Objectives: To compare the effectiveness of remineralizing agents in the prevention and reversal of white spot lesions (WSLs), which occur during fixed orthodontic treatment, through a systematic review and network meta-analysis. Materials and methods: We reviewed controlled randomized clinical trial (RCT) data querying nine databases combined with a manual search (last search date: March 10, 2020). Of 2273 identified studies, 36 RCTs were finally included. After study selection and data extraction, pair-wise and network meta-analyses were performed to analyze the effectiveness of remineralizing agents in the prevention and reversal of WSLs in the short term (≤ 3 months) and long term (> 3 months). The risk of bias was assessed based on the Cochrane guidelines. Statistical heterogeneity, inconsistencies, and cumulative ranking were also evaluated. Results: In terms of WSL prevention, sodium fluoride (NaF) varnish had the highest cumulative ranking for the short-term decalcification index (99.3%); acidulated phosphate fluoride (APF) foam ranked first for long-term incidence (96.9%), followed by difluorosilane (Dfs) varnish and high-concentration fluoride toothpaste (HFT) (79.4% and 77.4%, respectively). In the reversal of WSLs, no significant difference was found among different agents or their combinations for the two available outcomes (short-term integrated fluorescence loss and short-term percentage of fluorescence loss). Conclusions: In the prevention of WSLs, APF foam showed the best remineralizing effectiveness in the long term (after debonding), followed by Dfs varnish and HFT. It is unclear whether remineralizing agents can effectively reverse WSLs based on the existing evidence. Clinical relevance: APF foam may be recommended as a remineralizing agent for preventing orthodontically induced WSLs. Prospero registration number: CRD42019116852.

Background White spot lesions (WSLs) are common adverse effects in fixed orthodontic treatment. Remineralising agents are widely used to prevent WSLs formation and are the first-line treatment for existing WSLs. Previous systematic reviews have evaluated the effectiveness of remineralisation agents in the management of WSLs. However, their conclusions were contradictory. The objective of this study will be to compare the effectiveness and safety of current remineralising agents used in the management of WSLs in patients treated with fixed orthodontic appliances in any orthodontic setting. Methods Literature searches will be conducted in several electronic databases (from inception onwards): MEDLINE (via Ovid), Scopus, Embase, the Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), among others. Grey literature will be identified through searching clinical trials registries. Randomised controlled trials that compared the effectiveness of different remineralisation agents in the prevention and treatment of WSLs will be included. Two researchers will independently screen all citations, full-text articles, and abstract data. The study risk bias will be appraised using an appropriate tool. The primary outcomes will be WSLs incidence and severity of WSLs. Secondary outcomes will be subjective measures of WSLs and adverse effects. The mean difference (MD) and relative risk (RR) with corresponding 95% confidence intervals (CI) will be chosen as effect measures for continuous and binary outcomes, respectively. If feasible, fixed and random-effects pairwise meta-analyses and frequentist network meta-analyses will be conducted where appropriate. Discussion This network meta-analysis will compare the effectiveness of remineralising agents in the prevention and treatment of orthodontically induced WSLs. By integrating the evidence from direct and indirect comparisons and ranking all evaluated interventions, our findings have the potential to help clinicians make more accurate treatment decisions. Systematic review registration PROSPERO CRD42019116852, registered on March 15, 2019

Background: Numerous surveys have shown that orthodontic mini implants (OMIs) are underused in clinical practice. To investigate this implementation issue, we conducted a systematic review to (1) identify barriers and facilitators to the implementation of OMIs for all potential stakeholders and (2) quantify these implementation constructs, i.e., record their prevalence. We also recorded the prevalence of clinicians in the eligible studies that do not use OMIs. Methods: Methods were based on our published protocol. Broad-spectrum eligibility criteria were defined. A barrier was defined as any variable that impedes or obstructs the use of OMIs and a facilitator as any variable that eases and promotes their use. Over 30 databases including gray literature were searched until 15 January 2016. The Joanna Briggs Institute tool for studies reporting prevalence and incidence data was used to critically appraise the included studies. Outcomes were qualitatively synthesized, and meta-analyses were only conducted when pre-set criteria were fulfilled. Three reviewers conducted all research procedures independently. We also contacted authors of eligible studies to obtain additional information. Results: Three surveys fulfilled the eligibility criteria. Seventeen implementation constructs were identified in these studies and were extracted from a total of 165 patients and 1391 clinicians. Eight of the 17 constructs were scored by more than 50 % of the pertinent stakeholders. Three of these constructs overlapped between studies. Contacting of authors clarified various uncertainties but was not always successful. Limitations of the eligible studies included (1) the small number of studies; (2) not defining the research questions, i.e., the primary outcomes; (3) the research design (surveys) of the studies and the exclusive use of closed-ended questions; (4) not consulting standards for identifying implementation constructs; (5) the lack of pilot testing; (6) high heterogeneity; (7) the risk of reporting bias; and (8) additional shortcomings. Meta-analyses were not possible because of these limitations. Two eligible studies found that respectively 56.3 % (952/1691) and 40.16 % (439/1093) of clinicians do not use OMIs. Conclusions: Notwithstanding the limitations of the eligible studies, their findings were important because (1) 17 implementation constructs were identified of which 8 were scored by more than 50 % of the stakeholders; (2) the various shortcomings showed how to improve on future implementation studies; and (3) the underuse of OMIs in the selected studies and in the literature demonstrated the need to identify, quantify, and address implementation constructs. Prioritizing of future research questions on OMIs with all pertinent stakeholders is an important first step and could redirect research studies on OMIs towards implementation issues. Patients, clinicians, researchers, policymakers, insurance companies, implant companies, and research sponsors will all be beneficiaries.