Development of differential diagnostic method for etiology of acquired FGF23 related hypophosphatemic osteomalacia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Ito Nobuaki 東京大学, 医学部附属病院, 助教 (10731862)
• Co-Investigator(Kenkyū-buntansha): 小林 寛 東京大学, 医学部附属病院, 講師 (20407951)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 低リン血症 / くる病 / 骨軟化症 / 骨粗鬆症 / FGF23 / 病理 / 免疫染色 / ナノ技術

Outline of Final Research Achievements

FGF23 is a phosphaturic hormone derived from osteocytes, which physiologically regulates serum phosphate level. Tumor-induced osteomalacia (TIO) due to FGF23 producing tumor is the most common cause of acquired FGF23-related hypophosphatemic osteomalacia, however, the causative tumor couldn’t be recognized among about 20-30% of cases. In TIO patients, FGF23 production in the bone was physiologically suppressed while not suppressed in, such as, inherited FGF23-related hypophosphatemia. However, the conventional immunostaining method could not detect the suppression of FGF23 due to low sensitivity. In this research, PID: nano-immunostaining method with high sensitivity developed by KONICA MINORTA was adopted and the suppression of regional FGF23 in the bone surrounding FGF23 producing tumor in TIO patients was successfully recognized compared to femur bone samples gained during the surgery in the subjects without bone metabolic diseases.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

本検討の結果により、生後にFGF23関連低リン血症性骨軟化症を惹起したと思われる症例において腸骨生検などで骨検体を採取し、高感度ナノ免疫染色（PID）によってFGF23の骨での産生抑制の有無を確認することで、その原因がFGF23産生腫瘍による腫瘍性骨軟化症であるか、それ以外の遺伝性疾患などであるかを明確に鑑別できる技術が完成した。また同時にこれまで悪性腫瘍の発現マーカーなどを定量的に検出し抗癌剤の効果判定などへの応用が期待されていた高感度ナノ免疫染色技術が、今回の検討のようにホルモンの血中濃度が非常に低値である内分泌疾患などでの病因の鑑別などにも用いることができる可能性を示すことが出来た。