A silver bullet for caries?

This article by Professor Hien Ngo was first published in the ADA's News Bulletin, November 2022
 

Introduction

It is well accepted that dental caries is a multifactorial and chronic disease, which is associated with oral biofilms. In the past, dental caries was associated mainly with specific bacteria, such as the mutans- group of Streptococci. However, recent developments using 16S rRNA gene sequencing and next-generation sequencing, has revealed a much more complex situation. Species belonging to the genera Actinomyces, Bifidobacterium, Veillona, Selenomonas, Propionibacterium and Atopobium are now all considered to be perpetrators in the caries process, and surprisingly, Candida, which is an opportunistic fungal pathogen is now considered a major contributor in root caries and can be found at the base of deep carious dentine.

The question of how much affected dentine should be left, at the base of a cavity preparation, is still being without consensus. Selective caries removal is recommended, to lessen the risk of pulp exposure, so to avoid complications that can compromise the longevity of the tooth. However, clinical criteria indicating the caries-free status of the cavity preparation are still crude and very subjective.

Initially, it was thought that the clinical success of the selective caries removal technique is solely dependent on a hermetically sealed restoration, so to avoid subsequent microbial proliferation. The assumption was that viable microbes left entombed under the restoration will undergo a process of prolonged starvation, leading to dormancy and eventual death. However, recent studies showed that some entrapped microbes can survive such adverse ecosystem, by relying on the metabolism of glycoproteins and amino acids from pupal fluids.

Given the variety of factors that affect the microbial survival under sealed restorations, it was suggested that it could be advantageous to treat the affected dentine with silver compounds prior to placing a restoration. These silver compounds appear to be good candidates for sanitising deep dentinal lesions to reduce the bacterial and fungal burden after conservative caries removal.

Since the 1900s, silver compounds have been used to arrest caries lesions. It was proposed that the antibacterial and antifungal effects of silver ions could be attributed to the disruption of cell membranes, inhibition of metabolic enzymes and inactivation of DNA and RNA. The most popular silver compound is Silver Diamine Fluoride (SDF), it received FDA approval for dental and related purpose in 2014. The recent development is silver nanoparticles (AgNP), with the highest antibacterial effect in the 1-10nm size range. Discolouration of treated surfaces is a major clinical concern, and this was partially addressed by retreating a SDF treated dentine with a wash with a saturated solution of potassium iodine (KI).

The primary objective of this project was to systematically review the clinical application and antimicrobial potential of silver compounds for caries arrest. The secondary objective was to summarise the in vitro evidence to support the potency and the effectiveness of silver compounds used in eradicating cariogenic microbes in carious dentine.

This review started with 289 studies, 29 of which were selected for full-text review and only 14 articles were deemed suitable for final analysis. These studies investigated the antimicrobial effectiveness of SDF, SDF/KI, AgNP and AgNO3 in caries-affected dentine of primary and permanent teeth.
 

Primary objective: in vivo studies

in vivo studies in the management of carious dentine using SDF and SDF/KI:

Milgrom et al (2018) tested 38% SDF in a randomised, double-blind, placebo-controlled trial with parallel groups of 66 preschool children. The samples were collected at three time slots of before, 14 and 21 days after. They concluded that the lesions were arrested 70%, 14 days, and 38%, 21 days, SDF treated group and SDF acted as a broad-spectrum biocide with non-selective antimicrobial effect. 

Mitwally et al (2019) used 16SRNA sequencing to assess the biocidal effects of 38% SDF on root caries in permanent teeth. They observed a trend towards a reduction in abundance of some acidogenic taxa.

Karched et al (2019) compared SDF and SDF/KI with a 2% chlorhexidine, as positive control, and sterile saline, as negative control. Phenotypic microbiological assessment of dentine samples before and after treatments were used. There was complete elimination of mutans-streptococci in 75% of cases and a significant reduction of total viable counts by over 95% anaerobes after the SDF/KI treatment.

The common design issue with the above studies was the limited sample size and also the difference between the sample sizes of the three reviewed clinical trials. Therefore, the results could not be combined or compared and should be interpreted cautiously. Further, even though randomisation was reported, the method of allocation concealment was unclear in all three studies.

in vivo randomised clinical trials (RCT) on effectiveness of SDF: 

Urquhart et al (2019) reviewed 44 RCT studies, these compared the relative effcacy of 22 different interventions in a cumulative 7,000 subjects. These publications studied the following chemical agents SDF, AgNO3, fluoride, casein phosphopeptide-ACP, other calcium-containing compounds. They concluded that 38% SDF was the most effective, in arresting carious dentine lesions, in comparison to the other interventions.

Seifo et al (2019) conducted an umbrella review of 11 systematic reviews, with four focused on SDF effcacy in arresting root caries and seven on coronal caries. SDF was compared with fluoride varnish and atraumatic restorative treatment. They reported that the reviewed data consistently support the superior effectiveness of SDF in caries arrest.

in vivo Silver nanoparticles (AgNP) compounds in the management of dentine caries

Santos et al (2014) conducted a prospective, randomised, double-blinded, controlled clinic trial on 60 children. Caries activity status of the lesion was recorded, using ICDAS, at 7 days, 5 months and 12 months. They reported caries arrest of 81%, 72.7% and 66.7% at the respective time intervals. However due to this being the only RCT using AgNP and it contained several methodological biases, it could be concluded that the evidence derived from this study is of poor quality.
 

Secondary objective: in vitro studies

in vitro SDF on artificial dentine caries lesions

The data from four in vitro studies, which were reviewed in this section, indicated that SDF was effcacious in reducing residual cariogenic bacteria in artificially demineralised dentine lesions. The major limitation of these studies was the limited bacterial spectrum used in forming the biofilm and they only measured the cultivable bacteria and not the total microbiome. It would be diffcult to extrapolate these laboratory-based studies to clinical situations.

in vitro application of AgNP as tooth disinfectant for the treatment of dental caries

Besinis et al (2014) tested the biocidal effcacy of AgNP (56.8nm) and AgNO3 (52.8nm) against streptococcus mutans grown on dentine discs, with the positive control being chlorhexidine. Both silver-compounds were effective and comparable to chlorhexidine, however AgNO3 caused dentine discolouration.

In a comprehensive study, Noronha et al (2017) reviewed 155 studies involving AgNP in caries control. They concluded that nano silver particles in the size range between 5 and 20nm showed good biocidal effect in the Streptococcus species, and that nano silver demonstrated good potential in managing caries. There is still uncertainty about its safety for dental applications.

The authors of this systematic review concluded that there was strong in vitro and in vivo evidence supporting the use of SDF in controlling caries. Even though its bactericidal effect is broad spectrum, it is particularly effective against specific cariogens belonging to the Streptococcus genus and the combination of SDF/KI had shown effectiveness against Candidas.

The current gaps in our knowledge are in the optimum dosage and therapeutic regimens for the use of silver compounds against the polymicrobial consortia of caries affected dentine. Discolouration of the treated surfaces is still a major concern.