1. Alimohammad Fatemi Assistant Professor of Rheumatology 1

2. OSTEOPOROSIS A skeletal Disorder: – Compromised Bone Strength – Increased Risk of Fracture 2 Adams, Nat Rev Endocrinol. 2013

3. Bone Quality Bone Mineral Bone Material 3 BONE STRENGTH Adams, Nat Rev Endocrinol. 2013

4. Vertebra Body 4 NormalOsteoporosis

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6. Epidemiology 200 million women worldwide 1/3 women aged 60-70 2/3 women aged >80 6 IOF, 2015 ( http://www.iofbonehealth.org/osteoporosis)

7. Epidemiology 7 IOF, 2015 ( http://www.iofbonehealth.org/osteoporosis)

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9. Diagnosis 9 Comparison to Young-Adult Mean BMD

10. WHO CLASSIFICATION Superior to Normal Normal Osteopenia Osteoporosis T +1 0 -2.5 10

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12. FRACTURE RISK 50 YEARS AND OVER WOMEN MEN Femur22.9% 10.7% Spine15.18.3 Wrist20.84.6 Any Fracture46.4 22.4 Kanis JA et al, Osteoporos Int, 2000:11:669-674 12

13. Vertebrae Hip Wrist 50607080 40 30 20 10 Age (Years) Annual incidence per 1000 women Incidence of Osteoporotic Fractures in Women Wasnich RD, Osteoporos Int 1997;7 Suppl 3:68-72

14. Incidence of Osteoporotic Fractures in Men Age (Years) Vertebrae Hip Wrist 50 60 70 80 4000 2000 0 Annual incidence per 100,000 men Wasnich RD, Osteoporos Int 1997;7 Suppl 3:68-72

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16. Cooper C, Am J Med, 1997;103(2A):12S-17S 80% One year after a hip fracture: Patients (%) Unable to carry out at least one independent activity of daily living All Fractures Are Associated With Morbidity

17. 40% Unable to walk independently 80% One year after a hip fracture: Patients (%) Unable to carry out at least one independent activity of daily living Cooper C, Am J Med, 1997;103(2A):12S-17S

18. All Fractures Are Associated With Morbidity 40% Unable to walk independently 30% Permanent disability 80% One year after a hip fracture: Patients (%) Unable to carry out at least one independent activity of daily living Cooper C, Am J Med, 1997;103(2A):12S-17S

19. All Fractures Are Associated With Morbidity 40% Unable to walk independently 30% Permanent disability 20% Death within one year 80% One year after a hip fracture: Patients (%) Unable to carry out at least one independent activity of daily living Cooper C, Am J Med, 1997;103(2A):12S-17S

20. Survival After Hip Fracture Trombetti A et al, Osteoporos Int, 2002;13:731-737 Hip fractured Women Hip fractured Men Women Men Expected Survival In The General Population 2468 10 0.00 0.25 0.50 0.75 1.00 Survival probability Time after hip fracture (years) 0

22. LIFE STYLE DIET Dairy Products SPORT Walking Aerobic WRONG HABITS Smoking Alcohol Excess Coffee Excess Protein

24. CALCIUM Need – 1000 mg Men, Women before Menopause – 1500 mgWomen after Menopause

25. CALCIUM Need – 1000 mg Men, Women before Menopause – 1500 mgWomen after Menopause Source – Dairy ProductsMilk, Yoghourt, Cheese

26. CALCIUM Need – 1000 mg Men, Women before Menopause – 1500 mgWomen after Menopause Source – Dairy ProductsMilk, Yoghourt, Cheese  Milk 300 mg/cup  Cheese 300 mg/Oz  Yogurt 300 mg/cup

27. CALCIUM Need – 1000 mg Men, Women before Menopause – 1500 mgWomen after Menopause Source – Dairy ProductsMilk, Yoghourt, Cheese – VegetablesBroccoli

28. CALCIUM Need – 1000 mg Men, Women before Menopause – 1500 mgWomen after Menopause Source – Dairy ProductsMilk, Yoghourt, Cheese – VegetablesBroccoli – TabletsCalcium Carbonate, Citrate

29. CALCIUM Are Calcium Tab safe? – Risk of Cardiovascular event 29 BMJ 336, 262–266 (2008) JAMA Intern. Med. http://dx.doi.org/10.1001/jamainternmed.2013.3283

30. Patients should be encouraged to obtain 500– 1,000 mg of calcium from their daily diet 30 CALCIUM Nat. Rev. Endocrinol. 9, 255–256 (2013)

31. VITAMIN D Need – 50 to 70 years400 units – > 70 years600 units

34. WHO? History of hip or vertebral fracture T-score ≤-2.5

35. WHO? History of hip or vertebral fracture T-score ≤-2.5 T-score between -1 and -2.5

36. CLINICAL RISK FACTORS for FRACTURE Age Sex Weight Height History of Fracture Parental History of Fracture Current Smoking Steroid Use Alcohol Use RA Secondary Osteoporosis 36

37. FRAX 37

38. WHO? History of hip or vertebral fracture T-score ≤-2.5 T-score between -1 and -2.5 AND: – 10-year probability of hip fracture ≥3 percent or – 10-year probability of any major osteoporosis-related fracture ≥20 percent

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40. Drugs Used In Osteoporosis Treatment HRT SERM/Raloxifene Calcitonin Bisphosphonates - Alendronate - Zoledronate - Ibandronate  Parathyroid Hormone (PTH) Denosumab Strontium Ranelate

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42. ESRTROGEN Antiresorptive Fracture Risk Its effect lost 1 year after stop it 42

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44. SERM Raloxifene 60 mg – Vertebral Fracture – Breast Cancer – DVT 44

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46. Calcitonin Nasal Spray (200 unit/day) – Vertebral Fracture – No effect on Hip fracture – Minimal effect on Bone Density 46

47. Calcitonin Safe? 47

48. Calcitonin Safe? – May Increase Skin Cancer 48 http://www.ema.europa.eu

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50. BISPHOSPHONATES Fracture Risk – Vertebral – Non Vertebral Bone Density 50

51. BISPHOSPHONATES Adverse Effects: – Atypical fracture of Femur – Osteonecrosis of Jaw – Esophageal Cancer? 51

52. 52 FORTEO

53. PTH Anabolic Agent 20 μg Daily SC (18-24 months) 53

54. Indications: – Vertebral Compression Fracture – Other Osteoporotic-Fracture with Low BMD – T-score < -3 54 PTH

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56. DENOSUMAB An antiresorptive Suppress Osteoclasts 60 mg every 6 months (SC) Injection site reaction 56

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58. STRONTIUM RANLEATE Bone Formation Bone Resorption 58

59. STRONTIUM RANLEATE Bone Formation Bone Resorption Powder 2g/ Day 59

60. STRONTIUM RANLEATE Bone Formation Bone Resorption Powder 2g/ Day But, Increases DVT 60

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62. Menopause Prevention HRTif no contraindication (WHI)

63. Menopause Prevention HRTif no contraindication (WHI) Anti-Resorptive Agents Alendronate 70 1 /week

64. Menopause Prevention HRTif no contraindication (WHI) Anti-Resorptive Agents Alendronate 70 1 /week Calcium + Vitamin D

65. FOLLOW-UP Every 6 Months Ca, P, Alkaline Phosphatase, 24 h Calciuria Every 1.5 to 3 Years BMD Change of Treatment Strategy Side Effects Non-Responsive

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