UCLA

BACKGROUND: Dental implants are subject to peri-implantitis, which is an inflammatory condition mediated by bacterial insult that leads to irreversible crestal peri-implant bone loss. Unfortunately, treatment modalities to arrest the condition from progressing are unpredictable. With an estimated 45% of all patients with implants that suffer from this condition, it is imperative to further study the disease to improve treatment protocols. A CXCR3-antagonist drug has been developed to inhibit immune cell migration by preventing CXCL9 and CXCL10-dependent chemotaxis. The drug, AMG-487, acts by blocking the CXCR3 receptor. Preliminary studies have shown its effectiveness in reducing periodontal bone loss in mouse models. In this study, we wish to explore its role in reducing peri-implant bone loss.

OBJECTIVE: To evaluate the efficacy of AMG-487 to reduce peri-implant bone loss.

MATERIALS AND METHODS: One-month old C57BL/6J mice had their left maxillary molars extracted. Custom-made titanium implants were placed after eight weeks of healing and were allowed to osseointegrate for one month. The mice were separated into control, ligature, and CXCR3 antagonist groups. 6-0 silk ligatures were placed around the head of the implants, and the mice were injected twice daily for two weeks with vehicle or AMG-487. The mice were then sacrificed and fixed for histology, and scanned with micro-CT for radiographic analysis.

RESULTS: The experimental groups experienced significant bone loss compared to the control group. However, there were no statistically significant differences between the ligature group and the CXCR3 antagonist group. Both experimental groups revealed soft tissue swelling and increased inflammatory infiltrates relative to the control group, but no clear differences were observed between the experimental groups. The osteoclast numbers increased significantly in the experimental groups. The CXCR3 antagonist group showed greater COX-2 staining than control, but appeared to have stained less than the ligature group.

CONCLUSION: This current study was not able to demonstrate the efficacy of the CXCR3 antagonist to sufficiently reduce ligature-induced peri-implant inflammation and bone loss.