1. R R R R C C OSTEOPOROSIS R heumatology R esearch C enter INTERNAL MEDICINE CONGRESS 1382

2. R R R R C C R R R R C C

3. R R R R C C DEFINITION Systemic Skeletal Disease Low Bone Mass Micro Architectural Deterioration –Increase in Bone Fragility –Susceptibility to Fracture Am J Med 1993;94:644-650 Bone Densitometry –t score: –2.5SD WHO 1990 Systemic Skeletal Disease Low Bone Mass Micro Architectural Deterioration –Increase in Bone Fragility –Susceptibility to Fracture Am J Med 1993;94:644-650 Bone Densitometry –t score: –2.5SD WHO 1990

4. R R R R C C EPIDEMIOLOGY

5. R R R R C C USA (NHANESS III 1997) –Women 13 - 18% –Men 1 - 4% IRAN 4,575,000 - 7,150,000 USA (NHANESS III 1997) –Women 13 - 18% –Men 1 - 4% IRAN 4,575,000 - 7,150,000

6. R R R R C C FRACTURE RISK 50 YEARS AND OVER WOMEN MEN Femur17.5%6.0% Spine15.65.0 Wrist16,02.5 Any Fracture39.7 13.1 WOMEN MEN Femur17.5%6.0% Spine15.65.0 Wrist16,02.5 Any Fracture39.7 13.1

7. R R R R C C BONE PHYSIOLOGY

8. R R R R C C Bone Resorption –Osteoclast Bone Formation –Osteoblast Bone Remodeling Unit –Positive < age 30 –Negative > age 30 Bone Resorption –Osteoclast Bone Formation –Osteoblast Bone Remodeling Unit –Positive < age 30 –Negative > age 30 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1015202530354045505560657075

9. R R R R C C OSTEOBLAST Origin: Mesenchymal Cell Activation: PTH, Vitamin D Function –Matrix Formation –Bone Mineralization –Matrix Degradation  RANK L Origin: Mesenchymal Cell Activation: PTH, Vitamin D Function –Matrix Formation –Bone Mineralization –Matrix Degradation  RANK L

10. R R R R C C OSTEOCLAST Origin –Blood Mononuclear Cells Differentiation –CSF-1 –RANK L Lymphocyte Osteoblast Action –Acidification –Protein Degradation Origin –Blood Mononuclear Cells Differentiation –CSF-1 –RANK L Lymphocyte Osteoblast Action –Acidification –Protein Degradation H2O + CO2 HCO3 H+ Cl

11. R R R R C C BONE REMODELING UNIT................... ResorptionFormationCompletion

12. R R R R C C STIMULATION IL-1 TNF-  IL-6 IL-11 PTH Vit D RANK BONE RESORPTION M-CSF IL-1 TNF-  IL-6 IL-11 PTH Vit D RANK STIMULATION

13. R R R R C C PROGESTERONE ANDROGEN ILGF PTH Vit D ESTROGEN STIMULATION CALCITONIN INHIBITION COUPLING FACTOR IL-1 TNF-  IL-6 IL-11 INHIBITION PTH Vit D RANK BONE FORMATION

14. R R R R C C CLINICAL MANIFESTATIONS

15. R R R R C C Symptoms Non Complications Fractures –Macroscopic Vertebra Femoral Neck Wrist Others –Microscopic Vertebrae: Mechanical Pain, Spine Deformity Symptoms Non Complications Fractures –Macroscopic Vertebra Femoral Neck Wrist Others –Microscopic Vertebrae: Mechanical Pain, Spine Deformity

16. R R R R C C DIAGNOSIS

17. R R R R C C OLD DAYS

18. R R R R C C 20 th CENTURY X-RAY BONE BIOPSY X-RAY BONE BIOPSY RRC

19. R R R R C C NOWADAYS BONE DENSITOMETRY

20. R R R R C C D ual E nergy X -ray A bsorptiometry (Gold Standard) NON INVASIVE –Irradiation: 1/100 Chest X-ray –1 h. Sun Exposure SENSITIVITY1.0% ACCURACY 2.8% REPEATABLE LONGITUDINAL STUDY NON INVASIVE –Irradiation: 1/100 Chest X-ray –1 h. Sun Exposure SENSITIVITY1.0% ACCURACY 2.8% REPEATABLE LONGITUDINAL STUDY

21. R R R R C C B ONE M INERAL D ENSITY SPINE FEMUR FOREARM OTHERS –Whole Body –Heel –hand SPINE FEMUR FOREARM OTHERS –Whole Body –Heel –hand

22. R R R R C C RESULT BMD0.857 Comparison To Young Adult –%76% –t Score-2.4 Comparison To Same Age –%101% –z Score+0.1 BMD0.857 Comparison To Young Adult –%76% –t Score-2.4 Comparison To Same Age –%101% –z Score+0.1

23. R R R R C C SPINE

24. R R R R C C

25. R R R R C C FEMUR

26. R R R R C C

27. R R R R C C FOREARM

28. R R R R C C

29. R R R R C C DIFFERENT STANDARDS COUNTRIES and ETHNICITIES MACHINES –Hologic –Lunar –MediLink –Norland COUNTRIES and ETHNICITIES MACHINES –Hologic –Lunar –MediLink –Norland

