The objective was to identify and summarize the outcomes and evaluation methods used in clinical trials regarding the prevention and treatment of orthodontically induced white spot lesions (WSLs).
Three electronic databases were searched to identify studies that were (1) clinical trials on prevention and/or treatment of orthodontically induced WSLs, (2) reported in English, and (3) published between January 2010 and October 2019. At least 2 authors assessed the eligibility and extracted the characteristics, outcomes, and evaluation methods from included studies. All disagreements were resolved through discussion.
Among 1328 studies identified, 51 were eligible and included. A total of 48 different outcomes and 11 different evaluation methods were used in these studies. The most frequently used outcomes were WSLs clinical visual examination scores (n = 22, 43.1%), DIAGNOdent values (n = 14; 27.5%), fluorescence loss measured with quantitative light-induced fluorescence (QLF) (n = 10; 19.6%), and lesion area measured with QLF (n = 10; 19.6%). The most frequently used evaluation methods were clinical examination (n = 25; 49.0%), visual inspection by photographs (n = 15; 29.4%), DIAGNOdent (n = 14; 27.5%), and QLF (n = 10; 19.6%). None of the included studies reported data on quality of life.
Substantial outcome heterogeneity exists among studies regarding the prevention and treatment of orthodontically induced WSLs. Most of the identified outcomes are aimed to assess morphologic changes of WSLs and may not reflect patient perspectives.
The Core Outcome Set for trials on the prevention and treatment of enamel White Spot Lesions (COS-WSL) project was registered in the COMET Initiative database (No. 1399).
This review identified outcomes in trials regarding orthodontically induced white spot lesions.
Substantial outcome heterogeneity exists among relevant studies.
Morphologic changes of white spot lesions are the most frequently measured outcomes.
Most of the identified outcomes may not reflect patient perspectives.
Enamel white spot lesions (WSLs), resulting from the demineralization of enamel surfaces and subsurfaces, are the first clinically detectable signs of the caries process, which occurs in the plaque biofilm and affects the enamel surface. For orthodontic patients, the presence of appliances makes conventional oral hygiene procedures more difficult and can lead to plaque accumulation. The incidence of WSLs during fixed orthodontic treatment has been estimated at around 45.8%. In addition, WSLs are also frequently found in patients treated with full-coverage bonded acrylic splint expanders and clear aligners. ,
WSLs can be seen as early as 4 weeks after fixed appliance placement. Without effective intervention, orthodontically induced WSLs can persist indefinitely, with some even progressing to cavitated carious lesions. , They can jeopardize the aesthetics and health of affected teeth and decrease patients’ satisfaction with orthodontic treatment results. ,
Previously, a large number of clinical trials pertaining to the prevention and treatment of orthodontically induced WSLs have been conducted and published. Many interventions have been proposed to prevent or treat enamel WSLs, including the use of fluorides, casein phosphopeptide-amorphous calcium phosphate, probiotics, fissure sealants, resin infiltration, microabrasion, external bleaching, and laser therapy. , However, despite a large number of relevant clinical trials available, systematic reviews related to this topic have not produced conclusive findings. This is mainly because of the large variations in outcome selection and reporting and differences in evaluation methods used to measure those outcomes in different clinical trials. ,
One proposed solution to reduce such heterogeneity in outcome selection and reporting is the development and application of core outcome sets (COS). A COS is defined as “an agreed standard set of outcomes that should be measured and reported, as a minimum, in all clinical trials in specific areas of health or healthcare.” The development of a COS can reduce unwanted variation in outcome selection and reporting while also providing an evidence-based list of outcomes important to both patients and clinicians. This aids the subsequent data synthesis, increases the clinical relevance of research, and helps to reduce avoidable research waste. ,
At present, a few COS have been established in dentistry, including the COS for traumatic dental injuries and orthodontic treatment, whereas some ongoing projects exist, including the COS for management of caries lesions, periodontal diseases, and recurrent aphthous stomatitis. A common first step in developing a COS, as already initiated in the projects mentioned above, is to identify and characterize all outcomes used in the existing literature through a scoping review.
