FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting

Mara Riminucci, Michael T. Collins, Neal S. Fedarko, Natasha Cherman, Alessandro Corsi, Kenneth White, Steven Waguespack, Anurag Gupta, Tamara Hannon, Michael Econs, Paolo Bianco, Pamela Gehron Robey

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475 Scopus citations

Abstract

FGF-23, a novel member of the FGF family, is the product of the gene mutated in autosomal dominant hypophosphatemic rickets (ADHR). FGF-23 has been proposed as a circulating factor causing renal phosphate wasting not only in ADHR (as a result of inadequate degradation), but also in tumor-induced osteomalacia (as a result of excess synthesis by tumor cells). Renal phosphate wasting occurs in approximately 50% of patients with McCune-Albright syndrome (MAS) and fibrous dysplasia of bone (FD), which result from postzygotic mutations of the GNAS1 gene. We found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro. In situ hybridization analysis of FGF-23 mRNA expression identified "fibrous" cells, osteogenic cells, and cells associated with microvascular walls as specific cellular sources of FGF-23 in FD. Serum levels of FGF-23 were increased in FD/MAS patients compared with normal age-matched controls and significantly higher in FD/MAS patients with renal phosphate wasting compared with those without, and correlated with disease burden bone turnover markers commonly used to assess disease activity. Production of FGF-23 by FD tissue may play an important role in the renal phosphate-wasting syndrome associated with FD/MAS.

Original languageEnglish (US)
Pages (from-to)683-692
Number of pages10
JournalJournal of Clinical Investigation
Volume112
Issue number5
DOIs
StatePublished - Jan 1 2003

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ASJC Scopus subject areas

  • Medicine(all)

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Riminucci, M., Collins, M. T., Fedarko, N. S., Cherman, N., Corsi, A., White, K., Waguespack, S., Gupta, A., Hannon, T., Econs, M., Bianco, P., & Robey, P. G. (2003). FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. Journal of Clinical Investigation, 112(5), 683-692. https://doi.org/10.1172/JCI18399