Abstract
The relationships among cortical volumetric bone mineral density (CortBMD) and comprehensive measures of mineral metabolism have not been addressed in chronic kidney disease (CKD). The aim of the study was to identify the determinants of CortBMD in childhood CKD. A secondary objective was to assess whether CortBMD was associated with subsequent fracture. This prospective cohort study included 171 children, adolescents, and young adults (aged 5-21 years) with CKD stages 2-5D at enrollment and 89 1 year later. Serum measures included vitamin D [25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25(OH)₂D), 24,25-dihydroxyvitamin D], vitamin D-binding protein, intact PTH, fibroblast growth factor 23, calcium, and phosphorus. Tibia quantitative computed tomography measures of CortBMD were expressed as sex-, race-, and age-specific Z-scores based on 675 controls. Multivariable linear regression identified the independent correlates of CortBMD Z-scores and the change in CortBMD Z-scores. Lower calcium (β = .31/1 mg/dL, P = .01) and 25(OH)D (β = .18/10 ng/mL, P = .04) and higher PTH (β = -.02/10%, P = .002) and 1,25(OH)₂D (β = -.07/10%, P < .001) were independently associated with lower CortBMD Z-scores at baseline. The correlations of total, free, and bioavailable 25(OH)D with CortBMD did not differ. Higher baseline 1,25(OH)₂D (P < .05) and greater increases in PTH (P < .001) were associated with greater declines in CortBMD Z-scores. Greater increases in calcium concentrations were associated with greater increases in CortBMD Z-scores in growing children (interaction P = .009). The hazard ratio for fracture was 1.75 (95% confidence interval 1.15-2.67; P = .009) per SD lower baseline CortBMD. Greater PTH and 1,25(OH)₂D and lower calcium concentrations were independently associated with baseline and progressive cortical deficits in childhood CKD. Lower CortBMD Z-score was associated with increased fracture risk.
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