White Spots: Prevention in Orthodontics—Systematic Review of the Literature

Early-stage dental demineralization, called white spots (WS), get their name from the characteristic colour that enamel takes on due to the acid attack of salivary cariogenic bacteria. They are often associated with fixed orthodontic therapy (FOT) and, if left untreated, evolve into caries with repercussions on oral health and dental aesthetics. This review aims to identify the most effective prophylaxis strategies to prevent WS during FOT. The search for the reviewed studies was conducted on the Pubmed, Scopus, and Web of Science databases, selecting English-only articles published in the 5 years from January 2018 to January 2023. The keywords used were “WS” and “fixed orthodontic*”, using “AND” as the Boolean operator. A total of 16 studies were included for qualitative analysis. Prevention begins with maintaining proper oral hygiene; fluoride in toothpaste, mouthwashes, gels, varnishes, and sealants can be added to prophylaxis and used regularly. Using a laser in combination with fluoride helps prevent the occurrence of WS and assists in the repair processes of initial lesions. Further studies are needed to establish international guidelines for preventing WS in orthodontically treated patients.


Introduction
White spots (WS) frequently occur during orthodontic therapy with fixed appliances [1][2][3][4][5]. They usually appear at the gingival and buccal parts of teeth. The teeth most affected by these lesions are the canines and the upper lateral incisors [6,7]. In these areas, losses of enamel mineralization have been determined, which clinically present as more or less extensive areas that are chalky white or brown, porous, and rough to the touch, a phenomenon related to the different diffusion of light compared to normally mineralized enamel [8]. These irreversible lesions of the enamel, if left untreated, evolve into caries [9,10]. The incidence of WS is strictly related to oral hygiene maneuvers and should always be detected by orthodontists at early stages. The recent pandemic situation could have reduced the capability to manage these clinical situations due to the reduced number of appointments [11]. In cases of extended WS or decay, there is a need to perform esthetic restorations; modern restorative materials have several colours and various translucency qualities, allowing them to mirror the optical behaviour of teeth and provide a natural appearance [12]. Their impact on patients' oral health and smile aesthetics can be very important, hence the importance of WS prevention, which is mainly based on the right selection of patient candidate for orthodontics. The patient in need of orthodontic therapy should first be educated in the most proper home oral hygiene techniques, should acquire a good level of hygiene before even starting orthodontic therapy, and should know that the orthodontic device will hinder common hygiene manoeuvers by representing a receptacle for plaque and bacteria [13]. In addition to hygiene, other factors associated with the occurrence of WS include: sex, age, length of therapy, type of treatment [14], characteristics of the oral bacterial flora, diet followed by the patient, and changes in the microbiota of his or her mouth, all of which have been analyzed in several studies [15][16][17] (Figure 1).
important, hence the importance of WS prevention, which is mainly based on the right selection of patient candidate for orthodontics. The patient in need of orthodontic therapy should first be educated in the most proper home oral hygiene techniques, should acquire a good level of hygiene before even starting orthodontic therapy, and should know that the orthodontic device will hinder common hygiene manoeuvers by representing a receptacle for plaque and bacteria [13]. In addition to hygiene, other factors associated with the occurrence of WS include: sex, age, length of therapy, type of treatment [14], characteristics of the oral bacterial flora, diet followed by the patient, and changes in the microbiota of his or her mouth, all of which have been analyzed in several studies [15][16][17] (Figure 1).

Protocol and Registration
This systematic review was conducted according to the standards of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) [18]. The present systematic review has been performed in accordance with the principles of PRISMA and the International Prospective Register of Systematic Review Registry guidelines (ID 405569).

Search Processing
The keywords used in the databases (Scopus, Web of Science, and Pubmed) for the selection of the publications under review were "White Spots" and "fixed orthodont*", using the word "AND" as the Boolean operator.
The search focused exclusively on articles published in English in the past 5 years (January 2018-January 2023) ( Table 1).

