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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

Objective: This study examines the association between incident mobility limitation and 4 lifestyle factors: smoking, alcohol intake, physical activity, and diet in well-functioning obese (n = 667) and non-obese (n = 2027) older adults. Research Methods and Procedures: Data were from men and women, 70 to 79 years of age from Pittsburgh, PA and Memphis, TN, participating in the Health, Aging and Body Composition (Health ABC) study. In addition to individual lifestyle practices, a high-risk lifestyle score (0 to 4) was calculated indicating the total number of unhealthy lifestyle practices per person. Mobility limitation was defined as reported difficulty walking 1/4 mile or climbing 10 steps during two consecutive semiannual assessments over 6.5 years. Results: In non-obese older persons, significant risk factors for incident mobility limitation after adjustment for socio-demographics and health-related variables were current and former smoking [hazard ratio (HR) = 1.51; 95% confidence interval (CI), 1.20 to 1.89; HR = 1.40; 95% CI, 1.12 to 1.74), former alcohol intake (HR = 1.30; 95% CI, 1.05 to 1.60), low and medium physical activity (HR = 1.78; 95% CI, 1.45 to 2.18; HR = 1.29, 95% CI, 1.07 to 1.54), and eating an unhealthy diet (HR = 1.57; 95% CI, 1.17 to 2.10). In the obese, only low physical activity was associated with a significantly increased risk of mobility limitation (HR = 1.44; 95% CI, 1.08 to 1.92). Having two or more unhealthy lifestyle factors was a strong predictor of mobility limitation in the non-obese only (HR = 1.98; 95% CI, 1.61 to 2.43). Overall, obese persons had a significantly higher risk of mobility limitation compared with non-obese persons, independent of lifestyle factors (HR = 1.73; 95% CI, 1.52 to 1.96). Conclusions: These results underscore the importance of a healthy lifestyle for maintaining function among non-obese older adults. However, a healthy lifestyle cannot overcome the effect of obesity in obese older adults; this stresses t

Objective: This study examines the association between incident mobility limitation and 4 lifestyle factors: smoking, alcohol intake, physical activity, and diet in well-functioning obese (n = 667) and non-obese (n = 2027) older adults. Research Methods and Procedures: Data were from men and women, 70 to 79 years of age from Pittsburgh, PA and Memphis, TN, participating in the Health, Aging and Body Composition (Health ABC) study. In addition to individual lifestyle practices, a high-risk lifestyle score (0 to 4) was calculated indicating the total number of unhealthy lifestyle practices per person. Mobility limitation was defined as reported difficulty walking 1/4 mile or climbing 10 steps during two consecutive semiannual assessments over 6.5 years. Results: In non-obese older persons, significant risk factors for incident mobility limitation after adjustment for socio-demographics and health-related variables were current and former smoking [hazard ratio (HR) = 1.51; 95% confidence interval (CI), 1.20 to 1.89; HR = 1.40; 95% CI, 1.12 to 1.74), former alcohol intake (HR = 1.30; 95% CI, 1.05 to 1.60), low and medium physical activity (HR = 1.78; 95% CI, 1.45 to 2.18; HR = 1.29, 95% CI, 1.07 to 1.54), and eating an unhealthy diet (HR = 1.57; 95% CI, 1.17 to 2.10). In the obese, only low physical activity was associated with a significantly increased risk of mobility limitation (HR = 1.44; 95% CI, 1.08 to 1.92). Having two or more unhealthy lifestyle factors was a strong predictor of mobility limitation in the non-obese only (HR = 1.98; 95% CI, 1.61 to 2.43). Overall, obese persons had a significantly higher risk of mobility limitation compared with non-obese persons, independent of lifestyle factors (HR = 1.73; 95% CI, 1.52 to 1.96). Conclusions: These results underscore the importance of a healthy lifestyle for maintaining function among non-obese older adults. However, a healthy lifestyle cannot overcome the effect of obesity in obese older adults; this stresses t

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- (<1 m/s) and low risk (≥1 m/s) groups) was identified based on persistent lower extremity limitation events. The predictive value of the identified cutpoints for major health-related events (persistent severe lower extremity limitation, death, and hospitalization) was evaluated in Sample B using Cox regression analyses. RESULTS: A graded response was seen between risk groups and health-related outcomes. Participants in the high-risk group had a higher risk of persistent lower extremity limitation (rate ratio (RR) = 2.20, 95% confidence interval (CI) = 1.76-2.74), persistent severe lower extremity limitation (RR = 2.29, 95% CI = 1.63-3.20), death (RR = 1.64, 95% CI = 1.14-2.37), and hospitalization (RR = 1.48, 95% CI = 1.02-2.13) than those in the low-risk group. CONCLUSION: Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people. Provision of a clinically meaningful cutpoint for usual gait speed may facilitate its use in clinical and research settings. © 2005 by the American Geriatrics Society.

