Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia

Kenneth B. Jonsson, Richard Zahradnik, Tobias Larsson, Kenneth E. White, Toshitsugu Sugimoto, Yasuo Imanishi, Takehisa Yamamoto, Geeta Hampson, Hiroyuki Koshiyama, Östen Ljunggren, Koichi Oba, In Myung Yang, Akimitsu Miyauchi, Michael J. Econs, Jeffrey Lavigne, Harald Jüppner

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BACKGROUND: Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it. METHODS: Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted for arginine at position 179 (R179Q), and synthetic human FGF-23(207-244)amide. Plasma or serum samples from 147 healthy adults (mean [±SD] age, 48.4±19.6 years) and 26 healthy children (mean age, 10.9±5.5 years) and from 17 patients with oncogenic osteomalacia (mean age, 43.0±13.3 years) and 21 patients with X-linked hypophosphatemia (mean age, 34.9±17.2 years) were studied. RESULTS: Mean FGF-23 concentrations in the healthy adults and children were 55±50 and 69±36 reference units (RU) per milliliter, respectively. Four patients with oncogenic osteomalacia had concentrations ranging from 426 to 7970 RU per milliliter, which normalized after tumor resection. FGF-23 concentrations were 481±528 RU per milliliter in those with suspected oncogenic osteomalacia and 353±510 RU per milliliter (range, 31 to 2335) in those with X-linked hypophosphatemia. CONCLUSIONS: FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, suggesting that this growth factor has a role in phosphate homeostasis. FGF-23 measurements might improve the management of phosphate-wasting disorders.

Original languageEnglish (US)
Pages (from-to)1656-1663
Number of pages8
JournalNew England Journal of Medicine
Issue number17
StatePublished - Apr 24 2003

ASJC Scopus subject areas

  • Medicine(all)

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    Jonsson, K. B., Zahradnik, R., Larsson, T., White, K. E., Sugimoto, T., Imanishi, Y., Yamamoto, T., Hampson, G., Koshiyama, H., Ljunggren, Ö., Oba, K., Yang, I. M., Miyauchi, A., Econs, M. J., Lavigne, J., & Jüppner, H. (2003). Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. New England Journal of Medicine, 348(17), 1656-1663.