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Caries prevalence among children in developed countries has dropped exponentially in recent decades. However, dental caries remains a significant chronic health problem for a small group of high-risk children.1,2 In the United States, higher caries prevalence is correlated with lower socioeconomic status: according to recent statistics, 56.3% of youth below the federal poverty level had dental caries, compared with 34.8% of children from families with incomes greater than 300% of the poverty level.1 Prevention of dental caries in children is a pivotal part of the modern pediatric dental practice. A personalized, comprehensive, risk-based preventive plan should address multiple factors; appropriate use of fluoride is considered to be one of the most important components.3
Fluoride and Fluoride Varnish
Fluoride's cariostatic action was first discovered in the 1920s. Initially the systemic caries protection effect of fluoride was the emphasis, but during recent decades, the interest in fluoride's action has shifted to its topical effects.3
Topical fluoride plays a critical role in caries prevention by inhibiting demineralization, enhancing remineralization, and inhibiting plaque bacteria.4 The most common ways of receiving topical fluoride include toothpaste, mouthrinse, gel, foam, and varnish. The fluoride ion content in each product varies, ranging from 225 to 22,600 ppm.3
In 1964, the first fluoride varnish (FV) was introduced to the market in Europe. FV products became available in the United States after the Food and Drug Administration approved them to be used as cavity liner and desensitization agents in 1994.3 The common therapeutic use of FV for caries prevention is considered "off label." Although the therapeutic agent in FV is mostly sodium fluoride, the carrier is the varnish, which forms an adherent film holding the sodium fluoride in contact against tooth enamel.5 Since entering market, FV has become one of most commonly used professional topical fluoride agents.6 The main advantages of FV include ease of application, fast setting, prolonged contact time, slow and gradual fluoride release, smaller amounts needed for treatment, and safety.5,6 These features have contributed to its popularity in pediatric dental practice, particularly in pre-cooperative children, children with special healthcare needs, children exposed to head-and-neck radiation treatment, and children who have an exaggerated gag reflex.5 The amount of fluoride placed through FV packaged in unit doses is approximately one-tenth that of other professional products, posing lower potential for harm caused by accidental ingestion.7
Fluoride Varnishes: Properties and Action
Application of topical fluoride agents leads to the formation of calcium fluoride on the enamel surface. When stabilized by intraoral protein phosphates, these calcium fluoride globules can act as a fluoride reservoir at neutral pH. When pH is reduced during a cariogenic challenge, the dissolution of calcium fluoride releases fluoride, increases the saturation of calcium phosphate in saliva and plaque, and enhances the precipitation of fluoridated apatite, thus promoting remineralization and preventing demineralization.8 Fluoridated apatite is more resistant to future acidic challenges.8 FV is believed to have improved cariostatic efficiency through increased exposure time due to direct effects on the enamel surface and fluoride diffusion into saliva and plaque.5 Compared with other topical fluoride agents, FV is able to provide more gradual fluoride release.9 Studies have shown that salivary fluoride levels returned to baseline 2 hours after a fluoride rinse, whereas they remained elevated for an average of 24 hours after FV application.9 FV exposes the enamel to fluoride for longer periods than gels or rinses and may result in a deeper penetration of the fluoride into the enamel surface.9
Prolonged, slightly elevated fluoride levels ( > 0.4 ppm) in saliva can shift the balance from demineralization to remineralization at the tooth-oral fluid interface,6 playing an important role in the effectiveness of topical fluoride agents.9 After topical fluoride agents are applied, the resulting fluoride levels released into whole saliva are considered as the indicator of fluoride available for interaction with the enamel surface.10 Salivary fluoride levels are influenced by the initial fluoride concentration applied, time since exposure, delivery method, fluoride retention, and fluoride clearance from the oral cavity.6 More than 30 fluoride-containing varnish products are on the market today, and they have different compositions and delivery mechanisms.7 Fluoride-release profiles from different products have been studied, mainly in the laboratory setting.6,11-14 Limited in vivo or clinical studies have been conducted on these products.9,10 Although most FV products contain the same fluoride concentration of 22,600 ppm, significantly different fluoride-releasing profiles have been noted among different products, most likely due to different resin carriers or additives used.6,12-14 Both in vivo9,10 and in vitro6,12,14,15 studies have shown that the amount of fluoride released is greatest soon after application, usually occurs in the first 3 weeks, and then tapers down with time.9,11,15
Maintaining low levels of fluoride release over longer periods would be a desirable feature of FV in long-term caries prevention. Many in vitro studies have shown that fluoride can be released over extended periods after application.6,11,12 However, it is notable that these studies were performed on enamel slabs stored in buffered calcium phosphate solution—the factors influencing fluoride retention and release were missing in the controlled laboratory settings. In clinical settings, fluoride release is more rapid due to the dynamic effects of saliva and oral function on fluoride retention and release, such as salivary flow, pH content, dietary acidic challenges, chewing, swallowing, brushing, flossing, and tongue movement.12 The clinical implication of long-term fluoride release in the laboratory is unclear for most FV products because their retention in the oral cavity is usually hours rather than weeks.
