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

3 Citations (Scopus)


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
Pages (from-to)380-392
Number of pages13
JournalCalcified Tissue International
Issue number3
Publication statusPublished - Mar 2022


  • 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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