Association of serum creatinine-to-cystatin C ratio with incident hip fracture in community-dwelling older adults: a prospective cohort study from the China Health and Retirement Longitudinal Study (CHARLS)

The serum creatinine-to-cystatin C ratio (CCR) is a promising biomarker of muscle mass, yet its prospective link with hip fracture in Asian older adults remains unclear. We included 2,636 participants aged ≥ 65 from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020). CCR was derived from serum creatinine and cystatin C. Incident hip fractures were self-reported in follow-up interviews. We used cause-specific Cox models and Fine–Gray subdistribution hazard models, treating death as a competing risk. The mean CCR was 0.73 ± 0.19 (mean ± SD). During a median follow-up of 9 years, we identified 155 incident hip fracture events and 784 deaths. Higher CCR was consistently and inversely associated with hip fracture risk in a graded manner. Specifically, in fully adjusted cause‑specific Cox models, each 0.1‑unit increase in CCR was associated with a 12% reduction in the instantaneous hazard of hip fracture (HR = 0.88; 95% CI: 0.79–0.99). Participants in the highest CCR quartile had a 56% lower hazard compared with those in the lowest quartile (HR = 0.44; 95% CI: 0.25–0.77). Fine–Gray subdistribution models, which estimate effects on the cumulative incidence function accounting for death as a competing event, yielded estimates of similar direction and magnitude (per 0.1-unit increase: SHR = 0.88; 95% CI: 0.79–0.99; highest vs. lowest quartile: SHR = 0.44; 95% CI: 0.25–0.78). The inverse association was approximately linear and robust across sensitivity analyses. While generally consistent in most prespecified subgroups, sex-stratified analysis revealed a pronounced association in females (per 0.1-unit increase: HR = 0.83, 95% CI: 0.70–0.98) but not in males (HR = 1.00, 95% CI: 0.84–1.18). The interaction by sex was not statistically significant (P = 0.12), and limited power precludes definitive interpretation of effect modification. In this nationally representative prospective cohort of older Chinese adults, a higher CCR was observed to be associated with a lower risk of incident hip fracture, even after accounting for competing mortality. CCR may serve as an associative biomarker, pending external validation and cost-effectiveness evaluation.