It is critical for the performance of FV that the fluoride released is incorporated into the enamel crystal structure. Is there a correlation between fluoride release and deposition on enamel? Laboratory studies have noted that there is no clear relationship between these two properties. In a recent report, although one FV released the lowest and the other the highest amount of fluoride after 4 hours, the fluoride uptake of these two products was not statistically different.16 These results show that enamel fluoride uptake cannot be predicted from the fluoride release of a product.16 Although widely studied, fluoride release into saliva may not be a meaningful measurement of the efficacy of FV.
The therapeutic agent in most FV is 5% sodium fluoride (22,600 ppm). However, different components have been added by manufacturers to improve features of FV such as migration properties, color, taste, fluoride release and uptake, and remineralization efficacy.6,13,17 Some of these added ingredients have cariostatic properties of their own, such as xylitol and calcium phosphate compounds.6,17 For example, one FV containing xylitol claims better migration properties and higher salivary fluoride levels.6 Improved migration ability is beneficial for treating difficult-to-reach surfaces, such as interproximal spaces. Xylitol has been shown to reduce the levels of Streptococcus mutans in plaque and saliva. Xylitol and fluoride potentially have a synergistic effect when used simultaneously due to their different mechanism of action.6 However, whether added xylitol improves FV's clinical performance remains unclear.
The addition of bioavailable calcium and phosphate ions to the fluoride ion has been shown to enhance remineralization of early caries lesions in a randomized controlled clinical trial.18 Calcium and inorganic phosphate ions have been included in FV by several manufacturers to improve efficacy. FV is now available containing tricalcium phosphate modified by fumaric acid (fTCP), amorphous calcium phosphate (ACP), and casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP).13 The desired effect of calcium and phosphate is to increase the levels of calcium and fluoride available intraorally to protect the enamel against demineralization, thus improving the clinical efficacy of FV.13 However, adding calcium and phosphate salts together with fluoride ions in dental materials may lead to the formation of poorly soluble calcium fluoride phosphate phases in the material, decreasing fluoride ion bioavailability.13 One FV containing CPP-ACP has shown more rapid and higher calcium, phosphate, and fluoride release at 24 hours during in vitro studies compared with fluoride-only varnish.13,19 Laboratory studies have also shown that when compared with fluoride-alone varnish, CPP-ACP FV is superior in reduction of mineral loss and reduction of lesion depth.13,20 However, although CPP-ACP-containing fluoride products are effective in preventing and treating whit spot lesions in orthodontic patients, they do not offer a superior effect to fluoride-alone varnish.17 The clinical significance of added calcium phosphate compound remains to be determined.
With so many different brands on the market, it can be confusing to practitioners when making decisions on the appropriate choice of commercially available FV. Although studies on their properties have been performed in the laboratory setting, it is challenging to predict in vivo clinical performance of FV based on in vitro studies. There are minimal studies to evaluate and compare clinical efficacy among different products. Therefore, it remains largely unknown whether different formulations will affect efficacy.
Evidence on the Efficacy of FV
The clinical efficacy of FV has been extensively studied.21-23 Apart from preventing dental caries, FV has been used to remineralize incipient enamel lesions, as well as to arrest dentin caries. Although evidence for the benefits of FV on permanent teeth is well established, the evidence for the efficacy of FV on primary teeth is less clear.24
The benefits of FV for caries prevention has been evaluated extensively. Several meta-analyses and systematic reviews have shown that application of FV every 6 months is the most cost-effective method of caries prevention for young children with high and medium risk.21,22,25 The most recent Cochrane review on this subject included 22 clinical trials with a total of 12,455 subjects in randomized studies.25 Their results showed an average 43% reduction in decayed, missing, and filled tooth surfaces (DMFT) in permanent teeth and a 37% reduction in dmft in primary teeth. The protective effect of FV did not appear to be related to baseline caries levels, background fluoride exposure, prior prophylaxis, or frequency of application.25 However, the quality of the evidence was assessed as moderate due to high risk of bias among included studies.25 The efficacy of FV in preventing white spot lesions during fixed orthodontic treatment was also evaluated. A systematic review on this topic included just three studies; one of the studies found a nearly 70% reduction in white spot lesion occurrence when FV was applied at orthodontic adjustment visit every 6 weeks.26
Occlusal surfaces are the most caries-prone sites. Pit-and-fissure sealants are the commonly used professional therapy to prevent caries in the occlusal surface of molars, especially young permanent molars. FV has been investigated in comparison with dental sealants in preventing occlusal caries. In a 2016 Cochrane review addressing this question, only eight trials met the inclusion criteria.27 The methodologies used in this small number of trials varied significantly, making it impossible to draw a clear conclusion. Overall, resin-based sealants are more effective at preventing occlusal caries than FV—for as long as 9 years in one study. However, the size of the difference is unclear. There is also a low level of evidence supporting the benefits of resin-based sealant combined with FV versus FV alone. No conclusions can be drawn regarding glass-ionomer sealant versus FV or the added benefits of using FV and sealants together compared with their use alone.27 In a more recent report from a randomized clinical trial in the United Kingdom, the clinical effectiveness of FV versus sealants in preventing caries in first permanent molars in high caries-risk 6- to 7-year-olds in a community oral health program was assessed.28 Semi-annual application of FV resulted in caries prevention that was not significantly different from that obtained by applying and maintaining sealants after 36 months.28 These findings support the use of FV at a public health level, which is less expensive than sealants.
