Inflammatory and necrotic effects of nitrogen-containing bisphosphonates: involvement of phosphate transporters

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11672
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tohoku University
• Principal Investigator: Endo Yasuo 東北大学, 歯学研究科, 学術研究員 (50005039)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: bisphosphonate / 炎症 / 顎骨壊死 / etidronate / clodronate / 鎮痛作用

Outline of Final Research Achievements

Bisphosphonates (BPs) are widely used anti-bone-resorptive drugs. Among them, the anti-bone-resorptive effects of nitrogen-containing BPs (NBPs) are much stronger than those of non-NBPs. However, NBPs have inflammatory/necrotic side effects, and the osteonecrosis of the jaw induced by NBPs is intractable and serious problem in dentistry. The present study, together with previous studies, demonstrtates that NBPs enter soft-tissue cells via phosphate transporters and non-NBPs inhibit this. These findings suggest that non-NBPs are applicable to treat and prevent the side effects of NBPs. In addition, we found that non-NBPs exhibit analgesic effects, too, via inhibition of neuronal phosphate transporters.

Free Research Field

炎症と免疫の薬理学

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症は高齢者の生活低下の大きな原因である．窒素含有bisphosphonates (NBPs) は現在，骨粗鬆症の予防・治療の第一選択薬であり，宇宙での無重力による骨粗鬆の予防薬にも期待されている．しかし残念ながら，NBPsの副作用 (顎骨壊死や発熱などの急性炎症) が大きな問題となっており，その安全な利用法の確立は急務の課題である．臨床成績も含めて私達の研究成果は，NBPsの副作用に対する予防・治療薬として，non-NBPの etidronateとclodronateの有効性を明確に示している．いくつかの方法が報告されているが，有効性は低く，私たちの提案する方法が最善と思われる．