The Effect of Bisphosphonate on Bone Formation After Tooth Extraction in Ovariectomized Rats

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Because dentists often see patients who are taking bisphosphonate (BIS) drugs, it is important for dentists to be aware of bisphosphonate-related osteonecrosis of the jaw (BRONJ). However, many aspects of the pathogenesis of BRONJ have not yet been clarified. The present study examined the healing process of tooth extraction sockets in ovariectomized rats to elucidate the pathogenesis of BRONJ, particularly the impact of BIS administration in new bone formation. Nine-week old female Wistar rats (6 weeks old during surgical removal of the ovaries) were divided into control (saline treated) and BIS-treated groups (6 in each condition). Alendronate was used for BIS treatment. The maxillary second molar was extracted. Specimens were decalcified with EDTA and embedded in paraffin for serial section. New bone formation and osteoclast counts were determined in H-E and tartrate-resistant acid phosphatase stain, respectively. Bone mineral density was also measured using micro-CT in non-decalcified samples. Contact microradiography (CMR) was taken in polished specimens. Granulation tissue was observed in extraction sockets of both groups at 1 week, and new bone formation was observed at 4 weeks. In the BIS-treated group, the number of multinucleated osteoclasts away from the bone surface increased. New bone formation after tooth extraction increased over time, but it was clearly less in the BIS-treated group compared to the control group. Results showed that BIS inhibited the formation of new bone at extraction socket during the early stage, causing low-density bone trabeculae and the spread of abnormal osteoclasts leading to BRONJ.

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