Serum vitamin D and fracture risk in children and adolescents: A systematic review and meta-analysis highlighting age and altitude as key moderators

The present systematic review and meta-analysis aimed to synthesize current comparative evidence to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and fracture risk in children and adolescents. Observational studies comparing serum 25(OH)D levels between pediatric fracture and non-fracture groups were systematically searched in PubMed, Embase and Cochrane databases up to October 1, 2025. Data were pooled using random-effects models. The primary outcomes were the mean difference (MD) in 25(OH)D levels and the odds ratio (OR) for fracture risk associated with vitamin D deficiency (≤20 ng/ml). Subgroup and meta-regression analyses were performed to investigate heterogeneity. A total of 28 studies involving 10,479 participants were included. Meta-analysis revealed significantly lower 25-hydroxyvitamin D (25(OH)D) levels in the fracture group [MD: -1.94 ng/ml; 95% confidence interval (CI): -2.89 to -0.99; P<0.00001]. Vitamin D deficiency was associated with a 71% increased odds of fracture (OR: 1.71; 95% CI: 1.29-2.27; P<0.0001), which remained significant after adjustment for confounders (adjusted OR: 2.41; 95% CI: 1.74-3.34). Meta-regression identified specific age (8.3-9.5 years) and altitude residence (≥600 m) as core moderators explaining the heterogeneity. Vitamin D deficiency is markedly associated with an elevated fracture risk in children and adolescents, with the association being particularly pronounced in early adolescence and at ≥600 m altitudes. These findings highlighted the need for targeted screening and preventive nutritional strategies in these high-risk subgroups.