To our knowledge, the outcomes and evaluation methods used among trials in the specific field of orthodontically induced WSLs have not been reviewed in a systematic approach. Therefore, the objectives of this scoping review were (1) to identify and summarize outcomes and evaluation methods used in existing trials regarding the prevention and treatment of orthodontically induced WSLs, and (2) to categorize these outcomes into a series of outcome domains and explore whether any domains could be underrepresented.
Material and methods
The Core Outcome Set for trials on the prevention and treatment of enamel White Spot Lesions (COS-WSL) project was registered with the Core Outcome Measures in Effectiveness Trials initiative on August 12, 2019 (registration no. 1399). The protocol for the project was previously published. The present scoping review was conducted according to the Joanna Briggs Institute methodological guidance and written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), with no important discrepancies between the protocol and this final report.
Clinical trials regarding the prevention and treatment of orthodontically induced WSLs were eligible for inclusion. Only randomized controlled trials and controlled clinical trials published between January 2010 and October 2019 were included. Studies not published in English, basic science research, in vitro and in situ studies, observational studies, and secondary analyses of clinical trials were excluded.
MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials databases were searched to identify all eligible studies. The detailed search strategies for the above databases are listed in Supplementary Tables I–III . Additional studies were sought by manually checking the reference lists of included studies and relevant review articles.
Two authors (Y.W and F.G) screened the titles and abstracts of all records yielded from the literature searches, independently and in duplicate. The full texts of records that appeared to meet our eligibility criteria were retrieved for further examination. Any disagreement was resolved by discussion and consultation with the other authors until consensus was reached. In the event of multiple publications for the same study, only the most recent publication was included.
All reported outcomes, including primary outcomes and secondary outcomes as well as their stated evaluation methods, were identified and recorded in a standardized data extraction form by 2 authors (Y.W and F.G) independently, together with information on authors, year of publication, study design, participants, interventions and duration of follow-up. When delineation of primary or secondary outcomes was unclear, the primary outcome was inferred from the following information sources in order: corresponding trial registration record, the outcome for sample size calculation, the reported objectives of the trial, and the first outcome reported in the Results section (any subsequent outcomes reported in the Results section were identified and recorded as secondary outcomes). When uncertainty persisted concerning primary or secondary outcomes, all outcomes were recorded as primary, and a note was made in the data extraction sheet. ,
All identified outcomes were finally categorized into a series of different domains by 2 authors (Y.W and F.H) independently and in duplicate. The outcome domains were developed on the basis of relevant studies and the classification of outcomes proposed by the Core Outcome Measures in Effectiveness Trials initiative. The final list of outcome domains was determined through group discussion. Disagreements in the categorization process were resolved by discussion with the other authors. Descriptive statistics were used to report the characteristics of included studies, the frequency of different outcomes, their distribution in different outcome domains, and the frequency of different evaluation methods.
A total of 1328 studies were identified by electronic searches, and 846 studies remained after removing duplicates. After initial screening, a total of 77 studies met the predetermined inclusion criteria. After the full-text review, 50 studies were included for this review. In addition, 1 eligible study was identified via hand searches. As a result, 51 studies were included in this scoping review ( Fig 1 ).
Characteristics of included studies
Among the included studies, 38 (74.5%) were randomized controlled trials, and 13 (25.5%) were controlled clinical trials. In terms of the type of intervention, the majority of the included trials were about prevention (n = 32; 62.7%), whereas the rest were focused on the treatment of WSLs (n = 19; 37.3%). Forty-nine trials focused on fixed orthodontic appliances, and 2 trials investigated participants with full-coverage rapid maxillary expanders. No trials included patients with clear aligners. The characteristics of all included trials are shown in Supplementary Table IV .
