#1950 Burosumab activity on osteomalacia—a TIO case report

Abstract

Abstract Background and Aims Tumor-Induced Osteomalacia (TIO) is a rare paraneoplastic disorder caused by a tumor (PMT), usually of small size and benign, secreting FGF23. FGF23 suppresses the reabsorption of phosphate and the synthesis of 1,25(OH)2 vitamin D in the proximal tubular cells of the kidney; consequently, affected patients develop hypophosphatemia and osteomalacia, resulting in bone pain and pathological fractures. The treatment of choice is the surgical resection of the tumor, but when the latter is not detected or cannot be removed, phosphate salts and active vitamin D can be employed to improve TIO symptoms. Burosumab, a monoclonal antibody directed against FGF23 introduced for the treatment of X-linked hypophosphatemic rickets, has recently been tested for the treatment of TIO non-surgical patients with encouraging results, even if few data are currently available. Method Starting from January 2021, a 56M patient affected by TIO without identified PMT has been treated with burosumab at the dosage of 1 mg/kg s.c. every 4 weeks. Results Before the introduction of burosumab, his blood exams showed hypophosphatemia (1.9 mg/dL), low 1,25(OH)2 vitamin D levels (15 pg/mL) and hyperparathyroidism (81 pg/mL) secondary to previous administrations of phosphate salts. He also reported widespread bone pain, suspect of multiple fractures and pseudofractures, confirmed by whole skeleton bone scintigraphy (BS) as numerous areas of pathological accumulation in the ribs, sacrum, bilateral femur, right proximal tibia, sternoclavicular joint and vertebral bodies. After the initiation of burosumab, serum phosphate, PTH and 1,25(OH)2 vitamin D levels gradually normalized. The patient also reported an improvement in bone pain, and later BS described a notable and continuous reduction in pathological accumulations, which almost completely disappeared after 24 months, confirming the absence of new fractures and the improvement of existing ones. Conclusion Therefore, burosumab is suggested as an alternative treatment for non-surgical TIO patients, especially since, unlike conventional therapy with phosphate salts and active vitamin D, its therapeutic action seems to contribute to the further improvement of osteomalacia.