Fibroblast growth factor 23: roles in health and disease.

A lthough phosphate is important in skeletal mineralization, energy metabolism, and multiple enzymatic processes, little has been understood about the regulation of phosphate in health and disease until recently. Genetic and acquired disorders of phosphate homeostasis have begun to reveal important mechanisms for the regulation of phosphate metabolism. Candidate phosphate-regulating hormones (“phosphatonins”) have been discovered, and their actions and interactions continue to be elucidated in an exciting area of ongoing clinical and basic research. Autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), tumor-induced osteomalacia (TIO), and fibrous dysplasia (FD) have similar phenotypes of hypophosphatemia, urinary phosphate wasting as measured by a low tubular maximum reabsorption of phosphate per deciliter of glomerular filtrate (TmP/GFR), osteomalacia, and rickets. The phenotypic similarities suggest a common metabolic pathophysiology. In addition, recent evidence concerning tumoral calcinosis, which results in hyperphosphatemia, inappropriately elevated calcitriol concentrations, and soft tissue calcifications and can be considered the phenotypic “converse” of the phosphate wasting disorders, indicates that this disorder may result from perturbations of some of the same metabolic pathways. Fibroblast growth factor 23 (FGF23) is a recently discovered, novel, secreted protein hormone involved in the pathogenesis of these disorders. This review focuses on the relationship of FGF23 to various disorders of phosphate homeostasis and its potential regulation and function in normal physiology.