Muscle Strength and Physical Performance Improve Fracture Risk Prediction Beyond Garvan and FRAX: The Osteoporotic Fractures in Men (MrOS) Study

Background: Muscle strength and physical performance are associated with fracture risk in men. However, it is not known whether these measurements enhance fracture prediction beyond Garvan and FRAX tools. Methods: 5665 community-dwelling men, aged 65+, from the Osteoporotic Fractures in Men (MrOS) Study, who had data on muscle strength (grip strength) and physical performance (gait speed and chair stand tests), were followed from 2000 to 2019 for any fracture, major osteoporotic fracture (MOF), initial hip and any hip fracture. Tool-specific analysis approaches and outcome definitions were used. The added predictive values of muscle strength and physical performance beyond Garvan and FRAX were assessed using categorical net reclassification improvement (NRI) and relative importance analyses. Findings: During a median follow-up of 13(IQR:7-17) years, there were 1014 fractures, 536 MOFs, 215 initial hip and 274 any hip fractures. Grip strength and chair stand improved prediction of any fracture (NRI for grip strength: 3·9% and for chair stand: 3·2%) and MOF (5·2% and 6·1%). Gait speed improved prediction of initial hip (5·7%) and any hip (7·0%) fracture. Combining grip strength and the relevant performance test further improved the models (5·7%, 8·9%, 9·4% and 7·0% for any, MOF, initial, and any hip fractures, respectively). Improvements were predominantly driven by reclassification of fracture cohort to higher risk categories. Apart from age and FNBMD, muscle strength and performance were ranked equal to or better than the other risk factors included in fracture models including prior fractures, falls, smoking, alcohol, and glucocorticoid use. Interpretation: Muscle strength and performance measurements improved fracture risk prediction in men beyond Garvan and FRAX. They were as or more important than other established risk factors. These measures should be considered for inclusion in fracture risk assessment tools. Funding: National Institutes of Health, NIA, NIAMS, NCATS, NIH Roadmap for Medical Research, MRFF, and RTP. Declaration of Interest: Alajlouni, Tran, Bliuc, and Cawthon reported no competing interests. Blank has been a consultant for Bristol Myers Squibb, served on an advisory board for Amgen, received authorship royalties from Wolters Kluwer, received an editorial stipend from Elsevier, received travel support from Amgen, and owns stock in Abbott Labs, Abbvie, Amgen, JangoBio, and Procter & Gamble. Orwoll has received consulting support from Bayer and Biocon and served on an advisory board for Radius. Center has received support from Amgen for attending educational meetings, received advisory board honoraria from Amgen and Bayer, and received educational talks honoraria from Amgen. Ethical Approval: The Institutional Review Boards at each site and the San Francisco Coordinating Center (University of California, San Francisco, and California Pacific Medical Center Research Institute) approved the study.