Physiology of FGF23 and overview of genetic diseases associated with renal phosphate wasting

Metabolism. 2020 Feb;103S:153865. doi: 10.1016/j.metabol.2019.01.006. Epub 2019 Jan 19.


Phosphate is a cornerstone of several physiological pathways including skeletal development, bone mineralization, membrane composition, nucleotide structure, maintenance of plasma pH, and cellular signaling. The kidneys have a key role in phosphate homeostasis with three hormones having important functions in renal phosphate handling or intestinal absorption: parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1-25-dihydroxyvitamin D (1,25(OH)2D). FGF23 is mainly synthesized by osteocytes; it is a direct phosphaturic factor that also inhibits 1,25(OH)2D and PTH. In addition to crucial effects on phosphate and calcium metabolism, FGF23 also has 'off-target' effects notably on the cardiovascular, immune and central nervous systems. Genetic diseases may affect the FGF23 pathway, resulting in either increased FGF23 levels leading to hypophosphatemia (such as in X-linked hypophosphatemia) or defective secretion/action of intact FGF23 inducing hyperphosphatemia (such as in familial tumoral calcinosis). The aim of this review is to provide an overview of FGF23 physiology and pathophysiology in X-linked hypophosphatemia, with a focus on FGF23-associated genetic diseases.

Keywords: FGF23; PHEX; X-linked hypophosphatemia.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Familial Hypophosphatemic Rickets / genetics*
  • Fibroblast Growth Factors / deficiency
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / physiology*
  • Homeostasis / genetics
  • Homeostasis / physiology
  • Humans
  • Hyperphosphatemia / genetics
  • Kidney / physiopathology*
  • Phosphates / physiology*
  • Phosphorus Metabolism Disorders / genetics*
  • Phosphorus Metabolism Disorders / physiopathology
  • Vitamin D / physiology


  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Calcium