Intervention of interest
A total of 20 different interventions were used in 51 included trials. The majority of included trials (n = 43) were 2-arm, whereas the rest 8 trials compared more than 2 interventions. The 5 most investigated interventions were topical fluorides (n = 21; 41.2%), casein phosphopeptide-amorphous calcium phosphate fluoride (n = 6; 11.8%), sealant (n = 4; 7.8%), adhesives (n = 4; 7.8%), casein phosphopeptide-amorphous calcium phosphate (n = 4; 7.8%), and resin infiltration (n = 4; 7.8%) ( Table I ).
|Interventions||Frequencies (n)||Proportion (%)|
|CO 2 laser||2||3.9|
|Drink fluoridated milk daily||1||2.0|
|Types of brackets||1||2.0|
|Chlorhexidine with antidiscoloration system||1||2.0|
Outcomes and outcome domains
A total of 48 different outcomes were identified, of which 26 were related to the clinical appearance or degree of mineralization of WSLs. The total frequency of outcomes used in 51 included trials was 157. On average, each trial used about 3.1 outcomes. The 5 most frequently used outcomes were WSLs clinical visual examination scores (n = 22; 43.1%), DIAGNOdent values (n = 14; 27.5%), fluorescence loss measured with quantitative light-induced fluorescence (QLF) (n = 10; 19.6%), lesion area measured with QLF (n = 10; 19.6%), and incidence of WSLs (n = 9; 17.6%). Only 3 studies reported outcomes regarding adverse events (including the adhesive remnant index of bands, the bracket failure incidence, and patient-reported side-effects). One study used an outcome developed by the trial authors. None of the studies provided data on quality of life. Among outcomes in trials regarding the prevention of WSLs, the 5 most frequently used outcomes were WSLs clinical visual examination scores (n = 16; 31.4%), incidence of WSLs (n = 9; 17.6%), DIAGNOdent values (n = 8; 15.7%), plaque scores (n = 7; 13.7%) and gingival scores (n = 6; 11.8%). Among outcomes in trials regarding the treatment of WSLs, the 5 most frequently used outcomes were WSLs clinical visual examination scores (n = 6; 11.8%), DIAGNOdent values (n = 6; 11.8%), fluorescence loss (n = 5; 9.8%), lesion area (n = 5; 9.8%), and color difference between sound tooth surface and WSL (n = 4; 7.8%). The number of studies reporting different outcomes is listed in Table II .
|Outcomes||No. of studies|
|WSLs clinical visual examination scores||16||6||22|
|Incidence of WSLs||9||0||9|
|Percentage of WSLs area||1||3||4|
|Area of WSLs||2||1||3|
|No. of WSLs||3||0||3|
|Improvement of WSLs||0||2||2|
|Prevalence of WSLs||3||0||3|
|Total bacterial numbers||1||2||3|
|Salivary Streptococcus mutans colonies||3||0||3|
|Salivary Lactobacilli colonies||3||0||3|
|Proportions of aciduric bacteria||0||2||2|
|Proportions of Streptococcus mutans||0||2||2|
|Proportions of Lactobacillus spp.||0||2||2|
|Distribution of WSLs score||1||0||1|
|Mineral content of WSLs||0||1||1|
|Presence of visible supragingival dental plaque||1||0||1|
|ATP-driven bioluminescence units||1||0||1|
|Plaque Streptococcus mutans colonies||1||0||1|
|Proportions of fungus Candida albicans||0||1||1|
|Acidogenicity of plaque||0||1||1|
|Stimulated salivary flow rate||0||1||1|
|Saliva buffer capacity||0||1||1|
|Salivary fluoride levels||1||0||1|
|The ARI of bands||1||0||1|
|The bracket failure incidence||1||0||1|
All reported outcomes identified from 51 included trials were categorized into 5 outcome domains: WSLs clinical visual examination (n = 36; 70.6%), WSLs assessment with devices (n = 28; 54.9%), oral hygiene status (n = 16; 31.4%), caries experience (n = 2; 3.9%), and adverse events (n = 3; 5.9%) ( Table III ).
