ICCBH2013 Oral Communications Chronic diseases (6 abstracts)
Mineral metabolism, cortical volumetric bone mineral density and fracture risk in childhood chronic kidney disease
Michelle Denburg 1, , Anne Tsampalieros 1, , Ian de Boer 3 , Justine Shults 1, , Heidi Kalkwarf 4 , Babette Zemel 1, , Debbie Foerster 1 , David Stokes 1 & Mary Leonard 1,
1The Children’s Hospital of Philadelphia, Pennsylvania, USA; 2Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada; 3Kidney Research Institute, University of Washington, Seattle, Washington, USA; 4Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; 5Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Background and Objectives: The relations among cortical volumetric bone mineral density (CortBMD) and comprehensive measures of mineral metabolism have not been addressed in chronic kidney disease (CKD). The aim was to identify determinants of CortBMD in childhood CKD. A secondary objective was to assess if CortBMD was associated with subsequent fracture.
Design/participants: This prospective cohort study in children, adolescents and young adults (ages 5–21 years) with CKD stages 2-5D included 171 participants at enrollment and 89 1 year later.
Outcomes: Serum measures included vitamin D (25(OH)D, 1,25(OH)2D, 24,25(OH)2D), vitamin D-binding protein (DBP), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), calcium, and phosphorus. Tibia pQCT measures of CortBMD were expressed as sex-, race-, and age-specific Z-scores based on 675 controls. Multivariable linear regression identified independent correlates of CortBMD-Z and change in CortBMD-Z. Cox regression analysis, adjusted for sex and age, was used to determine if baseline CortBMD-Z was associated with fracture (hazard ratio for time to first fracture).
Results: Lower calcium (β=0.31/1 mg/dl, P=0.01) and 25(OH)D (β=0.18/10 ng/ml, P=0.04) and higher PTH (β=−0.02/10%, P=0.002) and 1.25(OH)2D (β=−0.07/10%, P<0.001) were independently associated with lower baseline CortBMD-Z. The correlations of total, free and bioavailable 25(OH)D with CortBMD did not differ. Higher baseline 1.25(OH)2D (P<0.05) and greater increases in PTH (P<0.001) were associated with greater declines in CortBMD-Z (Table). Greater increases in calcium concentrations were associated with greater increases in CortBMD-Z in growing children (interaction P=0.009). The hazard ratio for fracture was 1.75 (95% CI: 1.15, 2.67; P=0.009) per S.D. lower baseline CortBMD-Z.
| Covariate | β | 95% CI | P-value |
| Change in tibia length* | −1.21 | −2.06, −0.37 | 0.006 |
| Change in calcium* | −0.78 | −1.58, 0.01 | 0.053 |
| Change in calcium by change in tibia length interaction | 0.45 | 0.12, 0.79 | 0.009 |
| Change in PTH* | −0.26 | −0.37, −0.14 | <0.001 |
| Baseline 1,25(OH)2D* | −0.07 | −0.13, −0.0003 | 0.049 |
| Also adjusted for age, study site, baseline CortBMD-Z, baseline calcium, and change in renal function. | |||
| *Natural log transformed. | |||
Conclusions: 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 was associated with increased fracture risk.
Declaration of interest: I de Boer receives research funding from Abbott Laboratories. The remaining authors have nothing to disclose.
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