Osteomalacia inducida por tumor en inicio de tratamiento específico con Burosumab anticuerpo monoclonal anti FGF23

Abstract

Tumor-induced osteomalacia (TIO) is a rare disease characterized by an overproduction of fibroblast growth factor 23 (FGF 23) by tumors,
hypophosphatemia secondary to phosphaturia, and an alteration in the active vitamin D synthesis. This causes osteomalacia, bone pain, fractures,
muscle weakness, and fatigue. When mesenchymal tumors secretory of FGF23 are completely resected, disease is cured. Medical treatment involves
phosphorus salts and calcitriol. Treatment with burosumab, monoclonal antibody anti-FGF23, is in phase II.
Case report: Woman of 50 yrs. old, with evolution of the disease of more than 14 yrs., with progressive disabling symptomatology of musculoskeletal
pain, functional muscle deficit, multiple fractures in spine, humerus, and shoulder, and total hip arthroplasty (right and left). Musculoskeletal pain is
resistant to the analgesic. At every moment, hyperphosphaturia and hypophosphatemia (1,2 mg/dl average) did not produce a significant therapeutic
response to the phosphorus salts and gastric intolerance to the salts, which led to interruptions and modifications of the dose depending on tolerance.
The patient was also treated with calcium and calcitriol. Serum FGF-23 levels were 1102,56 pg/dl (VN: 0-134 pg/dl). Besides, a secondary
hyperparathyroidism with neither hypercalcemia nor hypercalciuria was confirmed. In 2008 a tumor was removed from left ischio-pubian region, whose
anatomopathological study showed fibromuscular and adipose fragments, and bone fragments with pathological diagnose compatible with fibrous
dysplasia. After surgery, the patient remained asymptomatic for about 3 yrs. Afterwards, progressively and uninterruptedly, TIO reappeared. Numerous
studies were carried out to localize the tumor responsible for the TIO, which included biopsies of suspicious areas, with a negative result.
Patient with serious tumor-induced osteomalacia, of long-term evolution, with an unsatisfactory response to conventional treatment at the beginning of
treatment with burosumab. Up to the present, this constitutes the first and only case of tumor-induced osteomalacia in the world, which has begun to be
treated with burosumab, without an investigation protocol.

Keywords: tumor-induced osteomalacia;  hypophosphatemia;  fgf23;  burosumab