Vitamin D supplementation for children with cancer: A systematic review and consensus recommendations

Jenneke E. van Atteveld, Iris E. Verhagen, Marry M. van den Heuvel-Eibrink, Hanneke M. van Santen, Inge M. van der Sluis, Natascia Di Iorgi, Jill H. Simmons, Leanne M. Ward, Sebastian J.C.M.M. Neggers

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


Background: Prevalent vitamin D deficiency (VDD) and low bone mineral density (BMD) have led to vitamin D supplementation for children with cancer, regardless vitamin D status. However, it remains unsettled whether this enhances bone strength. We sought to address this issue by carrying out a systematic review of the literature. Methods: We conducted a literature search using PubMed, Embase, and Cochrane databases. Studies including children up to 5 years after cancer therapy were assessed for the association between 25-hydroxyvitamin D (25OHD) levels and BMD Z-scores or fractures, and the effect of vitamin D supplementation on BMD or fractures. Evidence quality was assessed using the GRADE methodology. Results: Nineteen studies (16 observational and 3 interventional, mainly involving children with hematologic malignancies) were included. One study which analyzed 25OHD as a threshold variable (≤10 ng/ml) found a significant association between 25OHD levels and BMD Z-scores, while 25OHD as a continuous variable was not significantly associated with BMD Z-scores in 14 observational studies. We found neither a significant association between lower 25OHD levels and fractures (2 studies), nor between vitamin D (and calcium) supplementation and BMD or fracture frequency (3 studies) (very low quality evidence). Conclusion: There is a lack of evidence for an effect of vitamin D (and calcium) supplementation on BMD or fractures in children with cancer. Further research is needed; until then, we recommend dietary vitamin D/calcium intake in keeping with standard national guidelines, and periodic 25OHD monitoring to detect levels <20 ng/ml. Vitamin D/calcium supplementation is recommended in children with low levels, to maintain levels ≥20 ng/ml year-long.

Original languageEnglish
Pages (from-to)4177-4194
Number of pages18
JournalCancer Medicine
Issue number13
Publication statusPublished - Jul 2021


  • acute lymphoblastic leukemia
  • bone mineral density
  • childhood cancer
  • fractures
  • vitamin D


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