Bisphosphonates related osteonecrosis: Aim to elucidate and treatment mechanism

• Project/Area Number: 25861910
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Tohoku University
• Principal Investigator: Oizumi Takefumi 東北大学, 歯学研究科(研究院), 大学院非常勤講師 (40547262)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 顎骨壊死 / ビスフォスフォネート

Outline of Final Research Achievements

Bisphosphonates(BPs) agent with strong bone resorption inhibitory effect have been used for various enhanced bone-resorptive diseases. However, since BP-related osteonecrosis of the jaw (BRONJ), first reported in 2003, is increasing, with few effective strategies. BRONJ is exclusively associated with the use of nitrogen-containing BPs (NBPs). We previously reported that in mice, the non-NBP etidronate can reduce the inflammatory/necrotic effects of NBPs by inhibiting their intracellular entry and antagonize NBPs’ binding to bone hydroxyapatite absorption. We applied papers that the BRONJ 14 patients case and BRONJ patient of diabetes control bad case which tried to etidronate substitute replacement therapy of non-NBP.

Research Products

• [Journal Article] In vitro cytotoxicity of zoledronate (nitrogen-containing bisphosphonate: NBP) and/or etidronate (non-NBP) in tumor cells and periodontal cells. (2013)
  • Author(s): Takefumi Oizumi
  • Journal Title: Archives Oral Biology Volume: 58(6) Pages: 628-37
  • DOI: 10.1016/j.archoralbio.2012.11.010
  • Peer Reviewed
• [Journal Article] Inhibition of Phosphate Transporters Ameliorates the Inflammatory and Necrotic Side Effects of the Nitrogen-Containing Bisphosphonate Zoledronate in Mice (2013)
  • Author(s): Satoru Okada, Tomomi Kiyama, Eri Sato, Yukinori Tanaka, Takefumi Oizumi, Toshinobu Kuroishi, Tetsu Takahashi, Keiichi Sasaki, Shunji Sugawara, Yasuo Endo.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 231 Issue: 2 Pages: 145-158
  • DOI: 10.1620/tjem.231.145
  • NAID: 130004822384
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Presentation] BRONJに対するダイドロネルへの置換療法 (2015)
  • Author(s): 大泉丈史
  • Organizer: 第３回宮城県口腔外科研究会
  • Place of Presentation: 東北大学歯学部（仙台）
  • Year and Date: 2015-02-28
  • Invited
• [Presentation] BRONJ (bisphosphonate-related osteonecrosis of the jaw) の治療：etidronate 置換療法の試み (2015)
  • Author(s): 大泉丈史
  • Organizer: 第３６回東北骨代謝研究会
  • Place of Presentation: 江陽グランドホテル（仙台）
  • Year and Date: 2015-02-07
• [Presentation] 窒素含有 bisphosphonates (N-BPs) 治療患者での顎骨壊死：N-BPsのetidronate (non-N-BP) への置換の試み (2014)
  • Author(s): 大泉丈史
  • Organizer: 第５６回歯科基礎医学会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 窒素含有 bisphosphonates(N-BPs)の炎症壊死作用:LPS による増強 (2014)
  • Author(s): ○鈴木 飛佳理，大泉丈史
  • Organizer: 第５６回歯科基礎医学会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Zoledronate の軟組織細胞への取り込み：リン酸transporter関与の可能性． (2013)
  • Author(s): 岡田諭，木山朋美，大泉丈史，佐々木啓一，高橋 哲，菅原俊二，遠藤康男
  • Organizer: 歯科基礎医学会
  • Place of Presentation: 岡山，岡山コンベンションセンター