Comparative Evaluation of Biomarker Levels in Gingival Crevicular Fluid Among Patients Treated with Clear Aligners and Fixed Orthodontic Appliances: A Systematic Review and Meta-analysis

Background Orthodontic force application induces an inflammatory response in periodontal tissues, resulting in bone remodeling. Gingival crevicular fluid (GCF) provides a non-invasive medium to evaluate these biological changes. With the increasing use of clear aligner therapy, it is clinically relevant to compare its biological effects with those of fixed orthodontic appliances. Aim To systematically review and compare biomarker levels in GCF among patients treated with clear aligners and fixed orthodontic appliances. Materials and Methods Electronic searches were conducted in PubMed, Cochrane Central, Web of Science, Scopus, LILACS, and Google Scholar from January 1, 2000, to June 30, 2025. Clinical studies evaluating GCF biomarkers during active orthodontic treatment with clear aligners or fixed appliances were included. Risk of bias was assessed using the Cochrane RoB tool and ROBINS-I. Meta-analysis was performed using a random-effects model. Results Ten studies (six randomized controlled trials, two non-randomized trials, and two observational studies) involving 380 participants were included. Clear aligner therapy was associated with higher levels of interleukin-2, interleukin-6 (IL-6), and interleukin-8, while fixed appliances demonstrated elevated tumor necrosis factor-alpha and IL-6 levels. Meta-analysis of IL-1β levels revealed no statistically significant difference between the two groups (SMD = 1.11; 95% CI = −2.54 to 4.77; P = .55). Substantial heterogeneity was observed ( I 2 = 98%). Conclusion Both clear aligners and fixed orthodontic appliances elicit inflammatory responses during active treatment, reflected by increased GCF biomarker levels. While cytokine expression patterns differ between modalities, current evidence does not establish a clear association with the rate of tooth movement. Due to the high heterogeneity, the findings should be interpreted cautiously, and further standardized longitudinal studies are required.