Effect of fluoride on preventing orthodontics treatments-induced white spot lesions: an umbrella meta-analysis

ABSTRACT

Purpose

Orthodontic treatments have been associated with certain drawbacks, including an increased risk of dental plaque, demineralization of teeth, and tooth discoloration. Localized enamel porosities that result from tooth demineralization are known as white spot lesions (WSL), which can lead to caries development. The results of the published meta-analysis are inconsistent in some aspects. Therefore, this meta-analysis of meta-analyses was conducted to provide a clear conclusion on the effect of fluoride therapy on orthodontics-induced WSLs.

Methods

To identify relevant studies, scientific databases like Web of Science, PubMed, Scopus, Cochrane Central Library, and EMBASE were searched until February 2023. Meta-analysis studies investigating the effect of fluoride in preventing orthodontics treatments-induced white spot lesions. A random-effects model was employed to evaluate the pooled results. Sensitivity and subgroup analyses were conducted. The quality of the included meta-analyses was assessed using the AMSTAR2 questionnaire.

Results

A total of 7 studies were incorporated in the analysis involving 7963 participants with a mean age of 16.94 years. The random-effects analysis demonstrated that fluoride interventions significantly reduced the incidence of white spot lesions (ES = −0.39; 95%CI:-0.63,-0.15,p = 0.001;I² = 77%, p = 0.002). In addition, the forest plot presented evidence that topical fluoride reduced the risk of white spot lesions by 40% (ES = 0.60; 95%CI:0.35,0.86, p = 0.001;I² = 85%, p = 0.001).

Conclusion

Fluoride interventions are effective in reducing the occurrence of white spot lesions during orthodontic treatment. Topical fluoride interventions were found to be particularly effective, especially in smaller and moderate-quality studies. The findings have significant clinical implications and highlight the importance of preventive measures in orthodontic care.

KEYWORDS:

• Orthodontics
• white spot lesions
• fluoride therapy
• umbrella meta-analysis

1. Introduction

Orthodontic treatments have been established to improve teeth’ positions and aesthetic aspects. Despite their beneficial aspects, fixed appliances have been associated with an increased risk of dental plaques, tooth demineralization, and discoloration of teeth as an adverse effect of orthodontic treatments [1,2]. Among the problems caused by orthodontic treatments, the chief complaint of patients is white spot lesions (WSL) due to their unpleasing appearance which might even progress into dental caries, which necessitates restorative management [3]. WSL is the caries lesion localized enamel porosities of sub-surfaces caused by the demineralization of a tooth [4]. The presence of braces and wires creates additional surfaces for dental plaque accumulation, fostering the growth of bacteria, in company with oral microflora alteration, and an increase in the amount of lactobacillus and S. mutant- -acids produced by S. mutans can lead to demineralization of the tooth enamel- results in WSL formation [5]. Additionally, prolonged treatment duration increases the exposure time to potential risk factors, emphasizing the need for preventive measures and regular dental monitoring throughout the orthodontic process. Clinical presentation includes alterations in the colour of teeth, and opaque white appearance [6]. Studies suggested that the prevalence of WSL varied between 23.4 to 96% [7]. Various preventive strategies have been proposed to prevent or minimize the occurrence of white spot lesions (WSLs) during orthodontic treatment with fixed appliances. These include using fluoride-releasing glass ionomer cement for bonding and banding, daily fluoride mouth rinses, and lingual orthodontic appliances [8]. However, a previous Cochrane review [9] has indicated that while these preventive measures may show promise in the short term, subsequent research should extend its examination beyond the conclusion of orthodontic treatment to assess the impact of White Spot Lesions (WSL) on patient satisfaction with the overall treatment experience.

