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SYSTEMATIC REVIEW
Year : 2022  |  Volume : 40  |  Issue : 3  |  Page : 230-238
 

Nanosilver fluoride as a caries arresting agent in children: A systematic review and meta- analysis


1 Department of Pediatric Dentistry, MA Rangoonwala College of Dental Science and Research Centre, Pune, Maharashtra, India
2 MGM Dental College, Mumbai, Maharashtra, India

Date of Submission05-May-2022
Date of Decision16-Sep-2022
Date of Acceptance17-Sep-2022
Date of Web Publication18-Oct-2022

Correspondence Address:
Shikha Choubey
Department of Pediatric Dentistry, MA Rangoonwala College of Dental Science and Research Centre, Azam Campus, Hidayatulla Road, Camp, Pune - 411 001, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jisppd.jisppd_224_22

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   Abstract 


Background: Dental caries is one of the most common concerns in oral health of children. Arresting these lesions is a treatment which is gaining momentum as against conventional restorative approaches. Aim: The aim is to evaluate the efficacy of nanosilver fluoride (NSF) as a caries arresting agent in primary teeth or first permanent molars in children. Design: The protocol for the systematic review has been registered with PROSPERO database (CRD42020162386). Several databases, such as PubMed®/MEDLINE, Web of Science™, Scopus®, Google Scholar, LILACS, Cochrane Library, ProQuest, and BBO, were searched for randomized controlled trials (RCTs) which evaluated the arrestment of caries, in primary teeth and first permanent molars in children, with a minimum follow-up of 6 months. The Risk of Bias tool by Cochrane reviews system software, Revman 5.4.1, was used for quality assessment of the included RCTs. The quality evaluation was done using the GRADE approach. Heterogeneity was assessed using Cochrane's Q and I2 statistics. Results: Five studies were included for qualitative and quantitative analysis. The Risk Ratio for NSF versus active control group was assessed to be 1.09 (0.93-1.28) with 95% Confidence Interval and for placebo control was 0.49 (0.35-0.67). Conclusion: NSF shows promise as a caries arrestment agent when applied in primary teeth.
PROSPERO Registration: This review was registered with the PROSPERO database (CRD42020162386)


Keywords: Arrestment of caries, nanosilver fluoride, preventive dentistry, systematic review


How to cite this article:
Choubey S, Patil A, Talekar AL, Kalra D. Nanosilver fluoride as a caries arresting agent in children: A systematic review and meta- analysis. J Indian Soc Pedod Prev Dent 2022;40:230-8

How to cite this URL:
Choubey S, Patil A, Talekar AL, Kalra D. Nanosilver fluoride as a caries arresting agent in children: A systematic review and meta- analysis. J Indian Soc Pedod Prev Dent [serial online] 2022 [cited 2022 Nov 27];40:230-8. Available from: http://www.jisppd.com/text.asp?2022/40/3/230/358831





   Introduction Top


Dentistry within the last 20 years has undergone a paradigm shift; however, dental caries remains an omnipresent chronic disease around the world.

A huge amount of cavitations are left untreated since oral health care demands are on the far side of the capacities of the oral health care organizations.[1]

One of the major reasons is dentists are still relying on conventional laborious techniques of drilling and filling to endure caries; furthermore, preventive measures are either omitted or yet to be acquired globally.

To overcome this issue medical model of caries management should supplant the surgical model of drilling and filling; is a philosophy with a goal to prevent new and recurrent caries and arrest ongoing caries processes. This can be done by alteration of the cariogenic environment, and supporting the remineralization process.[2]

Professional topical fluorides were the most commonly used remineralizing agent until the twentieth century. Despite their effectuality and cost-effectiveness topical fluorides necessitate patient cooperation and multiple applications through a year;[3] Hence, the alternative preparations providing more edge over these were studied, and silver diamine fluoride (SDF) has emerged remarkably as a silver bullet.

