Search

Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Objectives: To examine the association between physical fitness, assessed according to ability and time to complete a 400-m walk, on changes in body composition and muscle strength over a 7-year period. Design: Prospective observational cohort study. Setting: Memphis, Tennessee, and Pittsburgh, Pennsylvania. Participants: Two thousand nine hundred forty-nine black and white men and women aged 70 to 79 participating in the Health, Aging and Body Composition Study. Measurements: Body composition (fat and bone-free lean mass) was assessed using dual-energy X-ray absorptiometry in Years 1 to 6 and 8. Knee extension strength was measured using isokinetic dynamometry and grip strength using isometric dynamometry in Years 1, 2, 4, 6, and 8. Results: Less fit people weighed more and had a higher total percentage of fat and a lower total percentage of lean mass than very fit men and women at baseline (P

OBJECTIVES: To determine how three different physical performance measures (PPMs) combine for added utility in predicting adverse health events in elders. DESIGN: Prospective cohort study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Three thousand twenty-four well-functioning older persons (mean age 73.6). MEASUREMENTS: Timed gait, repeated chair stands, and balance (semi- and full-tandem, and single leg stands each held for 30 seconds) tests were administered at baseline. Usual gait speed was categorized to distinguish high- and low-risk participants using the previously established 1-m/s cutpoint. The same population-percentile (21.3%) was used to identify cutpoints for the repeated chair stands (17.1 seconds) and balance (53.0 seconds) tests. Cox proportional hazard analyses were performed to evaluate the added value of PPMs in predicting mortality, hospitalization, and (severe) mobility limitation events over 6.9 years of follow-up. RESULTS: Risk estimates for developing adverse health-related events were similarly large for each of the three high-risk groups considered separately. Having more PPM scores at the high-risk level was associated with a greater risk of developing adverse health-related events. When all three PPMs were considered, having only one poor performance was sufficient to indicate a highly significantly higher risk of (severe) lower extremity and mortality events. CONCLUSION: Although gait speed is considered to be the most important predictor of adverse health events, these findings demonstrate that poor performance on other tests of lower extremity function are equally prognostic. This suggests that chair stand and standing balance performance may be adequate substitutes when gait speed is unavailable. © 2009, Copyright the Authors.

OBJECTIVES: To identify levels of knee extensor strength that are associated with high and low risk of incident severe mobility limitation (SML) in initially well-functioning older adults. DESIGN: Prospective cohort study. SETTING: University clinic center. PARTICIPANTS: One thousand three hundred fifty-five men and 1,429 women (aged 73.6±2.85) who reported no mobility limitation. MEASUREMENTS: Unilateral knee extensor isokinetic strength of participants was obtained. Participants were followed over a median of 5.90 years for the onset of SML, defined as two consecutive reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. Deciles of knee extension strength relative to body weight were evaluated to identify cutpoints most predictive of incident SML. Cutpoints were then compared with prevalence of having slow gait speed (

OBJECTIVES: To define clinically relevant cutpoints for usual gait speed and to investigate their predictive value for health-related events in older persons. DESIGN: Prospective cohort study. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Three thousand forty-seven well-functioning older persons (mean age 74.2). MEASUREMENTS: Usual gait speed on a 6-m course was assessed at baseline. Participants were randomly divided into two groups to identify (Sample A; n = 2,031) and then validate (Sample B; n = 1,016) usual gait-speed cutpoints. Rates of persistent lower extremity limitation events (mean follow-up 4.9 years) were calculated according to gait speed in Sample A. A cutpoint (defining high- (