Studies have provided evidence that fluoride is an effective measure to prevent the occurrence of WSLs [10]. The application of fluoride aids in the process of remineralizing tooth enamel, rendering it more resilient to acid demineralization [11]. For instance, in the absence of fluoride therapy, demineralization of enamel will accelerate as early as 4 weeks from the initiation of orthodontic treatment [5]. Studies indicate that the use of topical fluoride treatments, such as mouth rinses, gels, and varnishes, is effective in diminishing the occurrence and severity of WSLs throughout orthodontic therapy. These treatments can be administered either by a dental professional in a clinical setting or self-applied by the patient at home [10]. Apart from topical fluoride application, the utilization of orthodontic materials that release fluoride, such as brackets and wires, has demonstrated effectiveness in diminishing the frequency and severity of WSLs during orthodontic treatment. These materials gradually release fluoride over time, serving as a continual source of fluoride that helps to ward off enamel demineralization [12]. To mitigate the frequency and intensity of WSLs in patients, orthodontists and dentists may wish to include fluoride as a component of their treatment plans [13].

A present umbrella meta-analysis was conducted to determine the overall and definitive impact of preventive effects of fluoride regarding WSL avoidance or reduction.

2. Method and materials

This umbrella review protocol has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines.

2.1. Search strategy and study selection

The scientific international databases like Web of Science, PubMed, Scopus, Cochrane Central Library, and EMBASE were searched up to February 2023 to identify relevant studies. The search strategy was developed using the following MeSH and title/abstract keywords: ((((‘Orthodontics’[Mesh]) OR ‘Orthodontic Appliances, Fixed’[Mesh]) OR ((((((‘fixed appliance’[Title/Abstract]) OR (orthodon*[Title/Abstract])) OR (‘fixed orthodontic’[Title/Abstract])) OR (bracket*[Title/Abstract])) OR (‘fixed brace’[Title/Abstract])) OR (multibracket[Title/Abstract]))) AND ((‘Dental Caries’[Mesh]) OR (((((demineralization[Title/Abstract]) OR (remineralization[Title/Abstract])) OR (decalcification[Title/Abstract])) OR (‘Dental Caries’[Title/Abstract])) OR (‘white spot’[Title/Abstract])))) AND (((meta-analysis[Publication Type]) OR (meta-analysis[Title/Abstract])) OR (meta[Title/Abstract])).

The same terms are used also to search in other databases. The wild-card term’*’ was utilized to enhance the sensitivity of the search method. Also, the articles were confined to the English language.

2.2. Inclusion and exclusion criteria

Meta-analysis studies investigating the effects of fluoride therapy regarding WSL avoidance or reduction providing effect sizes (ESs), odds ratio (OR), or relative risk (RR), and their corresponding confidence interval (CI) were included in the data synthesis. In vitro, in vivo, and ex-vivo studies were excluded from this meta-analysis of meta-analyses.

2.3. Quality assessment

The quality evaluation of the included studies’ methodology was examined by two reviewers, using the AMSTAR2 questionnaire [14] independently. The AMSTAR questionnaire consists of 16 questions to which reviewers must respond with ‘yes’, ‘no’, ‘not applicable’ or ‘can’t answer’. Sixteen is the highest score. Any disagreements were resolved by consensus with the third reviewer.

2.4. Data extraction

Two independent reviewers screened the studies based on the eligibility criteria. In the first stage, the title and abstract were evaluated. Second, the full text of relevant papers was reviewed to determine whether the study could be included in the umbrella meta-analysis. All discrepancies were resolved by a senior author’s decision.

2.5. Data synthesis and statistical analysis

The overall effect size was calculated by combining the effect size for each included meta-analysis with its CI. A random-effects model was performed to obtain the overall effect size. I² statistic and Cochrane’s Q test were used to determine between-study heterogeneity; in the matter of I² value >50% or p < 0.1 for the Q-test, it was regarded as significant heterogeneity. Subgroup analyses were performed according to predefined variables to identify potential sources of heterogeneity including quality of studies, duration of treatment, and sample size. Sensitivity analysis was conducted to determine whether the overall effect size was associated with a specific study. Begg’s test was used to evaluate publication bias. If the p-value for Begg’s test was <0.05, trim and fill analysis was carried out to adjust the publication bias. This method then imputes hypothetical missing studies on the ‘empty’ side of the funnel plot and recalculates the effect size estimate. Stata software version 16.0 (Stata Corporation, College Station, TX, US) was used for all of the statistical analyses. p < 0.05 was considered a significant level.

