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

36. Treatment Medications mentioned in the NOF guideline: Bisphosphonates (Alendronate, Ibandronate, Risendronate, Zolendronic acid) Calcitonin Estrogen/Hormone therapy (no testosterone therapy mentioned) Estrogen Agonist/Antagonist (FKA “SERMs”) Parathyroid hormone (Teriparatide) Denosumab National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013.

37. Florence R, Allen S, Benedict L, Compo R, Jensen A, Kalogeropoulou D, Kearns A, Larson S, Mallen E, O’Day K, Peltier A, Webb B. Institute for Clinical Systems Improvement. Diagnosis and Treatment of Osteoporosis. Updated July 2013.

40. Ann Intern Med. 2008;148:680-684.

41. Target Patient Population: Men older than age 50 Objective: Determine risk factors for osteoporosis in men Objective: Determine if there are validated tools to screen for osteoporosis in men Objective: Determine the risk factors for low BMD-mediated fracture? Ann Intern Med. 2008;148:680-684.

42. Risk Factors for Osteoporosis in men: 1.Age (>70yr) 2.Low body weight (BMI <20-25) 3.Weight loss (>10%) (compared with adult weight) 4.Physical inactivity 5.Use of corticosteroids 6.Previous fragility fracture Ann Intern Med. 2008;148:680-684.

43. Other POTENTIAL Risk Factors for Osteoporosis in men this review looked at: 1.Alcohol (increased probability of fracture but not assoc’d with decreased BMD) 2.Androgen Deprivation Therapy (ADT) (pharmacologic and orchiectomy) 3. Cigarette Smoking 4. Low dietary intake of calcium 5. Spinal cord injury (moderate predictor of low BMD and osteoporotic fracture) Ann Intern Med. 2008;148:680-684.

44. Data for these possible risk factors is insufficient in men: Respiratory disease (independent of steroid use) Type 2 DM Dietary vitamin D Thyroid disease and thyroid replacement therapy GI malabsorption Rheumatoid arthritis hyperparathyroidism Ann Intern Med. 2008;148:680-684.

45. Screening Tests: DXA – expensive, not portable, not available everywhere Goal: identify & evaluate efficacy of non-DXA screening tests 1.Calcaneal Ultrasound 2.Osteoporosis self-assessment screening tool (OST) *neither is sufficiently sensitive or specific at predicting DXA-determined bone mass to be recommended as a substitute for DXA RECOMMENDATION: Clinicians should obtain DXA for men who are at increased risk for osteoporosis and are candidates for drug therapy Ann Intern Med. 2008;148:680-684.

46. Final Recommendation: Further research is needed to evaluate osteoporosis screening tests in men Ann Intern Med. 2008;148:680-684.

47. USPSTF 2014

52.  Evidence is sparse regarding the effectiveness of therapies to prevent or treat osteoporosis in men.  Studies have not directly compared the antifracture effectiveness of longer durations of therapy among the various medications. Thus, it is unclear how long patients should remain on therapy. The benefits and harms of drug holidays are also unclear.  Data are insufficient to determine the comparative effectiveness among individual bisphosphonates or between bisphosphonates and calcium, raloxifene, or teriparatide. Gaps in Knowledge (2 of 3) Newberry SJ, Crandall CC, Gellad WG, et al. Comparative Effectiveness Review No. 53. Available at www.effectivehealthcare.ahrq.gov/lbd.cfm.

54. FRAX tool National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2013. Baseline risk case: 65 year-old woman*; 10 year risk of ANY osteoporotic fracture - 9.3%

55. How do we detect osteoporosis in patients? Bone measurement tests to measure bone density dual-energy x-ray absorpitometry (DXA) quantitative ultrasonography of the calcaneus Clinical risk assessment instruments - estimated to have only modest predictive value for low bone density of fractures FRAX – estimates 10 year risk of major osteoporotic fracture Final Recommendation Statement: Osteoporosis: Screening. U.S. Preventive Services Task Force. October 2014. http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/osteoporosis-screening

56. Benefits of Detection Intervention! Evidence exists that drug therapy reduces the risk for fractures in postmenopausal women (without prior osteoporotic fracture) *due to lack of relevant studies, USPSTF notes inadequate evidence that drug therapies reduce the risk for fractures in men who have had no previous osteoporotic fractures Lack of randomized trials of primary fracture prevention in men who have osteoporosis was identified by the USPSTF as critical gap in the evidence

57. Interventions to prevent osteoporotic fracture include: – Pharmacologic agents – Dietary and supplemental vitamin D and calcium – Weight-bearing exercise These interventions have also been studied and used (with less frequency) in patients with osteopenia (T-score between -2.5 and -1.0). Interventions To Prevent Osteoporotic Fracture Newberry SJ, Crandall CC, Gellad WG, et al. Comparative Effectiveness Review No. 53. Available at www.effectivehealthcare.ahrq.gov/lbd.cfm.

58. Googleimages.com

60. $$Medicare$$ Does Medicare cover DXA testing in men? J Clin Endocrinol Metab 97: 1802–1822, 2012

61. www.medicare.gov

62. Medicare.gov website – link to NIH site -nice, patient-friendly summary page on osteoporosis that mentions yet another organization… ICSD (International Society for Clinical Densitometry)

63. ©ICSD January 2014

64. $$Medicare$$ Does Medicare cover DXA testing in men? Only in men who have: – Vertebral fractures – Radiographic osteopenia – Hyperparathyroidism – On oral glucocorticoid therapy J Clin Endocrinol Metab 97: 1802–1822, 2012

67. o Specifically focused on distal radius fractures o Retrospective review of medical records o Men (95) and women (344) over age 50 who were treated for distal radial fracture (at a single institution) over 5 year time period o Purpose: Compare demographic & fracture characteristics, and… o Question: did these patients receive DXA testing and osteoporosis treatment within 6 months following the injury?

68. n= 439 female: 344 male: 95 Average age: 66y (range 50-100)

69. Comparing Eval & Treatment DXA Scan Following distal radial fracture: 184 women (184/344) – 53% 17 men (17/95) – 18% Initiation of treatment with Calcium & vitamin D: women: 55% men: 21% Initiation of treatment with bisphosphonates: women: 22% men: 3%

73. Summary -Lots of guidelines and recommendations -Be aware of osteoporosis in the male population (and how osteoporosis can be screened for in men) -Additional research on the horizon (?)