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

KB Jonsson, R Zahradnik, T Larsson… - … England Journal of …, 2003 - Mass Medical Soc
KB Jonsson, R Zahradnik, T Larsson, KE White, T Sugimoto, Y Imanishi, T Yamamoto…
New England Journal of Medicine, 2003Mass Medical Soc
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 …
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.
The New England Journal Of Medicine