|WSLs clinical examination (n = 36)||WSLs assessment by devices (n = 28)||Oral hygiene status (n = 16)||Caries experience (n = 2)||Adverse events (n = 3)|
|WSLs clinical visual examination scores (n = 22)||ΔF (n = 10)||Plaque scores (n = 8)||DMFT (n = 2)||The ARI of bands (n = 1)|
|Distribution of WSLs score (n = 1)||A (n = 10)||Presence of visible supragingival dental plaque (n = 1)||DMFS (n = 2)||The bracket failure incidence (n = 1)|
|Area of WSLs (n = 3)||ΔFmax (n = 4)||Gingival scores (n = 7)||Side-effects (n = 1)|
|Percentage of WSLs area (n = 4)||ΔQ (n = 4)||Total bacterial numbers (n = 3)|
|Prevalence of WSLs (n = 3)||IFL (n = 2)||ATP-driven bioluminescence units (n = 1)|
|Incidence of WSLs (n = 9)||ΔR (n = 1)||Salivary Streptococcus mutans colonies (n = 3)|
|No. of WSLs (n = 3)||ΔE (n = 4)||Plaque Streptococcus mutans colonies (n = 1)|
|Mineral content of WSLs (n = 1)||WSL luminance (n = 1)||Salivary Lactobacilli colonies (n = 3)|
|WSLs activity (n = 4)||L (n = 2)||Proportions of aciduric bacteria (n = 2)|
|Improvement of WSLs (n = 2)||a (n = 1)||Proportions of Streptococcus mutans (n = 2)|
|Success rate (n = 1)||b (n = 1)||Proportions of Lactobacillus spp. (n = 2)|
|ΔL(WSL/SAE) (n = 1)||Proportions of fungus Candida albicans (n = 1)|
|Δa(WSL/SAE) (n = 1)||Acidogenicity of plaque (n = 1)|
|Δb(WSL/SAE) (n = 1)||Stimulated salivary flow rate (n = 1)|
|DIAGNOdent scores (n = 14)||Saliva buffer capacity (n = 1)|
|Salivary fluoride levels (n = 1)|
|OHI-S scores (n = 2)|
A total of 11 different evaluation methods were used in these studies. Most of the studies used a combination of multiple measures to summarize participants’ WSLs status. The number of studies using different evaluation methods is listed in Table IV . The 5 most frequently used evaluation methods were clinical examination (n = 25; 49.0%), visual inspection by photographs (n = 15; 29.4%), DIAGNOdent (n = 14; 27.5%), QLF (n = 10; 19.6%), and manual measurement by photographs (n = 8; 15.7%). Among evaluation methods used in trials regarding the prevention of WSLs, the 5 most frequently used were clinical examination (n = 21; 41.2%), visual inspection by photographs (n = 11; 21.6%), DIAGNOdent (n = 8; 15.7%), QLF (n = 5; 9.8%), and commercial test machine (n = 4; 7.8%). Among evaluation methods in trials regarding the treatment of WSLs, the 5 most frequently used were DIAGNOdent (n = 6; 11.8%), QLF (n = 5; 9.8%), manual measurement by photographs (n = 5; 9.8%), clinical examination (n = 4, 7.8%), and visual inspection by photographs (n = 4; 7.8%). The distribution of evaluation methods is shown in Figure 2 .
|Evaluation methods||No. of studies|
|Visual inspection by photographs||11||4||15|
|Manual measurement by photographs||3||5||8|
|Commercial test machine||4||1||5|
|VistaCam iX (by fluorescent images)||0||1||1|
|Self-evaluation by patients||1||0||1|
Length of follow-up
The length of follow-up among studies varied considerably, ranging from 4 weeks to 12 years. , Among trials regarding the prevention of WSLs (n = 32), in 6 trials, the follow-up was <6 months, whereas it was >2 years in 3 trials. The timepoint of measurement was before or after bonding in the majority of trials (n = 28), whereas 4 trials started measurements at some point during orthodontic treatment. Among trials regarding the treatment of WSLs (n = 19), in 9 trials, the follow-up <6 months, whereas it was >2 years only in 1 trial. The timepoint of measurement was after debonding in the majority of trials (n = 17), whereas 2 trials started measurements at some point during orthodontic treatment. The length of follow-up in trials regarding prevention or treatment of WSLs is shown in Figure 3 , and the follow-up length of different outcomes and evaluation methods are listed in Tables V and VI .
