1. Osteoporosis Internal Medicine Lecture Series Danielle Hansen DO, MS September 26, 2007

2. Definition Skeletal Disorder Characterized by Compromised Bone Strength Predisposing to an Increased Risk of Fracture. Skeletal Disorder Characterized by Compromised Bone Strength Predisposing to an Increased Risk of Fracture. Bone Strength = Bone Density + Bone Quality NIH Consensus Conference, 2000

3. Epidemiology 8 Million Women and 2 Million Men have Osteoporosis 1 8 Million Women and 2 Million Men have Osteoporosis 1 34 Million Americans have Low Bone Mass 1 34 Million Americans have Low Bone Mass 1 50% of Women and 25% of Men >50 yo will Suffer an Osteoporosis-related Fracture within their Lifetime 2 50% of Women and 25% of Men >50 yo will Suffer an Osteoporosis-related Fracture within their Lifetime 2 1.National Osteoporosis Foundation. America’s Bone Health: The state of Osteoporosis and Low Bone mass in our Nation. 2002 2.Chrischilles EA, et al. Arch Intern. Med. 1991; 151, 2026-32 20022020 Women with Osteoporosis 7.810.5 Women with Low Bone Mass 21.830.4 Men with Osteoporosis 2.33.3 Men with Low Bone Mass 11.817.1 Numbers in Millions Projected Prevalence in Those >50

4. Osteoporotic Fracture Incidence 2 Million Fractures Annually in Pts >50 yo 2° to Osteoporosis 300,000 Hip Fx 300,000 Hip Fx 550,000 Vertebral Fx 550,000 Vertebral Fx 400,000 Wrist Fx 400,000 Wrist Fx 810,000 Other 810,000 Other Burge, et al. JBMR. 2007. 465-75 MIBreast CA Annual Incidence of Common Diseases

5. Cost of Osteoporosis Osteoporotic Fractures Account for: Osteoporotic Fractures Account for: $17 Billion in Direct medical Costs 1 $17 Billion in Direct medical Costs 1 >400,000 Hospital Admissions 3 >400,000 Hospital Admissions 3 2.5 Million Physician Visits 3 2.5 Million Physician Visits 3 >180,000 Nursing Home Admissions 3 >180,000 Nursing Home Admissions 3 Projected Annual Direct Costs: Projected Annual Direct Costs: $25.3 Billion by 2025 1 $25.3 Billion by 2025 1 $50 Billion by 2040 2 $50 Billion by 2040 2 1.Burge, et al. JBMR. 2007. 465-75. 2.Ray, NF, et al. J Bone Min Res. 1997; 12: 24-35. 3.National Osteoporosis Foundation, Osteoporosis Int. 1998; 8: S1-S88.

6. Risk Factors for Osteoporotic Fx Genetics Genetics Low Peak Bone Mass 1 Low Peak Bone Mass 1 Small, Thin Frame 2 Small, Thin Frame 2 Race Race Whites and Asians > Latinas > AA 3 Whites and Asians > Latinas > AA 3 Women > Men Women > Men Adult Fracture Adult Fracture Relative with Adult Fracture Relative with Adult Fracture Smoking Smoking Advancing Age Advancing Age Imparied Vision Imparied Vision Dementia Dementia Poor Health Poor Health Estrogen Deficiency < 45 yo Estrogen Deficiency < 45 yo Frequent Falls Frequent Falls Lifelong Low Calcium Intake Lifelong Low Calcium Intake Sedentary Lifestyle Sedentary Lifestyle EToH Consumption EToH Consumption 1. Riggs, BL et al. N Eng J Med. 1986; 314(26): 1676-86. 2. Gunnes, M, et al. Bone. 1996; 4: 407-13. 3. NOF, 2007.

7. Osteoporosis 2° to Disease RA RA Other Autoimmune Other Autoimmune Hyperparathyroidism Hyperparathyroidism Hypogonadism Hypogonadism Hyperprolactinemia Hyperprolactinemia Acromegaly Acromegaly Hypercortisolism Hypercortisolism Hyperthyroidism Hyperthyroidism IBD IBD Celiac Disease Celiac Disease Malabsorption Syndromes Malabsorption Syndromes Biliary Sclerosis Biliary Sclerosis Sclerosing Choangitis Sclerosing Choangitis Alcoholic Cirrhosis Alcoholic Cirrhosis Autoimmune Hepatitis Autoimmune Hepatitis IDDM IDDM Organ Transplantation Organ Transplantation Multiple Myeloma Multiple Myeloma Osteogenesis Imperfecta Osteogenesis Imperfecta Pernicious Anemia Pernicious Anemia Sarcoidosis Sarcoidosis Anorexia/Bulimia Anorexia/Bulimia Calcium Deficiency Calcium Deficiency Excessive Vitamin A Excessive Vitamin A TPN TPN Stroke Stroke MS MS Parkinson’s Disease Parkinson’s Disease Spinal Cord Injury Spinal Cord Injury Immobilization Immobilization Renal Disease Renal Disease Addison’s Disease Addison’s Disease Amyloidosis Amyloidosis Ankylosing Spondylitis Ankylosing Spondylitis COPD COPD Cushing Syndrome Cushing Syndrome Endometriosis Endometriosis Hemophilia Hemophilia Hemochromatosis Hemochromatosis Lymphoma Lymphoma Leukemia Leukemia

8. Osteoporosis 2° to Medications Glucocorticoids Glucocorticoids Aromatase Inhibitors Aromatase Inhibitors Gonadotropin- releasing Hormone Agonists Gonadotropin- releasing Hormone Agonists Immunosuppressants Immunosuppressants Cytotoxics Cytotoxics Phenobarbital Phenobarbital Phenytoin Phenytoin Lithium Lithium Heparin Heparin Depo-Provera Depo-Provera TPN TPN ? PPIs ? ? SSRIs ?

9. Bone Loss with Aging Lose 20% of Bone in First 5-7 years after Menopause Lose 20% of Bone in First 5-7 years after Menopause

10. Fracture Risk with Aging Hip Fractures Increase Sharply >70 Hip Fractures Increase Sharply >70 Vertebral Fractures Increase Linearly >40 Vertebral Fractures Increase Linearly >40

11. Fracture Risk with Bone Density Exponential Increase in Risk of Fracture with Worsening BMD Exponential Increase in Risk of Fracture with Worsening BMD

12. Vertebral Fractures Prior Vertebral Fracture: Prior Vertebral Fracture: Increases Vertebral Fracture Risk 5-fold 1 Increases Vertebral Fracture Risk 5-fold 1 Increases Hip Fracture Risk 2-fold 2 Increases Hip Fracture Risk 2-fold 2 Silent Fractures Common Silent Fractures Common 1.lindsay, R et al. JAMA. 2001 Jan 17;285(3):320-3. 2.Black, DM, et al. J Cone Miner Res. 1999 May;14(5):821-8.

13. Hip Fracture 10-24% Death in Year Following Fx 1 10-24% Death in Year Following Fx 1 Up to 30% Require ECF Up to 30% Require ECF 15% Walk Unaided 6 Months after Fx 15% Walk Unaided 6 Months after Fx <20% Regain Premorbid Level of Functioning 2 <20% Regain Premorbid Level of Functioning 2 <5% Fracture Admissions <5% Fracture Admissions are Evaluated for Osteoporosis are Evaluated for Osteoporosis 1.Forsen, L et al. Osteoporosis Int. 1999;10:73-78. 2.Van Balen, R et al. Disabil Rehab. 2003 May 20;25(10):507-19.

14. Diagnosis: DXA Central Machine Peripheral Machine Hip, Sine, Forearm, Total Body Wrist, Heel, Finger Diagnostic Identify Pts at Risk Monitor Response to Tx q 1- 2 years Cannot Monitor Tx Response

15. Diagnosis: WHO Criteria Defines Osteoporosis in Relation to Expected Distribution of BMD for Young, Normal Adults of Same Sex Defines Osteoporosis in Relation to Expected Distribution of BMD for Young, Normal Adults of Same Sex T-Score Expressed as Standard Deviations Above (+) or Below (-) the Young Reference Mean Value T-Score Expressed as Standard Deviations Above (+) or Below (-) the Young Reference Mean Value One SD = 10-15% of BMD One SD = 10-15% of BMD Criteria Apply to Hip, Spine, Wrist Criteria Apply to Hip, Spine, Wrist

16. Indications for DXA Women >64 Women >64 Younger Postmenopausal Women with 1 Other Risk Factor Younger Postmenopausal Women with 1 Other Risk Factor Postmenopausal Women with Fracture Postmenopausal Women with Fracture