OBJECTIVES: To determine the influence of anxiety on the progression of disability and examine possible mediators of the relationship. DESIGN: Community-based observational study. SETTING: Women's Health and Aging Study I, a prospective observational study with assessments every 6 months for 3 years. PARTICIPANTS: One thousand two functionally limited women aged 65 and older. MEASUREMENTS: Anxiety symptoms were assessed using four questions from the Hopkins Symptom Checklist (nervous or shaky, avoidance of certain things, tense or keyed up, fearful). Participants who reported experiencing two or more of these symptoms at baseline were considered anxious. Anxiety as a predictor of the onset of four types of disability was examined using Cox proportional hazards models. Three models were tested: an unadjusted model, a model adjusted for confounding variables (age, race, vision, number of diseases, physical performance, depressive symptoms), and a mediational model (benzodiazepine and psychotropic medication use, physical activity, emotional support). RESULTS: Nineteen percent of women reported two or more symptoms of anxiety at baseline. Unadjusted models indicate that anxiety was associated with a greater risk of worsening disability: activity of daily living (ADL) disability (relative risk (RR) = 1.40, 95% confidence interval (CI) = 1.10-1.79), mobility disability (RR =1.41, 95% CI = 1.06-1.86), lifting disability (RR = 1.54, 95% CI = 1.20-1.97), and light housework disability (RR = 1.77, 95% CI = 1.32-2.37). After adjusting for confounding variables, anxiety continued to predict the development of two types of disability: ADL disability (RR = 1.41, 95% CI = 1.08-1.84) and light housework disability (RR = 1.56, 95% CI = 1.14-2.14). Finally, benzodiazepine and psychotropic medication use, physical activity, and emotional support were not significant mediators of the effect of anxiety on the development of a disability. CONCLUSION: Anxiety is a significant risk factor for the progression of disability in older women. Studies are needed to determine whether treatment of anxiety delays or prevents disability. © by the American Geriatrics Society.

OBJECTIVES: To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use. DESIGN: Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study. SETTING: Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Black and white, well-functioning men and women (N = 3,075), aged 70 to 79. MEASUREMENTS: Interviewer-administered questionnaires of previous-week household, walking, exercise, and occupational/volunteer physical activities. Analysis of covariance was used to examine the association between activity level and serum C-reactive protein (CRP), interleukin-6 (IL-6), and plasma tumor necrosis factor alpha (TNFα) with covariate adjustment. Antioxidant supplement use (multivitamin, vitamins E or C, beta carotene) was evaluated as an effect modifier of the association. RESULTS: Higher levels of exercise were associated with lower levels of CRP (P < .01), IL-6 (P < .001), and TNFα (P =.02) (e.g., CRP = 1.95 mg/L for no exercise and 1.72 for > 180 min/wk). Adjustment for body fatness attenuated the associations somewhat. Use of antioxidant supplements modified the CRP (P

OBJECTIVES: To examine the relationship between indicators of inflammation and the incidence of mobility limitation in older persons. DESIGN: Prospective cohort study: the Health, Aging and Body Composition Study. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: A total of 2,979 men and women, aged 70 to 79, without mobility limitation at baseline. MEASUREMENTS: Serum levels of interleukin (IL)-6, tumor necrosis factor alpha (TNFα), and C-reactive protein (CRP) and soluble cytokine receptors (IL-2sR, IL-6sR, TNFsR1, TNFsR2) were measured. Mobility limitation was assessed and defined as reporting difficulty or inability to walk one-quarter of a mile or to climb 10 steps during two consecutive semiannual assessments over 30 months. RESULTS: Of the 2,979 participants, 30.1% developed incident mobility limitation. After adjustment for confounders (demographics, prevalent conditions at baseline, body composition), the relative risk (RR) of incident mobility limitation per standard deviation (SD) increase was 1.19 (95% confidence interval (CI) = 1.10-1.28) for IL-6, 1.20 (95% CI = 1.12-1.29) for TNFα and 1.40 (95% CI = 1.18-1.68) for CRP. The association between inflammation and incident mobility limitation was especially strong for the onset of more severe mobility limitation and when the levels of multiple inflammatory markers were high. When persons with baseline or incident cardiovascular disease events or persons who were hospitalized during study follow-up were excluded, findings remained similar. In a subset (n = 499), high levels of the soluble receptors IL2sR and TNFsR1 (per SD increase: RR = 1.23 (95% CI = 1.04-1.46) and RR = 1.28 (95% CI = 1.04-1.57), respectively) were also associated with incident mobility limitation. CONCLUSION: Findings suggest that inflammation is prognostic for incident mobility limitation over 30 months, independent of cardiovascular disease events and incident severe illness.