Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicentre phase 3 double-blind randomised placebo-controlled trial (ViDiKids)

BACKGROUND: Relationships between vitamin D status, parathyroid hormone (PTH), bone mineral content (BMC) and fracture risk differ between children of White European vs. Black African ancestry. However, randomised controlled trials (RCT) to determine the influence of vitamin D supplements on BMC and fracture risk in African children are lacking.  

METHODS: We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in Cape Town schoolchildren aged 6-11 years. Sub-study outcomes were BMC at the whole body minus head and lumbar spine sites, determined by dual-energy x-ray absorptiometry (DXA), serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3), PTH, alkaline phosphatase (ALP), C-terminal telopeptide (CTX) and procollagen type 1 N propeptide (P1NP). Incidence of fractures was a secondary outcome of the main trial.  

FINDINGS: 1682 children of Black African ancestry attending 23 schools were enrolled in the main trial (829 vs. 853 randomised to vitamin D vs. placebo, respectively) of whom 450 also participated in the nested sub-study (228 vs. 222 randomised to vitamin D vs. placebo, respectively). In the sub-study population, end-trial serum concentrations of 25(OH)D3 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 nmol/L, 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 BMC at the whole body minus head (aMD -8.0 g, 95% CI -30.7 to 14.7) or the lumbar spine (aMD -0.3 g, 95% CI -1.3 to 0.8), or for serum concentrations of alkaline phosphatase, CTX or P1NP (P≥0.28). In the main trial population, allocation to vitamin D vs. placebo did not influence the proportion of participants reporting one or more fractures (adjusted odds ratio 0.70, 95% CI 0.27 to 1.85, P=0.48).  
INTERPRETATION: Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations among Cape Town schoolchildren of Black African ancestry but did not influence BMC, serum concentrations of bone turnover markers or fracture risk.