Peri‐implant inflammation increases the risk of osteonecrosis in mice treated with bisphosphonate

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BACKGROUND: Bisphosphonates (BPs) are effective in managing bone diseases due to their anti-resorptive properties but are linked to medication-related osteonecrosis of the jaw (MRONJ), particularly concerning dental implants. This study explored the combined impact of ligature-induced peri-implant inflammation and zoledronic acid (ZA), a BP, using a murine model. METHODS: Twenty-four mice underwent bilateral maxillary molar extractions and implant placements, with ZA or vehicle treatment and ligature placement on the left side. Two groups were defined: group 1 (vehicle-treated) with control (Veh-C) and ligature (Veh-L) implants, and group 2 (ZA-treated) with control (ZA-C) and ligature (ZA-L) implants. Clinical, micro-CT, histological, and immunohistochemical analyses were performed. We hypothesized that peri-implant inflammation elevates MRONJ risk with BP treatment. RESULTS: Ligature groups showed increased soft tissue edema compared to controls, without differences between vehicle and ZA treatments. The Veh-L group exhibited significantly greater bone loss than other groups. Histology showed higher inflammatory infiltrate in ligature groups. Osteocyte empty lacunae and osteonecrosis were significantly greater in ZA-L. Picrosirius red staining revealed disorganized collagen fibers and separation in ZA-L. Immunohistochemistry showed increased neutrophils (NIMP-R14+) and monocytes/macrophages (CD11b+) in the ligature groups, with no significant differences between Veh-C and ZA-C. CONCLUSION: Ligature treatment enhances peri-implant inflammation, with ZA heightening the risk of MRONJ. These findings highlight the critical importance of early detection and management of peri-implant inflammation in patients undergoing BP therapy, particularly those at high risk of MRONJ. Clinicians should emphasize preventive measures, such as regular monitoring of peri-implant health and reducing local inflammatory triggers, to mitigate the adverse effects of BPs on peri-implant bone health. PLAIN LANGUAGE SUMMARY: Dental implants are a reliable solution to replace missing teeth. However, like natural teeth, implants can develop inflammation around them-peri-implantitis. Our study found that, when this inflammation occurs in patients taking BPs (a medication commonly used to treat osteoporosis and other bone diseases), the risk of developing a serious jaw condition called osteonecrosis (ONJ) increases significantly. ONJ prevents the jawbone from healing properly, leading to pain, infection, and even exposed bone. These findings highlight the importance of preventing and managing inflammation around dental implants to reduce the risk of complications, especially in patients taking BPs. Our research suggests regular dental check-ups and proper oral hygiene can help maintain implant health and prevent severe bone-related conditions. Patients and healthcare providers can take proactive steps to improve long-term oral health outcomes by understanding these risks.

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