|Outcomes||Follow-up length, mo (Study no.)||Mean, mo||Median, mo||Minimum, mo||Maximum, mo||Mode, mo|
|WSLs clinical visual examination scores||1 ( S4 ) ; 1.5 ( S6 ) ; 2 ( S15 ) ; 3 ( S7 , S22 ) ; 4 ( S50 ) ; 5 ( S33 ) ; 6 ( S23 , S25 , S31 , S35 , S43 , S48 ) ; 9 ( S44 ) ; 12 ( S10 , S36 , S37 , S42 ) ; 18 ( S2 , S14 ) ; 20.4 ( S49 ) ; 36 ( S39 ) ; 37 ( S18 )||10.52||6.00||1.00||37.00||6.00|
|DIAGNOdent scores||1.5 ( S6 ) ; 3 ( S29 ) ; 6 ( S5 , S8 , S19 , S25 , S31 , S43 , S46 ) ; 12 ( S10 , S24 , S26 , S36 ) ; 36 ( S39 )||9.32||6.00||1.50||36.00||6.00|
|ΔF||1 ( S4 ) ; 2 ( S28 ) ; 2.1 ( S47 ) ; 3 ( S1 , S13 , S22 ) ; 6 ( S 27 ) ; 10.3 ( S45 ) ; 12 ( S37 ) ; 17.9 ( S51 )||6.03||3.00||1.00||17.90||3.00|
|A||1 ( S4 ) ; 2 ( S28 ) ; 2.1 ( S47 ) ; 3 ( S1 , S13 , S22 ) ; 6 ( S27 ) ; 10.3 ( S45 ) ; 12 ( S37 ) ; 17.9 ( S51 )||6.03||3.00||1.00||17.90||3.00|
|Incidence of WSLs||6 ( S43 , S48 ) ; 7.5 ( S34 ) ; 12 ( S20 ) ; 17 ( S30 ) ; 18 ( S14 ) ; 24 ( S11 ) ; 30 ( S9 ) ; 37 ( S18 )||17.50||17.00||6.00||37.00||6.00|
|Plaque scores||6 ( S19 , S23 , S35 ) ; 9 ( S44 ) ; 12 ( S32 , S42 ) ; 24 ( S11 ) ; 30 ( S9 )||13.10||10.50||6.00||30.00||6.00|
|Gingival scores||3 ( S22 ) ; 5 ( S33 ) ; 6 ( S19 , S23 , S35 ) ; 9 ( S44 ) ; 24 ( S11 )||8.40||6.00||3.00||24.00||6.00|
|Percentage of WSLs area||2 ( S16 ) ; 6 ( S12 , S35 , S43 )||5.00||6.00||2.00||6.00||6.00|
|ΔFmax||2 ( S28 ) ; 2.1 ( S47 ) ; 10.3 ( S45 ) ; 17.9 ( S51 )||8.08||6.20||2.00||17.90||N/A|
|ΔQ||2 ( S28 ) ; 6 ( S27 ) ; 10.3 ( S45 ) ; 17.9 ( S51 )||9.05||8.15||2.00||17.90||N/A|
|ΔE||3 ( S40 ) ; 6 ( S46 ) ; 12 ( S21 ) ; 24 ( S41 )||11.25||9.00||3.00||24.00||N/A|
|Area of WSLs||3 ( S40 ) ; 12 ( S36 ) ; 144 ( S3 )||53.00||12.00||3.00||144.00||N/A|
|WSLs activity||3 ( S29 ) ; 6 ( S35 ) ; 12 ( S42 ) ; 36 ( S39 )||14.25||9.00||3.00||36.00||N/A|
|No. of WSLs||3 ( S32 ) ; 6 ( S38 ) ; 12 ( S36 )||7.00||6.00||3.00||12.00||N/A|
|Prevalence of WSLs||12 ( S20 , S32 ) ; 20.4 ( S49 )||14.80||12.00||12.00||20.40||12.00|
|Improvement of WSLs||2 ( S16 , S17 )||2.00||2.00||2.00||2.00||2.00|
|Total bacterial numbers||3 ( S1 ) ; 12 ( S10 , S37 )||9.00||12.00||3.00||12.00||12.00|
