Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan

Abstract

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...

Effect of competing mortality risks on predictive performance of the QFracture-2012 risk prediction tool for major osteoporotic fracture and hip fracture: external validation cohort study in a UK primary care population

“…Equally, prediction in elderly people requires specific attention, building on small existing studies of prediction in this population. 36 Updating the FRAX model, which accounts for competing mortality, 37 is planned, but publication of the prediction algorithm will be critical in establishing its external validity. 24…”

Derivation and validation of the CFracture competing risk fracture prediction tool compared with QFracture in older people and people with comorbidity: a population cohort study

“…32 FRAX has also been criticised for only using binary clinical risk factors that do not account for exposure response. 33 This makes robust head-to-head comparisons between CFracture and FRAX difficult (although they should still be performed). The Garvan calculator has also been used to individualise the risk of fragility fractures over 10 years.…”

Romosozumab efficacy and safety in European patients enrolled in the FRAME trial

“…Previous results from FRAME reported that patients from Central and Southern America had a lower baseline height than patients from other regions, and that fracture risk was lower despite a consistent number of falls, suggesting that skeletal differences may have contributed to a lower fracture risk in this population when considering the physical mechanics of a fall [ 9 ]. Aside from genetic and physical differences, other studies have reported on the relationship between dietary habits and osteoporosis [ 14 ], whilst a recent review summarising updates to the FRAX® tool note a number of new clinical risk factors that will increase applicability of FRAX®, including severity and treatment of type 2 diabetes, site, number of, and time since previous fracture, and prevalent falls, together emphasising the multi-factorial nature of fracture risk [ 15 ]. Further study would be required in order to determine whether such factors influenced the results observed in these post hoc analyses.…”