The Systemic Impact of Peri-Implantitis: A Systematic Review

To systematically evaluate the available evidence regarding the association between peri-implantitis and systemic inflammatory biomarkers and/or systemic diseases, and to assess whether peri-implantitis treatment influences systemic inflammatory burden. Particular attention was given to the methodological limitations of the available evidence and the potential role of residual confounding.

A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Electronic searches were performed in MEDLINE, Embase, Scopus, and Web of Science from inception to December 2025, and updated in April 2026. Observational studies comparing systemic inflammatory biomarkers and/or presence of systemic diseases between individuals with and without peri-implantitis, as well as interventional studies evaluating the impact of any peri-implantitis treatment on the systemic inflammatory burden, were included. Random-effects meta-analyses were performed using Hedges' g (standardized mean difference).

Of 2399 records screened, 21 studies were included in the qualitative synthesis. Fourteen observational studies evaluated systemic inflammatory biomarkers, three randomized clinical trials assessed the effect of peri-implantitis treatment on systemic outcomes, and four observational studies investigated associations with systemic diseases. Comparative meta-analysis demonstrated significantly higher conventional CRP concentrations in patients with peri-implantitis than in healthy implant controls (Hedges' g = 3.73; 95% CI: 0.63-6.83; p = 0.02), although heterogeneity was considerable (I² = 99%). In contrast, no significant differences were observed for high-sensitivity CRP (hsCRP) (Hedges' g = -0.29; 95% CI: -0.61 to 0.04; p = 0.09; I² = 2%), IL-6, TNF-α, IL-10, or IL-1β. Evidence regarding systemic diseases was limited and heterogeneous, precluding quantitative synthesis. Interventional studies suggested modest and predominantly short-term reductions in selected inflammatory biomarkers following peri-implantitis treatment, whereas consistent improvements in systemic metabolic outcomes were not demonstrated.

Current evidence suggests that patients with peri-implantitis may exhibit higher circulating conventional CRP concentrations in some observational studies. However, this finding should be interpreted cautiously given the substantial heterogeneity of the pooled analysis, the absence of significant differences for high-sensitivity CRP, and the limited control of major confounding factors, in particular previous or concomitant periodontitis and other shared inflammatory and metabolic risk factors. Consequently, it remains uncertain whether peri-implantitis represents an independent source of systemic inflammation or rather reflects a susceptible host phenotype characterized by shared inflammatory and metabolic risk factors. Well-designed longitudinal and interventional studies are required before clinically meaningful systemic implications can be established.