17. DXA Medicare Coverage Every 2 Years for: Every 2 Years for: Estrogen Deficient Women at Risk Estrogen Deficient Women at Risk Vertebral Abnormalities Vertebral Abnormalities Long-Term Glucocorticoid Therapy Long-Term Glucocorticoid Therapy Primary Hyperparathyroidism Primary Hyperparathyroidism Assess Response to Treatment Assess Response to Treatment

18. Universal Prevention/Treatment Strategies Risk Reduction Risk Reduction Adequate Daily Intake of Calcium and Vitamin D Adequate Daily Intake of Calcium and Vitamin D Weight-Bearing and Muscle Strengthening Exercises Weight-Bearing and Muscle Strengthening Exercises Fall Prevention Fall Prevention Tobacco Cessation Tobacco Cessation EToH Cessation EToH Cessation

19. CalciumAgeMg/day1-8500-800 9-181300 19-491000 >501200 Recommendations Meals700mg Supplement500mg 1200mg +

20. Vitamin D Essential for Absorption of Calcium from GI Tract Essential for Absorption of Calcium from GI Tract >50 need 800-1000 IU/day >50 need 800-1000 IU/day <50 need 400-800 IU/day <50 need 400-800 IU/day Vitamin D Synthesized in Skin Upon Exposure to Sunlight Vitamin D Synthesized in Skin Upon Exposure to Sunlight Blocked by Sunscreen (SPF 8 Blocks 95%) Blocked by Sunscreen (SPF 8 Blocks 95%) Fortified Foods Fortified Foods 1,25-dihydroxyvitamin D 3 is Biologically Active Form 1,25-dihydroxyvitamin D 3 is Biologically Active Form Monitor Serum 25-hydroxyvitamin D 3 (Goal >80nmol/L) Monitor Serum 25-hydroxyvitamin D 3 (Goal >80nmol/L)

21. Indications for Pharmacologic Therapy

22. Options for Pharmacologic Therapy Antiresorptives (Bone Retaining) Antiresorptives (Bone Retaining) Bisphosphonates Bisphosphonates Inhibit Osteoclasts Inhibit Osteoclasts Administration Guidelines Administration Guidelines Calcitonin Calcitonin Estrogen/Hormone Therapy Estrogen/Hormone Therapy Raloxifene Raloxifene Anabolics Anabolics Synthetic PTH Synthetic PTH

23. Bisphosphonates Dosage: Dosage: 35mg q wk for Prevention 35mg q wk for Prevention 70mg q wk for Treatment 70mg q wk for Treatment FIT-I 51% Reduction in Hip Fractures at 3yrs FIT-I 51% Reduction in Hip Fractures at 3yrs Also Effective with Glucocorticcoids Also Effective with Glucocorticcoids Dosage: 35mg q wk Trials: 61-65% Reduction in Vertebral Fractures 55% Reduction in Hip Fractures 70% Reduction in vertebral Fractures in Glucocorticcoid Pts

24. Calcitonin At Least 5 Years Postmenopausal and Unable to Tolerate Other Therapy At Least 5 Years Postmenopausal and Unable to Tolerate Other Therapy Reduced Risk of Vertebral Fractures but Not Other Fractures Reduced Risk of Vertebral Fractures but Not Other Fractures Nasal Spray or Injectable Nasal Spray or Injectable

25. Evista Selective Estrogen Receptor Modulator that Acts as an Estrogen Agonist on Bone but as an Estrogen Antagonist on Breast and Uterus Selective Estrogen Receptor Modulator that Acts as an Estrogen Agonist on Bone but as an Estrogen Antagonist on Breast and Uterus Reduced Risk of Vertebral Fractures, but Not Other Fractures Reduced Risk of Vertebral Fractures, but Not Other Fractures Significant Fracture Reduction in Glucocorticcoids but no Indication Significant Fracture Reduction in Glucocorticcoids but no Indication Reduced Risk of Breast Cancer by 66-72% Reduced Risk of Breast Cancer by 66-72%

26. Hormone Therapy WHI Findings: WHI Findings: 34% Reduction in Hip Fractures 34% Reduction in Hip Fractures 23% Reduction in Other Osteoporotic Fractures 23% Reduction in Other Osteoporotic Fractures 24% Reduction in all Fractures 24% Reduction in all Fractures Controversial Controversial

27. Treatment Summary

28. Challenge Identify and Treat High Risk Patients Identify and Treat High Risk Patients Recognize Risk Factors that Call For Screening Recognize Risk Factors that Call For Screening Assess Diet and Lifestyle Assess Diet and Lifestyle Treat Appropriately Treat Appropriately Rule out Other Diseases Rule out Other Diseases