Cystatin-C, renal function, and incidence of hip fracture in postmenopausal women

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 (eGFR(cys-c)) were calculated using a validated equation and categorized into three groups (>= 90.0 mL/min per 1.73 m(2), 60.0-89.9 mL/min per -1.73 m(2), and < 60.0 mL/min per 1.73 m(2) 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 eGFR(cys-c) less than 60 mL/min per 1.73 m(2) 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 eGFR(cys-c) of 60 to 90 mL/min per 1.73 m(2) (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 m(2) to 1.83 (95% CI = 0.93-3.61). CONCLUSION: Women with eGFR(cys-c) levels less than 60 mL/min per 1.73 m(2) have a substantially greater risk of hip fracture. Effects of renal function on homocysteine levels may partially mediate, or accompany, this association.