Influence of vitamin D supplementation on fracture risk, bone mineral density and bone biochemistry in Mongolian schoolchildren: multicenter double-blind randomized placebo-controlled trial.

ABSTRACT

Background: Randomized controlled trials (RCT) of vitamin D supplementation to reduce fracture risk in children are lacking. Methods: We conducted a Phase 3 RCT of weekly oral supplementation with 14,000 IU vitamin D3 for 3 years in Mongolian schoolchildren aged 6-13 years. Serum 25-hydroxyvitamin D (25[OH]D) concentrations and the proportion of participants reporting ≥1 fracture were secondary outcomes for the main trial. Radial bone mineral density (BMD) was assessed in a nested sub-study, with serum concentrations of parathyroid hormone (PTH) and bone-specific alkaline phosphatase (BALP) determined in a subset of participants. Findings: 8851 children were enrolled in the main trial, of whom 1465 also participated in the sub-study. Vitamin D deficiency was prevalent at baseline (25[OH]D <20 ng/mL in 90.1%). The intervention elevated 25(OH)D concentrations (adjusted inter-arm mean difference [aMD] 20.3 ng/mL, 95% CI 19.9 to 20.6) and suppressed PTH concentrations (aMD -13.6 pmol/L, 95% CI -23.5 to -3.7), but it did not influence fracture risk (adjusted risk ratio 1.10, 95% CI 0.93 to 1.29, P=0.27) or radial BMD z-score (aMD -0.06, 95% CI -0.18 to 0.07, P=0.36). Vitamin D suppressed serum BALP concentrations more among participants with baseline 25(OH)D concentrations <10 vs. ≥10 ng/mL (Pinteraction=0.04). However, effects of the intervention on fracture risk and radial BMD were not modified by baseline vitamin D status (Pinteraction≥0.67). Interpretation: Weekly oral vitamin D supplementation elevated serum 25(OH)D concentrations and suppressed PTH concentrations in vitamin D-deficient schoolchildren in Mongolia. However, this was not associated with reduced fracture risk or increased radial BMD. Funding: National Institutes of Health.