Canadian Multicentre Osteoporosis Study (CaM os )

1. Canadian Multicentre Osteoporosis Study(CaMos)

2. What is CaMos? • 10 year prospective population based epidemiologic study • Sample frame: 40% Canadian of population • Random sample: 9,423 subjects initial recruitment • Recruitment: July 1995 to Sept. 1997 • Women and men ³ 25 years • Questionnaire, DXA, US, spine x-ray

3. Investigators • David Goltzman: Principal Investigator • Nancy Kreiger: Principal Investigator (Epidemiologist) • Alan Tenenhouse: P.I.Emeritus (P.I., 1993-2004) • Brian Lentle: Consultant for X-ray QC • Bill Leslie: Associate Investigator (PI of First Nations Study): Consultant for DXA QC

4. Investigators:Centre Directors C. Joyce, C. Kovacs ………………… St John’s S. Kirkland, S. Kaiser ……………..… Halifax J. Brown, L. Bessette ……….……… Quebec City T. Anastassiades, T. Towheed ….... Kingston R. Josse, S. Jamal ………………..… Toronto T. Murray (Emeritus) ……………….. Toronto J. Adachi, A. Papaioannou ……….. Hamilton W. Olszynski, S. Davison …………. Saskatoon D. Hanley …………………………….. Calgary J. Prior ……………………………….. Vancouver

5. Support Centres • The National Coordinating Centre is located in Montreal in the McGill University Health Centre Suzette Poliquin: National Coordinator • Regional Coordinating Centres are located at each of the nine sites • The Imaging Centre for DXA and X-ray Analysis is in Quebec City at Centre Hospitalier Universite Laval Marc Gendreau: Chief Coordinator • The Data Entry and Analysis Centre is in Montreal in the McGill University Health Centre Claudie Berger: Chief Statistician • The Blood and Urine Collection and Analysis Centre is in the McGill University Health Centre in Montreal

6. Regional Centres and National Coordinating Centre (Montreal)

7. Organizational Structure BOARD: Chair Committee chairs Executive External Members (1) EXECUTIVE: Principal Investigator Chair of the the Board Chair Centre Director PI Emeritus National Coordinator NATIONAL COORDINATING CENTRE: National coordinator Administrative Secretary COMMITTEES: Centre Directors Finance Design, Analysis & Publications Communication Quality Control Industry Forum Regional Centres (9): Coordinators Interviewers Technologists Data Entry Centre: Research Assistant Data entry Clerk Data Analysis Centre: Statisticians Bone Markers & Genetics Centre: Technician Imaging Centre: Coordinator Quality Control Centre: Coordinator Ultrasound Data Centre: Coordinator

8. Data Acquisition Original Cohort 6539 women, mean age (SD): 63.1 (12.8) 2884 men, mean age (SD): 59.9(14.5) • Atbaseline, a “long” questionnaire was administered and participants underwent bone mineral density, height and weight measurement and ultrasound testing. • Participants aged 50 years and older also had thoracic and lumbar spine X-rays taken at baseline to assess the prevalence of fractures. • Blood and urine samples were obtained at 2 centres.

9. Data Acquisition (cont’d) • Participants received a follow up “short” questionnaire annually. Self reported fractures were confirmed by medical report or hospital discharge. • Respondents had a “long” questionnaire repeated at three (participants age 40-60), five and ten years after the baseline assessment.

10. Data Acquisition (cont’d) • At the five and ten year follow-up, all participants underwent a repeat bone mineral density test, height and weight measurement, ultrasound and spine X-rays (aged ³ 50 years) • Blood and urine samples collected in 6 centres at year ten follow-up • Participant retention was: 86% at 5 year >72% at year 9

11. Data Acquisition (cont’d) Youth cohort • 1 000 participants 16-25 years • Both males and females were recruited between August 2004 and June 2006 as a “Youth Cohort” • They participated in a long questionnaire and in BMD studies • Blood and urine samples collected in 5 centres

12. What is unique about CaMos? • Random sample of Canadian population • Men and women ³ 25 years of age are included • Prospective, annual follow-up, 3 (40-60 years of age), 5 and 10 year extensive follow-up • Imaging (BMD, ultrasound, spine X-rays at ³50 years of age) • Blood and urine samples (including biochemical markers), in 6 centres • Excellent cohort retention

13. CaMos Objectives • Demographics of Osteoporosis • Risk Factors • Impact of Osteoporosis

14. 1. Demographics of Osteoporosis • To estimate the prevalence of main fractures associated with osteoporosis (hip, wrist and vertebra) in Canadian women and men aged ³ 50 years; • To estimate the annual incidence of : - fractures of the hip and wrist and - fractures of the vertebrae, in women and men aged ³ 50 years.