Protocol and Registration
This systematic review was conducted according to the standards of Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) [18]. The present systematic review has been performed in accordance with the principles of PRISMA and the International Prospective Register of Systematic Review Registry guidelines (ID 405569).

Search Processing
The keywords used in the databases (Scopus, Web of Science, and Pubmed) for the selection of the publications under review were "White Spots" and "fixed orthodont*", using the word "AND" as the Boolean operator.
The search focused exclusively on articles published in English in the past 5 years (January 2018-January 2023) ( Table 1).

Eligibility Criteria
The reviewers worked in pairs, identifying work that met the following inclusion criteria: (1) studies performed only on human subjects; (2) clinical studies or case reports; (3) studies performed on subjects who were in orthodontic therapy (fixed therapy); and (4) studies regarding WS prophylaxis in subjects who were in orthodontic therapy (fixed therapy).

Data Processing
The screening process, which was conducted by reading the titles and abstracts of the articles selected in the previous identification phase, has allowed excluding all those publications that deviated from the topics examined. Subsequently, the full texts of publications deemed to meet the agreed inclusion criteria, were read. Disagreements between reviewers on article selection were discussed and resolved.

Results
Keyword searches of the Web of Science (432), Scopus (309), and Pubmed (274) databases yielded a total of 1015 articles. The subsequent elimination of duplicates (456) resulted in the inclusion of 559 articles. Of these 559 studies, 483 were excluded-62 because they were review and 421 because they were off topic. The writers successfully sought the remaining 76 papers for retrieval, and evaluated their eligibility. The eligibility phase ended with the inclusion of 16 publications for this work ( Figure 2). Results of each study were reported in Table 2. The excluded articles have been reported in the Appendix A (Table A1). Individuals in fixed therapy for a period of one year had a higher incidence and increase in active carious lesions than did those without fixed braces. In four areas (gingival, incisal, mesial, and distal), at both the initial period and six months following CO 2 laser irradiation, the incidence, extent, and gravity of lesions were evaluated.
The incidence of WS seems to be reduced thanks to CO 2 laser irradiation. Throughout the duration of orthodontic therapy, there was no significant difference between the group using antibacterial monomer primers and the control group, in terms of demineralization reduction. The best way to prevent WS during fixed therapy is still considered to be good oral hygiene. Use of one of the three products for four months in each of three groups of patients receiving fixed therapy.
The products tested were all able to prevent WS.

Discussion
Among the most well-known and scientifically validated preventive measures is the use of fluoride in toothpastes, mouthwashes, varnishes, mousses, and cements for bonding brackets and other fixed orthodontic devices [35]. Some strategies, such as antimicrobial toothpastes, amorphous calcium casein phosphopeptides, sealants, lasers, and the presence of antimicrobial substances in orthodontic biomaterials, can effectively prevent WSL in orthodontics [36]. The purpose of this work is to investigate the possible roles of fluoroprophylaxis and other preventive strategies which can help patients and clinicians reduce the occurrence of WS during orthodontic therapy [24,26,37].
Fixed orthodontics can have negative repercussions on oral health, as they make home oral hygiene manoeuvres more difficult and are receptacles for bacteria and food debris. This is associated with a higher incidence of WS, caries, and periodontal problems.

Fixed Orthodontics and Salivary Changes
In a clinical study published in 2019 by Jurela et al., 83 patients with a medium age of 15.14 ± 1.66 (52 men and 31 women) receiving FOT were examined [22]. The study's goal was to estimate the patients' clinical and salivary changes and see whether there were statistically meaningful variations concerning the type of braces they wore (conventional vs. self-ligating brackets) [21,38].
The DMFT index is the most common population-based measure of caries experience. This index evaluates the total of a person's decaying, missing, and filled permanent teeth or surfaces. It was considered at the beginning and after six months of orthodontic treatment.
The consequences of treatment on salivary flow, the aspects of WS, and the plaque index were also considered.
Six months following the start of therapy, the study discovered an important rise in DMFT index and salivary flow in all patients, without discrimination depending on the type of fixed appliance utilized (different types of brackets or ligatures). The considerable drop in salivary pH and rise in plaque index may be one cause of the rise in DMFT index. Because increased salivary flow is associated with a rise of the plaque index, which reduces pH, it does not seem to be good to reduce the possibility of carious lesion occurrence [28,39].

