Vitamin D supplements and future fracture risk among Mongolian schoolchildren
Authors: Ning Ma, Xia Cui, Wenquan Niu
Journal: The Lancet Diabetes & Endocrinology (2024)

We read with great interest the study by Ganmaa and colleagues,1Ganmaa D Khudyakov P Buyanjargal U et al.Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial.Lancet Diabetes Endocrinol. 2024; 12: 29-38Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar who examined the effect of vitamin D supplements on 3-year fracture risk among 11 475 Mongolian schoolchildren aged 6–13 years. We commend Ganmaa and colleagues1Ganmaa D Khudyakov P Buyanjargal U et al.Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial.Lancet Diabetes Endocrinol. 2024; 12: 29-38Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar for providing solid, albeit statistically insignificant, data from a phase 3, randomised controlled trial on the potential benefits of vitamin D in the prevention of fracture. The authors did outstanding work; however, we have three concerns. First, we express concern over a possible ethical issue. Ganmaa and colleagues1Ganmaa D Khudyakov P Buyanjargal U et al.Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial.Lancet Diabetes Endocrinol. 2024; 12: 29-38Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar had randomly assigned either vitamin D or placebo capsules to 8348 schoolchildren, the majority of whom (95·5%) were deficient in vitamin D, with serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L. The reduction in the risk of 3-year fracture events was similar between the two trial groups. In our opinion, it is unethical to randomly assign schoolchildren with placebo who have vitamin D deficiency for as long as 3 years, given the existence of supportive evidence on the significant association of serum 25-hydroxyvitamin D insufficiency with high fracture incidence in children.2Thompson RM Dean DM Goldberg S Kwasny MJ Langman CB Janicki JA Vitamin D insufficiency and fracture risk in urban children.J Pediatr Orthop. 2017; 37: 368-373Crossref PubMed Scopus (0) Google Scholar We believe that the right way to assess the benefits of vitamin D supplementation would be to compare it with the standard of care in the presence of vitamin D deficiency. Our second concern rests with the potential confounding effect of obesity on fracture risk in schoolchildren, as obesity is closely related to paediatric vitamin D deficiency. Epidemiological data have revealed that the prevalence of vitamin D deficiency ranges from 6·5% to 96·2% in children and adolescents with obesity.3Simunovic M Supe-Domic D Karin Z et al.The relationship of vitamin D status, adherence to the mediterranean diet, and physical activity in obese children and adolescents.J Med Food. 2021; 24: 385-393Crossref Scopus (4) Google Scholar, 4Al-Ajlan BY Freije A Allehdan S Perna S Prevalence and risk factors for vitamin D deficiency in children and adolescents in the Kingdom of Bahrain.Nutrients. 2023; 15: 494Crossref Scopus (1) Google Scholar Additionally, there is evidence that excess body fat can increase the risk of paediatric fracture.5Lopes KG Rodrigues EL da Silva Lopes MR et al.Adiposity metabolic consequences for adolescent bone health.Nutrients. 2022; 143260Crossref Scopus (9) Google Scholar As such, it is of added interest to consider obesity as a classifier to see whether the percentage of fracture events differs across children with underweight, normal weight, overweight, and obesity. The third concern is the lack of consideration of physical activity when monitoring adherence to capsules and adverse events during weekly face-to-face visits in this study.1Ganmaa D Khudyakov P Buyanjargal U et al.Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial.Lancet Diabetes Endocrinol. 2024; 12: 29-38Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar It is universally accepted that physical activity is a major non-pharmacological intervention that cannot only increase the absorption of vitamin D and calcium from food but also enhance bone mineral density and geometry. Hence, whether physical activity can modify or confound the beneficial effect of oral vitamin D supplementation on reduced future fracture risk among Mongolian schoolchildren is an important question that deserves further exploration. We declare no competing interests. Vitamin D supplements and future fracture risk among Mongolian schoolchildren – Author's replyWe thank Ning Ma and colleagues for their comments on our work.1 With regard to ethics, our protocol was reviewed and approved by institutional review boards in both Mongolia and the USA, and the trial was monitored by an external data and safety monitoring board whose members were independent of the study. Random assignment of children with unknown but potentially low baseline serum 25-hydroxyvitamin D concentrations to vitamin D versus placebo was approved by all these parties on the grounds that evidence supporting health benefits of weekly vitamin D supplementation in the study population (which excluded children with signs of rickets) was equivocal, and that a situation of ethical equipoise therefore existed. Full-Text PDF