Systematic Review on White Spot Lesions Treatments

,


Introduction
The enamel translucency is a characteristic related to the composition of the inter-crystalline space and could be quantitatively defined by the enamel refractive index (ERI). 1herefore, any clinical situation that leads to an alteration of the enamel organization determines a variation of the ERI (1.62). 1 The difference in refractive index between the healthy enamel and the demineralized area generates a lesion with a milky white opaque appearance, clearly distinguishable from the surrounding healthy enamel. 2,3he white spot lesions (WSLs) pathogenesis may be various.The main cause is related to an overtime plaque accumulation; moreover, many other factors as diet and levels of calcium, phosphate, bicarbonate, fluoride in saliva as well as genetic factors are reported. 4he WSLs are a frequent finding in patients with fixed orthodontic treatments (46%) due to plaque retention caused by presence of brackets and bands. 5r J Dent 2022;16:41-48.

Keywords
► white spot lesion ► resin infiltration ► enamel demineralization ► aesthetics ► enamel remineralization ► microabrasion Several treatments have been described in the literature to prevent the possible WSL progression and the cavitation and dyschromia appearance related.
Microabrasion could improve teeth aesthetic eliminating the outer defective enamel layer.This invasive technique uses 6.6% hydrochloric acid and 20-to 160-μm sized silicon carbide microparticles to remove superficial parts of the lesion. 6,7][10][11] This minimally invasive approach does not solve the aesthetic problem in advanced lesions due to the limited infiltrating capacity of the agent that act in the enamel external part and therefore could result in an untreated discolored area. 12,13he resin infiltration technique (RIT) consists in etching with a 15% hydrochloric acid that increases enamel porosity followed by the infiltration of a highly viscous and highly penetrating resin in the thickness of WSLs.
The resin stops the progression of the WSLs and creates a barrier against further cariogenic attacks. 14The resin refractive index is similar to the ERI one and masks the opaque white appearance typical of WSLs.
The resolution of these lesions exploits the camouflage effect resulted from different techniques to mask the dichromatism and to obtain an additional aesthetical clinical success.
The aim of this systematic review was to evaluate if the infiltration technique is the most efficient treatment to resolve a WSL when compared with remineralization and microabrasion techniques.

Protocol and Registration
This systematic review was conducted according to the guidelines of the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. 15Before starting the review, a detailed protocol of the methodology was developed.The review was registered in the CRD York website PROSPERO.The protocol number is CRD42020164187.

Search Strategy
The research was performed on electronic databases, including Ovid MEDLINE, PubMed, and web of science.The search was conducted up to April 1, 2020.
The following terms and their combination were searched: "White Spot," "Resin Infiltration," "Remineralization," and "Microabrasion."The choice of keywords was intended to collect and to record as much relevant data.The research was conducted by using a search formula as follows: (((((white spot) AND resin infiltration) OR white spot) AND remineralization) OR white spot) AND microabrasion.
The following focus question was developed according to the population, intervention, comparison, and outcome (PICO) study design: "In enamel WS lesion, the infiltration treatment compared to remineralization or microabrasion treatments is more or less effective in the camouflage effect?." The review included randomized clinical trial and in vitro studies that compared the results of the RIT to remineralization and microabrasion techniques for the WSL treatment.
Only studies published between January 2013 and April 2020 were considered.

Eligibility Criteria
The full texts of all possibly relevant studies were selected considering the following inclusion criteria: • Study that compared the results of WSLs treatment using the infiltration technique to remineralization and microabrasion techniques.Human trial (randomized controlled trial and clinical trial) and in vitro study.
The exclusion criteria applied to the following studies:

Risk of Bias Assessment
The evaluation of in-vitro studies was based on a methodological index that use a checklist for in-vitro studies on dental materials (CONSORT).The checklist items focus on reporting how the study was designed, analyzed, and interpreted by using 14 domains. 16Randomized clinical trials were assessed according to the modified Cochrane Collaboration. 17Bias is assessed as a judgment (high, low, or unclear) for individual elements from five domains (selection, performance, attrition, reporting, and other).

