• chronic kidney disease;
  • hip fracture;
  • cystatin-C;
  • renal function

OBJECTIVES: To evaluate the association between chronic kidney disease and incident hip fracture using serum cystatin-C as a biomarker of renal function calculated without reference to muscle mass.

DESIGN: Case-control study nested within a prospective study.

SETTING: The Women's Health Initiative Observational Study conducted at 40 U.S. clinical centers.

PARTICIPANTS: From 93,676 women aged 50 to 79 followed for an average of 7 years, 397 incident hip fracture cases and 397 matched controls were studied.

MEASUREMENTS: Cystatin-C levels were measured on baseline serum using a particle-enhanced immunonepholometric assay. Estimated glomerular filtration rates (eGFRcys-c) were calculated using a validated equation and categorized into three groups (≥90.0 mL/min per 1.73 m2, 60.0–89.9 mL/min per 1.73 m2, and <60.0 mL/min per 1.73 m2 indicating chronic kidney disease Stages 3 to 4).

RESULTS: The odds ratio (OR) for hip fracture was 2.50 (95% confidence interval (CI)=1.32–4.72) for eGFRcys-c less than 60 mL/min per 1.73 m2 compared with Stages 0 to 1, after adjustment for body mass, parental hip fracture, smoking, alcohol consumption, and physical function. No association was observed for eGFRcys-c of 60 to 90 mL/min per 1.73 m2 (OR=1.04, 95% CI=0.66–1.64). Additional adjustment for poor health status, hemoglobin, serum 25-hydroxy vitamin D, and bone metabolism markers did not affect these associations. Adjustment for plasma homocysteine reduced the OR for eGFRcys-c less than 60 mL/min per 1.73 m2 to 1.83 (95% CI=0.93–3.61).

CONCLUSION: Women with eGFRcys-c levels less than 60 mL/min per 1.73 m2 have a substantially greater risk of hip fracture. Effects of renal function on homocysteine levels may partially mediate, or accompany, this association.