MON-815 - Clinical Manifestations and Diagnostic Challenges of Oncogenic Osteomalacia

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by excess fibroblast growth factor 23 (FGF23), leading to renal phosphate wasting, hypophosphatemia, impaired bone mineralization, chronic musculoskeletal pain, proximal muscle weakness, and fragility fractures. Diagnosis is challenging and often delayed, most of the phosphaturic mesenchymal tumors (PMTs) are small, slow-growing, and may arise in any anatomical location. Patients typically present with similar clinical features, and genetic testing is essential to exclude hereditary hypophosphatemic disorders. We report three cases of TIO with shared clinical presentation, negative genetic panels (including PHEX), and distinct tumor locations.
Case reports: Case 1: A 62-year-old woman presented with a 10-year history of progressive bone pain, proximal muscle weakness, impaired ambulation, bilateral femoral fractures, and multiple rib fractures. Laboratory evaluation showed severe hypophosphatemia (1.4 mg/dL), elevated alkaline phosphatase (579 U/L), reduced TRP (77%) and TmP/GFR, normal calcium, PTH, and vitamin D levels, and markedly elevated FGF23 (469 kRU /L RR 26-110) . CT Scan identified a PMT in the right temporal bone. Partial surgical resection reduced FGF23 levels, but persistent hypophosphatemia required phosphate supplementation. Burosumab was initiated, resulting in phosphate normalization and significant clinical improvement. Case 2: A 60-year-old man presented with recent generalized weakness and severe weight loss. Laboratory tests revealed hypophosphatemia, hyperphosphaturia, elevated alkaline phosphatase, normal calcium, PTH, and vitamin D levels, and elevated FGF23 (227 kRU /L RR 26-110). MRI demonstrated a lesion in the left lateral mass of C1 with invasion of the left C1–C2 neural foramen. Biopsy confirmed a PMT. The patient was treated with calcitriol, vitamin D, and high-dose phosphate supplementation to control hypophosphatemia. Case 3: A 69-year-old woman with 10 years of diffuse bone pain and multiple fragility fractures showed persistent hypophosphatemia, elevated FGF23 levels (up to 425kRU /L RR 26-110), normal renal function, and normal vitamin D and PTH levels. The patient had undergone partial surgical resection of a frontal meningioma in 2009, and follow-up MRI demonstrated lesion growth. No other suspicious lesions were identified on the imaging studies performed. In all three cases, genetic testing excluded pathogenic mutations in the PHEX gene.

Conclusion: TIO should be suspected in adults with hypophosphatemia, bone pain, and fractures after exclusion of genetic causes. Early recognition, tumor localization, and surgical resection when feasible, as well as targeted therapy, including burosumab, are essential to improve outcomes.

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