15. Demographics of osteoporosis (cont’d) • To estimate the distribution of bone mineral densities (BMD) as measured by Dual Energy X-Ray Absorptiometry (DXA), in women and men aged ³ 25 years; • To estimate the distribution of stiffness (SOS, BUA) as measured by Ultrasound of the Calcaneus (US), in women and men aged ³ 25 years; • To estimate the pattern of change in distributions of BMD and US measures over time, in women and men aged ³ 25 years;

16. Demographics of osteoporosis (cont’d) • To develop a Canadian reference standard for age-matched BMD (Z-scores) in females and males age 16 to 24 • To estimate the age of peak bone mass at different skeletal sites as measured by DXA in women and men.

17. 2. Risk Factors • To assess the relationship between socio-demographic characteristics (e.g. sex, age, race, geographic region) or exogenous exposure (e.g. hormones and medication, diet, physical activity) and occurrence of: minimum trauma clinical fractures and morphometric vertebral fractures in women and men aged ³ 50 years

18. Risk Factors (cont’d) • To assess the relationship between certain socio-demographic characteristics (e.g. sex, age, race, geographic region) and exogenous exposures (e.g. exogenous hormones and medication, diet, physical activity) and DXA and US measurements, in women and men aged ³ 25 years.

19. 3. Impact of Osteoporosis • To assess the relationship between osteoporosis and/or fractures, and health status • To examine the burden of illness as a result of fracture.

20. Selected Results • Demographics of Osteoporosis • Risk Factors • Impact of Osteoporosis

21. 1. Demographic of Osteoporosis

22. A. BMD Changes with Age in Women BMD of the Lumbar Spine and Femoral Neck in Women 25 Years and Older Tenenhouse et al. Osteoporosis Int 2000;11:897-904

23. B. BMD Changes with Age in Men BMD of the Lumbar Spine and Femoral Neck In Men 25 Years and Older Tenenhouse et al. Osteoporosis Int 2000;11:897-904

24. C. Mean PBM in Women and Men CaMos* compared to NHANES** *CaMos subjects were 25-29 years for the femoral neck and 25-39 for the trochanter ** Looker et al, J Bone Miner Res 1997;12:1761-1768 Tenenhouse et al. Osteoporosis Int 2000;11:897-904

25. D. Prevalence of Vertebral Deformity Jackson et al. Osteoporos Int 2000;11:680-687

26. E. What is the Prevalence of Undiagnosed Osteoporosis (as defined by BMD or prevalent minimal trauma fractures) ?

27. CaMos Care Gap Analysis Goal • To examine the state of the diagnostic care gap in Canada over a 5-year period of time using CaMos data. Inclusion Criteria • All men and women 50 years of age and older at baseline. Papaioannou et al. CaMos Annual Scientific Meeting 2006

28. CaMos Care Gap Analysis (cont’d) Fracture Categories All minimal trauma fractures (excluding: toes, fingers, skull, face), including: • Vertebral (clinical) • Hip • Pelvis • Rib • Wrist Treatments categories • Bisphosphonates • HRT • Raloxifene • Calcitonin/Fluoride

29. Diagnostic Care Gap Difference in % Diagnosed with OP (Year 0 to 5): Women:+35%Men:+20%

30. Diagnostic Care Gap (cont’d) General Conclusions • After 5 years in the study, only • 55% of women • 25% of men with osteoporosis (determined by CaMos DXA) were actually diagnosed with OP. • At baseline, < 20% of participants with fragility fracture were diagnosed with OP (further analyses needed to examine change over time)

31. Summary • Osteoporosis is common in Canadians ≥ 50 years of age. • Most men and women do not know that they have osteoporosis by BMD criteria or after a minimal trauma fracture.

