BRONJ pathogenesis and treatment method targeting macrophages

• Project/Area Number: 17K11822
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: Satoh Akira 北海道大学, 大学病院, 講師 (90271684)
• Co-Investigator(Kenkyū-buntansha): 南川 元 北海道大学, 歯学研究院, 助教 (70625607)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 歯学 / ビスフォスフォネート製剤 / 顎骨壊死 / マクロファージ / ビスフォスフォネート関連顎骨壊死 / BRONJ発症機序

Outline of Final Research Achievements

Bisphosphonate preparations are widely used bone resorption inhibitors, such as for the prevention of bone-related events associated with osteoporosis and bone metastases of cancers. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been regarded as one of its significant side effects. However, BRONJ do not have a uniform view on treatment modalities because the pathogenesis is not clear. In this study, we investigated how macrophages are involved in the development of BRONJ on the pathogenesis of BRONJ.

Academic Significance and Societal Importance of the Research Achievements

生後8週齢のC57BL/6J雌マウスに対して、第3世代BP製剤であるゾレドロン酸水和物（Zoledronic Acid Hydrate：ZOL）と抗悪性腫瘍薬であるメルファラン（Melphalan：MEL）を投与することによりBRONJ様マウスを作製した。
ZOLおよびMEL投与群では典型的なBRONJの病理所見が確認されたが、単独投与群ではBRONJ様症状は認められないことより、BRONJ様症状の発症にはMELによる薬理作用（骨髄機能抑制）による免疫応答の不均衡が関与していることが明らかになった。