SDF is the only ion-based topical fluoride substance that combines sodium fluoride's remineralization of tooth structures with silver nitrate's antibacterial effect on caries-causing bacteria.[4]

SDF is effortless to use and quite reasonable. Since its application does not need dental instruments, it can be used outside the clinical atmosphere. SDF is not only user-friendly but also it is well accepted by the children as there is no need for caries removal.[4] Various clinical trials conducted recently stated that SDF has anticariogenic and antibacterial efficacy and can be considered the foremost tool in minimally invasive dentistry. Systematic reviews on SDF published till 2018 have been thoroughly analyzed and summarized by Seifo et al. in an umbrella review affirming the superiority of SDF in caries arrest in children.[5]

An Important reason that prevents this treatment from gaining wider acceptance is that silver causes a black discoloration of carious lesions and gives a metallic taste, which is a major drawback of its usage.[1] The discoloration proves to be a major shortfall in anterior teeth.

As a result, it is vital to see if other noninvasive treatments are as effective as SDF in preventing caries[4] without the above-mentioned disadvantages.

As a consequence of the rising interest in the future of dental nanotechnology applications, a new field called nanodentistry is forming.[6] Nanotechnology was founded on the idea that if we go to the heart of things, we can discover the endless possibilities and potential of fundamental particles. Nanosilver fluoride (NSF), a new experimental formulation combining silver nanoparticles, chitosan, and fluoride, was created to be an efficient anticaries agent that does not stain porous dental tissues black like SDF does. NSF is not only safe but it has antimicrobial properties against Streptococcus mutant and lactobacillus. NSF has additional advantage of being eco-friendly and inexpensive as well.

Precision robustness and evidence quality are all dependent on an exceedingly critical appraisal of clinical research to provide the best available evidence in a systematic review. We used this strategy to collect and analyze data from randomized controlled trials in order to evaluate the long-term effects of NSF application in caries prevention, focusing on a stringent methodology that examines the risk of bias in the available studies and meta-analyzing with only similar outcomes.

Research question

The objective of the present systematic review was to evaluate the efficacy of NSF as a caries arresting agent in primary teeth or first permanent molars in children. Poulation, Intervention, Comparison, Outcomes and Study (PICOS) criteria were set as arrestment of active caries in primary teeth and first permanent molars in children using NSF versus placebo or other active treatments with a minimum follow-up of 6 months in randomized controlled trials (RCT's).


   Methodology Top


Research protocol

The protocol for the systematic review has been registered with the PROSPERO database (CRD42020162386), which can be freely accessed at https://www.crd.york.ac.uk/prospero/#recordDetails. The study was completed by including articles between April 1990 and March 2020. The PRISMA protocol[7] was followed for the review.

Search strategy (literature search)

The keywords along with their Mesh terms, were used for search on the PubMed database and the free keywords were used for other electronic searches. The search was carried out using the following search engines: PubMed®/MEDLINE, Web of Science™, Scopus®, LILACS, Cochrane Library and BBO. Abstracts from Association for Dental Research, Google Scholar, ProQuest, ProQuest Dissertation and Thesis full-text databases and Periodicos Capes, Theses Database, Clinical trial registries for unpublished and ongoing trials were also used. A search of the unpublished/ongoing trials were carried out in the clinical trials registries such as Clinical Trials Registry of India (www.ctri.nic.in), Ethos-e-thesis online services (www.ethos.bl.uk), EBSCO Open Dissertation (www.ebsco.com), JSTOR (www.jstor.org), ClinicalTrials.gov (www.clinicaltrials.gov) and EU Clinical Trials Register (http://www.clinicaltrialsregister.eu). Full text versions of the papers that met our criteria were extracted for further assessment.

Appropriate medical subject headings and textual words were selected and combined with Boolean operators (AND, OR). The search done in PubMed® was done as follows:(((((((((((((((dental caries) OR dentinal caries [MeSH Terms]) OR enamel caries [MeSH Terms]) OR carious tooth [MeSH Terms]) OR primary tooth) OR deciduous tooth [MeSH Terms]) OR milk tooth [MeSH Terms]) OR carious lesion [MeSH Terms]) OR first permanent molar [MeSH Terms]) OR tooth [MeSH Terms]) OR teeth [MeSH Terms]) AND Nano Silver Fluoride [MeSH Terms]) OR NSF [MeSH Terms]) OR Chitosan [MeSH Terms]) OR Fluoride Varnish [MeSH Terms]) OR Nano silver [MeSH Terms]) OR silver Fluoride [MeSH Terms]) OR silver Nitrate [MeSH Terms]) OR Cariostatic agent [MeSH Terms]) OR Caries Arrestment [MeSH Terms]) AND Randomised Controlled Trial [MeSH Terms]) OR Clinical trial [MeSH Terms]) OR Randomised trial [MeSH Terms]) OR Double blind [MeSH Terms]) OR Single blind [MeSH Terms]) OR random [MeSH Terms]) OR research design [MeSH Terms]) OR prospective study [MeSH Terms]) OR clinical study [MeSH Terms]) NOT animals [MeSH Terms]. Similar search strategy was applied for in all search operators mentioned.

