Silver diamine fluoride – A review

INTRODUCTION

Dental caries is one of the widespread diseases of stomatognathic system and its prevalence ranges from 49% to 83% across different countries.^[1] Various data suggest that there has been a drop globally but still at significantly different rates in high- and middle-/low-income countries. The use of fluorides and established preventive programs were attributed to the declining rates in high-income countries. In low- and middle-income countries, there decline has been less or contrary because of the increasing consumption of sugars and refined foods.^[2] According to a national survey conducted in India, the prevalence of dental caries in children aged 5 years was 50%; 52.5% in 12 years old; 61.4% in 15 years old; 79.2% in 35–44 years old; and 84.7% in 65–74 years old.^[3] Early childhood caries (ECC) is one of the most commonly uncared disease affecting infants and young children. In India, the prevalence of ECC was found to be 44% among 8–48 months olds, and in rural South India, the prevalence was 40.6% among 0–3-year-old children.^[4]

With increased knowledge and understanding of the carious process, the treatment for dental caries takes a paradigm shift from surgical removal of tooth structure to prevention of its occurrence and inhibition of its progression.^[5] Conventionally, the management of dental caries has been excavation and drilling to remove the infected and affected portions of teeth which requires skills and creates noise which will be a major downfall while treating pediatric patients. Most of the children affected are young, anxious, and from low socioeconomic families less invasive procedures must be considered to combat the progression of ECC disease process.^[6]

A minimal invasive and more bearable treatment is done using 38% silver diamine fluoride (SDF) which can be used in the management of dental caries. It certainly has an advantage of more ease in psychological management of the children and no demand of local anesthesia or no drilling or use of rubber dam and has additional benefits of avoiding anxiety and being economical.^[7] The metal silver has become uncovered to the world as early as 4000 BC by Caldeans^[8] During 980 AD, Avienna brought silver nitrate to medical attention using it as a blood purifier. However, in early 1600s, many scientists and doctors utilized silver nitrate as purgative, counter irritant and for the therapy of brain infections.^[9] However, the first use of silver nitrate in dentistry was in 1840. Later in 1917, ammoniacal solution of silver nitrate has been used for its antimicrobial property and their ability to penetrate dentin.^[10] In Japan, silver fluoride is used for a millennium, to which amine was added 80 years ago and used for treating carious lesions^[11] and it was approved as cariostatic agent by Central Pharmaceutical Council of Ministry of Health and Welfare and marketed with a trade name of Saforide.^[12]

SDF is approved and being used for the past 80 years. On August 2014 in the USA, Food and Drug Administration stated it as Class II medical device. This perceived SDF as a “drug to treat serious or life-threatening conditions” and declares that “exploratory clinical evidence of SDF indicates that it may validate a valuable improvement over existing therapies.”^[13] This strikes SDF as a pioneer to substantially state that oral disease is being designated as a serious medical state and promoted its significance in health welfare issues.

HISTORY AND EVOLUTION

In 1969, SDF was first scrutinized by a Japanese scientist Mizuho Nishuro at Osaka University. She explored it to know about the amalgamated effects of silver and fluoride which are known for their antimicrobial and remineralization properties, respectively.^[14] In 1970, Western Australia School of Dental Service used a new approach called “two step metal fluoride” by application of silver fluoride and stannous fluoride to prevent new carious lesions.^[14] Initially, 10–12% concentration of SDF was explored to know about their effects but they proved to be less effective than 38% SDF.^[15]

Several researches are being done by merging different materials in different concentrations such as use of 40% SDF and 10% stannous fluoride and another research with the use of 25% silver fluoride and 5% silver fluoride varnish. However, their beneficial effects evinced to be less effective or similar to that of 38% SDF.^[16]

MECHANISM OF ACTION

SDF has antimicrobial action on bacteria causing caries such as strains of Streptococcus mutans, Actinomyces naeslundii, Lactobacillus acidophilus, and Lactobacillus rhamnosus.^[27,28,32] It also acts on organic and inorganic portion of tooth by inhibiting the degeneration and promoting remineralization, respectively [Figure 1]. SDF penetrates enamel of about 25 μ^[17] and dentin of about 16–200 μ.^[33] SDF arrested lesions of 150 μ thick.^[28]

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Figure 1:

Flowchart of mechanism of action of silver diamine fluoride.

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SDF reacts with hydroxyapatite (HA) crystals (Ca10(PO4)6(OH)2) to form silver phosphate (Ag3PO4) and calcium fluoride (CaF2) as its major byproducts.^[21,34]

Ca10(PO4)6(OH)2 + Ag(NH3)2 → CaF2 + Ag3PO4 +NH4OH

SDF can react in the following possible mechanisms:

1. Calcium fluoride is one of the major by-products of the reaction. It reacts with HA to form fluorohydroxyapatite. Fluoride acts on peritubular and intertubular dentin and they improve their resistance against acid decalcification.^[35] Fluoride also mends any lattice imperfection^[36] and ameliorates their crystallinity,^[37] thereby promoting remineralization

   Step 1: CaF2 → Ca++ + 2F−

   Step 2: Ca10(PO4)6(OH)2 + 2F− → Ca10(PO4)6F2 + 2OH−

2. The silver phosphate formed in the reaction forms a silver protein layer and obturates the dentinal tubules. This reduces the possibility of bacteria and bacterial byproducts invading into dentin. Researchers also mentioned that SDF has demineralization inhibiting property^[29,38]

3. The antibacterial action of SDF is by its anti-enzymatic activity and dextran-induced agglutination of cariogenic strains of S. mutans. ^[15] SDF-treated dentin is resistant to trypsin, bacterial collagenase, matix metalloproteinases,^[39] and cathepsins^[29]

4. Silver in SDF has its effect on both bacteria and tooth. Silver interacts with sulfhydryl group of proteins, damage to deoxyribonucleic acid, alteration in hydrogen bonding, and inhibits cell wall synthesis and cell division. These effects cause bacterial killing and inhibit biofilm formation^[15,32]

5. Suzuki et al. proposed anti-plaque activity of SDF and stated that they have a minimal inhibitory concentration of 0.12 μ mole/ml against S. mutans and completely inhibits the dextran-induced agglutination of S. mutans at 0.59 μ mole/ml and sucrase activities of S. mutans at 0.2 μ mole/ml. SDF inhibits the adsorption of salivary proteins by HA which prevent plaque formation^[17]

6. Zombie effect:^[40] Silver is said to act according to Le Chatelier’s principle. This is because the bacteria that are killed by silver have conspicuous biocidal activity against living bacteria. This is due to the following important characteristics: (i) While killing the bacteria, the metallic silver is not deactivated and (ii) the bacteria that are dead acts as a reservoir for metallic silver and cause sustained release of silver.

CONCLUSION

The main advantages of SDF are its low cost, easy availability, and not technique sensitive. It does not require any special instruments or gadgets for application. With proper training, SDF is considered as an ideal material for mass community application to arrest caries at least to underdeveloped and disadvantaged people where there is limited or no access to dental care. In India, it is available in the name of Fagamin (Tedequim, Cordoba, Argentina). Longitudinal studies are expected in this regard to prove its efficacy in arresting dental caries for a prolonged period of time.