Risk factors for hip and vertebral fractures in chronic kidney disease: the CRIC study

Abstract

Fracture risk is high in chronic kidney disease (CKD) and underlying pathophysiology and risk factors may differ from the general population. In a cohort study of 3939 participants in the chronic renal insufficiency cohort (CRIC), we used Cox regression to test associations of putative risk factors with the composite of first hip or vertebral fracture assessed using hospital discharge codes. Mean age was 58 years, 45% were female, 42% were Black, and 13% were Hispanic. There were 82 hip and 24 vertebral fractures over a mean (SD) 11.1 (4.8) years (2.4 events per 1000 person-years [95% CI: 2.0, 2.9]). Measured at baseline, diabetes, lower body mass index (BMI), steroid use, proteinuria, and elevated parathyroid hormone (PTH) were each associated with fracture risk after adjusting for covariates. Lower time-updated estimated glomerular filtration rate (eGFR) was associated with fractures (HR 1.20 per 10 mL/min/1.73m2 lower eGFR; 95% CI: 1.04, 1.38) as were lower time-updated serum calcium and bicarbonate concentrations. Among time-updated categories of kidney function, hazard ratios (95% CI) for incident fracture were 4.53 (1.77, 11.60) for kidney failure treated with dialysis and 2.48 (0.86, 7.14) for post-kidney transplantation, compared with eGFR ≥60. Proton pump inhibitor use, dietary calcium intake, measures of vitamin D status, serum phosphate, urine calcium and phosphate, and plasma fibroblast growth factor-23 were not associated with fracture risk. In conclusion, lower eGFR in CKD is associated with higher fracture risk, which was highest in kidney failure. Diabetes, lower BMI, steroid use, proteinuria, higher serum concentrations of PTH, and lower calcium and bicarbonate concentrations were associated with fractures and may be modifiable risk factors.

Keywords: PTH/Vit D/FGF23; biochemical markers of bone turnover; fracture prevention; fracture risk assessment; osteoporosis.

Figure 1

Associations of eGFR and PTH as continuous variables with risk of hip and vertebral fractures. The generalized additive models estimate the hazard ratio of hip and vertebral fractures according to (A) time-updated eGFR and (B) baseline PTH. The models are adjusted for age, sex, race and ethnicity, diabetes, smoking status, self-reported physical activity, systolic blood pressure, body mass index, dietary calcium intake from food and supplements, dietary vitamin D intake from food and supplements, anti-hypertensive use, statin use, bisphosphonate use, estrogen-containing medications, steroid use, log-transformed proteinuria. The PTH model additionally adjusts for eGFR. Covariates in the time-updated eGFR model are also time-updated. The shaded areas represent the 95% CI. The histogram shows the distribution of PTH concentration at baseline. eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone; CI, confidence interval.