Commensal Microbiota Protects Development of Periapical Periodontitis-Mediated BRONJ in Mice

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare intraoral lesion that occurs in patients with long-term and/or high-dose use of nitrogen-containing bisphosphonates such as zoledronic acid (ZOL). The pathological role of bacteria in BRONJ development at the early stage remains controversial. Previously, we demonstrated that commensal microbiota protects against BRONJ development in the ligature-induced periodontitis mouse model. Here, we examined whether the commensal microbiota plays an etiologic role in BRONJ development exacerbated in pulp-exposed periapical periodontitis mouse model.
Methods: Twenty-four C57/BL6 female mice were used. Intragastric broad-spectrum Abx was administered for 1 week and Abx in drinking water was supplied for throughout the experiment. Pulp was exposed, then the mice were left for 5 weeks after which 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.
Results: When antibiotic was treated in mice (Abx mice), these mice had no weight changes, but developed significantly enlarged ceca, and reduced oral and fecal 16S rDNA expression compared to the control group (CTL mice). Bone resorption was similarly prevented in both CTL and Abx mice when treated with ZOL. However, ZOL treatment without Abx treatment significantly increased bone necrosis as determined by empty lacunae, necrotic bone amount. Furthermore, ZOL with Abx treatment further increased bone necrosis.
Conclusions: Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.