Abstract
FGF-23 was recently shown to be involved in the development of several hypophosphatemic diseases, including X-linked hypophosphatemic rickets/osteomalacia (XLH) and tumor-induced rickets/osteomalacia (TIO). FGF-23 is processed between Arg179 and Ser180, and only full-length FGF-23 was shown to cause hypophosphatemia. Two assays for FGF-23 have been reported. One assay detects only full-length FGF-23. In contrast, the C-terminal assay recognizes both full-length and processed C-terminal fragment of FGF-23. However, discrepant results concerning circulatory levels of FGF-23 in patients with TIO and XLH have been reported using these two assays. We simultaneously measured FGF-23 levels in 13 patients with adult-onset hypophosphatemic osteomalacia and 29 patients with XLH by these two assays. The full-length assay indicated that FGF-23 was above the upper limit of the reference range in all patients with osteomalacia and in 24 of 29 patients with XLH. However, the C-terminal assay in dicated that FGF-23 was within the reference range in 3 of 13 patients with osteomalacia and 16 of 29 patients with XLH. In addition, there was no correlation between FGF-23 levels measured by these assays in patients with XLH whose FGF-23 was within the reference range by C-terminal assay. These results indicate that FGF-23 within the reference range by C-terminal assay does not rule out an increase in full-length FGF-23. In addition, because FGF-23 was high in most of these hypophosphatemic patients, these results support the notion that FGF-23 plays a major role in the development of hypophosphatemia in patients with TIO and XLH.
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References
InstitutionalAuthorNameThe Hyp Consortium (1995) ArticleTitleA gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets Nat Genet 11 130–136
S Fukumoto T Yamashita (2002) ArticleTitleFibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin Curr Opin Nephrol Hypertens 11 385–389 Occurrence Handle10.1097/00041552-200207000-00003 Occurrence Handle12105387
T Yamashita M Yoshioka N Itoh (2000) ArticleTitleIdentification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain Biochem Biophys Res Commun 277 494–498 Occurrence Handle10.1006/bbrc.2000.3696 Occurrence Handle11032749
InstitutionalAuthorNameThe ADHR Consortium (2000) ArticleTitleAutosomal-dominant hypophosphataemic rickets is associated with mutations in FGF23 Nat Genet 26 345–348
T Shimada S Mizutani T Muto T Yoneya R Hino S Takeda Y Takeuchi T Fujita S Fukumoto T Yamashita (2001) ArticleTitleCloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia Proc Natl Acad Sci USA 98 6500–6505 Occurrence Handle10.1073/pnas.101545198 Occurrence Handle11344269
T Shimada T Muto I Urakawa T Yoneya Y Yamazaki K Okawa Y Takeuchi T Fujita S Fukumoto T Yamashita (2002) ArticleTitleMutant FGF-23 responsible for autosomal-dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo Endocrinology 143 3179–3182 Occurrence Handle10.1210/en.143.8.3179 Occurrence Handle12130585
Y Yamazaki R Okazaki M Shibata Y Hasegawa K Satoh T Tajima Y Takeuchi T Fujita K Nakahara T Yamashita S Fukumoto (2002) ArticleTitleIncreased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia J Clin Endocrinol Metab 87 4957–4960 Occurrence Handle10.1210/jc.2002-021105 Occurrence Handle12414858
KB Jonsson R Zahradnik T Larsson KE White T Sugimoto Y Imanishi T Yamamoto G Hampson H Koshiyama O Ljunggren K Oba IM Yang A Miyauchi MJ Econs J Lavigne H Juppner (2003) ArticleTitleFibroblast growth factor-23 in oncogenic osteomalacia and X-linked hypophosphatemia N Engl J Med 348 1656–1663 Occurrence Handle10.1056/NEJMoa020881 Occurrence Handle12711740
TJ Weber S Liu OS Indridason LD Quarles (2003) ArticleTitleSerum FGF23 levels in normal and disordered phosphorus homeostasis J Bone Miner Res 18 1227–1234 Occurrence Handle12854832
A Benet-Pages P Orlik TM Strom B Lorenz-Depiereux (2005) ArticleTitleAn FGF-23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia Hum Mol Genet 14 385–390 Occurrence Handle10.1093/hmg/ddi034 Occurrence Handle15590700
R Kumar (1997) ArticleTitlePhosphatonin – a new phosphaturetic hormone? (lessons from tumour-induced osteomalacia and X-linked hypophosphataemia) Nephrol Dial Transplant 12 11–13 Occurrence Handle10.1093/ndt/12.1.11 Occurrence Handle9027763
T Berndt TA Craig AE Bowe J Vassiliadis D Reczek R Finnegan SM Jan De Beur SC Schiavi R Kumar (2003) ArticleTitleSecreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent J Clin Invest 112 785–794 Occurrence Handle10.1172/JCI200318563 Occurrence Handle12952927
PSN Rowe Y Kumagai G Gutierrez IR Garrett R Blacher D Rosen J Cundy S Navvab D Chen MK Drezner LD Quarles GR Mundy (2004) ArticleTitleMEPE has the properties of an osteoblastic phosphatonin and minhibin Bone 34 303–319 Occurrence Handle10.1016/j.bone.2003.10.005 Occurrence Handle14962809
T Shimada M Kakitani Y Yamazaki H Hasegawa Y Takeuchi T Fujita S Fukumoto K Tomizuka T Yamashita (2004) ArticleTitleTargeted ablation of Fgf23 demonstrates an essential physiological role of FGF-23 in phosphate and vitamin D metabolism J Clin Invest 113 561–568 Occurrence Handle10.1172/JCI200419081 Occurrence Handle14966565
Y Aono T Shimada Y Yamazaki R Hino Y Takeuchi T Fujita S Fukumoto N Nagano T Yamashita (2003) ArticleTitleThe neutralization of FGF-23 ameliorates hypophosphatemia and rickets in Hyp mice J Bone Miner Res 18 S16
S Liu R Guo LG Simpson ZS Xiao CE Burnham LD Quarles (2003) ArticleTitleRegulation of FGF-23 expression but not degradation by PHEX J Biol Chem 278 37419–37426 Occurrence Handle10.1074/jbc.M304544200 Occurrence Handle12874285
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Ito, N., Fukumoto, S., Takeuchi, Y. et al. Comparison of two assays for fibroblast growth factor (FGF)-23. J Bone Miner Metab 23, 435–440 (2005). https://doi.org/10.1007/s00774-005-0625-4
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DOI: https://doi.org/10.1007/s00774-005-0625-4