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Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.
N Engl J Med. 2003 Apr 24; 348(17):1656-63.NEJM

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.

Authors+Show Affiliations

Endocrine Unit, Department of Medicine, and MassGeneral Hospital for Children, Massachusetts General Hospital and Harvard Medical School, Boston, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12711740

Citation

Jonsson, Kenneth B., et al. "Fibroblast Growth Factor 23 in Oncogenic Osteomalacia and X-linked Hypophosphatemia." The New England Journal of Medicine, vol. 348, no. 17, 2003, pp. 1656-63.
Jonsson KB, Zahradnik R, Larsson T, et al. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med. 2003;348(17):1656-63.
Jonsson, K. B., Zahradnik, R., Larsson, T., White, K. E., Sugimoto, T., Imanishi, Y., Yamamoto, T., Hampson, G., Koshiyama, H., Ljunggren, O., 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. The New England Journal of Medicine, 348(17), 1656-63.
Jonsson KB, et al. Fibroblast Growth Factor 23 in Oncogenic Osteomalacia and X-linked Hypophosphatemia. N Engl J Med. 2003 Apr 24;348(17):1656-63. PubMed PMID: 12711740.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. AU - Jonsson,Kenneth B, AU - Zahradnik,Richard, AU - Larsson,Tobias, AU - White,Kenneth E, AU - Sugimoto,Toshitsugu, AU - Imanishi,Yasuo, AU - Yamamoto,Takehisa, AU - Hampson,Geeta, AU - Koshiyama,Hiroyuki, AU - Ljunggren,Osten, AU - Oba,Koichi, AU - Yang,In Myung, AU - Miyauchi,Akimitsu, AU - Econs,Michael J, AU - Lavigne,Jeffrey, AU - Jüppner,Harald, PY - 2003/4/25/pubmed PY - 2003/4/30/medline PY - 2003/4/25/entrez SP - 1656 EP - 63 JF - The New England journal of medicine JO - N Engl J Med VL - 348 IS - 17 N2 - 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. SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/12711740/Fibroblast_growth_factor_23_in_oncogenic_osteomalacia_and_X_linked_hypophosphatemia_ L2 - https://www.nejm.org/doi/10.1056/NEJMoa020881?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -