Biological Consequences and Assessment Methods Analysis of Fixed Orthodontic Appliances on Oral Epithelial Cells: A Systematic Review

Introduction: Fixed orthodontic appliances (OAs) expose the oral mucosa to mechanical traumas and metal ions throughout the whole orthodontic therapy. This review aims to understand the cytological and genetic changes consequent to fixed orthodontic therapy, their clinical implications, and how they can be assessed. Materials and Methods: A comprehensive search was conducted in PubMed (MEDLINE), Scopus, and Web of Science using MeSH terms related to cytology, DNA damage, mutagenicity, and orthodontic appliances. The PICO model and PRISMA guidelines were followed. The risk of bias was assessed using the ROBINS-I tool, and study quality was evaluated with the NHLBI Quality Assessment Tools. Two independent evaluators assessed the methodological quality of the included studies using the Joanna Briggs Institute (JBI) levels of evidence; inter-reviewer agreement was measured using Cohen's kappa coefficient (κ = 0.80). Results: Nineteen prospective and cross-sectional studies were included in the analysis. The findings suggest the presence of higher metal cellular content, as well as cytological changes, nuclear alterations, and cytotoxic and genotoxic effects. Different appliance compositions and treatment durations may influence the biological consequences. The analysis shows a tendency toward regression, especially for nuclear alterations. No dysplastic changes have been observed in any of the studies included. Conclusion: OAs cause cellular alterations, which tend to be reversible and do not seem to evolve into dysplastic changes. Future research should focus on longitudinal studies with standardized methodologies to better understand the persistence and reversibility of the changes associated with OAs, as well as exploring alternative materials that pose less risk during orthodontic treatment.