Hypophosphatemic Rickets: Unraveling the Role of FGF23

MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, 7 York Rd, Parktown, Johannesburg, 2193, South Africa, .
Calcified Tissue International (Impact Factor: 3.27). 11/2012; 91(5). DOI: 10.1007/s00223-012-9651-0


The classification of the various forms of hypophosphatemic rickets has been rationalized by the discovery of the central role that fibroblast growth factor 23 (FGF23) plays in the pathogenesis of a number of genetic and acquired forms of the disease. Although the details of the interaction of FGF23 with other osteoblast/osteocyte-derived proteins remain unclear at present, the measurement of circulating levels of FGF23 appears to be a useful biochemical test in determining the various causes of hypophosphatemic rickets. Furthermore, animal studies suggest that agents interfering in the action of FGF23 might play important roles in the future management of the FGF23-mediated forms of rickets. Phase 1 and phase 2 trials in humans with X-linked hypophosphatemic rickets are currently under way.

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Available from: John Pettifor, Oct 11, 2015
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    ABSTRACT: A decade ago, only two hormones, parathyroid hormone and 1,25(OH)2D, were widely recognized to directly affect phosphate homeostasis. Since the discovery of fibroblast growth factor 23 (FGF23) in 2000 (1), our understanding of the mechanisms of phosphate homeostasis and of bone mineralization has grown exponentially. FGF23 is the link between intestine, bone, and kidney together in phosphate regulation. However, we still do not know the complex mechanism of phosphate homeostasis and bone mineralization. The physiological role of FGF23 is to regulate serum phosphate. Secreted mainly by osteocytes and osteoblasts in the skeleton (2,3), it modulates kidney handling of phosphate reabsorption and calcitriol production. Genetic and acquired abnormalities in FGF23 structure and metabolism cause conditions of either hyper-FGF23 or hypo-FGF23. Hyper-FGF23 is related to hypophosphatemia, while hypo-FGF23 is related to hyperphosphatemia. Both hyper-FGF23 and hypo-FGF23 are detrimental to humans. In this review, we will discuss the pathophysiology of FGF23 and hyper-FGF23 related renal phosphate wasting disorders (4).
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