Regulation of phosphate homeostasis by the phosphatonins and other novel mediators

Abstract

A variety of factors regulate the efficiency of phosphate absorption in the intestine and phosphate reabsorption in kidney. Apart from the well-known regulators of phosphate homeostasis, namely parathyroid hormone (PTH) and the vitamin D-endocrine system, a number of peptides collectively known as the "phosphatonins" have been recently identified as a result of the study of various diseases associated with hypophosphatemia. These factors, fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein 4 (sFRP-4), fibroblast growth factor 7 (FGF-7) and matrix extracellular phosphoglycoprotein (MEPE), have been shown to play a role in the pathogenesis of various hypophosphatemic and hyperphosphatemic disorders, such as oncogenic osteomalacia, Xlinked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemia and tumoral calcinosis. Whether these factors are true hormones, in the sense that they are regulated by the intake of dietary phosphorus and the needs of the organism for higher or lower amounts of phosphorus, remains to be firmly established in humans. Additionally, new information demonstrates that the intestine "senses" luminal concentrations of phosphate and regulates the excretion of phosphate in the kidney by elaborating novel factors that alter renal phosphate reabsorption.

High iFGF23 level despite hypophosphatemia is one of the clinical indicators to make diagnosis of XLH

“…The current view is that, loss of PHEX function probably results in accumulation of phosphatonins which are circulating factors that regulate phosphate homeostasis and mineralization of bone. FGF23 [7], matrix extracellular phosphoglycoprotein (MEPE) [8], frizzled related protein 4 (FRP-4) [9] and FGF7 are the putative phosphatonins [10,11].…”

Effects of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women in short term

“…In hyperphosphatemic states, elevated phosphate and FGF23 concentrations may inhibit 1-a hydroxylase (16).…”

Effects of dietary phosphate on glucose and lipid metabolism

“…Fast foods or processed foods have high energy density and also frequently contain a large amount of P i as a food additive. Recent epidemiological studies have suggested that a high dietary P i intake can be associated with increased cardiovascular risk and other metabolic disorders.P i is an essential nutrient that significantly affects skeletal formation, energy metabolism, and intracellular signaling (43,45). P i homeostasis is regulated by the absorption of P i in the intestine, bone formation/resorption, and reabsorption of P i in the kidney.…”

“…P i is an essential nutrient that significantly affects skeletal formation, energy metabolism, and intracellular signaling (43,45). P i homeostasis is regulated by the absorption of P i in the intestine, bone formation/resorption, and reabsorption of P i in the kidney.…”