FV is becoming an important part of professional treatment to prevent and control early childhood caries (ECC) in children.24 The effectiveness of FV for ECC has been documented; however, the prevention fraction was low and the quality of evidence was weak.24 A new systematic review was conducted with 20 trials, 17 of which were included in at least one meta-analysis, to assess FV effectiveness in preschoolers, using qualitative and quantitative syntheses.23 More than 13,650 children between 2 and 5 years old were included. It was reported that a large number of the children still developed new dentine caries lesions, regardless of FV use.23 Newer clinical trials in high-risk children have shown that the protective effect of FV may be insignificant and has limited value as a supplement to daily supervised toothbrushing in preschoolers.23,24 Interestingly, evidence showed that FV application had the greatest efficacy on surfaces that were sound at the baseline.24 This finding highlights the importance of starting early with FV application to maximize the outcome, especially in high-risk populations.24 Despite the uncertainty around the size of the effectiveness estimates, FV could still be a cost-effective alternative in certain circumstances.23 Clearly, other components of an ECC prevention plan should not be overlooked. Oral health education can be effective in reducing caries in younger children; FV application twice a year may not have much added benefit.29 Excessive exposure to sugar should also be considered when controlling the progression of ECC.
Besides preventing caries, FV may be effective in arresting the disease. Based on a recent systematic review, FV may be an effective treatment for the reversal of incipient carious lesions in primary and permanent dentition.30 Baseline caries level did not appear to affect results. However, the frequency and intervals for the FV application varied among studies and was not well established. Both 4 applications at a weekly interval and 2 applications over 4 months were effective. The duration of the clinical trials also varied considerably. The clinical data included in the review was limited and needs further validation.30
Recommendations for Clinical Use
So far, despite the moderate quality of evidence, the protective effects of FV are considered evidence-based and widely recognized by the dental community and professional organizations, such as the American Dental Association (ADA), American Academy of Pediatric Dentistry, and Centers for Disease Control and Prevention. In the 2013 clinical recommendations on topical fluoride use for caries prevention from the ADA Council on Scientific Affairs, only FV (2.26% fluoride) given at least twice a year was recommended for children younger than 6 years with increased caries risk, due to dose reductions, safety, and efficacy.5,7 For patients 6 years or older, both FV and fluoride gel can be considered7; however, FV is highly recommended in this age group due to superior safety and efficacy.5 Furthermore, the benefits of FV are known beyond dental professionals. The US Preventive Services Task Force recommended "that primary care clinicians apply fluoride varnish to the primary teeth of all infants and children starting at the age of primary tooth eruption."2 This is an expansion of the ADA risk-based guidelines. The panel justified their decision based on lack of validation on existing caries risk assessment tools in the primary care setting and the possibility of a missed opportunity for early intervention.2
FV application is fast, is well tolerated by young patients, and requires minimal training. Therefore, it is well suited to be used in the community setting, school-based programs, or physician offices. FV should be applied every 3 to 12 months, unless the individual has no risk of caries.7,22 A single-dose package of FV, vigorously stirred before application, is recommended to ensure that any precipitated fluoride is dissolved.7,22 After application, instructions to resume oral hygiene practice after a manufacturer's suggested period, usually ranging from waiting 4 to 6 hours to up to 24 hours, are important for FV to achieve its full efficacy; these instructions are determined based on the product's fluoride-release profile and are intended to maximize fluoride-enamel contact.5 Postoperative dietary instructions on a soft diet for up to 12 hours should also be included.5
When including use of FV in a patient's preventive plan, a dental professional must first consider a patient's risk of developing disease.7 Patients at low risk of developing caries may not need additional fluoride therapy, whereas sometimes even intensive fluoride therapy can be ineffective in patients with very high caries risk.7 In addition to considering FV, it is good clinical practice to include other complementary preventive strategies, such as oral health education, daily toothbrushing with fluoridated toothpaste, dietary modification, and sealants, in a patient's oral healthcare program.22
The use of FV for caries prevention is evidence based, endorsed by professional organizations, and a critical part of oral healthcare programs, especially for individuals with increased caries risk. Compared with other fluoride products, FV has demonstrated prolonged fluoride-enamel interaction, longer release of fluoride, lower risk of ingestion, and comparable-to-superior clinical effectiveness. When choosing between different FV products, practitioners should be mindful of their physical properties and chemical components, as well as their intended effects on clinical efficacy. More high-quality clinical studies are needed to assess and advance the clinical performance of FV.
About the Author
Zheng Xu, DMD, PhD
Department of Pediatric Dentistry
University of Washington
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