Advancement in immunological analysis and preventive/treatment methods for medication-related osteonecrosis of the jaw

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K11844
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyushu University
• Principal Investigator: Kakehashi Hiroe 九州大学, 歯学研究院, 助教 (30452775)
• Co-Investigator(Kenkyū-buntansha): 黒嶋 伸一郎 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (40443915)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 薬剤関連顎骨壊死 / 骨吸収抑制薬関連顎骨壊死 / ビスフォスフォネート / 抗RANKL抗体 / デノスマブ / MRONJ / ARONJ / 顎骨壊死

Outline of Final Research Achievements

The research collaborators revealed that the ratio of tissue-repairing M2 macrophages and inflammatory M1 macrophages significantly changes in both BRONJ-like pathology and its remission site in the BRONJ model mouse. In our study using the DRONJ model mouse, we also reported changes in the distribution of M1/M2 macrophages due to Dmab administration and the healing of jawbone necrosis-like lesions due to Dmab discontinuation.
Furthermore, we investigated the treatment effects and their relationship with patient backgrounds on patients who received conservative surgical treatment after being diagnosed with ARONJ and found that conservative surgical treatment was effective regardless of the disease stage, suggesting that it could be the first choice regardless of the disease stage classification.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

ARONJ発生の背景や機序、その予防法や治療法も確立されていない。ARONJモデルマウスを用いてARONJと免疫制御能低下の関連性を明らかにすることは今後のARONJ研究を発展させるうえで極めて重要であり、本研究成果はARONJのリスク診断法や予防法の開発を目指す新たな研究にもつながる可能性がある。
治療法として近年は積極的な外科的治療を推奨する傾向にあるが、腐骨の分離が確実に得られれば外科的治療の必要はなく、本患者は癌の多発骨転移やステロイドの長期投与などで全身状態が好ましくなかったり、患者自身が侵襲の高い治療法を望まないことも多いため、病期分類を問わず第一選択となりうることが示唆された。