The pathophysiology of hypophosphatemia

Best Pract Res Clin Endocrinol Metab. 2024 Mar;38(2):101851. doi: 10.1016/j.beem.2023.101851. Epub 2023 Nov 30.

Abstract

After identification of fibroblast growth factor (FGF) 23 as the pivotal regulator of chronic serum inorganic phosphate (Pi) levels, the etiology of disorders causing hypophosphatemic rickets/osteomalacia has been clarified, and measurement of intact FGF23 serves as a potent tool for differential diagnosis of chronic hypophosphatemia. Additionally, measurement of bone-specific alkaline phosphatase (BAP) is recommended to differentiate acute and subacute hypophosphatemia from chronic hypophosphatemia. This article divides the etiology of chronic hypophosphatemia into 4 groups: A. FGF23 related, B. primary tubular dysfunction, C. disturbance of vitamin D metabolism, and D. parathyroid hormone 1 receptor (PTH1R) mediated. Each group is further divided into its inherited form and acquired form. Topics for each group are described, including "ectopic FGF23 syndrome," "alcohol consumption-induced FGF23-related hypophosphatemia," "anti-mitochondrial antibody associated hypophosphatemia," and "vitamin D-dependent rickets type 3." Finally, a flowchart for differential diagnosis of chronic hypophosphatemia is introduced.

Keywords: fibroblast growth factor 23; fibroblast growth factor receptor 1; hypophosphatemia; osteomalacia; parathyroid hormone; parathyroid hormone-related protein; rickets; vitamin D.

Publication types

  • Review

MeSH terms

  • Familial Hypophosphatemic Rickets* / complications
  • Familial Hypophosphatemic Rickets* / diagnosis
  • Fibroblast Growth Factors / physiology
  • Humans
  • Hypophosphatemia* / diagnosis
  • Hypophosphatemia* / etiology
  • Osteomalacia* / complications
  • Osteomalacia* / etiology
  • Phosphates / metabolism
  • Vitamin D

Substances

  • Phosphates
  • Fibroblast Growth Factors
  • Vitamin D