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

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Introduction: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.Methods: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.Results: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.Conclusions: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.Highlights:Pulp exposure induced periapical periodontitis and periapical radiolucency (PARL) in mice.In the presence of bisphosphonates, pulp exposure induced periapical periodontitis without causing PARL.Periapical periodontitis exacerbated tooth extraction-induced bisphosphonate-related osteonecrosis of the jaw development in mice.

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