What is the role of FGF23 in phosphate metabolism, and which cells produce it?

• A. Produced by osteocytes; reduces renal phosphate reabsorption and suppresses 1α-hydroxylase, lowering calcitriol.
• B. Produced by osteoblasts; increases renal phosphate reabsorption and raises calcitriol.
• C. Produced by osteocytes; increases renal phosphate reabsorption.
• D. Produced by hepatic cells; suppresses calcitriol synthesis.

Answer: (A)

FGF23 acts as a phosphate-regulating hormone produced mainly by osteocytes in bone. Its main role is to prevent phosphate overload by signaling the kidney to waste phosphate and to limit active vitamin D production. In the kidney, FGF23 binds to its receptor complex on proximal tubule cells and reduces the expression of the sodium-phosphate co-transporters NaPi-IIa and NaPi-IIc, promoting phosphate excretion. It also suppresses the enzyme 1α-hydroxylase (CYP27B1), lowering the production of calcitriol (1,25-dihydroxyvitamin D). With less calcitriol, intestinal phosphate (and calcium) absorption decreases further. This combination keeps serum phosphate in check.