BACKGROUND: The association between low socioeconomic status and poor physical functioning has been well described; biomedical factors may play an important role in explaining these differences. This study examines the association between socioeconomic status and incident mobility limitation in well-functioning older adults, and seeks to determine whether this link could be explained by biomedical factors. METHODS: Data were obtained from 3066 men and women, aged 70--79 years from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition (Health ABC) study. Three indicators of socioeconomic status were used: education, income, and ownership of financial assets. Mobility limitation was defined as reporting difficulty walking 1/4 mile or climbing 10 steps during two consecutive semiannual assessments over 4.5 years. Biomedical factors included a wide range of diseases (e.g., heart and cerebrovascular disease) and biological risk factors (e.g. hypertension, poor pulmonary function, and high serum levels of inflammatory markers). RESULTS: Adjusted hazard ratios of incident mobility limitation were significantly higher in those persons with low education, low income, and few assets. Hazard ratios ranged from 1.66 to 2.80 in the lowest socioeconomic groups. Additional adjustment for biomedical factors reduced the hazard ratios by an average of 41% for education, 17% for income, and 29% for assets. CONCLUSION: Biomedical factors can account for some of the association between socioeconomic status and incident mobility limitation. However, to reduce physical disabilities and, in particular, the socioeconomic differences therein, it may not be sufficient to solely intervene upon biological risk factors and risks of diseases

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

BACKGROUND: The association between low socioeconomic status and poor physical functioning has been well described; biomedical factors may play an important role in explaining these differences. This study examines the association between socioeconomic status and incident mobility limitation in well-functioning older adults, and seeks to determine whether this link could be explained by biomedical factors. METHODS: Data were obtained from 3066 men and women, aged 70--79 years from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition (Health ABC) study. Three indicators of socioeconomic status were used: education, income, and ownership of financial assets. Mobility limitation was defined as reporting difficulty walking 1/4 mile or climbing 10 steps during two consecutive semiannual assessments over 4.5 years. Biomedical factors included a wide range of diseases (e.g., heart and cerebrovascular disease) and biological risk factors (e.g. hypertension, poor pulmonary function, and high serum levels of inflammatory markers). RESULTS: Adjusted hazard ratios of incident mobility limitation were significantly higher in those persons with low education, low income, and few assets. Hazard ratios ranged from 1.66 to 2.80 in the lowest socioeconomic groups. Additional adjustment for biomedical factors reduced the hazard ratios by an average of 41% for education, 17% for income, and 29% for assets. CONCLUSION: Biomedical factors can account for some of the association between socioeconomic status and incident mobility limitation. However, to reduce physical disabilities and, in particular, the socioeconomic differences therein, it may not be sufficient to solely intervene upon biological risk factors and risks of diseases

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

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- (<1 m/s) and low risk (≥1 m/s) groups) was identified based on persistent lower extremity limitation events. The predictive value of the identified cutpoints for major health-related events (persistent severe lower extremity limitation, death, and hospitalization) was evaluated in Sample B using Cox regression analyses. RESULTS: A graded response was seen between risk groups and health-related outcomes. Participants in the high-risk group had a higher risk of persistent lower extremity limitation (rate ratio (RR) = 2.20, 95% confidence interval (CI) = 1.76-2.74), persistent severe lower extremity limitation (RR = 2.29, 95% CI = 1.63-3.20), death (RR = 1.64, 95% CI = 1.14-2.37), and hospitalization (RR = 1.48, 95% CI = 1.02-2.13) than those in the low-risk group. CONCLUSION: Usual gait speed of less than 1 m/s identifies persons at high risk of health-related outcomes in well-functioning older people. Provision of a clinically meaningful cutpoint for usual gait speed may facilitate its use in clinical and research settings. © 2005 by the American Geriatrics Society.

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.