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.

Vitamin D supplementation for improving bone mineral density in children.

BACKGROUND: Results of randomised controlled trials (RCTs) of vitamin D supplementation to improve bone density in children are inconsistent. OBJECTIVES: To determine the effectiveness of vitamin D supplementation for improving bone mineral density in children, whether any effect varies by sex, age or pubertal stage, the type or dose of vitamin D given or baseline vitamin D status, and if effects persist after cessation of supplementation. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2009), MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), AMED (1985 to present) and ISI Web of Science (1945 to present) on 9 August 2009, and we handsearched key journal conference abstracts. SELECTION CRITERIA: Placebo-controlled RCTs of vitamin D supplementation for at least three months in healthy children and adolescents (aged from one month to < 20 years) with bone density outcomes. DATA COLLECTION AND ANALYSIS: Two authors screened references for inclusion, assessed risk of bias, and extracted data. We conducted meta-analyses and calculated standardised mean differences (SMD) of the percent change from baseline in outcomes in treatment and control groups. We performed subgroup analyses by sex, pubertal stage, dose of vitamin D and baseline serum vitamin D and considered these as well as compliance and allocation concealment as possible sources of heterogeneity. MAIN RESULTS: We included six RCTs (343 participants receiving placebo and 541 receiving vitamin D) for meta-analyses. Vitamin D supplementation had no statistically significant effects on total body bone mineral content (BMC), hip bone mineral density (BMD) or forearm BMD. There was a trend to a small effect on lumbar spine BMD (SMD 0.15, 95% CI -0.01 to 0.31, P = 0.07). There were no differences in effects between high and low serum vitamin D studies at any site though there was a trend towards a larger effect with low vitamin D for total body BMC (P = 0.09 for difference). In low serum vitamin D studies, significant effects on total body BMC and lumbar spine BMD were approximately equivalent to a 2.6% and 1.7 % percentage point greater change from baseline in the supplemented group. AUTHORS' CONCLUSIONS: These results do not support vitamin D supplementation to improve bone density in healthy children with normal vitamin D levels, but suggest that supplementation of deficient children may be clinically useful. Further RCTs in deficient children are needed to confirm this.

Determinants of skeletal age deviation in a cross-sectional study.

OBJECTIVE: Skeletal age deviation (SAD) is associated with bone mass and fracture risk in children, but factors determining this are unknown. The aim of this population-based cross-sectional study was to describe the factors associated with SAD. METHODS: A convenience sample of 640 male and female children aged 7-17 yr was studied. All were assessed for body composition (dual-energy x-ray absorptiometry), diet, strength, dexterity, habitual physical activity, sunlight exposure, smoking, and medication use. Skeletal age was assigned using the Tanner-Whitehouse-2 method. RESULTS: Subjects with a SAD greater than the 75th percentile had significantly higher height, weight, and Tanner stage compared with all other subjects. Bone-free lean mass, fat mass, and grip strength were positively associated with SAD. In multivariate analysis, ever smoking and use of inhaled corticosteroids were negatively associated with SAD, whereas milk drinking was positively associated with SAD. There was no significant association between sunlight exposure, television watching, light, or strenuous exercise and SAD. CONCLUSIONS: The results of this study should be regarded as hypothesis generating but are biologically plausible and suggest that body composition, strength, diet, ever smoking, and inhaled corticosteroid use may be determinants of bone maturity relative to age and thus affect fracture risk in children. However, more studies are necessary to explore other determinants of SAD such as genetic and perinatal factors and whether SAD influences peak bone mass.

Strontium ranelate--does it affect the management of postmenopausal osteoporosis?

This series of articles facilitated by the Cochrane Musculoskeletal Group (CMSG) aims to place the findings of recent Cochrane musculoskeletal reviews in a context immediately relevant to general practitioners. This article considers whether the availability of strontium ranelate affects the management of postmenopausal osteoporosis.