Two Cases of Improved Bone Mineral Density Following Treatment of Hypophosphatemic Osteomalacia Due to FGF23 Excess

Excess fibroblast growth factor-23 (FGF23) causes renal phosphorous wasting and impaired activation of vitamin D leading to osteomalacia. Tumor-induced osteomalacia (TIO) is a rare cause of FGF23-mediated hypophosphatemia. We present 2 patients with FGF23-mediated hypophosphatemia who had low bone mineral density (BMD) at diagnosis and remarkable improvements in BMD with treatment. Patient 1 is a 43-year-old man who had years of progressive pain, difficulty ambulating, and multiple fractures. Patient 2 is a 48-year-old nonverbal man with autism and intellectual disability who had months of progressively declining mobility, presumed pain, and multiple fractures. Workup in both cases revealed hypophosphatemia, evidence of renal phosphorous wasting, and elevated FGF23. Patient 1 was diagnosed with TIO when imaging identified a subcutaneous left flank mass and excision resulted in rapid symptom improvement; he experienced a 96% increase in lumbar spine (LS) BMD after surgery. Patient 2 has had multiple scans over several years, but no FGF23-secreting tumor has been identified. He has been maintained on medical treatment with phosphorous and calcitriol with improvement in functioning and 48% increase in LS BMD. Both patients had improvements in BMD with treatment, with more pronounced improvement in the patient with TIO managed surgically.