Streptococcus mutants and Lactobacillus
In a 2019 comparative prospective study, Jin et al. examined the evolution of these 2 bacterial species in the saliva of people treated with fixed therapy [25]. At four separate time points-T1 before therapy, T2 3 months after appliance fitting, T3 6 months after fitting, and T4 18 months after fitting-the saliva of 15 patients receiving FOT was examined. Lactobacillus increased slightly but not significantly over the 18 months of treatment, while total bacteria remained unchanged. The quantity of S. mutans was very different between the two types of brackets, after remaining stable for the first six months and increasing dramatically at T4 (p < 0.05) [40]. Patients with conventional brackets had a higher amount of S. mutans than did those with self-ligating brackets (p < 0.05), who had a stable concentration of S. mutans during this period. The levels of sIgA, MPO, and LDH did not modify during orthodontic treatment. There was no link between sIgA and bacterial quantity. In conclusion, S. mutans increased significantly in patients wearing traditional braces during the last treatment period, suggesting that WS may develop after prolonged orthodontic therapy [20].

Fixed Orthodontics and Caries
Pinto et al., [20] examined INSO (incidence of active caries lesions) in 135 people aged 10 to 30 years. They were split into 2 groups, the first including 70 people who received no orthodontic therapy (G0), and the second including 65 people who received FOT for one year (G1). The plaque index, gingival, and caries indices were assessed at 0 and one years after treatment. One operator evaluated all teeth for caries, examining both active and inactive and early-stage and cavitated lesions. According to the work, the orthodontically treated group had a statistically higher incidence of active caries than the G0 group. In addition, the G1 group had a statistically greater mean increase in active caries. According to the results of this study, people who received FOT for one year had a significantly higher incidence and growth of active caries lesions than did people who did not receive fixed orthodontic therapy.

Enamel Etching and WS
Enamel etching performed before the location of brackets is also believed to be responsible for the rise in caries in subjects undergoing fixed therapy. The study by Yagci et al., 2019 examined possible distinctions between partial and full etching [23]. This was a double-blind randomized controlled trial of 20 patients with a medium age of 16.75 years, excellent dental hygiene, malocclusion, and fixed orthodontic therapy. Full or partial etching treatment was randomly performed on 40 maxillary arches [41]. Quantitative fluorescence images were taken at the start of orthodontic treatment, three (T1) and six (T2) months later, and at the conclusion of the braces removal phase (T3). Using quantitative light fluorescence software, the presence of WS was assessed before and after drilling, and the results were rated with Student's t-test. The research showed that, in terms of Q and A scores at T2, the group with complete etching significantly outperformed the group with partial etching (p < 0.05). At every time point, F scores considerably increased in the TE group, but only at T1 and T3 in the PE group. There were no changes between the TE and PE groups at T3 (p > 0.05), though. Regardless of the etching approach, the study indicated that the presence of WS were primarily seen in the upper lateral incisors. Although PE is better during the initial 6 months, in terms of long-term WS creation, there is no distinction between PE and TE [42,43].

Prevention of WS in Orthodontics
During orthodontic treatment and in the post-orthodontic phase to achieve remineralization, numerous strategies are employed to prevent enamel demineralization. Use of casein phosphopeptide-containing products, antibacterial products, and fluoride-containing products are examples. Chlorhexidine is the most widely used antibacterial agent for dental usage because it is highly effective against Streptococcus mutans. A study by Shimpo et al., assessed the preventive impact of antimicrobial therapy in addition to fluoride application during FOT [30]. With the addictions of fluoride and professional mechanical teeth cleaning, it has been discovered that tooth surface disinfection therapy also helps WS reduction during FOT.

Prevention with Fluoride
Several studies have found the utility of fluoride toothpaste in the reduction of WS caused by orthodontic therapy [44][45][46][47].
In a prospective study by Kau et al., with three groups of patients receiving orthodontic care [26], Clinpro 5000 was administered to 35 people, Clinpro Tooth Crème was administered to 32 people, and MI Paste Plus was administered to 33 people in every group. For four months, the chosen product was used two times a day for two minutes. Subjects were examined once each month, for 4 months. At each visit, the Enamel Decalcification Index (EDI) was utilized to calculate the amount of WS per square. Compared to previous research, the usage of Clinpro 5000, Clinpro Crème, and MI paste Plus all had a decreasing effect on WS lesions. Clinpro 5000 slightly outperformed the other two test pastes in relation to effectiveness. The clinical trial conducted in 2019 by Smyth et al. came to similar conclusions [33].
A recently introduced fluoride varnish containing 1.5% ammonium fluoride was considered in a 2019 clinical study by Sonesson et al., who ascertained that regular varnish applications reduced the quantity of WS during fixed therapy [32].
Sealants act as physical barriers to bacterial acids and plaque. While good at preventing WS, sealants do peel off over time, predominantly in the gum area, leaving the enamel exposed to plaque and acid bacteria. Sealants like ProSeal have been proven to totally prevent mineral loss from enamel if they stay on the tooth surface, but the application of the product should be repeated every few months [48].
With the growing attention on the host's innate defense system, more minimally invasive and human-friendly therapies have been considered, like the use of formulas containing enzymes, probiotics, and plant extracts. Intrinsic defense factors in saliva are the enzymes peroxidase, lysozyme, and lactoferrin. These proteins can limit bacterial or fungal growth, interfere with bacterial glucose uptake or glucose metabolism, and promote bacterial aggregation and elimination [49]. Cheng et al., in a 2019 clinical work, compared the effects between enzyme-containing and conventional toothpastes on orthodontic patients [29]. The prevention of WS and plaque reduction effects among orthodontic patients in the first three months of treatment were not significantly different between enzymecontaining and conventional toothpastes, according to the study. In the first three months of treatment, neither gingival bleeding nor visible plaque among orthodontic patients who used fluoride-and enzyme-containing toothpastes significantly increased. However, the gingival bleeding and visible plaque significantly decreased [50,51].

Active Oxygen-Containing Toothpaste
George et al., in an experiment conducted in 2022, examined how streptococcus mutations and WS responded to toothpaste with active oxygen [34]. Active oxygen toothpaste resulted in a more pronounced reduction of WS than did fluoride toothpaste. Its impact was limited, though. Both toothpaste varieties had minimal effects on WSLs. Toothpaste containing active oxygen is effective in the same manner as toothpaste containing fluoride [52,53].

Prevention with CO 2 Laser
As a result of removing the organic matrix, improving fluoride absorption, and increasing the binding surface area of ions, including calcium and fluoride, fluoride and laser act synergistically to strengthen enamel resistance to acids.
Mahmoudzadeh et al.'s 2019 RCT aimed to estimate the effect of carbon dioxide (CO 2 ) laser on the prophylaxis of WS associated with fixed therapy [24]. In this work, 554 teeth from 95 patients were considered. The 95 patients were divided into 2 groups, at random: the laser group (278 teeth), and the control group (276 teeth from 47 patients). The front teeth of the maxilla in the laser group were made aware of the CO 2 laser with the following characteristics: wavelength 10.6 m, power 0.4 mw, frequency 5 Hz, diameter 0.2 mm, and pulse time 9 s. An operator applied laser irradiation for 20 s while maintaining a 5 mm distance from the buccal surface and moving back and forth continuously [58]. Similar placebo light exposure took place for the control group. Six months after receiving radiation, patients were brought back in to have the incidence, size, and cruelty of the injuries evaluated. Data were collected twice: immediately after adherence to the attack, and six months later. Better lesions and a decrease in lesion incidences were seen during six months with CO 2 laser use [59,60]. The laser is believed to cause a chemical change in enamel crystals, removing cavities through remineralization. According to the study's findings, gingival lesions were not affected by laser irradiation, even though it was effective on the incisal, mesial, and distal regions. Unlike the gingival area, where CO 2 laser had no noticeable impact, the extent of lesions in the incisal, mesial, and distal regions was drastically reduced after treatment. Additionally, while the mesial and incisal portions of the lesion showed a significant reduction in severity, the gingival and distal regions showed little improvement. In the gingival area, the laser was ineffective, most likely because of changes in the thickness and structure of the enamel. Since gingival regions are frequently affected by WSLs, laser settings at these locations should be modified to aid in the reduction of these lesions. Additionally, better oral hygiene can lower the incidence of gingival lesions (due to increased plaque accumulation) [61].
The study by Belcheva et al., which began in September 2021 and whose follow-up phase will last until September 2023, is intriguing in the line of research on the encouraging effects of lasers [21]. Investigating how fluoride varnish and CO 2 laser treatment can lessen the frequency, severity, and extent of WS lesions during fixed orthodontic therapy is the goal. An RCT will involve kids between the ages of 12 and 18 who need fixed therapy and are at a high risk of developing cavities. The buccal surfaces of the patient's upper anterior teeth will receive fluoride therapy alone in one group, and fluoride therapy in addition to bonding orthodontic brackets in the other group. Following radiotherapy, the patients' conditions will be reevaluated six and twelve months later [62,63].

Primer with Antibacterial
Numerous studies on bonding products containing antibacterial substances exist in the literature, and all have shown encouraging results [64][65][66][67].
The aim of the study by Oz et al., is to clinically evaluate an antibacterial primer containing monomer in the prophylaxis of WS during fixed therapy [28]. The study's findings demonstrate that there was no discernible difference between the antibacterial monomer-containing primer group and the control group in terms of their capacity to prevent demineralization during orthodontic treatment [68]. Degrazia et al., examined the demineralization and antibacterial properties of an experimental orthodontic adhesive made of triazine and niobium bioglass phosphate (TAT) around attachments placed on enamel surfaces [31]. From the results of this study, the growing of S. mutans and total streptococcus were inhibited by the adhesive in the triazine and niobium phosphate-based bioglass, which had an anti-demineralization impact. This product can prevent the loss of enamel minerals.

Conclusions
WS are a common and equally dreaded complication of fixed orthodontics, as they risk seriously compromising the aesthetic and functional outcomes. WS prophylaxis begins with the correct choice [43] and motivation of the subject to maintain good hygiene. In this regard, good oral hygiene with a fluoride-containing toothpaste is the essential starting point for the effective removal of food scraps and bacterial biofilm that are deposited on teeth and braces. In addition, fluoride administration with mouthwashes for home use as well as gels, varnishes, and sealants for periodic professional use may be considered, depending on the case. The use of lasers as an adjunct to fluoride is a readily available avenue for clinicians, effective in the prevention of demineralization but also in the repair processes of early-stage lesions. The hope is that international guidelines for the use of fluoride products, antibacterial agents, and laser use can be developed in the future. More research is required to establish precise and repeatable protocols for laser use. Countless studies in the literature have evaluated the efficacy of toothpastes and other products containing various substances with antibacterial effects, many of which have yielded encouraging results that merit further study. The orthodontist must always remember that the resolution of malocclusions is a goal that must be pursued hand-in-hand with the achievement and maintenance of the patient's oral and dental health, and in this sense, it is hoped that caries prevention campaigns will have an ever-increasing prevalence and following.

Articles Excluded Reason for Exclusion
Coordes

OFF TOPIC
Al-Khafaji TJ, Agha B, Alhumadi A, Alhamadi WW, Mills D, Davis GR, Cresswell-Boyes AJ, Fleming PS. An assessment of mineral concentration of dental enamel neighbouring hypothetical orthodontic brackets using X-ray microtomography. J Dent.