Eligibility

Inclusion criteria

  1. RCTs with a parallel design
  2. Minimum of 6 months follow-up
  3. Studies published between April 1990 and March 2020
  4. Studies done in primary teeth and or first permanent molars.


Exclusion criteria

  1. Less than 6 months follow-up
  2. Presence of active caries during enrolment to the RCT
  3. Literature published in other languages other than English
  4. In vitro and animal studies.


The quality of the included articles were assessed using GRADE.[8]

Data collection and selection of studies for systematic review (data extraction)

The studies were selected primarily based on the title and abstract as per the inclusion criteria. Duplicate articles from more than one database were included once. In case the title and abstract did not provide sufficient information, the full text was referred by three reviewers SC, AP and AT. An ID was generated with the combination of author name and year of publication for each included study. The relevant information was extracted in a customized form which was pilot tested [Figure 1].
Figure 1: PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only

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Assessment of risk of bias in included studies (quality appraisal)

This assessment was conducted by using the recommended approach for assessing the Risk of Bias Tool in studies included in Cochrane Reviews using the RevMan 5.4.1 software( Cochrane London W1G 0AN United Kingdom).[9]

We used the two-part tool to address the six specific domains (namely, sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other bias). Each domain included one or more specific entries in a “Risk of bias” table. Within each entry, the first part of the tool involved describing what was reported to have happened in the study. The second part of the tool involves assigning a judgment relating to the risk of bias for that entry: either low risk, unclear risk, or high risk.

The domains of sequence generation, allocation concealment, incomplete outcome data, and selective outcome reporting were addressed in the tool by a single entry for each study. For blinding, two entries were used because assessments needed to be made separately for-1-participants and operators and 2-outcome assessors. Whether the operator assessed the outcome of the trial, it was noted. The final domain (”other sources of bias”) were assessed as a single entry for studies as a whole. Two review authors SC and AP undertook the risk of bias assessment independently and in duplicate as part of the data extraction process. We resolved disagreements by discussion. After taking into account additional information provided by the authors of the trials, review authors grouped studies into the following categories-

  • Low risk of bias
  • High risk of bias
  • Unclear.


There was a good reliability between the two reviewers with a high kappa coefficient (k > 0.89).

Summary measures and result synthesis (data analysis)

Heterogeneity was assessed using Cochrane's Q and I2 statistics. Constant continuity corrections of + 1 were performed in case of no events in both test and control groups. Random-effect meta-analysis was performed using the DerSimonian–Laird estimator of variance. Risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated as effect estimates. Meta-analysis was performed using Cochrane Reviews tool RevMan® 5.4.1 and few other programs such as SPSS® version 21.0 (IBM, Armonk, New York United States). Apart from these, quality checks of individual articles were done using guidelines like CONSORT.[10]


   Results Top


The database screening resulted in 12,459 records. After removal of duplicates, a total of 8,556 records were available. The title screening resulted in 52 records. Reading the abstract further resulted in nine articles. Out of the nine selected titles, [Table 1] 5 full-text articles were finally selected for the review as they met the selection criteria.
Table 1: List of Initial Selected articles

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The characteristics of the selected studies are mentioned in [Table 2]. The selected studies were clinical trials with parallel designs.[1],[11],[12],[13] All the studies had samples comprising only primary teeth. The patients were all children, number ranging from 50 to 119. NSF was used in varying concentrations and varying protocols. There was one study where NSF was used in combination with Green Tea Extract.[1]
Table 2: Summary of results reported in the studies included in the systematic review

