2022 Fiscal Year Final Research Report

Development of novel screening method for ARONJ based on macrophage polarization

Research Project

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Project/Area Number	19K10351
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57060:Surgical dentistry-related
Research Institution	The University of Tokyo
Principal Investigator	Sugiyama Madoka 東京大学, 医学部附属病院, 客員研究員 (90451814)
Co-Investigator(Kenkyū-buntansha)	安部貴大神奈川歯科大学, 歯学部, 教授 (20383250) 星和人東京大学, 医学部附属病院, 教授 (30344451) 藤原夕子東京大学, 医学部附属病院, 客員研究員 (50466744) 石橋牧子東京大学, 医学部附属病院, 客員研究員 (60802395)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	ARONJ
Outline of Final Research Achievements	Antiresorptive agents such as bisphosphonates and denosumab have a risk of causing refractory osteonecrosis of the jaw, which is one of the most important issues of recent years in the field of oral surgery. The development of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is partially attributed to the anatomical location of jaw bones which are more susceptible to infection than other bones in the body, while local and systemic factors could be also involved. As pathophysiology of ARONJ has yet to be clarified, in this study, we prepared mice ARONJ model using bisphosphonates, and evaluated its pathophysiological changes focusing on osteoclasts derived from monocyte-macrophage lineage. Our results suggested that ARONJ could be caused by impaired angiogenesis around extraction sockets and myelosuppression in jawbone.
Free Research Field	口腔外科
Academic Significance and Societal Importance of the Research Achievements	ARONJ は，2003 年Marx により初めて報告されたが，その発生機序や病態は未だ明確にはなっていない。ARONJ患者のバックグラウンドは骨粗鬆症から担がん状態まで様々で、骨吸収抑制剤の種類や服薬期間もばらつきがあり、発症や経過にも一律性は認めない。本研究では、ARONJモデルマウスを複数のプロトコルで作製し、抜歯窩の骨露出面積、および新生骨などの解析を行い、ARONJに特徴的な所見を得る事ができた。ARONJの病態には、骨髄の変化、および骨髄をつなぐ新生血管の障害があることが示唆された。本研究で得られた知見は、ARONJ新規治療法開発の一助となることが期待される。