FGF23
FGF23 is the body's phosphate brake. When phosphate runs high, bone cells release this hormone to tell the kidney: stop hoarding phosphate, let more of it go in the urine. It is a relatively recent discovery that reshaped our understanding of how bone talks back to the rest of the body.
Made chiefly by osteocytes (the bone-buried sensor cells), FGF23 acts on the kidney with the help of a co-receptor called Klotho. It does two things: it makes the kidney excrete more phosphate, and it suppresses the enzyme that activates vitamin D, lowering calcitriol. Lower calcitriol then means less phosphate absorbed from food, reinforcing the phosphate-lowering effect. In this way bone, kidney, and the parathyroids form an interconnected loop with PTH.
FGF23 is at the heart of several mineral diseases. Too much of it (from certain genetic disorders or rare tumors) causes phosphate to be wasted in urine, producing soft, weak bones (rickets or osteomalacia). In chronic kidney disease, FGF23 rises very early as the kidney struggles, and high levels are linked to worse heart and bone outcomes, making it both a marker and a possible driver of disease.
A child with bowed legs that never responds to ordinary vitamin D turns out to have an inherited disorder of excess FGF23 wasting phosphate in the urine.
Vitamin-D-resistant rickets often points to excess FGF23.
FGF23 and PTH both lower blood phosphate by increasing its urinary loss, but they pull vitamin D in opposite directions: PTH raises active vitamin D, while FGF23 lowers it.