Vitamin D supplements and future fracture risk among Mongolian schoolchildren – Author's reply
Authors: Adrian R Martineau, Polyna Khudyakov, Davaasambuu Ganmaa
Journal: The Lancet Diabetes & Endocrinology (2024)

We thank Ning Ma and colleagues for their comments on our work.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 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. In retrospect, this judgement appears sound, since this intervention has subsequently been found to have no effect on incident tuberculosis infection,2Ganmaa D Uyanga B Zhou X et al.Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease.N Engl J Med. 2020; 383: 359-368Crossref PubMed Scopus (106) Google Scholar, 3Middelkoop K Stewart J Walker N et al.Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids).Int J Infect Dis. 2023; 134: 63-70Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar fracture risk,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, 4Middelkoop K Micklesfield LK Walker N et al.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).J Bone Miner Res. 2024; https://doiorg/101093/jbmr/zjae007Crossref Google Scholar or growth.5Ganmaa D Bromage S Khudyakov P Erdenenbaatar S Delgererekh B Martineau AR Influence of vitamin D supplementation on growth, body composition, and pubertal development among school-aged children in an area with a high prevalence of vitamin d deficiency: a randomized clinical trial.JAMA Pediatr. 2023; 177: 32-41Crossref PubMed Scopus (5) Google Scholar, 6Middelkoop K, Micklesfield LK, Stewart J, et al. Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids). BMJ Paediatr Open (in press).Google Scholar Obesity is extremely unlikely to have acted as a confounder, since baseline BMI-for-age Z scores were evenly distributed between children randomly assigned to intervention versus placebo.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 Physical activity levels are similarly likely to have been evenly distributed between groups. Exploratory subgroup analyses reveal no evidence to suggest that the effects of vitamin D on fracture risk were modified by either of these factors (table).TableProportion of participants reporting one or more bone fractures of any type by allocation, overall and by sub-groupVitamin D group (n=4176)Placebo group (n=4172)Adjusted risk ratio (95% CI) *Adjusted for random effects of school and individual.pp for interaction†p value for treatment-by-subgroup interaction.Overall268 (6·4%)253 (6·1%)1·10 (0·93 to 1·29)0·27..By baseline BMI-for-age Z-score<–2·002 (3·7%)4 (8·3%)0·44 (0·07 to 2·99)0·400·26−2·00 to +2·00244 (6·3%)232 (6%)1·05 (0·88 to 1·25)0·58>2·00 to 3·0019 (10·1%)13 (7·1%)1·42 (0·71 to 2·87)0·32>3·003 (7·1%)4 (7·7%)0·93 (0·21 to 4·09)0·92By baseline frequency of outdoor activity<1 h/week108 (6·1%)102 (5·9%)1·13 (0·88 to 1·44)0·330·071 to 2 h/week90 (7·0%)62 (4·8%)1·47 (1·07 to 2·01)0·02>2 h/week70 (6·2%)89 (7·7%)0·80 (0·59 to 1·09)0·16* Adjusted for random effects of school and individual.† p value for treatment-by-subgroup interaction. Open table in a new tab ARM declares receipt of funding to support vitamin D research from Pharma Nord, DSM Nutritional Products, Thornton & Ross, and Hyphens Pharma; receipt of vitamin D capsules for clinical trial use from Pharma Nord, Synergy Biologics, and Cytoplan; support for attending meetings from Pharma Nord and Abiogen Pharma; receipt of consultancy fees from DSM Nutritional Products and Qiagen; receipt of a speaker fee from the Linus Pauling Institute (Corvallis, OR, USA); participation on data and safety monitoring boards for the VITALITY trial (PACTR20200989766029) and the trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (NCT04641195); and unpaid work as a programme committee member for the Vitamin D Workshop. PK and DG declare no competing interests. Vitamin D supplements and future fracture risk among Mongolian schoolchildrenWe read with great interest the study by Ganmaa and colleagues,1 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 colleagues1 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. Full-Text PDF