3. Results

3.1. Study selection

The umbrella review identified 108 published meta-analyses of interventional research between 1995 to 2023 of which 18 were duplicates. After reviewing the titles and abstracts 77 articles were removed. At the full-text evaluation stage, 6 articles were excluded and finally, 7 articles were included in the umbrella meta-analysis. The PRISMA flow diagram of studies is illustrated in Figure 1. Overall, 7362 patients with a mean age of 17.11 years old were enrolled in the studies. Two of these studies were done in Australia [15,16], One in Brazil [17], One in Saudi Arabia [7], one in Greece [18], One in Hong Kong [19], and one in Iran [20]. The general characteristics of the seven eligible meta-analyses are summarized in Table 1. The Cochrane Risk of Bias Tool [21] was used for quality assessment among RCTs of included meta-analyses.

Figure 1. Flow chart of study selection.

Table 1. Study characteristics of included studies.

Citation (First author et al., year)	No. of Studies in Meta-analysis	Location Duration of flouride therapy	Type of fluoride therapy	No. of Participants in Meta-analysis	Age(year)	Quality Assessment Outcome
Sardana et al. (2019)	6	Hong Kong 18 weeks	Topical fluoride either in the form of gels, foams or varnishes	2422	17.24	Yes(Cochrane risk-of-bias) 5/6 Low
Yeoh et al. (2018)	9	Australia 18 weeks	Mouth rinse with neutral 0.025% sodium fluorid/Fluoride varnish/Duraphat contained 5% Na/5% acidulated NaF/Standard fluoride toothpaste/fluoridated (soaked in 0.5% sodium fluoride) miswak/	798	15.76	Yes (Cochrane risk-of-bias) 5/9 High
Alrebdi et al. (2021)	8	Saudi Arabia 24 weeks	Fluoride varnish (22,600 ppmNaF)	284	18.12	Yes (Cochrane risk-of-bias) NR Low
OKADA et al. (2016)	6	Brazil	Fluoride varnish	580	14.75	No/ NR
Thomas et al. (2019)	24	Greece 192 weeks	Fluridated toothbrush/F in drinking water of 0.2 pmm/F-elastic ties	1427	23	70% High
Justin et al. (2021)	18	Australia 98 weeks	Fluoride varnish/fluoride gel/5000ppm NaF paste/250ppm F rinse (100ppm AmF, 150ppm NaF)	433	13.9	Yes (Cochrane risk-of-bias) 10/18 High
Babadi Oregani et al. (2022)	7	Iran 70 weeks	Fluoride varnish/toothpaste (containing 5000 ppm sodium fluorid)	1418	17	Yes (Cochrane risk-of-bias) 5/7 Low

3.2. Risk of bias assessment

In the current study, the AMSTAR2 checklist was used to perform a methodological quality evaluation. Out of seven meta-analyses, three studies were of critically low, two studies were of moderate, and two studies were of high quality. The results of AMSTAR2 are summarized in Table 2.

Table 2. Results of the assessment of the methodological quality of the meta-analyses.

