The increasing popularity of orthodontic aligners has prompted concerns about their biocompatibility, especially since the primary target population is young and of reproductive age.

It is not possible to definitively confirm the presence of estrogenic or cytotoxic effects or the leaching of monomers such as BPA from the orthodontic aligners.

It is recommended that future studies adopt a more detailed and comprehensive analysis of BPA leaching, with a focus on conducting randomized controlled trials.

This umbrella review aims to determine if clear aligners promote cytotoxic and estrogenic effects.

The review was conducted in conformity with the PRISMA statement. A systematic search was carried out in March of 2025 in 5 databases (Medline through PubMed, Web of Science (all databases), Cochrane Library, Embase, and Epistemonikos). All systematic reviews (SRs) that reported the cytotoxicity and/or estrogenicity of orthodontic aligners were included. The quality of the included studies was evaluated using AMSTAR-2 and the degree of overlap was analysed using Corrected Covered Area (CCA).

The literature search resulted in 394 articles. Screening by title and abstract, resulted in 13 articles for full reading, and 4 articles were included in the umbrella review. According to the AMSTAR-2, all reviews were of low quality. The degree of overlap among SRs is high.

The included SRs indicate that aligners do not have significant estrogenic/cytotoxic capacity and, even in cases of bisphenol A (BPA) leaching, this occurs at levels well below what is considered toxic. The low quality, high risk of bias, considerable overlap, and significant heterogeneity among the included studies impacts the obtained results.

It is not possible to affirm or refute the presence of estrogenic or cytotoxic effects or the leaching of monomers such as BPA. In the future, it is recommended that studies adopt a more detailed and prolonged analysis of BPA leaching and it is necessary to carry out clinical studies that evaluate the safety and biocompatibility of orthodontic aligners.

Aligners

cytotoxicity

estrogenicity

monomer

Orthodontics

© 2025 The Authors. Published by Elsevier Inc.