Title: Canadian Multicentre Osteoporosis Study (CaMos)
1Canadian Multicentre Osteoporosis Study(CaMos)
2What 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
3Investigators
- 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
4InvestigatorsCentre Directors
- C. Joyce, C. Kovacs St Johns
- 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
5Support 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
6Regional Centres and National Coordinating Centre
(Montreal)
7Organizational Structure
BOARD Chair Committee chairs Executive External
Members (1)
EXECUTIVE Principal Investigator Chair of the
the Board Chair Centre Director PI
Emeritus National Coordinator
COMMITTEES Centre Directors Finance Design,
Analysis Publications Communication Quality
Control Industry Forum
NATIONAL COORDINATING CENTRE National
coordinator Administrative Secretary
Regional Centres (9) Coordinators Interviewers T
echnologists
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
8Data Acquisition
- Original Cohort
- 6539 women, mean age (SD) 63.1 (12.8)
- 2884 men, mean age (SD) 59.9(14.5)
- At baseline, 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.
9Data Acquisition (contd)
- 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.
10Data Acquisition (contd)
- 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
-
gt72 at year 9
11Data Acquisition (contd)
- 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
12What 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
³ 50 years of age) - Blood and urine samples (including biochemical
markers), in 6 centres - Excellent cohort retention
13CaMos Objectives
- Demographics of Osteoporosis
- Risk Factors
- Impact of Osteoporosis
141. 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.
15Demographics of osteoporosis (contd)
- 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
16Demographics of osteoporosis (contd)
- 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.
172. 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
-
18Risk Factors (contd)
- 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.
193. 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.
20Selected Results
- Demographics of Osteoporosis
- Risk Factors
- Impact of Osteoporosis
211. Demographic of Osteoporosis
22A. 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 200011897-904
23B. 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 200011897-904
24C. Mean PBM in Women and Men CaMos
compared to NHANES
BMD (g/cm2) (SD) BMD (g/cm2) (SD) BMD (g/cm2) (SD) BMD (g/cm2) (SD)
Women Women Men Men
Site CaMos NHANES CaMos NHANES
femoral neck 0.857 0.858 0.910 0.934
femoral neck (0.125) (0.120) (0.125) (0.137)
trochanter 0.700 0.708 0.790 0.778
trochanter (0.088) (0.099) (0.103) (0.118)
CaMos subjects were 25-29 years for the femoral
neck and 25-39 for the trochanter Looker et
al, J Bone Miner Res 1997121761-1768 Tenenhouse
et al. Osteoporosis Int 200011897-904
25D. Prevalence of Vertebral Deformity
Jackson et al. Osteoporos Int 200011680-687
26E. What is the Prevalence of Undiagnosed
Osteoporosis (as defined by BMD or prevalent
minimal trauma fractures) ?
27CaMos 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
28CaMos Care Gap Analysis (contd)
- 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
29Diagnostic Care Gap
Difference in Diagnosed with OP (Year 0 to
5) Women 35 Men 20
30Diagnostic Care Gap (contd)
- 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, lt 20 of participants with fragility
fracture were diagnosed with OP (further analyses
needed to examine change over time)
31Summary
- 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.
32F. What is the Prevalence of Untreated
Osteoporosis (as defined by BMD or prevalent
minimal trauma fractures) ?
33Therapeutic 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 year 5)
Women 23 Men 9
HRT, Bisphosphonate, Raloxifene or
Calcitonin/Fluoride
35 of Participants on therapy
Difference in treated (baseline to year 5)
Women 29 Men 29
HRT, Bisphosphonate, Raloxifene
,Calcitonin/Fluoride
36Bisphosphonate Use over 5-years (Women)
of Women with Minimal Trauma Fracture treated
with a Bisphosphonate
Difference in treated (baseline to year 5)
26
37Bisphosphonate Use over 5-years(Men)
of Men with Minimal Trauma Fracture, treated
with a Bisphosphonate
Difference in treated (baseline to year 5) 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
40General 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
41General Conclusions (contd)
- Men
- Significant care-gap remains
- At baseline, lt1 of men with a fragility fracture
- were being treated
- This rose to only 10 at Year 5
42- Risk Factors for Osteoporosis
43A. 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 BMDs than women
(Tenenhouse CaMos Scientific Meeting 2002.)
44B. Other Risk Factors for Non-vertebral
Fracture (RR 95CI)
- 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
568578)
45C. Other Risk Factors for Clinical Vertebral
Fracture ( RR 95CI)
- 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
568578)
46D. 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
47Aims (contd)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).
