Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.
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.
Jonsson
Kenneth B
KB
Endocrine Unit, Department of Medicine, and MassGeneral Hospital for Children, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
Zahradnik
Richard
R
Larsson
Tobias
T
White
Kenneth E
KE
Sugimoto
Toshitsugu
T
Imanishi
Yasuo
Y
Yamamoto
Takehisa
T
Hampson
Geeta
G
Koshiyama
Hiroyuki
H
Ljunggren
Osten
O
Oba
Koichi
K
Yang
In Myung
IM
Miyauchi
Akimitsu
A
Econs
Michael J
MJ
Lavigne
Jeffrey
J
Jüppner
Harald
H
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000097:blood; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010018:Osteomalacia / Q000097:blood*; D010257:Paraneoplastic Syndromes / Q000097:blood*; D012016:Reference Values; D012279:Rickets / Q000097:blood / Q000235:genetics
C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23