The association between cystatin C and hip fracture risk: A longitudinal cohort study of China Health and Retirement Longitudinal Study (CHARLS)

PURPOSE: Cystatin C, a cysteine protease inhibitor linked to kidney function, cardiovascular disease, and osteoporosis, has unclear associations with hip fracture risk. This study examines this relationship using longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS). METHODS: We conducted a prospective cohort analysis using five waves of CHARLS data (2011-2020) among participants aged ≥60 years. Serum cystatin C concentration served as the primary exposure variable, with incident hip fracture as the outcome measure. Cox proportional hazards models quantified the association between cystatin C and hip fracture risk, with adjustments for potential confounders. Restricted cubic splines (RCS) were employed to assess nonlinear relationships, while stratified analyses examined effect modification across demographic and lifestyle subgroups. RESULTS: In the unadjusted model, higher cystatin C levels were significantly associated with an increased risk of hip fracture (OR[95%CI] = 1.76[1.33-2.32], p = 6.38E-05). After adjusting for demographic variables, the association remained significant (OR[95%CI] = 1.60[1.12-2.29], p = 0.0098). In the fully adjusted model, the relationship was still evident (OR[95%CI] = 1.54[1.05-2.56], p = 0.0283). Nonlinear analysis revealed that the risk of hip fracture increased with cystatin C levels, with a threshold effect observed at higher levels. CONCLUSION: Our findings suggest serum cystatin C may represent a valuable biomarker for hip fracture risk assessment in older adults. Further studies are needed to explore the underlying mechanisms and to determine whether cystatin C can be incorporated into clinical risk assessments for hip fractures.