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)

SUMMARY BACKGROUND 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. METHODS We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D 3 in HIV-uninfected Cape Town schoolchildren of Black African ancestry aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum concentrations of 25-hydroxyvitamin D 3 (25[OH]D 3 ), parathyroid hormone (PTH) and bone turnover markers. Incidence of fractures was an outcome of the main trial. FINDINGS 1682 children were enrolled in the main trial, of whom 450 also participated in the sub-study. Among sub-study participants, end-trial serum 25(OH)D 3 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, P<0.001) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI -0.94 to -0.17, P=0.005). 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 for serum concentrations of bone turnover markers (P≥0.28). In the main trial, allocation did not influence fracture risk (adjusted odds ratio 0.70, 95% CI 0.27 to 1.85, P=0.48). INTERPRETATION Weekly vitamin D supplementation elevated serum 25(OH)D 3 concentrations and suppressed serum PTH concentrations in HIV-uninfected schoolchildren of Black African ancestry but did not influence BMC, bone turnover markers or fracture risk. FUNDING Medical Research Council RESEARCH IN CONTEXT EVIDENCE BEFORE THIS STUDY We searched PubMed from inception to 31 st December 2022 for randomised controlled trials (RCT) evaluating effects of vitamin D supplementation on bone mineral content (BMC), bone mineral density (BMD) and fracture risk in HIV-uninfected schoolchildren. A meta-analysis of data from 884 participants in six RCT reported no statistically significant effects of vitamin D on total body BMC, hip BMD, or forearm BMD, but a trend towards a small positive effect on lumbar spine BMD. RCT investigating fracture outcomes in HIV-uninfected children were lacking, as were RCT investigating effects of vitamin D on bone outcomes in HIV-uninfected children of Black African ancestry. ADDED VALUE OF THIS STUDY This is the first RCT to investigate effects of vitamin D supplementation on BMC and fracture risk in HIV-uninfected schoolchildren of Black African ancestry. We found that weekly oral supplementation with 10,000 IU vitamin D 3 for 3 years elevated serum 25(OH)D 3 concentrations and suppressed serum PTH concentrations, but did not influence serum concentrations of bone turnover markers, BMC at the whole body less head or lumbar spine sites, or fracture risk. IMPLICATIONS OF ALL THE AVAILABLE EVIDENCE Taken together with null findings from another recenty-completed phase 3 RCT of weekly oral vitamin D supplementation conducted in Mongolian schoolchildren, our findings do not support a role for vitamin D supplementation to increase BMC or reduce fracture risk in primary schoolchildren.