A Rare Case of Multiple Fragility Fractures Caused by Tumor-Induced Osteomalacia

Introduction:
Tumor-induced osteomalacia (TIO) is a rarely encountered paraneoplastic syndrome caused by a small, usually benign tumor of mesenchymal origin. It can present with severe hypophosphatemia and osteomalacia, usually in adulthood, but also in adolescence. The rarity of these tumors often leads to a late or missed diagnosis. Here we present a case of TIO with missed diagnosis for many years, which as a result, presented with multiple fractures.

Case Description:
A 54-year-old Asian woman presented to the emergency department with complaints of progressive lower back pain, weakness, and chronic myalgias. Imaging revealed diffuse osteoporosis, multiple rib and pelvic fractures, and bilateral coxa vera. Labs revealed normal corrected serum calcium 9.0 mg/dl (8.7-10.5), high PTH 144.9 mg/ml (9-77), low serum phosphorus 1.1 mg/dl (2.5-4.9), high alkaline phosphatase 474 u/ml (55-135), and 25-hydroxyvitamin D (25 Vit D) 45.8 ng/ml (30-100). Further labs showed high urinary phosphorus >90 mg/dl and low serum 1, 25-Dihydroxyvitamin D (1,25 Vit D) 18 pg/ml (20-79). Genetic testing for hypophosphatemic rickets was negative. Serum fibroblast growth factor 23 (FGF23) level was found to be elevated to 218 pg/ml ( <59). She was later found to have a left mandibular fracture. A 68Ga-DOTATATE PET/CT scan revealed gastric wall thickening. Several months after her initial presentation she reported ongoing left jaw pain and an enlarging left mandibular mass. Repeat PET scan revealed a hypermetabolic mandibular lesion. Pathologic analysis of the biopsied lesion was consistent with a phosphaturic mesenchymal tumor, and the lesion was resected. Labs three months following tumor resection revealed normalization of serum phosphorus, 1,25 Vit D, and PTH.

Discussion:
TIO is caused by overproduction of FGF23 and other phosphaturic proteins by a mesenchymal tumor. High serum FGF23 causes decreased renal phosphate reabsorption and increased 1,25 vit D production. This results in development of rickets/osteomalacia. These tumors are usually benign, small, slow growing neoplasms making them difficult to diagnose. Delay in diagnosis can result in complications such as fractures.

TIO, although rare, should be on the differential for patients with hypophosphatemia and progressive osteopenia. Analysis of serum 1,25 vit D, FGF23, and urine phosphorous levels is indicated, followed by tumor localization with PET/CT, CT, or MRI. Tumor resection is often curative, as in this case. Increased awareness of this condition may help to reduce the proportion of missed TIO cases and improve outcomes in recognized cases via earlier recognition and treatment.