Serum FGF23 Levels in Normal and Disordered Phosphorus Homeostasis

Thomas J. Weber, Shiguang Liu, Olafur S. Indridason, Leigh Quarles

Research output: Contribution to journalArticle

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Abstract

We investigated if the circulating levels of the phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, FGF23 levels were significantly correlated with the degree of hypophosphatemia in XLH. In contrast, FGF23 levels were markedly increased in subjects with ESRD and correlated inversely with the degree of hyperphosphatemia. Introduction: Inactivating mutations of PHEX cause renal phosphate wasting in X-linked hypophosphatemic rickets (XLH) because of the accumulation of a phosphaturic hormone called phosphatonin. The recent discovery that FGF23 is the circulating phosphaturic factor in autosomal dominant hypophosphatemia raises the possibility that FGF23 is phosphatonin. Methods: Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD). Associations between variables were examined using the Spearman's correlation coefficient and linear regression analysis. Results and Conclusions: FGF23 (RU/ml) concentrations were not different (p = 0.11) between control and hypophosphatemic XLH subjects, but were significantly increased in hyperphosphatemic subjects with ESRD (p < 0.001). Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects. There was a strong inverse correlation between FGF23 and serum phosphorus (r = -0.60) and calcium and phosphorus (Ca × P) product (r = -0.65) in XLH, and a strong positive relationship between FGF23 and Pi (r = 0.50) and Ca × P product (r = 0.62) in ESRD. FGF23 levels were variably elevated in subjects with hypophosphatemia of unknown cause, one of which had tumor-induced osteomalacia (TIO). Removal of the tumor resulted in rapid reduction in serum FGF23 levels. These findings suggest that FGF23 has a possible role in mediating hypophosphatemia in XLH and TIO, but the overlapping levels of FGF23 in hypophosphatemic disorders and normal subjects indicate that serum phosphorus and FGF23 can also be independently regulated.

Original languageEnglish (US)
Pages (from-to)1227-1234
Number of pages8
JournalJournal of Bone and Mineral Research
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2003

Fingerprint

Familial Hypophosphatemic Rickets
Phosphorus
Homeostasis
Hypophosphatemia
Chronic Kidney Failure
Serum
Calcium
Hyperphosphatemia
Linear Models
Fasting
Western Blotting
Enzyme-Linked Immunosorbent Assay
Phosphates
Regression Analysis
Hormones
Kidney
Mutation

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Serum FGF23 Levels in Normal and Disordered Phosphorus Homeostasis. / Weber, Thomas J.; Liu, Shiguang; Indridason, Olafur S.; Quarles, Leigh.

In: Journal of Bone and Mineral Research, Vol. 18, No. 7, 01.07.2003, p. 1227-1234.

Research output: Contribution to journalArticle

Weber, Thomas J. ; Liu, Shiguang ; Indridason, Olafur S. ; Quarles, Leigh. / Serum FGF23 Levels in Normal and Disordered Phosphorus Homeostasis. In: Journal of Bone and Mineral Research. 2003 ; Vol. 18, No. 7. pp. 1227-1234.
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