SAT-792 - When Osteoporosis Is Not Osteoporosis: Tumor-Induced Osteomalacia

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by a phosphaturic mesenchymal tumors (PMTs) that secrete excess fibroblast growth factor-23 (FGF23). Elevated FGF23 leads to renal phosphate wasting and impaired activation of vitamin D, resulting in defective bone mineralization. Because of its rarity and nonspecific manifestations, TIO is frequently misdiagnosed or diagnosed late, often as osteoporosis.

Case Presentation:
A 53-year-old man was referred to a metabolic bone clinic for evaluation of osteoporosis in the setting of persistently elevated ALP. He reported several months of progressive lower back pain and medial ankle pain, significantly limiting ambulation. Initial laboratory testing demonstrated normal calcium and 25-hydroxyvitamin D levels with markedly elevated ALP at 340 IU/L (44–121). Dual-energy X-ray absorptiometry revealed severe osteoporosis with T-scores of −5.0 at the lumbar spine, −2.0 at the total hip, and −3.1 at the femoral neck. He was placed on alendronate while awaiting a bone scan and referred to metabolic bone clinic for further evaluation and management.
The initial work-up revealed mild hypocalcemia at 8.2 mg/dl, high-normal PTH at 64 pg/ml (15-65), elevated ALP (216 IU/L) and profound hypophosphatemia at < 0.7 mg/dL (2.4-4.7). Subsequent studies showed decreased tubular reabsorption phosphate at 53.8% with high FGF23 at 447 RU/mL (44-215), suggesting FGF-23 induced renal phosphate wasting. While alendronate was discontinued, patients was placed on oral phosphate and calcitriol supplementation. Ga-68 DOTATATE PET/CT was performed for tumor localization and revealed a 1.7 × 1.3 cm somatostatin receptor–avid soft tissue mass in the plantar aspect of the left foot, along with multiple fractures. A biopsy showed bland spindle cell tumor with giant cells with focal osteoid deposition confirmed, compatible with a PMT. Surgical resection resulted in rapid normalization of serum phosphorus without supplementation and marked improvement in bone pain and muscle weakness.

Conclusion:
TIO should be considered in patients with unexplained bone pain, fractures, elevated ALP, and hypophosphatemia. Clinicians should recognize that serum phosphorus is not routinely included in standard metabolic panels and that non-fasting measurements may underestimate the severity of mild hypophosphatemia, contributing to delayed diagnosis. Tumor localization is challenging due to the small size and variable location of tumor and often requires functional imaging such as Ga-68 DOTATATE PET/CT. Surgical resection is curative; when not feasible, treatment with phosphate, calcitriol, or burosumab should be considered. Long-term monitoring with ALP, fasting phosphate, DXA is essential to assess recovery and detect recurrence.

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