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)). KeywordsEpidemiology • Fracture probability • FRAX • Hip fracture • Major osteoporotic fracture • Risk assessment Extended author information available on the last page of the article EligibilityStudies were eligible if the cohort described was prospective, included at least 200 participants, assessed an adequate number of clinical risk factors and reported an adequate number of incident fracture outcomes. Cohorts that had already contributed to FRAX as source or validation cohorts or that were previously identified but have not been used in any previous analysis were collectively categorised separately as "cohorts previously identified" (Fig. 1). Results Literature searchThe compu...

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Purpose-There is limited information available regarding the association between lung function and bone mineral density among healthy elderly subjects. We addressed this issue in the Hertfordshire Cohort Study.Methods-985 subjects (496 men and 489 women) aged 60-72 years were recruited from the above cohort. All subjects underwent bone density measurements using dual energy X-ray absorptiometry (DXA), and lung function tests using standardised spirometry. Chronic obstructive pulmonary disease (COPD) was defined as a Forced Expiratory Volume in 1 second (FEV 1) / Forced Vital Capacity (FVC) ratio < lower limit of normal (LLN), calculated using separate equations for men and women.Results-Measures of lung function (FEV 1 , FVC, FEV 1 /FVC) were not associated with bone mineral density at the lumbar spine, femoral neck and total hip in men or women; associations with bone mineral content and bone area were removed by adjustment for body size and lifestyle confounders. In this cohort, there were no associations observed between COPD and any measure of bone mass.Conclusions-There was no association between lung function and bone mass in this community dwelling cohort after adjustment for body size and other confounders.