Peri-implantitis and systemic inflammation: Current evidence, biological plausibility, and research gaps.

BACKGROUND: Peri-implantitis is a biofilm-associated inflammatory condition characterized by peri-implant mucosal inflammation and progressive bone loss. The prevalence of peri-implantitis continues to rise among patients with dental implants. Although peri-implantitis and periodontitis share similar inflammatory phenotypes, histopathological studies have shown that peri-implantitis lesions may exhibit larger inflammatory infiltrates compared with periodontal lesions. This pronounced local inflammatory response provides biological plausibility for potential systemic inflammatory effects. OBJECTIVE: To critically appraise the current evidence regarding the potential relationships of peri-implantitis with systemic inflammation and systemic diseases, distinguish peri-implantitis-specific findings from extrapolations based on periodontitis research, and highlight the principal methodological limitations and priorities for future investigations. METHODS: A comprehensive narrative review of clinical studies, animal studies, and mechanistic studies exploring the relationships between peri-implantitis, systemic inflammation, and systemic diseases was conducted. Evidence was synthesized according to local inflammatory characteristics, potential biological pathways linking peri-implantitis to systemic effects, circulating inflammatory and metabolic alterations, and the methodological limitations of the available studies. RESULTS: Some observational studies have reported elevated circulating inflammatory biomarkers, including C-reactive protein and selected cytokines, in patients with peri-implantitis. Limited interventional evidence also suggests that peri-implantitis treatment may influence some systemic inflammatory markers. However, evidence regarding specific systemic diseases and underlying biological mechanisms remains sparse and is largely indirect or extrapolated from periodontitis research. Most available studies are cross-sectional, involve small sample sizes, use heterogeneous methodologies, and provide limited control of confounding factors. CONCLUSIONS AND CLINICAL RELEVANCE: Current evidence suggests that peri-implantitis may be associated with systemic inflammatory changes. However, the available evidence is insufficient to establish causality or a clinically relevant systemic impact. Further adequately powered longitudinal, interventional, and mechanistic studies are needed to determine whether peri-implantitis independently contributes to systemic inflammation or whether the observed associations reflect shared risk factors and inflammatory pathways.