Study	Q1^1	Q2	Q3	Q4	Q5	Q6	Q7	Q8	Q9	Q10	Q11	Q12	Q13	Q14	Q15	Q16	Quality assessment
Sardana et al. (2019)	Yes	Partial Yes	Yes	Partial Yes	Yes	Yes	Yes	Yes	Partial Yes	Yes	Yes	Yes	Yes	No	Yes	No	Moderate
Yeoh et al. (2017)	No	Partial Yes	Yes	Partial Yes	No	Yes	Partial Yes	Partial Yes	Partial Yes	Yes	Yes	Yes	Yes	Yes	No	No	Critically Low
Alrebdi et al. (2021)	Yes	Partial Yes	Yes	Partial Yes	No	No	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	No	No	Critically Low
OKADA et al. (2016)	Yes	Partial Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	No	No	Critically Low
Thomas et al. (2019)	Yes	Partial Yes	Yes	Yes	Yes	Yes	Partial Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High
Justin et al. (2021)	Yes	Partial Yes	Yes	Yes	NO	NO	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Moderate
Babadi Oregan et al. (2022)	Yes	Partial Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	High

*1. Did the research questions and inclusion criteria for the review include the components of PICO? 2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol? 3. Did the review authors explain their selection of the study designs for inclusion in the review? 4. Did the review authors use a comprehensive literature search strategy? 5. Did the review authors perform study selection in duplicate? 6. Did the review authors perform data extraction in duplicate? 7. Did the review authors provide a list of excluded studies and justify the exclusions? 8. Did the review authors describe the included studies in adequate detail? 9. Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review? 10. Did the review authors report on the sources of funding for the studies included in the review? 11. If meta-analysis was performed, did the review authors use appropriate methods for statistical combination of results? 12. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis? 13. Did the review authors account for RoB in individual studies when interpreting/discussing the results of the review? 14. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review? 15. If they performed quantitative synthesis, did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review? 16. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?Each question was answered with ‘Yes’, ‘Partial Yes’ or ‘No’. When no meta-analysis was done, question 11, 12 and 15 were answered with ‘No meta-analysis conducted’.

3.3. Effect of fluoride in treating orthodontically-induced white spot lesions

The results of random-effects analysis revealed that fluoride interventions had a significantly decreasing effect on white spot lesions (ES = −0.39; 95% CI: −0.63, −0.15, p = 0.001; I² = 77, p = 0.002) (Figure 2). Also, a significant between-study heterogeneity among studies was detected (I² = 77, p = 0.002). Subgroup analysis by sample size and quality of studies revealed that a more prominent effect of fluoride was seen in studies with less than 1000 participants (ES = −0.52; 95% CI: −1.08, 0.03, p = 0.066; I² = 86.8, p = 0.001) and moderate quality of studies (ES = −0.57; 95% CI: −0.91, −0.23, p = 0.066; I² = 0, p < 0.001) (Table 3). Moreover, the findings of the subgroup analysis implied that fluoride intervention caused a reduction in white spot lesions in patients under the longer duration of treatment (≥18 weeks), although, it was not statistically significant (ES = −2.26; 95% CI: −6.31, 1.80, p = 0.27; I² = 93.3, p < 0.001) (Table 3). Sensitivity analysis showed that the estimated overall effect size for white spot lesions was not statically significant after excluding each study (Supple.file1).

Figure 2. Forest plot with mean difference and 95% confidence intervals (CIs) of the effect of fluoride therapy on orthodontics treatments-induced white spot lesions.

Table 3. Subgroup analyses for the effect of fluoride in treating orthodontically-induced white spot lesions.

			n	ES (95% CI)^1	P-within^2	I^2 (%)^3	P-heterogeneity^4
The effect of fluoride in treating orthodontically-induced white spot lesions
Effect size (Overall)			5	−0.39(−0.63, −0.15)	<0.001	77	0.002
Quality of studies
High			1	−0.32 (−0.43, −0.21)	0.001	0	<0.001
Moderate			1	−0.57 (−0.91, −0.23)	0.001	0	<0.001
Critically Low			3	−0.52(−1.08, 0.03)	0.066	86.8	0.001
Duration
<18			3	−0.33(−0.49, −0.16)	0.001	22.4	0.27
>18			2	−2.26(−6.31,1.80)	0.27	93.3	<0.001
Sample size
<1000			3	−0.52(−1.08, 0.03)	0.0066	86.8	0.001
≥1000			2	−0.39(−0.61, −0.17)	0.001	46.3	0.17
The association of topical fluoride appllication with treating orthodontically-induced white spot lesions
RR(Overall)			3	0.60 (0.35, 0.86)	<0.001	85	0.001

Abbreviations: n: number of effect sizes; ES; Effect size, CI: confidence interval¹; Obtained from the Random-effects model, ²Refers to the effect size (95% CI).

