Triennial Growth Symposium: a novel pathway for vitamin D-mediated phosphate homeostasis: implications for skeleton growth and mineralization.
Systemic factors that ultimately affect skeletal growth involve interrelationships among Ca, parathyroid hormone (PTH), and conversion of 25-OH vitamin D(3) to the active hormone, 1α,25-(OH)(2)D(3). These interrelationships, with a focus on mechanisms that affect Ca homeostasis, are referred to as the Ca, PTH, and vitamin D axis. Relatively little research has focused on these interrelationships and P homeostasis. In the past decade, discovery of a previously unrecognized hormone involved in a pathway for P homeostasis offers opportunities to improve P efficiency without compromising skeletal growth and animal well-being. The objective of this review was to summarize pivotal research discoveries that led to the current understanding of the roles of fibroblast growth factor 23 (FGF23) in P homeostasis that are independent from the well-described pathways involved with Ca homeostasis. The novel pathways are referred to as the FGF23, P, and vitamin D axis. The peptide, FGF23, directly affects P homeostasis via action on renal target tissues to regulate Na-P transport proteins and renal 25(OH)D(3)-1α hydroxylase activity. Identification of bone as the primary site for FGF23 production ascribes an endocrine gland function to bone. Within 9 h after a single injection of recombinant FGF23, mice displayed hypophosphatemia and urinary P wasting. In contrast, FGF23 knockout mice displayed hyperphosphatemia and renal P conservation. These responses were independent of PTH. Applications of the FGF23, P, and vitamin D axis in dietary strategies for animal agriculture need to be explored. Development of dietary inputs to balance both Ca and P homeostasis are needed to improve skeletal growth and nutrient efficiency.