Long-term trajectories and cumulative exposure of the triglyceride-glucose-frailty index in relation to hip fracture risk: evidence from a large-scale population-based cohort.

UNLABELLED: Long-term trajectories and cumulative burden of the triglyceride-glucose-frailty index (TyGFI) exhibited nonlinear associations with hip fracture risk. Persistent metabolic-frailty imbalance markedly increased fracture susceptibility, identifying TyGFI as a potential risk factor for early detection and prevention of hip fracture.

BACKGROUND

Hip fracture is a major cause of disability and mortality in older adults, yet traditional risk factors explain only part of its variability. Metabolic dysfunction and frailty may jointly contribute to skeletal fragility. The triglyceride-glucose-frailty index (TyGFI) integrates these domains, but its long-term association with hip fracture risk remains unclear.

METHODS

A total of 6130 adults aged ≥ 45 years from the China Health and Retirement Longitudinal Study were included. TyGFI was calculated as the product of the triglyceride-glucose index and frailty index. Participants were grouped into longitudinal trajectories using k-means clustering, and cumulative exposure was estimated as the area under the curve between 2012 and 2015. Cox regression and spline analyses evaluated associations with hip fracture risk.

RESULTS

Three distinct TyGFI trajectories were identified-low-stable, moderate-increasing, and high-increasing. Compared with the low-stable group, participants in the moderate- and high-increasing groups had higher hip fracture risks (HR = 1.97 and 3.79, both P < 0.001). Cumulative TyGFI showed a nonlinear association with fracture risk, with a potential threshold around 4.5. Incorporating cumTyGFI significantly improved predictive performance (C-statistic = 0.7340; NRI = 0.4330; IDI = 0.0097; all P < 0.001). Results were robust across subgroups and multiple sensitivity analyses.

CONCLUSIONS

Long-term trajectories and cumulative exposure of TyGFI were independently associated with hip fracture risk, suggesting that persistent metabolic-frailty imbalance contributes to skeletal fragility. TyGFI may serve as a practical integrative marker for early identification and prevention of high-risk individuals.