Song Minju, Alshaikh Abdullah, Kim Terresa, Kim Sol, Dang Michelle, Mehrazarin Shebli, Shin Ki-Hyuk, Kang Mo, Park No-Hee, Kim Reuben H
Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California.
Shapiro Family Laboratory of Viral Oncology and Aging Research, UCLA School of Dentistry, Los Angeles, California; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.
J Endod. 2016 Nov;42(11):1641-1646. doi: 10.1016/j.joen.2016.07.020. Epub 2016 Sep 13.
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.
诸如拔牙之类的外科手术会增加接受双膦酸盐(BP)治疗骨相关疾病的患者发生颌骨坏死的几率。拔牙通常是为了消除已存在的使牙齿无法保留的病理性炎症状况;然而,此类状况在拔牙后对双膦酸盐相关颌骨坏死(BRONJ)发展的作用尚未明确界定。在此,我们研究了根尖周炎对拔牙诱导的小鼠BRONJ发展的影响。
在静脉注射BP的C57/BL6小鼠中,通过暴露上颌第一磨牙的牙髓3周来诱导根尖周炎。拔除同一颗牙齿,再过3周后,处死小鼠以进行组织学、组织形态计量学和组织化学染色分析。
牙髓暴露诱导根尖周透射区,表现为炎症细胞、抗酒石酸酸性磷酸酶阳性破骨细胞增多以及骨吸收增加。给予BP时,尽管存在炎症细胞和抗酒石酸酸性磷酸酶阳性破骨细胞,但牙髓暴露并未诱导根尖骨吸收。虽然单独拔牙会诱导BRONJ病变,但牙髓暴露进一步增加了拔牙诱导的BRONJ发展,表现为更多骨坏死的存在。
我们的研究表明,诸如根尖周炎之类的已存在的病理性炎症状况是一个易感因素,可能会加剧拔牙后BRONJ的发展。我们的研究进一步提供了一个临床启示,即在对使用BP的患者进行拔牙之前,应控制根尖周炎,以降低发生BRONJ的风险。