Inconsistency, percentage of variation across studies due to heterogeneity, ⁴Obtained from the Q-test.

NR; Not reported.

Moreover, an umbrella meta-analysis of observational studies showed that topical fluoride decreased the risk of white spot lesion incidence by 40% (ES = 0.60; 95% CI: 0.35, 0.86, p < 0.001; I² = 85%, p < 0.001) (Figure 3). Sensitivity analyses revealed that there was no significant change following the three-study removal (Supple.file2).

Figure 3. Forest plot with mean difference and 95% confidence intervals (CIs) of the odds of incidence of orthodontics treatments-induced white spot lesions following fluoride therapy.

4. Discussion

Based on the results of 7 meta-analyses with 7362 patients, the study revealed a significant decrease in white spot lesions (WSL) incidence following fluoride interventions through orthodontic treatments. WSLs are common on teeth during orthodontic treatment, which are areas of demineralization that manifest as white spots on the tooth surface [22]. A widely employed approach during orthodontic treatment for preventing and treating WSLs is fluoride intervention [10]. Topical application of fluoride can occur through the use of gels, varnishes, or mouthwashes, while fluoride can also be ingested through water and other sources [23]. Untreated WSLs can develop into cavitated lesions and cause dental caries, which highlights their status as an early indication of tooth decay [24]. Therefore, preventing and treating WSLs is essential to orthodontic care [20]. Various systematic reviews and meta-analyses have been conducted to explore preventive strategies for reducing or preventing the formation of WSLs during orthodontic treatment. These strategies include the use of chlorhexidine, fluoride therapy, bioactive resin adhesive, and casein phosphopeptide amorphous calcium phosphate (CPP-ACP) [8,16].

Our study identified significant heterogeneity among the studies included in the analysis indicating the variability of results across the studies. While Justin Mathews [16] indicated a moderate heterogeneity. This could be attributed to fewer variations in the characteristics of the included studies, intervention protocols, and outcome measures evaluated.

Our study’s subgroup analysis revealed a stronger effect of fluoride interventions in studies with less than 1,000 participants and moderate study quality. These findings suggest that smaller studies and studies with moderate quality may contribute more to the overall effect size of fluoride interventions on white spot lesions. Our sensitivity analysis revealed that the estimated overall effect size for WSLs did not demonstrate statistical significance when each study was excluded. This finding suggests that no individual study substantially influenced the overall results. Furthermore, the forest plot demonstrated that the use of topical fluoride interventions resulted in a 40% reduction in the risk of WSLs. This discovery implies that the effectiveness of fluoride intervention in reducing WSLs during fixed orthodontic treatment may vary depending on the type of fluoride intervention utilized.

The outcomes of our meta-analysis hold significant clinical implications. Preventing WSLs during fixed orthodontic treatment is critical to circumvent the necessity for restorative treatment following the completion of orthodontic treatment. Our findings indicate that the implementation of fluoride interventions, specifically topical fluoride interventions, can effectively prevent the likelihood of WSLs during fixed orthodontic treatment. Our study results are consistent with most previous systematic reviews and meta-analyses that have reported the efficacy of fluoride interventions in preventing WSLs during fixed orthodontic treatment while the effect size reported by Alrebdi et al. [7] was stronger in our study. This suggests that fluoride varnish may be more effective in treating existing white spot lesions (WSLs) than in preventing their emergence. Several factors may explain why the effect size reported by Alrebdi et al. [7] was greater in comparison to our study. Differences in characteristics among the studies included, such as the type of fluoride intervention used, the frequency and duration of application, and the severity of WSLs at the beginning of the study, could influence the overall effect size. The results of the risk of bias assessment indicated that among the seven systematic reviews and meta-analyses, three studies were critically low, two studies were moderate, and two studies were of high quality.

