Phosphate homeostasis is coordinated and regulated by complex cross-organ talk 
through delicate hormonal networks. Parathyroid hormone (PTH), secreted in 
response to low serum calcium, has an important role in maintaining phosphate 
homeostasis by influencing renal synthesis of 1,25-dihydroxyvitamin D, thereby 
increasing intestinal phosphate absorption. Moreover, PTH can increase phosphate 
efflux from bone and contribute to renal phosphate homeostasis through 
phosphaturic effects. In addition, PTH can induce skeletal synthesis of another 
potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), which is able 
to inhibit renal tubular phosphate reabsorption, thereby increasing urinary 
phosphate excretion. FGF23 can also fine-tune vitamin D homeostasis by 
suppressing renal expression of 1-alpha hydroxylase (1α(OH)ase). This review 
briefly discusses how FGF23, by forming a bone-kidney axis, regulates phosphate 
homeostasis, and how its dysregulation can lead to phosphate toxicity that 
induces widespread tissue injury. We also provide evidence to explain how 
phosphate toxicity related to dietary phosphorus overload may facilitate 
incidence of noncommunicable diseases including kidney disease, cardiovascular 
disease, cancers and skeletal disorders.