Iron and fibroblast growth factor 23 in X-linked hypophosphatemia

Erik A. Imel, Amie K. Gray, Leah R. Padgett, Michael J. Econs

Research output: Contribution to journalArticle

19 Scopus citations


Background: Excess fibroblast growth factor 23 (FGF23) causes hypophosphatemia in autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH). Iron status influences C-terminal FGF23 (incorporating fragments plus intact FGF23) in ADHR and healthy subjects, and intact FGF23 in ADHR. We hypothesized that in XLH serum iron would inversely correlate to C-terminal FGF23, but not to intact FGF23, mirroring the relationships in normal controls. Methods: Subjects included 25 untreated outpatients with XLH at a tertiary medical center and 158 healthy adult controls. Serum iron and plasma intact FGF23 and C-terminal FGF23 were measured in stored samples. Results: Intact FGF23 was greater than the control mean in 100% of XLH patients, and >. 2SD above the control mean in 88%, compared to 71% and 21% respectively for C-terminal FGF23. In XLH, iron correlated negatively to log-C-terminal FGF23 (r = -0.523, p < 0.01), with a steeper slope than in controls (p < 0.001). Iron was not related to log-intact FGF23 in either group. The log-ratio of intact FGF23 to C-terminal FGF23 was higher in XLH (0.00. ±. 0.44) than controls (-0.28. ±. 0.21, p < 0.01), and correlated positively to serum iron (controls r = 0.276, p < 0.001; XLH r = 0.428, p < 0.05), with a steeper slope in XLH (p < 0.01). Conclusion: Like controls, serum iron in XLH is inversely related to C-terminal FGF23 but not intact FGF23. XLH patients are more likely to have elevated intact FGF23 than C-terminal FGF23. The relationships of iron to FGF23 in XLH suggest that altered regulation of FGF23 cleaving may contribute to maintaining hypophosphatemia around an abnormal set-point.

Original languageEnglish (US)
Pages (from-to)87-92
Number of pages6
StatePublished - Mar 2014


  • FGF23
  • Fibroblast growth factor 23
  • Iron
  • Phosphate
  • X-linked hypophosphatemia

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

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