Although areal bone mineral density (aBMD) assessed by dual-energy x-ray absorptiometry (DXA) is the clinical standard for determining fracture risk, most older adults who sustain a fracture have T ...scores greater than -2·5 and thus do not meet the clinical criteria for osteoporosis. Importantly, bone fragility is due to low BMD and deterioration in bone structure. We assessed whether indices of high-resolution peripheral quantitative CT (HR-pQCT) were associated with fracture risk independently of femoral neck aBMD and the Fracture Risk Assessment Tool (FRAX) score.
We assessed participants in eight cohorts from the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazard ratios (HRs) to estimate the association between HR-pQCT bone indices (per 1 SD of deficit) and incident fracture, adjusting for age, sex, height, weight, and cohort, and then additionally for femoral neck DXA aBMD or FRAX.
7254 individuals (66% women and 34% men) were assessed. Mean baseline age was 69 years (SD 9, range 40-96). Over a mean follow-up of 4·63 years (SD 2·41) years, 765 (11%) participants had incident fractures, of whom 633 (86%) had femoral neck T scores greater than -2·5. After adjustment for age, sex, cohort, height, and weight, peripheral skeleton failure load had the greatest association with risk of fracture: tibia HR 2·40 (95% CI 1·98-2·91) and radius 2·13 (1·77-2·56) per 1 SD decrease. HRs for other bone indices ranged from 1·12 (95% CI 1·03-1·23) per 1 SD increase in tibia cortical porosity to 1·58 (1·45-1·72) per 1 SD decrease in radius trabecular volumetric bone density. After further adjustment for femoral neck aBMD or FRAX score, the associations were reduced but remained significant for most bone parameters. A model including cortical volumetric bone density, trabecular number, and trabecular thickness at the distal radius and a model including these indices plus cortical area at the tibia were the best predictors of fracture.
HR-pQCT indices and failure load improved prediction of fracture beyond femoral neck aBMD or FRAX scores alone. Our findings from a large international cohort of men and women support previous reports that deficits in trabecular and cortical bone density and structure independently contribute to fracture risk. These measurements and morphological assessment of the peripheral skeleton might improve identification of people at the highest risk of fracture.
National Institutes of Health National Institute of Arthritis Musculoskeletal and Skin Diseases.
Observational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy-vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of ...disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease.
We measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254). DBP had a strong observational and causal association with 25OHD levels (p = 3.2 × 10(-19)). While DBP levels were observationally associated with calcium and body mass index (BMI), these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l 95% CI -0.01, 0.01; p = 1.00; n = 46,186); fasting insulin (0.01 pmol/l 95% CI -0.00, 0.01,; p = 0.22; n = 46,186); BMI (0.00 kg/m(2) 95% CI -0.01, 0.01; p = 0.80; n = 127,587); bone mineral density (0.01 g/cm(2) 95% CI -0.01, 0.03; p = 0.36; n = 32,961); mean arterial pressure (-0.06 mm Hg 95% CI -0.19, 0.07); p = 0.36; n = 28,775); ischemic stroke (odds ratio OR = 1.00 95% CI 0.97, 1.04; p = 0.92; n = 12,389/62,004 cases/controls); coronary artery disease (OR = 1.02 95% CI 0.99, 1.05; p = 0.31; n = 22,233/64,762); or type 2 diabetes (OR = 1.01 95% CI 0.97, 1.05; p = 0.76; n = 9,580/53,810).
DBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP. Please see later in the article for the Editors' Summary.
