Influence of vitamin D supplementation on bone mineral content, bone turnover markers and fracture risk in south African schoolchildren: multicentre double-blind randomised placebo-controlled trial (ViDiKids).

Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n=450) nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 vs. placebo for 3 years in HIV-uninfected Cape Town schoolchildren aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH), alkaline phosphatase, C-terminal telopeptide and procollagen type 1 N propeptide. Incidence of fractures was a secondary outcome of the main trial (n=1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (s.d. 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs. placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomised to vitamin D vs. placebo (7/755 vs. 10/758 attending at least one follow-up; adjusted odds ratio 0.70, 95% CI 0.27 to 1.85). In conclusion, a 3-year course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.