Changes in Serum C-Reactive Protein Following Nonsurgical Periodontal Therapy: A Systematic Review and Meta-Analysis

Background: Periodontitis is associated with elevated circulating C-reactive protein (CRP), but the extent to which CRP changes after nonsurgical periodontal therapy remains uncertain. This systematic review and meta-analysis examined within-participant changes in serum CRP and considered controlled evidence separately. Methods: PubMed/MEDLINE, the Cochrane Library, and SciELO were searched through August 2025. For uncontrolled pre-post studies reporting periodontitis-specific paired data, mean CRP reductions in mg/L were pooled using a random-effects model with restricted maximum likelihood and Hartung-Knapp confidence intervals. When the standard deviation (SD) of change was unavailable, it was calculated assuming a pre-post correlation of 0.50; correlations of 0.25 and 0.75 were examined in sensitivity analyses. Controlled trials were not pooled with uncontrolled studies. The protocol was retrospectively registered in the Open Science Framework before the quantitative analyses. Results: Five studies were included in the systematic review. Three uncontrolled studies comprising 119 participants contributed to the primary meta-analysis. The pooled within-participant reduction in CRP was 1.11 mg/L (95% CI: 0.21 to 2.01), with considerable heterogeneity (I² = 80.8%). The result was stable across the assumed correlations. In the only trial comparing periodontal treatment with a control condition for which an effect could be calculated, the difference in mean changes was 2.95 mg/L (95% CI: -0.50 to 6.40) and was not statistically significant. Conclusions: CRP decreased after nonsurgical periodontal therapy in uncontrolled pre-post studies, but this finding does not establish a controlled treatment effect. Controlled evidence was limited and imprecise, and the clinical relevance of the biomarker change remains uncertain.