|Salivary Streptococcus mutans colonies||6 ( S23 , S38 ) ; 17 ( S30 )||9.66||6.00||6.00||17.00||6.00|
|Salivary Lactobacilli colonies||6 ( S23 , S38 ) ; 17 ( S30 )||9.66||6.00||6.00||17.00||6.00|
|IFL||3 ( S1 ) ; 12 ( S37 )||7.50||7.50||3.00||12.00||N/A|
|L||6 ( S46 ) ; 24 ( S41 )||15.00||15.00||6.00||24.00||N/A|
|DMFT||6 ( S35 ) ; 24 ( S11 )||15.00||15.00||6.00||24.00||N/A|
|DMFS||3 ( S22 ) ; 24 ( S11 )||13.50||13.50||3.00||24.00||N/A|
|Proportions of aciduric bacteria||3 ( S1 ) ; 12 ( S37 )||7.50||7.50||3.00||12.00||N/A|
|Proportions of Streptococcus mutans||3 ( S1 ) ; 12 ( S37 )||7.50||7.50||3.00||12.00||N/A|
|Proportions of Lactobacillus spp.||3 ( S1 ) ; 12 ( S37 )||7.50||7.50||3.00||12.00||N/A|
|OHI-S scores||3 ( S29 ) ; 7.5 ( S34 )||5.25||5.25||3.00||7.50||N/A|
|ΔR||2.1 ( S47 )||2.10||2.10||2.10||2.10||2.10|
|WSL luminance||6 ( S35 )||6.00||6.00||6.00||6.00||6.00|
|a||24 ( S41 )||24.00||24.00||24.00||24.00||24.00|
|b||24 ( S41 )||24.00||24.00||24.00||24.00||24.00|
|ΔL(WSL/SAE)||24 ( S41 )||24.00||24.00||24.00||24.00||24.00|
|Δa(WSL/SAE)||24 ( S41 )||24.00||24.00||24.00||24.00||24.00|
|Δb(WSL/SAE)||24 ( S41 )||24.00||24.00||24.00||24.00||24.00|
|Distribution of WSLs score||18 ( S14 )||18.00||18.00||18.00||18.00||18.00|
|Mineral content of WSLs||3 ( S40 )||3.00||3.00||3.00||3.00||3.00|
|Success rate||6 ( S12 )||6.00||6.00||6.00||6.00||6.00|
|Presence of visible supragingival dental plaque||17 ( S30 )||17.00||17.00||17.00||17.00||17.00|
|ATP-driven bioluminescence units||12 ( S10 )||12.00||12.00||12.00||12.00||12.00|
|Plaque Streptococcus mutans colonies||6 ( S38 )||6.00||6.00||6.00||6.00||6.00|
|Proportions of fungus Candida albicans||12 ( S37 )||12.00||12.00||12.00||12.00||12.00|
|Acidogenicity of plaque||12 ( S37 )||12.00||12.00||12.00||12.00||12.00|
|Stimulated salivary flow rate||6 ( S35 )||6.00||6.00||6.00||6.00||6.00|
|Saliva buffer capacity||6 ( S35 )||6.00||6.00||6.00||6.00||6.00|
|Salivary fluoride levels||12 ( S42 )||12.00||12.00||12.00||12.00||12.00|
|The ARI of bands||12 ( S24 )||12.00||12.00||12.00||12.00||12.00|
|The bracket failure incidence||10.3 ( S45 )||10.30||10.30||10.30||10.30||10.30|
|Side-effects (patient-reported)||20.4 ( S49 )||20.40||20.40||20.40||20.40||20.40|