Vitamin D supplementation for improving bone density in vitamin D–deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Feitong Wu
  • Ghada El Hajj Fuleihan
  • Guoqi Cai
  • Christel Lamberg-Allardt
  • Heli T. Viljakainen
  • Maya Rahme
  • Ida M. Grønborg
  • Rikke Andersen
  • Anuradha Khadilkar
  • Mughal M. Zulf
  • Mølgaard, Christian
  • Larnkjær, Anni
  • Kun Zhu
  • Richard D. Riley
  • Tania Winzenberg

Background: Vitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D–deficient children are unclear. Objectives: This study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D–deficient individuals. Methods: This is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1–19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. Results: Eleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. Conclusions: Clinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets). This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772

OriginalsprogEngelsk
BogserieAmerican Journal of Clinical Nutrition
Vol/bind118
Udgave nummer3
Sider (fra-til)498-506
ISSN0002-9165
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
FW was supported by a National Health and Medical Research Council of Australia Early Career Fellowship ( 1158661 ). The authors reported no funding received for this study.

Funding Information:
GC reports a grant from National Natural Science Foundation of China, outside the submitted work. TW reports payment to self from AMGEN for preparation of osteoporosis education materials, outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work.

Publisher Copyright:
© 2023 American Society for Nutrition

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