Cochrane review: Interventions for bone disease in children with chronic kidney disease
Bibliographic record
Abstract
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. Plain Language Summary Interventions for bone disease in children with chronic kidney disease Chronic kidney disease (CKD) resulting in reduced kidney function and the need for dialysis and kidney transplant is associated with abnormalities in blood calcium and phosphorus levels leading to high levels of the parathyroid hormone (PTH) and to bone disease. This may result in bone deformities, bone pain, fractures and reduced growth rates. Commonly used treatments (Vitamin D compounds and phosphate binders) aim to prevent or correct these outcomes. However these treatments may raise levels of blood calcium, allow calcium and phosphorus deposition in blood vessels and lead to early cardiovascular disease, which is known to be a problem in adults with CKD. This review identified only 15 small RCTs involving 369 children comparing different vitamin D compounds, different routes and frequencies of administration of vitamin D compounds and different phosphate binders. Only five RCTs reported on growth rates and no differences were detected between treatments. Renal bone disease, as assessed by changes in PTH levels, was improved by all vitamin D preparations regardless of preparation used or the route or frequency of administration. Fewer episodes of high blood calcium levels and lower overall serum calcium levels occurred with the non calcium‐containing binder, sevelamer, compared with calcium‐containing binders. As newer treatments for renal bone disease are developed, comparisons with the current standard therapies will be required in well designed RCTs in children using outcome measures including those of direct clinical relevance to children and their families such as rates of growth, reduction in bone fractures and bone pain and reduction in calcification in blood vessels.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.008 | 0.007 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.015 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".