Discussion
The studies examined in this review mainly consist in-vitro studies.Five randomized clinical studies were also found.The risk of bias for these studies is presented in ►Tables 2 and 3.][29][30] To evaluate how different treatments modify the clinical outcome for the resolution of WSLs, different combinations of evaluation methods and clinical parameters were compared in the articles included in this review.
The authors of the included studies used different evaluation methods, such as spectrophotometry, digital camera combined with software analysis, and laser fluorescence, to evaluate the effect of various treatments on WSLs.
The researches included, investigated various parameters alone or in combination as clinical outcome, such as color change, superficial roughness alteration, microhardness alterations, ability to stop the WSL progression, and penetration depth of the treatment.These authors used different detection methods such as optical profilometer, confocal laser, and transverse microradiography.
All the in vivo studies evaluated the aesthetic resolution of the lesion, showing a significant regression of WSLs using RIT (ICON), remineralizing agents, and microabrasion.The lesions treated with RIT had a statistically significant improvement in camouflage effect, compared with those treated with fluoride varnish. 30,31Although using a varnish with a very high concentration of fluoride (22,600 ppm) the lesions treated with RIT still show a significantly greater color change. 29Microabrasion improves the aesthetic appearance of WSLs, but with a significantly less refractive index reduction than the infiltration technique; moreover, the results obtained with the resin infiltration also remain stable after 12 months, while the lesions treated with microabrasion tend to recur. 28Turska-Szybka et al showed that it is possible to improve the results obtained using a fluoride varnish if a RIT treatment is also added. 32n another study, RIT demonstrated a significantly better outcome than a resin-modified glass ionomer remineralizing agent (fluoride varnish), but after 3 and/or 6 months, the WSLs returned to be visible; however, lesion treated with fluoride varnish shows a superior long-term stability. 279][20][21][22][23][24][25][26] Attia et al. used bovine dental elements because these substrates have a similar behavior regarding staining effects. 33The in vitro studies analyzed does not concord among them when comparing their findings regarding the aesthetic results; moreover, one reported the failure of both RIT and remineralizing agents treatment for WSLs treatment.
][25][26] Silva et al conclude that both RIT infiltration and microabrasion were not able to restore the tooth color. 22owever, it should be noted that the etching technique used in this research (15% HCl for 2') was probably insufficient.The company suggests to repeat the application up to a maximum of three times lesions is still evident after the first etching agent application.Some authors reported that the number of etching applications can be correlated to WSLs characteristics.Wide, deep, smooth, and shiny lesions need more etching steps, and they might remain visible after resin infiltration. 34,35

Depth of Penetration
Some studies included in our review have analyzed the aesthetic results linked to penetration ability of the resin and remineralizing agents.
Arora et al reported that fluorinated varnish cannot penetrate enamel as deeply as RIT. 21The same result is confirmed by Rosianu et al; they show how 5% fluoride gel topical application does not remineralize the deep layers of the lesion.These authors state that the RITs are more efficient in deep layer infiltration of WSLs. 36he 15% hydrochloric acid required in the RIT, allows an enamel etching deeper than the orthophosphoric acid used in other remineralizing techniques. 37,38ccording to Kane et al, the etching penetration allows a better infiltration of the resin in the treated enamel.The absence of gap inhibits the bacterial proliferation and WSLs progression 39 (►Figs. 2 and 3).

Surface Microhardness
Two studies analyzed enamel microhardness variations subsequent to remineralizing or infiltrating treatment. 18,21ehrouzi et al show how topic application of two fluoride gel (900 and 1450 ppm fluoride concentration) significatively increase the enamel microhardness; this effect was not reported by using RIT. 18owever, Arora et al showed a significant hardness increase of enamel infiltrated with resin compared with the one treated with remineralizing sealants.Arora et al concluded that the resin fills the lesion and improves the mechanical strength. 21

Enamel Roughness
Arora et al showed that resin infiltration leaves the glazed surface smoother, while any modification is observed by using fluoride varnish. 21rnold et al in accordance with this study confirms that the infiltrated tooth surface is smoother, making more difficult plaque adhesion. 40

Water Absorption
Some authors have investigated the ability of treated enamel to avoid the pigmentation.
In the studies included in this review, RIT was more susceptible to pigmentation than any other technique evaluated. 22,25he resin used for infiltration is mainly composed by TEGDMA.It possesses a higher capacity of water absorption than BisGMA and UDMA. 41,42This property has been correlated to a possible late pigmentation due to water carrier effect for pigments. 43,44o prevent color alteration overtime, some authors suggest to repeat the polishing phase of the treated surface over time.An alternative is the walking bleach technique with carbamide peroxide. 45,46he results of in vivo prospective studies, in contrast, do not show WSLs pigmentations when treated with RIT.8][49][50][51][52][53][54][55] .This process changes the refractive index in the light of the treated area (healthy enamel, normal, and hydrated) by saliva has a refractive index of 1.62, while the demineralized one of the white spots is between 1.00 and 1.33.By treating the defect with resinous infiltration, the enamel acquires an index equal to 1.52: a figure very close to that of healthy enamel, with a slight difference not perceptible to the human eye.
In other words, this treatment allows you to modify the interaction of light with the enamel and therefore the visual perception by the external observer.
It should be noted, however, that not all white enamel defects can be successfully applied: the deeper the white spot goes into the thickness of the enamel, the more "resistant" it will be to infiltration procedures.In the case of very deep and pigmented lesions-that is, which also have dark areas-this type of treatment may be of little or no effect.
[58][59][60][61][62] Table 3 Summary of the risk of bias for randomized controlled trial studies according to the Cochrane Collaboration tool for assessing risk of bias

Limitations
The first limitation of this study is linked to the different methods used to evaluate the color change.These differences produce noncomparable results in a meta-analysis.Another limitation of in vitro studies considered is the high risk of bias due to the lack of blinded investigator and random sequence generation methodology.No RCT with long follow-up are present to date.

Conclusion
Based on the articles analyzed in this systematic review, the RIT seems to be the most effective and predictable treatment for the aesthetic resolution of WSLs.There is no strong evidence supporting microabrasion or remineralization technique.More RCT with a longer follow-up period are necessary to clarify the most effective approach for WSLs resolution.

►Tables 2 and 3
present the risk of bias of the in vitro studies and randomized clinical trials (RCT).

Fig. 1
Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart.

Table 1
Data extraction from selected studies

Table 2
Summary of the risk of bias for in-vitro studies according to Consolidated Standards of Reporting Trials