Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice

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Surgical interventions such as tooth extraction increase the chances of developing osteonecrosis of the jaw in patients receiving bisphosphonates (BPs) for the treatment of bone-related diseases. Tooth extraction is often performed to eliminate preexisting pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related osteonecrosis of the jaw (BRONJ) development after tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction–induced BRONJ development in mice.


Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BPs. The same tooth was extracted, and after an 3 additional weeks, the mice were harvested for histologic, histomorphometric, and histochemical staining analyses.


Pulp exposure induced periapical radiolucency as shown by increased inflammatory cells, tartrate-resistant acid phosphatase–positive osteoclasts, and bone resorption. When BPs were administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and tartrate-resistant acid phosphatase–positive osteoclasts. Although tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as shown by the presence of more bone necrosis.


Our study demonstrates that a preexisting pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development after tooth extraction. Our study further provides a clinical implication wherein periapical periodontitis should be controlled before performing tooth extraction in BP users in order to reduce the risk of developing BRONJ.

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