Hyperocclusive state and MRONJ

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18604
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57050:Prosthodontics-related
• Research Institution: Hiroshima University
• Principal Investigator: Mine Yuichi 広島大学, 医系科学研究科(歯), 講師 (60605989)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: MRONJ / 咬合性外傷 / 実験的過剰咬合 / 顎骨壊死 / ONJ / 薬剤関連顎骨壊死 / 過剰咬合

Outline of Final Research Achievements

Osteonecrosis of the jaw (ONJ) is a serious adverse event that is associated with antiresorptive agents, and it manifests as bone exposure in the maxillofacial region. This in vivo model exhibited ONJ in alveolar bone, particularly in the mandible. Moreover, the experimental hyperocclusion induced remarkable alveolar bone resorption in both mouse mandible and maxilla, whereas N-BP treatment completely prevented alveolar bone resorption. In this study, we also modeled trauma by exposing clumps of mesenchymal stem cells (MSCs)/extracellular matrix complex to hydrostatic pressure in combination with N-BP. Hydrostatic pressure loading induced lactate dehydrogenase (LDH) release by calcified cell clumps that were differentiated from MSCs; this LDH release was enhanced by N-BP priming. These in vivo and in vitro models may contribute further insights into the effect of excessive mechanical loading on ONJ onset in patients with occlusal trauma.

Free Research Field

骨生物学

Academic Significance and Societal Importance of the Research Achievements

補綴歯科治療において顎堤は、義歯やインプラントを支持する上で重要な役割を果たしており、その状態不良は補綴歯科治療の成功を妨げる大きな要因となる。薬剤関連顎骨壊死は、本邦を含め複数のポジションペーパーが関連学会から示されている。しかしながら、その発症メカニズムは未だ明確にはなっていない。本研究では、過剰な咬合力や義歯の使用による口腔内の刺激と薬剤関連顎骨壊死の関連について、その一端を明らかにすることを目指し研究を推進した。