FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. | Read by QxMD (original) (raw)

Journal Article

Research Support, Non-U.S. Gov't

Research Support, U.S. Gov't, P.H.S.

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

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.

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