Administration of adrenergic receptor agonist effect for Osteonecrosis of the Jaw

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K19188
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Yamada Takayuki 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (10826829)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: osteonecrosis of the jaw / PTH / β2 Adrenergic Receptor / alkaline phosphatase

Outline of Final Research Achievements

Although there are reports that human parathyroid hormone (PTH) improves osteonecrosis of the jaw, there are limitations in its application, and it is desirable to develop alternative drugs. Isoproterenol (ISO), an adrenergic β2 receptor agonist that has a similar signal transduction pathway to PTH, exhibited similar kinetics in vitro. The dynamics of osteopontin (OPN), which is involved in bone formation by ISO and PTH, was investigated by administering PTH to femoral nerve-resected mice (Nx).
PTH prevented Nx-induced bone loss. Nx suppressed the expression of Wnt3a and Fndc5, suggesting the existence of bone loss pathways such as the Wnt3a pathway and OPN-mediated irisin secretion. In the future, it will be necessary to consider whether PTH suppresses this route or whether ISO is a similar route.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

2003年にビスホスホネート系製剤による有害事象で「顎骨壊死」が報告され、骨代謝に関与する様々な薬剤からも顎骨壊死が発症する報告が散見されるようになった。顎骨壊死の治療は、手術で良好な結果を認めた報告が散見されるが、顎骨壊死患者の多くが高齢者であり、手術範囲や適応基準など課題がある。ヒト副甲状腺ホルモン(PTH)が顎骨壊死を改善させた報告もあるが、使用の適応・制限のため、代替薬開発が待たれる。
本研究で骨量減少経路の存在が示唆され、今後はPTHがその経路を抑制するのか、PTH同様のシグナル伝達経路を持つイソプロテレノールも同様の効果があるかを検討することにより、新たな局面に進める可能性を示した。