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Previous Volume 348:1656-1663 April 24, 2003 Number 17 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Carpenter, T. O. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

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.

Source Information

From the Endocrine Unit, Department of Medicine, and MassGeneral Hospital for Children, Massachusetts General Hospital and Harvard Medical School, Boston (K.B.J., H.J.); the Departments of Surgical Sciences (K.B.J., T.L.) and Medical Sciences (O.L.), University of Uppsala, Uppsala, Sweden; Immutopics, San Clemente, Calif. (R.Z., J.L.); the Departments of Medicine and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis (K.E.W., M.J.E.); the Division of Endocrinology and Metabolism, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan (T.S., A.M.); the Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine (Y.I.), the Department of Pediatrics, Minoh City Hospital, and the Department of Pediatrics, Osaka University Graduate School of Medicine (T.Y.) — all in Osaka, Japan; the Department of Chemical Pathology, St. Thomas' Hospital, London (G.H.); the Division of Endocrinology and Metabolism, Department of Medicine, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan (H.K.); the Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University and Aso-Iizuka Hospital, Fukuoka, Japan (K.O.); the Department of Internal Medicine, Kuyunghee University, Seoul, Korea (I.M.Y.); and National Hyogo-Chuo Hospital, Sanda Hyogo, Japan (A.M.).

Address reprint requests to Dr. Jüppner at the Endocrine Unit, Wellman 5, Massachusetts General Hospital, Boston, MA 02114, or at jueppner{at}helix.mgh.harvard.edu.

Full Text of this Article

Related Letters:

Fibroblast Growth Factor 23 in Oncogenic Osteomalacia and X-Linked Hypophosphatemia
Kida Y., Fukumoto S., Yamashita T., Jonsson K., Econs M., Jüppner H.
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N Engl J Med 2003; 349:505-506, Jul 31, 2003. Correspondence

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