Association of serum 25(OH)Vit-D levels with risk of pediatric fractures: a systematic review and meta-analysis

Osteoporos Int. 2021 Jul;32(7):1287-1300. doi: 10.1007/s00198-020-05814-1. Epub 2021 Mar 11.


The association between the risk of fractures and suboptimal vitamin D (Vit-D) status remains controversial in children. This meta-analysis suggested that serum 25(OH)Vit-D levels were lower in pediatric cases with fractures. 25-hydroxyvitamin D (25(OH)Vit-D) levels less than 50 nmol/L were associated with increased fracture risk in children.

Introduction: This study aimed to assess the association between serum 25(OH)Vit-D and the risk of fractures in children, and to explore the sources of heterogeneity and investigate their impact on results.

Methods: Systematic review and meta-analysis were conducted for observational studies comparing serum 25(OH)Vit-D levels between fracture and non-fracture pediatric cases. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS).

Results: Analysis on 17 case-control and 6 cross-sectional studies (2929 fracture cases and 5000 controls) suggested that 25(OH)Vit-D was lower in fracture cases than in controls (pooled mean difference (MD) = - 3.51 nmol/L; 95% confidence interval (CI): - 5.60 to - 1.42) with a heterogeneity (I2) of 73.9%. The sensitivity analysis which merged the case-control studies that had a NOS score ≥ 4 showed a pooled MD of - 4.35 nmol/L (95% CI: - 6.64 to - 2.06) with a heterogeneity (I2) of 35.9%. Pooled odds ratio of fracture in subjects with 25(OH)Vit-D ≤ 50 nmol/L compared to subjects with 25(OH)Vit-D > 50 nmol/L was 1.29 (95% CI: 1.10 to 1.53; I2 < 1%).

Conclusion: This study indicated that serum 25(OH)Vit-D levels were lower in pediatric patients with fractures. 25(OH)Vit-D ≤ 50 nmol/L was associated with increased fracture risk in children.

Keywords: 25(OH)Vit-D; Pediatric fracture; Seasonal variation; Vitamin D deficiency.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Child
  • Cross-Sectional Studies
  • Fractures, Bone* / epidemiology
  • Fractures, Bone* / etiology
  • Humans
  • Vitamin D
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / epidemiology
  • Vitamins


  • Vitamins
  • Vitamin D