Occlusal Trauma and Bisphosphonate-Related Osteonecrosis of the Jaw in Mice

Yuichi Mine, Karin Okuda, Reina Yoshioka, Yuuki Sasaki, Tzu Yu Peng, Masato Kaku, Yuji Yoshiko, Hiroki Nikawa, Takeshi Murayama

Research output: Contribution to journalArticlepeer-review


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. Previous clinical reports suggest that mechanical trauma would trigger ONJ in a manner that is similar to tooth extractions. To the best of our knowledge, there have been few detailed pathophysiological investigations of the mechanisms by which occlusal/mechanical trauma influences ONJ. Here, we developed a novel mouse model that exhibits ONJ following experimental hyperocclusion and nitrogen-containing bisphosphonate (N-BP) treatment. 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.

Original languageEnglish
JournalCalcified Tissue International
Publication statusAccepted/In press - 2021


  • 3D culture
  • Bisphosphonate
  • Hydrostatic pressure
  • Hyperocclusive state
  • Occlusal trauma
  • Osteonecrosis of the jaw

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology


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