Tumor-induced osteomalacia is a paraneoplastic syndrome characterized by what mechanism?

• A. A paraneoplastic syndrome where tumors produce excess FGF23 causing renal phosphate wasting and osteomalacia.
• B. Tumors produce PTH causing hypercalcemia.
• C. Tumors produce calcitriol causing hyperphosphatemia.
• D. Tumors cause bone resorption via RANKL activation.

Answer: (A)

Tumor-induced osteomalacia is driven by ectopic production of FGF23 from a mesenchymal tumor. FGF23 acts on the kidney to promote phosphate wasting by downregulating the proximal tubular NaPi cotransporters, leading to hypophosphatemia. It also suppresses 1α-hydroxylase, reducing calcitriol (1,25-dihydroxyvitamin D) production and thus intestinal phosphate absorption. The combination causes defective bone mineralization (osteomalacia) despite normal calcium, which is the hallmark of this paraneoplastic syndrome. Other mechanisms listed would cause hypercalcemia or increased bone resorption, not the phosphate-wasting osteomalacia seen in TIO.