30. R R R R C C AMERICAN STANDARD Standardized BMD PBM 1124 mg 1006 mg 829 mg Osteopenia Osteoporosis Female - Spine

31. R R R R C C IRANIAN STANDARD Standardized BMD PBM 1097 mg Female - Spine

32. R R R R C C COMPARISON Standardized BMD PBM diff 2.5% 1006 mg 829 mg Osteopenia Osteoporosis Female - Spine

33. R R R R C C DEFINITIONS NORMAL BONE –1.0 to -1.0 SD over/bellow PBM OSTEOPENIA –-1.0 to -2.4 SD bellow PBM OSTEOPOROSIS –-2.5 SD bellow PBM NORMAL BONE –1.0 to -1.0 SD over/bellow PBM OSTEOPENIA –-1.0 to -2.4 SD bellow PBM OSTEOPOROSIS –-2.5 SD bellow PBM

34. R R R R C C BMD REPORT FRACTURE RISK Spine Neck –t = -1 SD 2.2 2.6 –t = -2 SD 5.0 7.0 –t = -3 SD11.018.0 Comparison Iranian Standard Advice –Evaluation –Prevention/Treatment FRACTURE RISK Spine Neck –t = -1 SD 2.2 2.6 –t = -2 SD 5.0 7.0 –t = -3 SD11.018.0 Comparison Iranian Standard Advice –Evaluation –Prevention/Treatment

35. R R R R C C PURPOSE and APPLICATION DIAGNOSIS –Osteoporosis –Osteopenia –Normal Bone CALCULATION –Time to Osteopenia –Time to Osteoporosis DIAGNOSIS –Osteoporosis –Osteopenia –Normal Bone CALCULATION –Time to Osteopenia –Time to Osteoporosis

36. R R R R C C BONE LOSS % Age 22% Loss 35-65 Y Spine – Iranian Women

37. R R R R C C INDICATION (People at Risk) Menopause Inflammatory Diseases Endocrine Disorders Predisposing Drugs Familial History Fracture Menopause Inflammatory Diseases Endocrine Disorders Predisposing Drugs Familial History Fracture

38. R R R R C C BONE TRABECULA

39. R R R R C C

40. R R R R C C

41. R R R R C C

42. R R R R C C PREVENTION

43. R R R R C C PREDISPOSING FACTORS Genetic –Stature –Vitamin D Receptor: DD, Dd, dd Alimentation –Calcium, Protein Physical Activity Habits –Coffee, Alcohol, Smoking Disease –Endocrine, Inflammatory Diseases, Renal Disorders Drugs –Steroids, Cytotoxic, Anti-epileptic, Heparin, Thyroxine Genetic –Stature –Vitamin D Receptor: DD, Dd, dd Alimentation –Calcium, Protein Physical Activity Habits –Coffee, Alcohol, Smoking Disease –Endocrine, Inflammatory Diseases, Renal Disorders Drugs –Steroids, Cytotoxic, Anti-epileptic, Heparin, Thyroxine

44. R R R R C C PREVENTION (Normal Person, Normal BMD) Young –Alimentation –Sport Mid Age (up to menopause) –Habits Menopause –HRT (Allendronate?), Calcium, Exercises Senile –Exercises Young –Alimentation –Sport Mid Age (up to menopause) –Habits Menopause –HRT (Allendronate?), Calcium, Exercises Senile –Exercises

45. R R R R C C PREVENTION (Disease or Medication, Normal BMD) Same as for Normal Person Adequate Management of the Disease –Minimum Required Dose of Predisposing Drug Medication Calcium Exercise Same as for Normal Person Adequate Management of the Disease –Minimum Required Dose of Predisposing Drug Medication Calcium Exercise

46. R R R R C C

47. R R R R C C DRUGS Bone Forming –Synthetic PTH –Fluoride 20-40 mg/daily + Ca + Vit D –Progesterone –Anabolic agentsNandrolone Decanoate Resorption Preventing –Estrogen & AnalogsERT, HRT, Ralloxiphen –CalcitoninInjectable, Nasal Spray –BisphosphonateEtidronate, Allendronate Bone Forming –Synthetic PTH –Fluoride 20-40 mg/daily + Ca + Vit D –Progesterone –Anabolic agentsNandrolone Decanoate Resorption Preventing –Estrogen & AnalogsERT, HRT, Ralloxiphen –CalcitoninInjectable, Nasal Spray –BisphosphonateEtidronate, Allendronate

48. R R R R C C ALLENDRONATE Osteofos Prevention –5 mg daily Treatment –10 mg daily Precautions –30 Minutes Before Breakfast – Upright Position Side Effects Osteofos Prevention –5 mg daily Treatment –10 mg daily Precautions –30 Minutes Before Breakfast – Upright Position Side Effects

49. R R R R C C INTERNAL MEDICINE CONGRESS 1382 R heumatology R esearch C enter