Abstract Background Population-based incident fracture data aid fracture prevention and therapy decisions. Our purpose was to describe 10-year site-specific cumulative fracture incidence by sex, age ...at baseline, and degree of trauma with/without consideration of competing mortality in the Canadian Multicentre Osteoporosis Study adult cohort. Methods Incident fractures and mortality were identified by annual postal questionnaires to the participant or proxy respondent. Date, site and circumstance of fracture were gathered from structured interviews and medical records. Fracture analyses were stratified by sex and age at baseline and used both Kaplan–Meier and competing mortality methods. Results The baseline (1995–97) cohort included 6314 women and 2789 men (aged 25–84 years; mean ± SD 62 ± 12 and 59 ± 14, respectively), with 4322 (68%) women and 1732 (62%) men followed to year-10. At least one incident fracture occurred for 930 women (14%) and 247 men (9%). Competing mortality exceeded fracture risk for men aged 65 + years at baseline. Age was a strong predictor of incident fractures especially fragility fractures, with higher age gradients for women vs. men. Major osteoporotic fracture (MOF) (hip, clinical spine, forearm, humerus) accounted for 41–74% of fracture risk by sex/age strata; in women all MOF sites showed age-related increases but in men only hip was clearly age-related. The most common fractures were the forearm for women and the ribs for men. Hip fracture incidence was the highest for the 75–84 year baseline age-group with no significant difference between women 7.0% (95% CI 5.3, 8.9) and men 7.0% (95% CI 4.4, 10.3). Interpretation There are sex differences in the predominant sites and age-gradients of fracture. In older men, competing mortality exceeds cumulative fracture risk.
Measurement of bone mineral density is the most common method of diagnosing and assessing osteoporosis. We sought to estimate the average rate of change in bone mineral density as a function of age ...among Canadians aged 25-85, stratified by sex and use of antiresorptive agents.
We examined a longitudinal cohort of 9423 participants. We measured the bone mineral density in the lumbar spine, total hip and femoral neck at baseline in 1995-1997, and at 3-year (participants aged 40-60 years only) and 5-year follow-up visits. We used the measurements to compute individual rates of change.
Bone loss in all 3 skeletal sites began among women at age 40-44. Bone loss was particularly rapid in the total hip and was greatest among women aged 50-54 who were transitioning from premenopause to postmenopause, with a change from baseline of -6.8% (95% confidence interval CI -7.5% to -4.9%) over 5 years. The rate of decline, particularly in the total hip, increased again among women older than 70 years. Bone loss in all 3 skeletal sites began at an earlier age (25-39) among men than among women. The rate of decline of bone density in the total hip was nearly constant among men 35 and older and then increased among men older than 65. Use of antiresorptive agents was associated with attenuated bone loss in both sexes among participants aged 50-79.
The period of accelerated loss of bone mineral density in the hip bones occurring among women and men older than 65 may be an important contributor to the increased incidence of hip fracture among patients in that age group. The extent of bone loss that we observed in both sexes indicates that, in the absence of additional risk factors or therapy, repeat testing of bone mineral density to diagnose osteoporosis could be delayed to every 5 years.
Despite knowing better how to screen older adults, understanding how frailty progression might be modified is unclear. We explored effects of modifiable and non-modifiable factors on changes in ...frailty in community-dwelling adults aged 50+ years who participated in the Canadian Multicentre Osteoporosis Study (CaMos).
Rates of change in frailty over 10 years were examined using the 30-item CaMos Frailty Index (CFI). Incident and prevalent low-trauma fractures were categorized by fracture site into hip, clinical vertebral and non-hip-non-vertebral fractures. Multivariable generalized estimating equation models accounted for the time of frailty assessment (baseline, 5 and 10 years), sex, age, body mass index (BMI, kg/m
), physical activity, bone mineral density, antiresorptive therapy, health-related quality of life (HRQL), cognitive status, and other factors for frailty or fractures. Multiple imputation and scenario analyses addressed bias due to attrition or missing data.
The cohort included 5566 women (mean ± standard deviation: 66.8 ± 9.3 years) and 2187 men (66.3 ± 9.5 years) with the mean baseline CFI scores of 0.15 ± 0.11 and 0.12 ± 0.10, respectively. Incident fractures and obesity most strongly predicted frailty progression in multivariable analyses. The impact of fractures differed between the sexes. With each incident hip fracture, the adjusted mean CFI accelerated per 5 years by 0.07 in women (95% confidence interval CI: 0.03 to 0.11) and by 0.12 in men (95% CI: 0.08 to 0.16). An incident vertebral fracture increased frailty in women (0.05, 95% CI: 0.02 to 0.08) but not in men (0.01, 95% CI: -0.07 to 0.09). Irrespective of sex and prevalent fractures, baseline obesity was associated with faster frailty progression: a 5-year increase in the adjusted mean CFI ranged from 0.01 in overweight (BMI: 25.0 to 29.9 kg/m
) to 0.10 in obese individuals (BMI: ≥ 40 kg/m
). Greater physical activity and better HRQL decreased frailty over time. The results remained robust in scenario analyses.
