A Rare Case of Tumor Induced Osteomalacia from Phosphaturic Mesenchymal Tumor in a Patient with Ankylosing Spondylitis

Background Tumor Induced Osteomalacia (TIO) is a rare, paraneoplastic syndrome often caused by phosphaturic mesenchymal tumors (PMT). Tumoral overproduction of fibroblast growth factor 23 (FGF23) results in renal phosphate wasting, hypophosphatemia, and defective bone mineralization (osteomalacia). Symptoms are vague and include bone pain, myalgias, or fragility fractures.[1] Diagnosis is often delayed and misdiagnoses are common; mean disease duration before diagnosis is greater than 4 years. The most frequent misdiagnoses include osteoporosis and spondyloarthritis (37.2 % and 26.3% of patients respectively).[2] Case Report A 51-year-old man presented to rheumatology with severe, progressive inflammatory back pain since age 34, in addition to heel and rib border enthesitis. HLA-B27 was positive. There was a family history of ankylosing spondylitis in his father. MRI of the sacroiliac joints was negative for sacroiliitis. He was diagnosed with clinical spondyloarthritis. Trials of NSAIDs were ineffective. He trialed multiple biologics that were either ineffective or partially effective including etanercept, golimumab, secukinumab, adalimumab, upadacitinib. In November 2024, he presented to clinic with severe hip pain and antalgic gait in spite of upadacitinib and full dose oral diclofenac. In December 2024, repeat MRI SI joints and whole spine showed fatty metaplasia at bilateral SI joints suggestive of chronic sacroiliitis without active inflammation and no evidence of spinal involvement. In April 2025, an MRI bilateral hips and subsequent bone scan revealed an undisplaced right femoral neck stress fracture as well as a 2.4 × 2.5 × 3.2 cm enhancing mixed cystic and solid lesion within the left thigh involving the neurovascular bundle. He underwent open reduction internal fixation of the right femoral fracture in May 2025. A bone density scan revealed osteoporosis (femoral neck T score −3.5). The left thigh mass was biopsied and consistent with a PMT. Endocrinology consultation noted very low serum phosphate (0.45 mmol/L, ref. range 0.70-1.50) and diagnosed TIO. Surgical resection of the tumor was performed in August 2025. The patient noted a dramatic improvement in bone pain following PMT resection and has been able to taper both diclofenac and upadacitinib. There are plans to attempt discontinuation of upadacitinib in the future. Conclusion This case demonstrates an example of TIO due to a PMT mimicking spondyloarthropathy. Long-term hypophosphatemic osteomalacia can have axial involvement and cause enthesopathy.[2] This rare diagnosis should be considered in those with suspected spondyloarthropathy who have persistent pain despite biologic therapy, fragility fractures, and hypophosphatemia. References [1.] Drezner M. Rev Endocr Metab Disord 2001;2:175-86. [2.] Álvarez-Rivas N. Bone Reports 2024;21:1-8.