Abstract
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by hypersecretion of fibroblast growth factor 23 (FGF23) by typically benign phosphaturic mesenchymal tumors (PMTs). FGF23 excess causes chronic hypophosphatemia through renal phosphate losses and decreased production of 1,25-dihydroxy-vitamin-D. TIO presents with symptoms of chronic hypophosphatemia including fatigue, bone pain, weakness, and fractures. Definitive treatment is surgical resection of the PMT with wide margins. Other therapeutic options are necessary when the tumor is unable to be localized, not amenable to complete resection, or when the patient is not a good surgical candidate. Alternative ablative approaches such as radiotherapy, radiofrequency ablation, and cryoablation, have been used with variable success and limited follow up. Medical management is warranted both prior to definitive therapy and in non-operable cases to improve symptoms and allow for bone remineralization. Oral phosphate and calcitriol were the mainstay of medical therapy, however, the development of burosumab, a monoclonal blocking antibody to FGF23, has introduced an approved therapy that improves hypophosphatemia and symptoms in patients with TIO. In select cases, cinacalcet can be an effective adjuvant to phosphate and calcitriol. Continued monitoring for tumor growth is necessary while on medical therapy. Infigratinib, a selective FGFR tyrosine-kinase inhibitor targeting a causative tumoral fusion protein, can reverse the biochemical findings of TIO and possibly reduce tumor mass; however, its use is constrained by serious side effects. Overall, innovations in medical and interventional treatments have broadened therapeutic options for patients with PMTs, particularly in cases where a curative surgical resection is not possible.