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

Andrea Z. LaCroix, Jennifer S. Lee, LieLing Wu, Jane A. Cauley, Michael G. Shlipak, Susan M. Ott, John A Robbins, J. David Curb, Meryl Leboff, Douglas C. Bauer, Rebecca D. Jackson, Charles L. Kooperberg, Steven R. Cummings

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


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 m 2, 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 eGFR cys-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.

Original languageEnglish (US)
Pages (from-to)1434-1441
Number of pages8
JournalJournal of the American Geriatrics Society
Issue number8
StatePublished - Aug 2008


  • Chronic kidney disease
  • Cystatin-C
  • Hip fracture
  • Renal function

ASJC Scopus subject areas

  • Geriatrics and Gerontology


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