Osteoporosis International

, Volume 30, Issue 11, pp 2183–2193 | Cite as

Oral vitamin D3 supplementation increases serum fibroblast growth factor 23 concentration in vitamin D-deficient patients: a systematic review and meta-analysis

  • N. CharoenngamEmail author
  • P. Rujirachun
  • M.F. Holick
  • P. Ungprasert


Studies have suggested that vitamin D supplementation may increase serum fibroblast growth factor 23 (FGF23) among vitamin D-deficient patients although the results were inconsistent across the studies. This systematic review and meta-analysis was conducted to summarize all available data. A systematic review was conducted using MEDLINE and EMBASE database from inception to February 2019 to identify studies that provided oral vitamin D3 supplement to vitamin D-deficient participants (25-hydroxyvitamin D < 20 ng/mL). Mean serum FGF23 concentration and standard deviation of participants at baseline and after vitamin D3 supplementation were extracted to calculate standard mean difference (SMD). Pooled SMD was calculated by combining SMDs of each study using random effects model. Nine studies were eligible for the meta-analyses. Seven studies measured serum intact FGF23, and two studies measured serum C-terminal FGF23. The meta-analyses found that serum intact FGF23 increased significantly after oral vitamin D3 supplementation in vitamin D-deficient participants with the pooled SMD of 0.36 (95%CI, 0.14, 0.57; p = 0.001; I2 of 36%). Serum C-terminal FGF23 also increased after vitamin D3 supplementation in vitamin D-deficient participants with the pooled SMD of 0.28 although without reaching statistical significance (95%CI, − 0.08, 0.65; p = 0.13; I2 of 0%). Funnel plot of the meta-analysis of serum intact FGF23 did not provide a suggestive evidence for publication bias. Vitamin D supplementation leads to a significant increase in serum intact FGF23 among vitamin D-deficient patients. An increase in serum C-terminal FGF23 was also observed although the number of included studies was too small to demonstrate statistical significance. The present systematic review and meta-analysis revealed that serum intact FGF23 concentration increased significantly after oral vitamin D3 supplementation in vitamin D-deficient participants. An increase in serum C-terminal FGF23 concentration was also observed although the number of included studies was too small to demonstrate statistical significance.


Fibroblast growth factor 23 Meta-analysis Vitamin D deficiency Vitamin D3 supplementation 


Compliance with ethical standards

Conflict of interest

Nipith Charoenngam, Pongprueth Rujirachun, and Patompong Ungprasert declare that they have no conflict of interest. Michael F. Holick is a consultant for Quest Diagnostics Inc. and Ontometrics Inc., and on the speaker’s Bureau for Abbott Inc.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  • N. Charoenngam
    • 1
    • 2
    Email author
  • P. Rujirachun
    • 3
  • M.F. Holick
    • 2
  • P. Ungprasert
    • 4
  1. 1.Department of Medicine, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
  2. 2.Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, Vitamin D, Skin and Bone Research LaboratoryBoston University Medical CenterBostonUSA
  3. 3.Department of Microbiology, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
  4. 4.Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand

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