5. Risk factors for hip fracture in men l Low BMD and RF for low BMD l Previous fractures l Low body mass l Taller l Frequent falls and RF for falls

6. Risk factors for osteoporosis in men l Hypogonadism l Steroid therapy l Immobilization l Alcoholism l RA l Cancer l Thyrotoxicosis Causes of secondary osteoporosis

7. Risk factors for osteoporosis in men l Aging l Thinness l Low calcium intake l Very low protein intake l Inactivity l Decreased androgen l Decreased estrogen

9. Design of cohort studies Outcomes (death / disease / others) Exposure

10. Why do we need cohort studies? l Cross-sectional studies can only describe associations l Cohort studies can - Defined temporal relationship - Study multiple outcomes - Can be converted to RCCT

11. Determinants of validity of cohort studies l Sampling method l Sample size l Validity of measurements l Completeness of follow up

12. What is known about determinants of BMD and fractures? l Study of Osteoporotic fractures (SOF) l Dubbo study (Australia) l Rancho Bernando study l NHANES I, II, III l STORM

13. Correlates of femoral neck BMD (Orwoll) Factors% diff Age (5 years)-2.6 Weights (10 kg)5.4 Fracture history-7.4 Hypertension4.2 COAD-6.3 Gastrectomy-11.6 Current alcohol4.9 Current smoking-3.9

14. Sampling Method l Volunteer samples (independent walking) l Stratified by age group 65 - 69 33% 70 - 74 35% ≥ 75 31% l 2000 men and 2000 women

15. Questionnaire for Mr & Ms Os l General including falls (Stanford Health Assessment) l Cigarette smoking l Alcohol consumption

16. Questionnaire for Mr & Ms Os l Dietary intake (Block food frequency) l Medication use l Physical activity (PASE) l Mental status by MMSE l Depression by Geriatric Depression Scale

17. Physical examination for Mr & Ms Os l Height and Weight l BMD by DEXA (Hologic QDR 4500W) l Ankle / arm BP index l Visual function : acuity, depth l Neuromuscular : grip strength, walk speed, chair stand

18. Outcome measures l Fractures (History and X-Ray) l BMD l QCT

19. Characteristic of MrOs Subjects (Mean  SD) Mean (SD) Age72.4 (5) Height (cm)163.1 (5.7) Weight (kg)62.4 (9.4) BMI (kg/m 2 )23.4 (3.1) PASE score97.3 (50.3)

20. PASE Scoring Sitting Job + no exercise 33 Sitting Job + Aerobic Exercise 3-4 times per week 96 Job that requires standing and walking + No exercise 184 Job that requires standing and walking + Aerobic Exercise 3-4 times per week 221

21. Characteristic of MrOs Subjects (Mean  SD) Diet Mean (SD) Total calories intake (kcal)2161 (747) Protein intake (g)90 (41) Calcium intake (mg)649 (344)

22. Characteristic of MrOs Subjects Percentage Current cigarette smoking11.9% Alcoholism - drink  4 /day in p12m 0.4% - ever drink 5/day8.0% Had 1 or more fracture13.7% Diabetes mellitus14.7% Thyroid disease2.1% COPD11.6%

23. Determinants of BMD in Chinese men (Age-adjusted) What are the physical characteristics that are associated with BMD in Chinese men? What are the physical characteristics that are associated with BMD in Chinese men?

24. Percent difference Weight (5 kg): +3.6 Weight (5 kg): +3.6 Determinants of BMD in Chinese men (Age-adjusted)

25. What medical factors are associated with BMD in Chinese men? What medical factors are associated with BMD in Chinese men? Determinants of BMD in Chinese men (Age-adjusted)

26. Medical Diseases associated with lower BMD: Medical Diseases associated with lower BMD: Percent difference Percent difference –Chronic obstructive lung disease(- 5.8) –Gastrointestinal surgery(- 4.7) –Fracture after age 50 years(-5.7) Determinants of BMD in Chinese men (Age-adjusted)

27. Medical Diseases associated with higher BMD: Medical Diseases associated with higher BMD: Percent difference Percent difference –Hypertension (4.0) –Diabetes(6.9) –Hyperthyroidism(5.1) Determinants of BMD in Chinese men (Age-adjusted)

28. Medications associated with lower BMD: Medications associated with lower BMD: Percent difference Percent difference Inhaled corticosteroids (0.9%) (- 12.9) Oral corticosteroids (0.6%) (- 4.4) Medications associated with hiher BMD: –Thiazide diuretics(4.7) Determinants of BMD in Chinese men (Age-adjusted)

29. What about lifestyle factors? What about lifestyle factors? Determinants of BMD in Chinese men (Age-adjusted)

30. Cigarette Smoking: Cigarette Smoking: Percent difference Percent difference Current smokers(-4.6) Current smokers(-4.6) More than 46 packyrs (-3.1) Determinants of BMD in Chinese men (Age-adjusted)

31. Physical Activity: Physical Activity: Percent difference Percent difference –PASE(0.5) –Total number of city streets per day for normal routine and exercises: 20 or above (25% of subjects)(1.8) Determinants of BMD in Chinese men (Age-adjusted)

32. Dietary Factors: Dietary Factors: Percent difference Percent difference –Calcium (mg) per day (50mg)(0.2) –Protein (g) per day (10g)(0.2) Depression: Depression: –GDS score (3)(-1.4) Determinants of BMD in Chinese men (Age-adjusted)

33. Multivariate model of risk factors for total hip BMD (MrOs) % Diff (95% CI) Age (per 5 yr) -0.7 (-1.3, -0.1) Body weight (per 5 kg) 3.6 (3.3, 3.9) Grip strength (per 5 kg) 0.8 (0.3, 1.3)

34. Multivariate model of risk factors for total hip BMD (MrOs) 4.1 (0.2, 7.9)Thyroid disease 4.0 (2.4, 5.6)Diabetes mellitus -8.3 (-14.3, -2.3) -2.8 (-4.6, -1.0) -2.5 (-4.3, -0.8) % Diff (95% CI) Inhaled steroid GI surgery COPD

35. Multivariate model of risk factors for total hip BMD (MrOs) % Diff (95% CI) Current smoker-1.5 (-3.2, 0.2) Thiazide diuretic2.7 (-0.3, 5.6) Calcium intake (per 50 mg) 0.1 (-0.01, 0.2)