Gender Difference in Serum Fibroblast Growth Factor 23 with Tumor-Induced Osteomalacia in Japan

Presentation Number: SUN 337
Date of Presentation: April 2nd, 2017

Daisuke Murakami*1, Masayuki Fuwa2, Mikako Kawashima2, Taro Usui2, Masahiro Yamauchi2, Takahide Ikeda2, Kazuo Kajita2 and Hiroyuki Morita2
1Gifu Prefectural General Medical Center, gifu, Japan, 2Gifu University Graduate School of Medicine, gifu, Japan



Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by excessive tumor production of fibroblast growth factor 23 (FGF-23) which results in osteomalacia due to reduced 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) synthesis and hypophosphatemia by renal phosphate wasting. We present a case and reviewed 38 Japanese cases including ours and investigated the clinical characteristics.


A 52 year-old female who had complained of progressively worsening generalized musculoskeletal pain and fatigue for 4 years was in a functionally incapacitated bed-bound state. She had hypophosphatemia, low serum 1α,25(OH)2D3 and %TRP, and elevated serum alkaline phosphatase and FGF-23 (277 pg/ml). She was diagnosed as TIO due to a tumor originating in the right nasal cavity via a 18F-FDG PET/CT scan. Removal of the tumor led to a complete resolution of the symptoms and normalization of the serum biochemical abnormalities. The histology demonstrated a phosphaturic mesenchymal tumor.


Within the other 38 reported Japanese cases, 25 were male (69%) with a mean (±SE) age of 48±2 years. Characteristic biochemical patterns included low serum levels of phosphorus (1.60±0.07 mg/dL) and 1α,25(OH)2D3 (19.6 ±3.3 pg/ml), and elevated levels of alkaline phosphatase (901±67.2 IU/l), and FGF-23 (290.7±69.0 pg/ml). The tumors originated from soft tissue (69%) or bone (31%), and localized within the lower extremities (59%), the head (28%), or the trunk (9%) with a mean diameter of 19.6±2.1 mm. There was a negative correlation between serum FGF-23 and 1α,25(OH)2D3 with logarithmic conversion (r=-0.64, p<0.001). The serum FGF-23 levels were significantly higher in females (532.6±146.3 pg/ml) than those in males (187.5±75.2 pg/ml) (p=0.001). The serum 1α,25(OH)2D3 levels were significantly lower in females (8.2±2.2 pg/ml) than those in males (27.0±4.7 pg/ml) (p=0.002). The gender differences in serum FGF-23 levels were not due to influence of the female sex hormone because of no significant differences in them between over and under 50 years of age in females. On the other hand, the tumor volume in females (13816.9±5735.6 mm3) was comparatively larger than in males (8146.6±4458.3 mm3) (p=0.45). It has been reported that there are gender differences in serum leptin levels and that leptin promotes FGF-23 secretion. Unfortunately, serum levels were not available among all cases.


Higher serum FGF-23 levels were observed in Japanese females with TIO than those in males, possibly due to the larger size of FGF-23 producing tumors or higher serum leptin levels in the female patients.


Nothing to Disclose: DM, MF, MK, TU, MY, TI, KK, HM