SUN-364 Enthesophytes Are a Common Feature of FGF23-Mediated Hypophosphatemia Due to Tumor-Induced Osteomalacia

Abstract

Background: Tumor-induced osteomalacia (TIO) is a rare cause of FGF23-mediated hypophosphatemia in which mesenchymal tumors produce ectopic FGF23, leading to renal phosphate wasting, decreased 1,25-dihydroxy-vitamin D and hypophosphatemia. Clinical features include muscle weakness, fractures and bone pain. Entheses are sites where tendons, ligaments, fasciae and joint capsules attach to bones. Calcifications in entheses, called enthesophytes, are frequent in adults with X-linked hypophosphatemia (XLH), the most common genetic form of FGF23-mediated hypophosphatemia. One study reported 68% of XLH patients having enthesopathies at an average of 18 different insertion sites per person (Polisson, NEJM, 1985). However, the prevalence of enthesophytes in patients with TIO is not known. Methods: Skeletal surveys of 66 patients with TIO were reviewed by a single radiologist for the presence of enthesophytes, which were then grouped into the following sites: occiput, axial, upper extremities, pelvis/femur, tibia/fibula and feet. The data presented are from the 59 patients (33 men, 26 women) for whom near-complete skeletal surveys were available; feet radiographs were not available in 9 subjects. Descriptive statistics and regression analyses were performed, including analyses of concurrent intact FGF23 and phosphate levels. Data are presented as mean ± SD. Results: At the time of the skeletal survey, the age of the subjects was 48.7 ± 14.4 years; 78% were over 40 years. The estimated duration of TIO was 6.6 ± 5.3 years. Mean phosphate level was 1.7 ± 0.5 mg/dL (normal 2.5-4.5 mg/dL) and intact FGF23 was 743 ± 1213 pg/mL (normal < 50 pg/mL). Enthesophytes were identified in 51/59 patients (86.4%) with a mean of 4.5 ± 3.7 enthesophytes per patient (range 0-14). The most frequently affected site was the feet (35/50, 70%) followed by occiput (30/59, 51%), pelvis/femur (28/59, 48%), axial (22/59, 37%), upper extremities (18/59, 31%), tibia/fibula (18/59, 17%). In many subjects, more than one enthesophyte was seen within each region - the total number of enthesophytes in the cohort were: feet – 84, pelvis/femur -74, upper extremities – 40, occiput – 30, axial – 23, tibia/fibula – 16. Multiple linear regression demonstrated a significant positive relationship between number of enthesopathies with age and duration of TIO (p < 0.001). Intact FGF23 and phosphate did not significantly correlate with enthesophyte number. Conclusions: Similar to XLH, these data demonstrate that enthesopathies are a common feature of tumor-induced osteomalacia, increasing with both age and duration of disease. The underlying mechanism of enthesophytes in the general population is unclear and may be related to mechanical forces and/or inflammation. The additional factors of chronic hypophosphatemia and elevated FGF23 likely contribute to this mechanism.