Tumor-Induced Osteomalacia in a Patient with Metastatic Prostate Cancer Presenting with Refractory Hypophosphatemia

Abstract

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by fibroblast growth factor 23 (FGF23) overproduction, which leads to renal phosphate wasting and hypophosphatemia. Herein, we present the case of an 81-year-old man with metastatic prostate adenocarcinoma who presented with fatigue, diffuse bone pain, paresthesia, carpopedal spasms, and muscle cramps. Laboratory tests revealed severe hypophosphatemia, 0.28 mmol/L (0.87 mg/dL; reference, 0.80–1.50 mmol/L [2.5–4.5 mg/dL]) and markedly elevated serum levels of alkaline phosphatase (786 U/L) and FGF23 (>1,525 RU/mL; reference, <100 RU/mL). Despite intensive oral and intravenous phosphate supplementation and cholecalciferol therapy, serum phosphate levels remained persistently low. Phosphate wasting was confirmed with a 24-hour urine phosphate excretion test. The patient had mildly elevated parathyroid hormone level with normal 25-hydroxyvitamin D level and preserved renal function, excluding common secondary causes. Therefore, TIO secondary to metastatic prostate cancer was established as the final diagnosis. This case underscores that TIO should be considered in patients with refractory hypophosphatemia and musculoskeletal symptoms. Urine phosphate excretion and serum FGF23 level measurement is essential for timely diagnosis. Burosumab, an anti-FGF23 monoclonal antibody, can be considered for treatment, although its use in malignancy-associated cases is often limited to off-label use.