Atypical Location of Tumor-Induced Osteomalacia (TIO) and Its Clinical Implications

Introduction: Tumor Induced Osteomalacia (TIO) is a rare but potentially treatable paraneoplastic syndrome.Thus, increasing awareness,may lead to prompt recognition and effective management of TIO,which is crucial in reducing long-term disability and morbidity. Case Description: A 63-year-old woman was referred to our hospital with 2 years of muscle weakness and bone pain. She had progressive incapacity to walk and pathologic fractures. DEXA scan revealed osteoporosis.Initial laboratory measurements showed severe hypophosphatemia 1,6mg/dL,normal calcium, magnesium and creatinine values. Further work-up revealed low vitamin D1,25 <1,6 pg/mL, high serum alkaline phosphatase 459 U/L and high normal PTH 78 pg/mL.Urine testing showed high fractional excretion of phosphate 29%.Urinalysis didn’t show proteinuria or glicosuria. FGF-23 was abnormally high (348 UA/mL) and genetic testing was normal.A bone biopsy confirmed the diagnosis of osteomalacia. A 68 Ga-DOTANOC PET/CT scan showed a cervical infiltrative lesion. Following the surgical excision of the tumor, serum phosphate and FGF-23 levels returned to normal in three weeks, and the patient regained the ability to walk.One year later, the patient reported a recurrence of musculoskeletal symptoms.Laboratory results indicated hyphosphatemia and an elevated fractional excretion of phosphate, suggesting tumoral recurrence. The patient is currently being evaluated for burosumab treatment and surgical candidacy. Discussion: The initial presentation of TIO can be non-specific and misleading, posing a diagnostic challenge.Delayed diagnosis results in significant morbidity and, if left untreated, can be fatal. Complete surgical resection remains the optimal treatment.However, up to 14% of surgically treated cases may experience recurrence due to incomplete resection, leading to devastating implications.Historically, this condition has been treated with calcitriol and phosphate supplementation.However, this requires multiple daily doses, increasing the burden of disease and presenting risk of nephrocalcinosis and non-compliance. Additionally, in patients with CKD, dose titration is limited by renal disease and secondary hyperparathyroidism.Therefore, Burosumab, a monoclonal antibody against FGF-23, is a crucial second-line therapy for enhancing clinical outcomes and quality of life in patients with non-surgical or non-localized TIO.