Table 1 Inclusion and exclusion criteria

Participants

• Patients with at least one white spot lesion on the labial surface of the teeth induced by fixed orthodontic treatment.

• Patients who will receive fixed orthodontic treatment and will be observed about WSLs.

• No restrictions on patients’ sex, age, city, country, ethnicity, and socio-economic status.

• Laboratory animal.

• Patients with WSLs but were not induced by orthodontic treatment.

• Patients with any illness potentially affecting the study outcome, such as enamel hypoplasia, craniofacial deformities, ongoing medication, and so on.

• Patients with congenital anomalies for example with cleft lip and palate.

Interventions

• Remineralised agents used for already formed WSLs induced by orthodontic treatment or prevention of orthodontically induced WSLs formation.

• Different forms/active ingredients of remineralised materials will be distinguished as different interventions(e.g. NaF varnish and difluorosilane varnish will be distinguished as two interventions, NaF varnish, and NaF gel will be distinguished as two interventions).

• Similar forms/active ingredients of remineralised materials regardless of intervention doses, administration frequencies and duration of the interventions will be merged into the same node, so there will not be too many disconnected nodes that make the NMA unable to conduct.

• Non-remineralised methods for prevention and treatment orthodontically induced WSLs, such as bleaching, micro-abrasion, and resin infiltration.

• If remineralised methods and non-remineralised methods were jointly used as an intervention in the same study, we will include the article but not pool the data.

Comparisons

• No treatment or placebo.

• Any other kind of remineralised agents.

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Outcome

• Lesion severity (measured by WSL index, enamel decalcification index, DIAGNOdent pen reading, quantitative light-induced fluorescence, etc.).

• Lesion transition (progression, stability or regression).

• WSLs prevalence (in the prevention of WSLs).

• Other outcomes evaluate WSLs.

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Study design

• Randomised controlled trials (parallel or clustered).

• Non-randomised prospective or retrospective studies.

• Split-mouth trials, which are susceptible to “carry-across effect” and the resultant bias.

• Case reports/ case series.

• Non-clinical studies (in vitro, ex vivo, in silico, etc.).

• Systematic review.

Timing

• Any time points.

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Setting

• No restrictions by type of setting. e.g. university or private practice,.

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Language

• Studies written in all languages.

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Other imitations

• No other limitations will be imposed on unpublished studies, studies of all durations and those conducted during all points in time are eligible for inclusion.

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