There are several mechanisms through which fluoride can intervene in the development of WSLs. Fluoride helps prevent and treat WSLs by promoting the remineralization of tooth enamel. Fluoride achieves this by providing a source of calcium and phosphate ions, which aid in repairing demineralized areas [25]. Another way that fluoride can prevent and treat WSLs is by inhibiting the growth and metabolism of bacteria that contribute to their formation. Fluoride can prevent demineralization of the tooth enamel by decreasing bacterial activity, which in turn prevents the production of acids that can lead to WSLs [26]. In addition to promoting remineralization and inhibiting bacterial activity, fluoride can strengthen tooth enamel by facilitating the uptake of calcium and phosphate ions. This is accomplished by creating a fluoro hydroxy apatite layer on the tooth enamel that enhances the uptake of these ions and reduces enamel solubility [27]. Lastly, fluoride strengthens tooth enamel by boosting its resistance against acid attacks and mechanical wear. As a result, the enamel becomes less vulnerable to demineralization, which lowers the likelihood of developing WSLs [28].

Although this umbrella review yielded significant results, several limitations should be acknowledged. The first limitation is the small number of studies included, especially those conducted in specific geographic regions, which may limit the generalizability of the findings. The second limitation concerns the high heterogeneity observed among the studies, which could affect the accuracy of the pooled effect size. Furthermore, the quality of the studies varied, with some being of critically low quality, which could impact the reliability of the results. Finally, the author’s inability to access individual patient data prevented them from conducting a more comprehensive analysis of potential confounding factors. Based on the results of the umbrella meta-analysis, future clinical trials in the field of fluoride interventions for orthodontically-induced white spot lesions should focus on improving the methodological quality of the studies, especially those with critically low quality. It is also recommended that future studies should have larger sample sizes and longer durations of treatment to improve the statistical power and accuracy of the results. Furthermore, it would be beneficial to conduct studies with consistent and standardized outcome measures to facilitate comparison and meta-analysis of results across studies. Moreover, The impact of confounding factors, such as age and type of appliance, should be considered when assessing the effectiveness of fluoride interventions for orthodontically-induced white spot lesions. Younger patients may be more susceptible to developing white spot lesions due to a lack of oral hygiene practices and a higher prevalence of orthodontic treatment, making age a potential confounding factor that should be adjusted for in statistical models. Additionally, the type of appliance used during orthodontic treatment may affect the effectiveness of fluoride interventions, as fixed appliances may create more challenging cleaning conditions than clear aligners. Therefore, future studies should adjust for the type of appliance used and consider potential confounding factors to accurately assess the effectiveness of fluoride interventions for orthodontically-induced white spot lesions.

5. Conclusion

In conclusion, the study found that fluoride interventions significantly reduce the incidence of white spot lesions during orthodontic treatment. The effectiveness of fluoride was observed particularly in studies that used topical fluoride interventions, with smaller studies and studies with moderate quality having a more significant effect size. However, the study’s limitations, including the high heterogeneity among the included studies, should be considered. Nevertheless, the findings have important clinical implications and highlight the importance of preventive measures in orthodontic care.

Author contributions

- Conception or design of the work: H.J, K.M, N.N, M.Z, L.N, A.J.

- Data acquisition, analysis: H.J, K.M, N.N, M.Z, E.A., A.J.

- interpretation of data: H.J, K.M, N.N, M.Z, L.N, A.J.

-Drafted the work or substantively revised: H.J, K.M, N.N, M.Z, L.N, A.J.

All authors have read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data will be made available upon request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/27705781.2024.2342732