Renal Phosphate Wasting Due to Tumor-Induced (Oncogenic) Osteomalacia

Abstract

Osteomalacia is a widely prevalent bone disorder that is caused by an imbalance in body calcium and phosphate. Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia that is associated with mesenchymal tumors. It is caused by overproduction of fibroblast growth factor 23 (FGF-23), a hormone involved in phosphate regulation. A 59-year-old male with a history of factor V Leiden mutation, pulmonary embolism, and deep vein thrombosis was diagnosed with oncogenic osteomalacia in 2008 following laboratory findings significant for low phosphorus and elevated FGF-23 levels. He underwent a resection of a right suprascapular notch mass with the biopsy confirming a phosphaturic mesenchymal tumor. He was maintained on oral phosphorus and calcitriol replacements with a regular follow-up with oncology and nephrology. Eight years later, the patient’s phosphorus levels started declining despite replacement. A repeat test showed FGF-23 levels once again elevated. A whole-body magnetic resonance imaging (MRI) scan showed no significant findings. The patient was continued on oral replacement therapy with a close follow-up. Two years later, urine phosphorus excretion was elevated at 2494 mg per 24 hours with low plasma phosphorus (1.2 mg/dL) and an elevated FGF-23 level of 1005 relative units (RU)/mL. A repeat MRI of the right shoulder revealed a mass in the supraspinatus muscle and another in the spinal glenoid notch. The masses were resected and the biopsy was consistent with a recurrence of the phosphaturic mesenchymal tumor. Follow-up serum phosphate levels remained in the normal range. FGF-23 plays a critical role in bone mineralization through the regulation of phosphate levels. Overproduction, as seen in mesenchymal tumors, results in hyperphosphaturia, hypophosphatemia, and low calcitriol levels. While the definitive treatment of TIO involves the resection of the mesenchymal tumor, localization of the tumor is often challenging given its small size and slow growth. This leads to delayed diagnosis and treatment. For individuals whose tumor cannot be resected or detected, burosumab is the preferred form of therapy. Interestingly, FGF-23 is shown to have a potential cardiovascular (CV) morbidity and mortality through various mechanisms like activation of myocardial FGF-23 receptors, endothelial dysfunction, inflammation, and altered phosphorus and vitamin D metabolisms. While studies have shown possible FGF-23 effects on CV outcomes in patients with chronic kidney disease, this has not been proven in cases of TIO.