The effect of vitamin D supplementation and nutritional intake on skeletal maturity and bone health in socio-economically deprived children.

Purpose: 1. To determine the effect of vitamin D supplementation on bone age (BA), a marker of skeletal maturity, and Bone Health Index (BHI), a surrogate marker of bone density. 2. To characterise the differences in nutritional intake and anthropometry between children with advanced vs. delayed BA.

Methods: The current study is a post hoc analysis of radiographs obtained as part of a randomised controlled trial. In this double-blind, placebo-controlled trial, deprived Afghan children (n = 3046) aged 1-11 months were randomised to receive six doses of oral placebo or vitamin D3 (100,000 IU) every 3 months for 18 months. Dietary intake was assessed through semi-quantitative food frequency questionnaires at two time points. Anthropometric measurements were undertaken at baseline and 18 months. Serum 25OHD was measured at five time points on a random subset of 632 children. Knee and wrist radiographs were obtained from a random subset (n = 641), of which 565 wrist radiographs were digitised for post-hoc analysis of BA and BHI using BoneXpert version 3.1.

Results: Nearly 93% (522, male = 291) of the images were analysable. The placebo (n = 258) and vitamin D (n = 264) groups were comparable at baseline. The mean (± SD) age of the cohort was 2 (± 0.3) years. At study completion, there was no difference in mean 25-hydroxy vitamin D concentrations [47 (95% CI 41, 56) vs. 55 (95% CI 45, 57) nmol/L, p = 0.2], mean (± SD) BA SDS [- 1.04 (1.36) vs. - 1.14 (1.26) years, p = 0.3] or mean (± SD) BHI SDS [- 0.30 (0.86) vs. - 0.31 (0.80), p = 0.8] between the placebo and vitamin D groups, respectively. Children with advanced skeletal maturity (BA SDS ≥ 0) when compared to children with delayed skeletal maturity (BA SDS < 0), had consumed more calories [mean (± SD) calories 805 (± 346) vs 723 (± 327) kcal/day, respectively, p < 0.05], were significantly less stunted (height SDS - 1.43 vs. - 2.32, p < 0.001) and underweight (weight SDS - 0.82 vs. - 1.45, p < 0.001), with greater growth velocity (11.57 vs 10.47 cm/ year, p < 0.05).

Conclusion: Deprived children have significant delay in skeletal maturation but no substantial impairment in bone health as assessed by BHI. BA delay was influenced by total calorie intake, but not bolus vitamin D supplementation.