Older women and men with new vertebral fractures, hip fractures or obesity represent high-risk groups that should be considered for frailty interventions.
Abstract Our objective was to describe patterns and predictors of sedentary behavior (sitting time) over 10 years among a large Canadian cohort. Data are from the Canadian Multicentre Osteoporosis ...Study, a prospective study of women and men randomly selected from the general population. Respondents reported socio-demographics, lifestyle behaviors and health outcomes in interviewer-administered questionnaires; weight and height were measured. Baseline data were collected between 1995 and 1997 (n = 9418; participation rate = 42%), and at 5- (n = 7648) and 10-year follow-ups (n = 5567). Total sitting time was summed across domain-specific questions at three time points and dichotomized into “low” (≤ 7 h/day) and “high” (> 7 h/day), based on recent meta-analytic evidence on time sitting and all-cause mortality. Ten-year sitting patterns were classified as “consistently high”, “consistently low”, “increased”, “decreased”, and “mixed”. Predictors of sedentary behavior patterns were explored using chi-square tests, ANOVA and logistic regression. At baseline (mean age = 62.1 years ± 13.4) average sitting was 6.9 h/day; it was 7.0 at 5- and 10-year follow-ups ( p for trend = 0.12). Overall 23% reported consistently high sitting time, 22% consistently low sitting, 14% decreased sitting, 17% increased sitting with 24% mixed patterns. Consistently high sitters were more likely to be men, university educated, full-time employed, obese, and to report consistently low physical activity levels. This is one of the first population-based studies to explore patterns of sedentary behavior (multi-domain sitting) within men and women over years. Risk classification of sitting among many adults changed during follow-up. Thus, studies of sitting and health would benefit from multiple measures of sitting over time.
Summary
Most of the published epidemiology on osteoporosis is derived from White populations; still many countries have increasing ethno-culturally diverse populations, leading to gaps in the ...development of population-specific effective fracture prevention strategies. We describe differences in prevalent fracture and bone mineral density patterns in Canadians of different racial/ethnic backgrounds.
Introduction
We described prevalent fracture and bone mineral density (BMD) patterns in Canadians by their racial/ethnic backgrounds.
Methods
For this cross-sectional analysis, we used the Canadian Longitudinal Study on Aging baseline data (2011–2015) of 22,091 randomly selected participants of Black, East Asian, South or Southeast Asian (SSEA) and White race/ethnic backgrounds, aged 45–85 years with available information on the presence or absence of self-reported prevalent low trauma fractures and femoral neck BMD (FNBMD) measurement. Logistic and linear regression models examined associations of race/ethnic background with fracture and FNBMD, respectively. Covariates included sex, age, height, body mass index (BMI), grip strength and physical performance score.
Results
We identified 11,166 women and 10,925 men. Self-reported race/ethnic backgrounds were: 139 Black, 205 East Asian, 269 SSEA and 21,478 White. White participants were older (mean 62.5 years) than the other groups (60.5 years) and had a higher BMI (28.0 kg/m
2
) than both Asian groups, but lower than the Black group. The population-weighted prevalence of falls was 10.0%, and that of low trauma fracture was 12.0% ranging from 3.3% (Black) to 12.3% (White), with Black and SSEA Canadians having lower adjusted odds ratios (aOR) of low trauma fractures than White Canadians (Black, aOR = 0.3 95% confidence interval: 0.1–0.7; SSEA, aOR = 0.5 0.3–0.8). The mean (SD) FNBMD varied between groups: Black, 0.907 g/cm
2
(0.154); East Asian, 0.748 g/cm
2
(0.119); SSEA, 0.769 g/cm
2
(0.134); and White, 0.773 g/cm
2
(0.128). Adjusted linear regressions suggested that Black and both Asian groups had higher FNBMD compared to White.
Conclusion
Our results support the importance of characterizing bone health predictors in Canadians of different race/ethnic backgrounds to tailor the development of population-specific fracture prevention strategies.
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