48Aims (contd)
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 gt3 months
- then
- 10-Year Absolute Risk of Fracture increased by
10
49Aims (contd)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 lt20 kg/m2
- Rheumatoid Arthritis
50Risk 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
51The Prevalence of Osteoporosis in Women 50
Years, as Defined by Different Criteria
52The Prevalence of Osteoporosis in Men 50
Years, as Defined by Different Criteria
53Prevalence By Age-Groupwith 20 10-Year Fracture
Risk,Age-Adjusted to the CDN Population
Men
Women
Age (years)
54Prevalence By Age-Groupwith 25 10-Year Fracture
Risk, Age-Adjusted to the Canadian Population
Women
Men
Age (years)
55Conclusions
- The application of risk factor-based systems
results in an increased prevalence of the
diagnosis of osteoporosis in older women. - The prevalence of individuals with osteoporosis
at high risk for fracture may increase with
changes to the methods used to determine those
who are at risk and with the level of risk
considered high. - These data have important implications for the
pattern of care and costs of treating
osteoporotic fractures.
56The Effect of Selective Serotonin Reuptake
Inhibitors on Fracturesand Bone Mineral Density
Objective Examine the effect of daily SSRI use on
the risk of incident clinical fragility fracture
(Richards et al. Arh Intern Med (2007) 188-194
57Effects of SSRIs (contd)
- Results
- In 137 subjects using SSRIs daily
- Increased risk of incident clinical vertebral
fracture HR 2.1 (95 CI 1.3-3.4) - In addition
- Increased odds of falling or 2.2 (95 CI
1.4-3.5) - Lower BMD at the hip, and a trend towards lower
BMD in the spine
58Effects of SSRIs (contd)
Conclusion Daily SSRI use in adults over 50 years
associated with a 2-fold increased risk of
clinical fragility fracture after adjustment for
potential covariates
593. Impact of Osteoporosis
60What is the Influence of Osteoporotic
Fractureson Health Related Quality of Life
(HRQoL)in Community Dwelling Men and
WomenAcross Canada?
Adachi et al. Osteoporos Int 200112903908 Adach
i et al. Osteoporos Int 200314895904
61Fractures and HRQL SF-36
Adachi et al. Osteoporos Int 200112903908
62Fractures and HRQL SF-36 (contd)
Adachi et al. Osteoporos Int 200112903908
63Fractures and HRQL - HUI
Adachi et al. Osteoporos Int (2003) 14 895904
64Fractures and HRQL - HUI (contd)
Adachi et al. Osteoporos Int (2003) 14 895904
65Fractures and HRQL - HUI (contd)
Adachi et al. Osteoporos Int (2003) 14 895904
66CaMos HUI3 Scores Baseline differences between
diseases
Sawka et al. Osteoporos Int 200516 18361840
67Conclusions
- Fractures have a negative impact on SF-36 quality
of life, particularly on role-physical and
physical functioning. - Fractures have the most negative impact on HUI
measured ambulation, pain, and mobility.
68Selected Ongoing Projects
1. Demographics
- To determine the geographic variation and age and
sex specific cross-sectional distribution of bone
mineral density in Canadian adults - To determine the rates of change of BMD at
several skeletal sites (lumbar spine (L14)),
femoral neck, total hip, trochanter and wards
triangle) in Canadian women and men 25 years
from the CaMos cohort.
69Selected Ongoing Projects (contd)
2. Risk Factors
- A Comparison of Prevalent Morphometric Vertebral
Deformity versus Other Risk Factors as
Predictors of Fracture Risk in women and men - Depression as a Risk Factor for BMD and Fracture
- Beta-blockers, Bone Mineral Density and Fractures
- Physical Activity relationships with Bone Mineral
Density and Fracture
703. Impact of Osteoporosis
Selected Ongoing Projects (contd)
- Predictors of mortality in CaMos participants
with baseline fracture - Association between quality of life and incident
osteoporotic fractures
714. Interventions in Osteoporosis
Selected Ongoing Projects (contd)
- Effect of anti-resorptives on incident
osteoporotic fractures - Prevalence and correlates of complementary and
alternative medicine use in osteoporosis
72Summary
- Large cohort
- Women men
- Broad age range
- Excellent retention
- 10 year follow-up
- Large database
- Osteoporosis fracture
- Other medical demographic
73Summary (Cont)
- Imaging, repeated over 10 years
- DXA
- Spine x-rays
- Bone ultrasound
- Archived tissue samples
- Serum
- Urine
- DNA
- National international collaborations
- Excellent productivity in advancing knowledge re
osteoporosis