32. F. What is the Prevalence of Untreated Osteoporosis (as defined by BMD or prevalent minimal trauma fractures) ?

33. Therapeutic Care Gap • CaMos Participants, 50 years & older • Baseline – Year 5 Papaioannou et al. CaMos Annual Scientific Meeting 2006

34. % of Participants on therapy* Difference in % treated (baseline to year5): Women:+23% Men: +9% *HRT, Bisphosphonate, Raloxifene or Calcitonin/Fluoride

35. % of Participants on therapy* Difference in % treated (baseline to year5): Women: +29% Men: +29% *HRT, Bisphosphonate, Raloxifene ,Calcitonin/Fluoride

36. Bisphosphonate Use over 5-years (Women) % of Women with Minimal Trauma Fracture treated with a Bisphosphonate Difference in % treated (baseline to year5) =26%

37. Bisphosphonate Use over 5-years(Men) % of Men with Minimal Trauma Fracture, treated with a Bisphosphonate Difference in % treated (baseline to year5) =9% Papaioannou et al. Osteoporos Int 2007 (accepted)

38. % of fractures treated in year 5(Women) Vertebral fractures most commonly treated of all fracture types

39. % of fractures treated in year 5(Men) Hip fractures most commonly treated of all fracture types

40. General Conclusions Women • Increase in treatment for women: approximately 20-30% rise from baseline to year 5 (for all fracture types) • Still room for improvement in women with a fragility fracture; Year 5: • 1 in 2 women received any osteoporosis therapy • 1 in 3 of women received a bisphosphonate

41. General Conclusions (cont’d) Men • Significant care-gap remains • At baseline, <1% of men with a fragility fracture were being treated • This rose to only 10% at Year 5

42. Risk Factors for Osteoporosis

43. A. BMD as a Risk Factor for Fracture Mean femoral neck BMD in subjects with incident minimal trauma fracture: CaMos years 1,2,3 Men are fracturing at higher BMD’s than women (Tenenhouse CaMos Scientific Meeting 2002.)

44. B. Other Risk Factors for Non-vertebral Fracture (RR; 95%CI) • Forearm fracture after 50 (3.626; 1.876, 7.008) • Other minimal trauma fractures (1.957; 1.082, 3.540) • SF-36 physical summary score (0.965; 0.939, 0.991) • Femoral neck bone density (0.036; 0.001, 0.937) • Inflammatory bowel disease (2.207; 1.091, 4.465) (Papaioannou et al. Osteoporos Int (2005) 16: 568–578)

45. C. Other Risk Factors for Clinical Vertebral Fracture ( RR; 95%CI) • SF-36 physical summary score (0.959; 0.924, 0.996) • Femoral neck BMD (0.002; 0.00, 0.506) • Prevalent vertebral deformity (2.337; 0.897, 6.088) • Loss of height (1.075; 95% CI: 0.970, 1.193) (Papaioannou et al. Osteoporos Int (2005) 16: 568–578)

46. D. BMD versus Clinical Risk Factors for Fracture: Impact on Prevalence of Osteoporosis Aims To compare the prevalence of osteoporosis requiring treatment using three different classification systems: • BMD T-score ≤-2.5 SD • Simplified Clinical Risk Factor System (similar to OC system) • Comprehensive Clinical Risk Factor System (similar to WHO system) (Richards et al. J Bone Miner Res (2007) 167(2): 228-234

47. Aims (cont’d)1. Densitometric Method If T-score at the lowest site was ≤ -2.5 SD then the subject was considered to have osteoporosis (and to be a candidate for osteoporosis therapy).

48. Aims (cont’d) 2. Simplified Risk Factor System • Age, sex, BMD (lowest T-score) • 10-Year Absolute Risk of Fracture, based on age, sex and BMD was applied to each patient • if: • Fragility Fracture after age 40, or • Systemic Glucocorticoids >3 months • then: 10-Year Absolute Risk of Fracture increased by 10%

49. Aims (cont’d)3. Comprehensive Risk Factor System • Age, sex, BMD (Femoral Neck) • Current Cigarette Smoking • Parental History of Fracture (without regard to site) • Prevalent Fragility Fracture after 50 years • Ever use of Systemic Corticosteroids • Alcohol Intake Greater than 2 units/day • BMD <20 kg/m2 • Rheumatoid Arthritis

50. Risk Factor Assumptions • For both Risk Factor-Based Systems, subjects were assessed if their 10-year absolute risk was 15%, 20%, or 25% • All Classification Systems were Age-Adjusted to the General Canadian Population