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There was a variation in the control group as well. SDF was the control for 3 studies.[1],[13] Two studies used water/saline as control resulting in no active treatment for the control group.[11],[12] The follow-up period ranged from 6 months[1] to 1 year.[11],[12],[13]

The articles selected had a huge variation in the assessment criteria for the success of the material. The variation [Table 3] in reporting is as follows-(1) Number of active carious lesions[1] (2) Site of lesion[1],[11],[13] (3) Size of lesion[13] (4) Number of surfaces[11],[12] (5) Indices at baseline were mentioned in all the selected articles.[1],[11],[12],[13]
Table 3: Comparison of selected studies

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Assessment of risk of bias

The assessment of the risk of bias is presented in [Figure 2] and [Figure 3]. From the five selected studies, three were at Low Risk of Bias[1],[11],[13] since they fulfilled the required randomization and allocation norms. The study by Al-Nerabieah et al. 2020[1] was at risk of detection bias whereas the research by Nagireddy et al.[12] was not clear on the completeness of outcome data which may lead to attrition bias.
Figure 2: Risk of bias summary: Review authors' judgments about each risk of bias item for each included study

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Figure 3: Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies

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Meta-analysis

As seen in the summary of risk of bias [Figure 2], the five included studies had a low risk of bias. There was no data available for permanent first molars as the included studies were performed on primary teeth.

The meta-analysis was further subdivided based on the type of control group as active treatment and placebo so as the effect of the control group could also be assessed as well.

Assessment 1 (nanosilver fluoride versus active treatments)

The three studies which used an active control all had SDF (38%) application.[1],[13] The RR was assessed to be 1.09 (0.93-1.28) with 95% Confidence Interval (CI). The P value for the overall effect was 0.09, which was not significant. The data were not heterogeneous [Figure 4].
Figure 4: (RR or active treatment versus NSF. RR = Risk ratio; NSF = Nanosilver fluoride

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Assessment 2 (nanosilver fluoride versus placebo)

Two of the clinical trials used placebos as control.[11],[12] The RR was 0.49 (0.35-0.67) with 95% CI. The P value for the overall effect was 0.63 [Figure 5].
Figure 5: Forest plot on odds ratio for placebo

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GRADE assessment

The outcome of Arrestment of Caries, as assessed in the present systematic review shows high-grade quality for the follow-up as there were no serious limitations found [Table 4].
Table 4: GRADE Assessment Criteria

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Overall assessment

As seen in the Forest Plot, for most of the individual studies, the line of no effect, i.e. RR = 1, was crossed and also seen with 95% CI for each of the studies Tirupathi et al. 2019[13] and Al-Nerabieah 2020.[1]

However, the summary measure obtained was 0.85 (95% CI 0.63-1.13) also crossed 1 on either side, the tests for heterogeneity being high, Chi-square value being too high, which also indicates that heterogeneity was high; it can be concluded that there is no additional benefit of the test intervention over the control intervention [Table 5].
Table 5: Summary of findings NSF compared to other interventions for arrestment of caries

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[TAG:2]Discussion [/TAG:2]

This review aims to throw light on the use of NSF as a caries arrestment agent in clinical practice. In deprived nations, oral health is neglected, which leads to increase in the incidence of dental pain and also reduced quality of life for children. Therefore, cariostatic agents are in demand in such population.[1] Lower children's cooperation and higher expenses[1] of treatment are other factors which attribute to the need for such agents. Untreated caries is a challenge to any community, especially poor communities.[11]

There is notable literature on SDF, summarizing the effectiveness of SDF, proving sufficient antimicrobial and anticariogenic efficacy.[5],[14],[15] Three trials from the current review included SDF as one group with 38% concentration.[1],[13] The main disadvantage of the use of SDF is the black staining of the carious teeth and reversible soft-tissue staining, which raised concerns about parental satisfaction, esthetic appearance limiting its use in posterior teeth only. Soft-tissue irritation, which can be painful, metallic taste, and technique sensitivity are additional limitations.[5]

