title: Estimated GFR and risk of hip fracture in older men: comparison of associations using cystatin C and creatinine.
abstract: BACKGROUND
  Higher serum cystatin C level is associated with an increased risk of hip fracture in postmenopausal white women, but there is a paucity of data for men. Whether estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) is superior in predicting hip fracture risk to eGFR based on creatinine (eGFRcr) or the combination (eGFR(cr-cys)) also is uncertain.
  
  
  METHODS
  Nested case-cohort.
  
  
  METHODS
  Participants enrolled in the Osteoporotic Fractures in Men (MrOS) Study (5,994 men aged ≥ 65 years from 6 US centers) including a random subcohort of 1,602 men and 168 men with incident hip fractures (51 of whom were in the subcohort).
  
  
  METHODS
  eGFR(cys), eGFR(cr), and eGFR(cr-cys) computed using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and expressed in categories of <60, 60-74, and ≥ 75 mL/min/1.73 m(2) (referent group).
  
  
  RESULTS
  Incident hip fracture ascertained by participant contacts every 4 months and confirmed with radiographic reports.
  
  
  RESULTS
  Median eGFR(cys) was 72.9 (IQR, 60.5-85.7) mL/min/1.73 m(2). In unadjusted models, all measures of eGFR were associated with increased hip fracture risk. However, after adjustment for age, race, site, and body mass index, the association of lower eGFR(cys) (but not lower eGFR(cr) or lower eGFR(cr-cys)) with higher hip fracture risk remained: for <60 versus ≥ 75 mL/min/1.73 m(2), HRs were 1.96 [95% CI, 1.25-3.09], 0.84 [95% CI, 0.52-1.37], and 1.08 [95% CI, 0.66-1.77] for eGFR(cys), eGFR(cr), and eGFR(cr-cys), respectively. Similarly, after adjustment for age, race, site, and body mass index, eGFR < 60 mL/min/1.73 m(2) defined by eGFR(cys), but not eGFR(cr) or eGFR(cr-cys), was associated with higher hip fracture risk. The association between eGFR(cys) and hip fracture was not explained by levels of calciotropic hormones or inflammatory markers, but the relationship was attenuated and no longer reached significance (for <60 vs ≥ 75 mL/min/1.73 m(2): HR, 1.43; 95% CI, 0.88-2.34) after consideration of additional clinical risk factors and bone mineral density.
  
  
  CONCLUSIONS
  Findings not generalizable to other populations; residual confounding may exist.
  
  
  CONCLUSIONS
  Older community-dwelling men with lower eGFR(cys) have an increased risk of hip fracture that is explained in large part by greater burden of risk factors among men with lower eGFR(cys). In contrast, lower eGFR(cr) or lower eGFR(cr-cys) was not associated with a higher age-adjusted hip fracture risk.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN; Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN; Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, MN. Electronic address: ensru001@umn.edu.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA.
authors.forename: Neeta
authors.initials: N
authors.lastname: Parimi
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN; Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN; Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, MN.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fink
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN; Department of Nephrology, VA Health Care System, Minneapolis, MN.
authors.forename: Areef
authors.initials: A
authors.lastname: Ishani
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN; Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN; Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, MN.
authors.forename: Brent C
authors.initials: BC
authors.lastname: Taylor
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
authors.forename: Michael
authors.initials: M
authors.lastname: Steffes
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Division of Preventative Medicine, University of Alabama, Birmingham, AL.
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.affiliation: Bone & Mineral Unit, Oregon Health & Science University, Portland, OR.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orwoll
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D005919:Glomerular Filtration Rate; D006620:Hip Fractures / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D008297:Male; D015233:Models, Statistical; D058866:Osteoporotic Fractures / Q000175:diagnosis / Q000453:epidemiology; D011897:Random Allocation; D051437:Renal Insufficiency / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D003404:Creatinine
keywords: Kidney function; creatinine; cystatin C; elderly; hip fracture; men
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