Abstract: SA-PO0617
Prolonged Refractory Hypophosphatemia After Zoledronic Acid: Dual PTH-Fibroblast Growth Factor 23-Mediated Renal Phosphate Wasting in Metastatic Prostate Cancer
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Case Reports - 2
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Bilal, Muhammad, University of Kentucky, Lexington, Kentucky, United States
- Osman, Omar, University of Kentucky, Lexington, Kentucky, United States
- Sheikh, Adnaan, University of Kentucky, Lexington, Kentucky, United States
Introduction
Zoledronic acid is frequently used for hypercalcemia of malignancy. Although transient hypocalcemia is recognized, prolonged refractory hypophosphatemia remains uncommon and underreported.
Case Description
A 57-year-old male with metastatic prostate adenocarcinoma (prostate-specific antigen [PSA] >1500 ng/mL) complicated by pathologic vertebral fracture and spinal cord compression received zoledronic acid for hypercalcemia of malignancy four days prior to T6 corpectomy with T3–T9 posterior spinal fusion, followed by radiation therapy. Subsequently, he developed hypocalcemia and refractory hypophosphatemia. There was no evidence of refeeding syndrome, diuretic exposure, kidney dysfunction, or Fanconi syndrome.
Despite preserved kidney function (eGFR of 120 mL/min/1.73 m ) and aggressive phosphate replacement with intravenous supplementation frequently exceeding 100 mmol/day, hypophosphatemia persisted for approximately two months with a nadir serum phosphorus of 0.9 mg/dL, associated with weakness and paresthesias. Laboratory evaluation demonstrated elevated parathyroid hormone (PTH up to 240 pg/mL), elevated fibroblast growth factor-23 (FGF23 75 pg/mL; reference <59 pg/mL), low 25-hydroxyvitamin D (11.9 ng/mL), preserved 1,25-dihydroxyvitamin D (79.7 pg/mL), and inappropriate phosphaturia with fractional excretion of phosphate of approximately 50%. Persistent hypomagnesemia (nadir 1.6 mg/dL) despite intravenous replacement suggested concomitant renal magnesium wasting contributing to impaired parathyroid hormone responsiveness.
Discussion
This case demonstrates prolonged hypophosphatemia following zoledronic acid mediated through secondary hyperparathyroidism and FGF23-driven phosphaturia. In metastatic prostate cancer with osseous involvement, severe hypophosphatemia after zoledronic acid may reflect tumor-associated FGF23 excess analogous to tumor-induced osteomalacia physiology amplified following bisphosphonate exposure. Persistent hypophosphatemia following bisphosphonate therapy should prompt evaluation for ongoing FGF23-mediated phosphaturia, particularly when refractory to aggressive replacement.