Interventions for bone disease in children with chronic kidney disease

Abstract

Background: Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates.

Objectives: To investigate the benefits and harms of interventions for preventing and treating bone disease in children with CKD.

Search strategy: The Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts were searched without language restriction.

Selection criteria: Randomised controlled trials (RCTs) comparing different interventions used to prevent or treat bone disease in children with CKD stages 2-5D compared with placebo, no treatment or other agents were included. Studies examining different routes or frequency of treatment were also included.

Data collection and analysis: Data were extracted by two authors. The random-effects model was used and results were reported as risk ratios or risk differences for dichotomous outcomes and mean differences for continuous outcomes with 95% confidence intervals.

Main results: Fifteen RCTs (369 children) were identified. Compared with oral calcitriol, intraperitoneal calcitriol significantly reduced the level of serum parathyroid hormone (PTH) but there were no significant differences in bone histology or other biochemical measures (2 RCTs). There were no significant differences detected in growth, PTH, serum calcium or phosphorus between daily versus intermittent calcitriol (3 RCTs). Vitamin D therapy significantly reduced PTH levels compared with placebo or no treatment. The number of children with hypercalcaemia did not differ significantly between groups (4 RCTs). No significant differences were detected in growth rates, bone histology or biochemical parameters between calcitriol and either dihydrotachysterol or ergocalciferol (2 RCTs). Though fewer episodes of hypercalcaemia were reported with sevelamer, no significant differences were detected in serum calcium, phosphorus and PTH levels between calcium-containing phosphate binders and either aluminium hydroxide or sevelamer (4 RCTs).

Authors' conclusions: Bone disease, assessed by changes in PTH levels, is improved by all vitamin D preparations. However no consistent differences between routes of administration, frequencies of dosing or vitamin D preparations have been demonstrated. Though fewer episodes of high calcium levels occurred with the non calcium-containing binder, sevelamer, compared with calcium-containing binders, there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents. All RCTs were small with few data available on patient-centred outcomes (growth, bone deformities) and limited data on biochemical parameters resulting in considerable imprecision of results thus limiting the applicability to care of children with CKD.