Related Experiment Video
Updated: Jan 10, 2026
The Establishment of a Murine Mandibular Molar Extraction Socket Healing Model
Published on: January 13, 2023
Development of micro-sequestra and associated histological changes in tooth extraction sockets of zoledronate-treated
Gaku Koizumi1, Taku Murata1, Akira Takigawa1
1Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, 514-8507, Mie, Japan.
Objectives:
Administration of bisphosphonates to mice do not always impair healing after tooth extraction. However, it is unclear whether there are any histological differences between the macroscopically healed extraction sockets of bisphosphonate- and saline-injected mice.
Methods:
Mice received a single intravenous injection of 540 μg/kg zoledronic acid or saline, and the maxillary first molars were extracted one week later. Healing of the extraction sockets was examined histologically and by micro-computed tomography.
Results:
Zoledronic acid and saline did not impair gross wound healing. Microscopically, the soft and the hard tissues of the extraction sockets were completely regenerated two weeks post-extraction. However, there were small bone fragments that varied from 10 μm to 200 μm in size in the connective tissues of the oral mucosa in the zoledronic acid-treated mice. The bone fragments had empty osteocyte lacunae, indicating that they were micro-sequestra. There was recruitment of multinucleated giant cells and contact of pseudoepitheliomatous hyperplasia in association with the bone fragments. These features were not present four weeks post-extraction.
Conclusions:
This study demonstrated that there were micro-sequestra in tooth extraction sockets after zoledronic acid treatment, even if there was no osteonecrosis or bone exposure. Although the significance of bone fragments and the associated changes is unclear, these findings may assist in understanding the sub-clinical state of adverse effects induced by bisphosphonates.
