Volumetric bone mineral density and bone structure in childhood chronic kidney disease

Abstract

Chronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (vBMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomographic scans were obtained in 156 children with CKD [69 stages 2 to 3, 51 stages 4 to 5, and 36 stage 5D (dialysis)] and 831 healthy participants aged 5 to 21 years. Sex-, race-, and age- or tibia length-specific Z-scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with a higher TrabBMD Z-score in younger participants (p < .001) compared with healthy children; this association was attenuated in older participants (interaction p < .001). Mean CortArea Z-score was lower (p < .01) in CKD 4-5 [-0.49, 95% confidence interval (CI) -0.80, -0.18)] and CKD 5D (-0.49, 95% CI -0.83, -0.15) compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD Z-score (p < .01), and this association was significantly attenuated in older participants (interaction p < .05). Higher levels of PTH and biomarkers of bone formation (bone-specific alkaline phosphatase) and resorption (serum C-terminal telopeptide of type 1 collagen) were associated with lower CortBMD and CortArea Z-scores and greater EndoC Z-score (r = 0.18-0.36, all p ≤ .02). CortBMD Z-score was significantly lower in CKD participants with PTH levels above versus below the upper limit of the Kidney Disease Outcome Quality Initiative (KDOQI) CKD stage-specific target range: -0.46 ± 1.29 versus 0.12 ± 1.14 (p < .01). In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these alterations and to determine if cortical and trabecular abnormalities are reversible.

Figure 1. Trabecular BMD Z-scores Relative to Age, According to CKD Category

Trabecular volumetric BMD Z-scores were inversely associated with age in the CKD participants and this relation varied according to CKD category. The inverse association was significantly more pronounced among participants with greater CKD severity (test for interaction: p < 0.001). A: CKD Stage 2–3; B: CKD Stage 4–5; and C: CKD Stage 5D.

Figure 2. Cortical Volumetric BMD and Endosteal Circumference Z-scores according to iPTH Level

A. Cortical volumetric BMD Z-scores were significantly lower in participants with iPTH levels above the target range, compared to those with iPTH levels below the upper limit of the target range (p < 0.01). B. Endosteal Circumference Z-scores were significantly greater in participants with iPTH levels above the target range, compared to those with iPTH levels below the upper limit of the target range (p < 0.001). These data represent all CKD categories combined and were not adjusted for any covariates. The symbols above and below the box plots represent outliers.