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.

Study design: Nested case-cohort.

Setting & participants: 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).

Predictor: 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).

Outcome: 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.

Limitations: 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.

Keywords: Kidney function; creatinine; cystatin C; elderly; hip fracture; men.

Figure 1

a-c. eGFR as Calculated by Cystatin C and Creatinine-Based Equations and Risk of Hip Fracture: Effect of Adjustment for Potential Biologic Mediators *adjusted for age, race, site, and body mass index †analyses included 1590 men in subcohort and 128 hip fracture cases with baseline measures of cystatin C, creatinine and 25-hydroxyvitamin D (25(OH)D) and 1590 men in the subcohort and 128 hip fracture cases with baseline measures of cystatin C and PTH ‡analyses included 975 men in subcohort and 133 hip fracture cases with baseline measures of cystatin C, creatinine, and markers of inflammation