NSF is a recent formulation with silver nanoparticles, chitosan, and fluoride and has proved to be excellent antimicrobial and anticariogenic agents.[11],[16] NSF has an additional advantage with no staining and is less technique sensitive.[11] The bactericidal action of NSF is discussed in the literature with various theories. Molecules containing sulfur or nitrogen when bonds with Ag+ ions results in bactericidal action. The other possible mechanism of action is free radical formation damaging cell membrane, interaction with bacterial proteins and disrupting protein synthesis, interaction with bacterial (cytoplasmic) DNA, preventing DNA replication are documented in the literature.[17] Besinis et al. stated that the antibacterial activity of AgNP is 25-fold higher than chlorhexidine and additional antifungal and antiviral efficacy has been reported.[18]

This systematic review proves that NSF is an effective means for the arrestment of caries in primary teeth. RCTs on permanent teeth within our search criteria were not available; hence, a comment on the same would not be possible.

The quality of evidence used to conduct the present review was graded as high, with a low risk of bias. Higher heterogeneity was noted after assessment of the included trials due to variations in the designs of studies. Therefore, the results of this review are dependable and we are confident in the results presented. Four out of the five selected studies selected for meta-analysis had mentioned Clinical trial registration. The authenticity of a trial is greatly increased if such a registration exists. Such a registry helps to increase transparency and reducing bias in the publication or selective reporting.[19]

If the CONSORT statement is followed for reporting RCTs, the methodology of the RCTs is greatly improved.[10],[20] Four out of the five selected trials mentioned following the CONSORT guidelines,[1],[11],[13] whereas one was unclear.[12]

There were various similarities and differences in the articles selected for this meta-analysis. All five selected articles were double-blind RCTs with parallel group designs. Four articles[1],[11],[13] had mentioned that a single operator performed the treatment. The variation in the method of assessment of caries existed as three of the studies utilized ICDAS II tool[1],[11],[12] and two studies employed the dmft/deft tool.[1],[12] There were also differences in the method/timing of application of NSF. These differences add to the heterogeneity of the selected studies.

There were very few RCTs which evaluated arrestment of caries in primary teeth and we did not find any study evaluating the effect of NSF in arresting caries in permanent first molar in children. This led to a limited number of RCTs which met the selection criteria. Another limitation could be that the longest study was of 12 months and a longer follow-up is required for better assessment. One drawback of the review is that we have included studies that were reported in the English language only.

The results of this systematic review evaluated only one single effect of NSF in the arrestment of caries and found it to be noninferior to SDF, which is the current favorite in arresting caries. With the disadvantages of SDF, which do not occur with NSF it is safe to recommend NSF for arresting the progress of carious lesions. SDF is not commonly used in permanent teeth because of the discoloration of teeth,[21],[22] so it would be safe to recommend NSF for use in permanent teeth. There are many other effects of NSF that have been studied such as remineralization of initial enamel lesions,[23] growth of biofilm,[24] and caries prevention.[25] These direct the scope for further research of this agent.

The additional advantage of NSF is of nonstaining over SDF.[26] Recent literature by Espíndola-Castro et al. 2020[27] and Sayed et al., 2020[28] suggested NSF as an alternative to SDF. This can be attributed to the small particle size of silver, which is sufficient for antibacterial activity without staining due to low metal concentration.[11]

It has been proven that primary teeth enamel which are more prone to caries[29] are also more permeable to fluoride as compared to permanent teeth enamel.[30] This higher permeability allows for enhanced remineralization of enamel in deciduous teeth[31] with the added antimicrobial advantage of silver nanoparticles.[32] The antibacterial activity of silver is influenced by particle size, so smaller the particles, greater the effect.[33] Smaller particle size increases the surface area for antimicrobial action.[16] The silver particles can also damage the DNA of the bacteria apart from preventing adhesion in the biofilm.[34],[35]

Current literature definitely suggests that NSF will soon be established as an additional alternative on the minimally invasive dentistry bandwagon.

To establish guidelines for using NSF as an alternative anticariogenic agent more RCTs, with longer follow-up are needed to precisely assess the effectiveness of NSF with SDF as the control group.


   Conclusion Top


The current systematic review found that NSF was an effective means for arrestment of caries; however, the literature on its use is lacking. There is another limitation that there are not enough commercial products containing NSF.

Further research is required to solidify the finding of this review.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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    Abstract
   Introduction
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