Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis

OBJECTIVE To determine the effectiveness of vitamin D supplementation for improving bone mineral density in children and adolescents and if effects vary with factors such as vitamin D dose and vitamin D status. DESIGN Systematic review and meta-analysis. DATA SOURCES Cochrane Central Register of Controlled Trials, Medline (1966 to present), Embase (1980 to present), CINAHL (1982 to present), AMED (1985 to present), and ISI Web of Science (1945 to present), last updated on 9 August 2009, and hand searching of conference abstracts from key journals. Study selection Placebo controlled randomised controlled trials of vitamin D supplementation for at least three months in healthy children and adolescents (aged 1 month to <20 years) with bone density outcomes. Two authors independently assessed references for inclusion and study quality and extracted data. DATA SYNTHESIS Standardised mean differences of the percentage change from baseline in bone mineral density of the forearm, hip, and lumbar spine and total body bone mineral content in treatment and control groups. Subgroup analyses were carried out by sex, pubertal stage, dose of vitamin D, and baseline serum vitamin D concentration. Compliance and allocation concealment were also considered as possible sources of heterogeneity. RESULTS From 1653 potential references, six studies, totalling 343 participants receiving placebo and 541 receiving vitamin D, contributed data to meta-analyses. Vitamin D supplementation had no statistically significant effects on total body bone mineral content or on bone mineral density of the hip or forearm. There was a trend to a small effect on lumbar spine bone mineral density (standardised mean difference 0.15, 95% confidence interval -0.01 to 0.31; P=0.07). Effects were similar in studies of participants with high compared with low serum vitamin D levels, although there was a trend towards a larger effect with low vitamin D for total body bone mineral content (P=0.09 for difference). In studies with low serum vitamin D, significant effects on total body bone mineral content and lumbar spine bone mineral density were roughly equivalent to a 2.6% and 1.7% percentage point greater change from baseline in the supplemented group. CONCLUSIONS It is unlikely that vitamin D supplements are beneficial in children and adolescents with normal vitamin D levels. The planned subgroup analyses by baseline serum vitamin D level suggest that vitamin D supplementation of deficient children and adolescents could result in clinically useful improvements, particularly in lumbar spine bone mineral density and total body bone mineral content, but this requires confirmation.