Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.

细菌感染是患者的常见发现，这些患者因长期和/或高剂量使用双膦酸盐 (BPs) 等抗再吸收剂而发展为药物相关的颌骨坏死 (MRONJ)。然而，细菌在早期 MRONJ 发育中的病理作用仍存在争议。在这里，我们证明了在牙髓暴露的根尖周炎小鼠模型中，共生微生物群可以防止 MRONJ 的发展。C57/BL6 雌性小鼠用胃内广谱抗生素治疗 1 周。在整个实验过程中，通过静脉注射唑来膦酸（ZOL）和饮用水中的抗生素。牙髓暴露在左上颌第一磨牙上，然后将小鼠放置5周，然后拔除双侧上颌第一磨牙，再放置3周以使小鼠愈合。收获所有小鼠，收集盲肠、上颌骨和股骨。使用μCT和组织学分析评估ONJ发展。当对小鼠进行抗生素治疗时，这些小鼠的体重没有变化，但与对照组（CTL小鼠）相比，盲肠明显增大。当用抗生素治疗时，同样可以防止拔牙前的根尖周骨吸收，这通过减少破骨细胞和炎症得到证实。用牙髓暴露的 ZOL 治疗显着增加了骨坏死，这由空腔和坏死骨量确定。此外，抗生素治疗可进一步加剧骨坏死，增加破骨细胞数量。