Osteonecrosis of the jaw by bisphosphonates: approaches to the underlying mechanism, prevention, and treatment

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592978
• 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: YAMAGUCHI kouji 東北大学, 歯学研究科(研究院), 大学院非常勤講師 (10372319)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: bisphosphonates / 顎骨壊死 / 副作用 / 炎症

Outline of Final Research Achievements

Nitrogen-containing bisphosphonates (N-BPs) have greater anti-bone-resorptive effects than non-nitrogen-containing BPs (non-N-BPs). However, N-BPs have side effects including osteonecrosis of the jaw. In the present study, we obtained the following results. (i) Minodronate, an N-BP produced in Japan, has inflammatory/necrotic side effects (INSEs) in mice. (ii) Lipopolysaccharide (LPS) of bacterial cell wall markedly exacerbates INSEs of N-BPs at the site of injection. (iii) N-BPs, irrespective of their side chain structures, are taken within cells via the phosphate transporters SLC20/34 and induce INSEs. (iv) We previously found that etidronate (Eti, a non-N-BP) could prevent and/or reduce the inflammatory/necrotic effects of N-BPs, and that Eti could replace N-BPs that had already bound to bones, leading us to propose “Eti-replacement therapy”. In the present study on patients with osteonecrosis of the jaw, we obtained effective results of the therapy.

Free Research Field

医歯薬学