Beyond static frailty: longitudinal trajectories, nonlinear associations, and muscle strength mediation in osteoporosis risk

Background: Frailty, a multidimensional indicator of declining physiological reserve, has been consistently linked to adverse health outcomes. However, whether dynamic trajectories of the Frailty Index (FI) predict new-onset osteoporosis remains unclear. Methods: For this longitudinal cohort study, we retrieved data on adults aged ≥50 years from the Health and Retirement Study, the English Longitudinal Study of Ageing, and the Survey of Health, Ageing and Retirement in Europe. We assessed frailty using the FI and identified longitudinal frailty trajectories, examined associations of baseline FI and frailty trajectories with incident osteoporosis, and explored nonlinear relationships and the potential mediating role of grip strength. Results: Over median follow-up periods of 4, 6, and 8 years, 244, 2,693, and 1,986 participants in the ELSA, the SHARE, and the HRS cohorts developed osteoporosis, respectively. Higher baseline FI was independently associated with greater osteoporosis risk across all cohorts, with adjusted hazard ratios of 1.43 (95% confidence interval (CI) = 1.36-1.50, P < 0.001) in the HRS, 1.36 (95% CI = 1.19-1.57, P < 0.001) in the ELSA, and 1.39 (95% CI = 1.33-1.45, P < 0.001) in the SHARE cohort. We identified four FI trajectories. Compared with the low frailty group, participants in higher frailty trajectory groups generally exhibited increased risks of osteoporosis across cohorts. Nonlinear analyses pointed to threshold effects in the HRS and the SHARE, with steeper risk increases at lower FI levels. Grip strength partially mediated this association. Conclusions: In our sample, baseline FI and its longitudinal trajectories were significantly associated with osteoporosis. Our findings suggest that the early identification and monitoring of frailty, as well as muscle strength improvement, may help reduce osteoporosis risk.