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


METHODS
Case-control study nested within a prospective study.


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


METHODS
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.


METHODS
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 (>or=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 eGFR(cys-c) less than 60 mL/min per 1.73 m(2) to 1.83 (95% CI=0.93-3.61).


CONCLUSIONS
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.
LaCroix
Andrea Z
AZ
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. alacroix@whi.org
Lee
Jennifer S
JS
Wu
LieLing
L
Cauley
Jane A
JA
Shlipak
Michael G
MG
Ott
Susan M
SM
Robbins
John
J
Curb
J David
JD
Leboff
Meryl
M
Bauer
Douglas C
DC
Jackson
Rebecca D
RD
Kooperberg
Charles L
CL
Cummings
Steven R
SR
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006620:Hip Fractures / Q000097:blood / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000097:blood / Q000453:epidemiology*; D007677:Kidney Function Tests; D008875:Middle Aged; D016017:Odds Ratio; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000453:epidemiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins