The current use of anti cariogenic agents and fluoride agents to cure write spot lesion: A systematic analysis

To find the best option to treat White Spot Lesion in existing caries treatments, and to identify the selected articles discussing etiology of caries along with White spot lesion. Null hypothesis was that "Only anticariogenic agent can cure White Spot Lesion". PRISMA guidelines were used to conduct the systematic analysis. An electronic customized search was performed using mesh terminologies on PubMed database based on inclusion criteria that included studies with; any treatment option that can treat or prevent WSL; and minimally invasive treatment options that may be altered to treat WSL. While exclusion criteria comprised studies with treatment of rampant caries, severe early childhood caries and root caries. Inclusion criteria for etiological factors incorporated studies with factors that lead to white spot lesion or carious lesion. Finally, therapeutic agents of dental caries were analyzed. Only the use of anti-cariogenic agent cannot cure White Spot Lesion. Hence study fails to prove the null hypothesis. Although combination of anti-cariogenic agents with a re-mineralizing agent can provide additional options for the treatment or prevention of WSL.


Introduction
Dental caries is a disease affecting people of all ages. 1 Carious lesion has the ability to hurt the quality of life if left untreated. 2Treatment of such lesions at the earliest possible stage with minimally invasive options is the utmost requirement.Trend from drilling of carious lesion is moving towards reversal of early form of caries.[5][6] There is a fine line to differentiate between the White Spot Lesion (WSL) and caries lesion.This study seeks to present a systematic analysis on the current trends of minimal to non-invasive treatments of dental caries.8][9] WSL is considered the first step in the formation of carious lesion.PubMed medical subject heading (MeSH) terminology explains WSL tooth de-mineralisation separately from carious lesion even though it can lead to carious lesion.Considering de-mineralisation or WSL as a separate entity will clearly isolate the treatment options of WSL from dental caries.
Available non-invasive options in use for the treatment of WSL include fluoride gel application and desensitising agents. 9While treatment options at dental clinic include filling or coating with veneers using porcelain or composite, bonding agent to correct flaw or decay, crowns or inlays and vital tooth crowning.Non-invasive treatment options in use are mostly symptomatic.On the other hand, invasive treatment options are not attractive as it involves removal of vital tooth structure. 7,10test treatment options in literature focus on remineralising the WSL. 9,11A visible change in trend over 50 years can be seen in literature (Figure -1) which is an evidence of increasing number of research studies in this related field.Considering that present research on treating WSL is fixated on re-mineralising agents, there was a possibility of finding additional treatment options in latest research on prevention and treatment of dental caries.The current systematic review was planned to put on emphasis on the current trends in minimal to non-invasive anti-cariogenic agents that can be used to treat WSL.
The initial run of search yielded 2374 articles pertaining to the topic.After search term optimisation, 86(3.62%)articles were short-listed.This was the first level of automatic filtering applied to the search engines using Boolean Logic.The search result was further refined by introducing various filters, like availability of full text, free access and publication history (last 20 years to last 5 years) etc.Each of the filters provided a sharper focus towards the current trends in research.After reducing the time span to 5 years (January 1, 2010, to January 1, 2015), the total number of studies left was 68(2.84%)(3.62%).

Inclusion Criteria
1. Any treatment option that can treat WSL.
2. Any preventive anti-cariogenic treatment that may also prevent WSL.
3. Minimally invasive treatment options that may be altered to treat WSL. 4. Factors that may lead to WSL or carious lesion.

Exclusion Criteria
1. Treatment of rampant caries and severe early childhood caries.

Treatment of root caries.
On the basis of the above criteria, the study rejected 38(1.6%)studies.Of the 30(1.26%)articles identified, 26(87%) pertained to therapeutic agents of dental caries that may be effective in treating or preventing WSL, and 6(20%) covered aetiological factors of caries and WSL.The search was done using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Figure -2).

Randomized clinical trial
In vitro study

Review
In vivo animal study In vitro

Review on In vivo studies
In vitro study

Randomized clinical trial
In

Discussion
After combining the results of therapeutic agents used in minimal invasive treatment options, viability of specific agents to be used as definitive treatment option can be analysed.

Aetiological factors related to demineralization and dental caries
Different aetiological factors were found in studies.General causes included free sugar intake, sweetened beverages, orthodontic treatment, bad oral hygiene, diet, tobacco, stress and alcohol.Specific aetiologies covered in these studies were presence of specific gene, anaerobe bacteria especially streptococcus mutans (SM), frequent reduction in potential of hydrogen (pH), surface adhesive properties of bacteria, biofilm formation and production of organic acid.Most of the studies were related to eradication of cause (Table -2).And a few additional factors were also noted (Table -1).Method and mechanism of these aetiology-specific treatments may help in treating WSL.

In vitro
In situ

In vitro
In potential is also explained.

1: Established therapies
There are various options used in clinics that treat caries with minimal invasion.Considering these for treating WSL may have certain issues.Use of Pit and fissure sealants by covering WSL was found to be controversial. 12,136][17] make enamel more resistant to de-mineralisation but does not re-mineralise WSL.Xylitol wipes were only tested for deciduous teeth.These issues may be resolved by combining different treatment options.

2: Antibacterial / anti-cariogenic agents of plant origin
9][20][21][22][23][24] In view of these antibacterial agents, Psidium Cattleianum leave extracts (PCLE) showed interesting results.PCLE increased the hardness of enamel but use of surfactant in the study may act as confounder.Hence, further studies are required for testing its use in the treatment of WSL.Most of these agents target the cariogenic bacteria, specifically SM.WSL that are caused by bleaching or by etching does not result from cariogenic bacteria or formation of biofilm.Hence, antibacterial agents of plant origin cannot solely resolve de-mineralisation.

3: Changing the oral habitat
Changing oral habitat by use of probiotics, 25 mutants of SM 26 or alkali-producing bacteria 27 are at initial stages of research.These reduce the cariogenic bacteria and their activity.6][27] Further research is required to establish its use in the treatment of WSL.

4: Vaccination against cariogenic bacteria
DNA vaccine that can be used via nasal cavity against SM is at initial stages of development.This might prevent SM activity but still cannot prevent de-mineralisation of tooth surface resulting due to reasons other than SM. 28

5: Nano-emulsion
It acts as disinfectant and reduces surface energy.It protects the surface of enamel. 29,30It might be considered a preventive option for WSL, but on the contrary it may hinder the etching or bleaching process.Thus its use may be controversial in certain situations.

6: Novel composite with antibacterial properties as well as re-mineralising efficiency
Combination of antimicrobial properties and the ability to re-mineralise may be effectively used during orthodontic treatment to prevent WSL.Further research is required in this field to establish its use for bonding or banding during orthodontic treatment. 31

Conclusion
Most of the treatment options found in literature related to treatment of anti-cariogenic agents fail to provide a complete cure of WSL.The possible treatment option may be further explored.Further research in combining anticariogenic agents with a re-mineralising agent may effectively treat or prevent a WSL.

Table - 1
: Studies with aetiological factors of White spot lesion.

Table - 2
: Characteristics of studies with anti-cariogenic agents and details on results.