Topical fluoride acts as catalyst for the diffusion of calcium and phosphate into the tooth and rebuilds tooth surfaces due to formation of fluoridated hydroxyapatite and fluorapatite crystals, which are more resistant to acid attack than hydroxyapatite (Selwitz et al., 2007). Also,
topical fluoride has an effect on the glycolytic cycle of oral microorganisms, thus reducing the production of acid and affecting metabolism of intracellular carbohydrates (MINSAL, 2008). Topical administration of fluoride allows fluoride ions, at very high concentrations, to directly reach the interface between the tooth and dental biofilm, without having to pass through the circulatory system. This avoids fluoride ions reaching other parts of the organism. However, given the high concentrations used, the risk of acute fluoride intoxication through ingestion increases. The probable toxic dose, defined as the dose that requires therapeutic intervention and hospitalization, has been calculated to be 5 mg F/kg (Shulman and Wells, 1997). Such information is extremely important for children under the age of 6 who have less control of deglutition or swallowing reflexes. Topical fluorides come in various forms such as toothpaste, gels, mouthwashes, FV, etc. They will be discussed in the following sections.
Fluoride toothpastes
In a systematic review, dos Santos et al. (2013) compared fluoride toothpastes associated with oral health education against no intervention. This review included individual or cluster randomized or quasi-randomized controlled trials in children with primary dentitions not older than 7-year-olds at the end of the eligible studies. They found that children who used standard fluoride toothpaste (1,000-1,500 ppm) had significant caries reduction at surface levels with a prevention fraction or PF (defined as the measure of treatment effect presented for caries increment) of 31% (95% CI, 18 to 43), as well as at the level of the tooth (PF = 16%; 95% CI, 8 to 25). The effect of toothpastes with fluoride concentrations over 1,000 ppm was similar to that reported by a Cochrane systematic review performed by Walsh et al. (2010) who compared different concentrations of fluoride and showed that the pooled estimate was statistically significant (RR 0.87; 95% CI ,0.81 to 0.93) in favour of a higher fluoride concentration (>1,000 ppm).
The same authors (dos Santos et al., 2013), found that low concentration fluoride toothpastes (<600 ppm) compared with no interventions, were not statistically significant (RR = 0.87; 95% CI 0.65 to 1.17) at reducing the percentage of children that developed caries. On the other hand, they found that a standard fluoride toothpaste (1,000-1,500 ppm) resulted in a statistically significant reduction in the percentage of children that developed caries (RR = 0.86; 95% CI, 0.81 to 0.93). Nevertheless, the use of such toothpastes was associated with mild but not aesthetically objectionable fluorosis (or enamel defects during the tooth formation).
Based upon the evidence discussed above, the suggestion made by MINSAL (2012c) to use toothpastes with fluoride concentrations less than 600 ppm should be re-evaluated.
Fluoride gels and mouthwashes
Marinho et al. (2015) conducted a Cochrane systematic review about the use of fluoride gels, including randomised or quasi-randomised controlled trials where ’blind outcome assessment’ was stated or indicated. They found a prevention fraction of 20% (95% CI 1 to 38; p = 0.04) at the surface level (dmfs) in children aged 2 to 6.5 years. The authors highlighted the wide CI and recommended that the results should be viewed with caution, given that standard deviations of two of the three studies were imputed. At the same time, they found scarce evidence about the frequency of accidental swallowing of the gel during treatment.
Fluoride gels typically used contain acidulated phosphate fluoride with a concentration of 12,300 ppm. The Chilean Ministry of Health has used this technology in non-water-fluoridated schools for more than 15 years. However, given that most of the Chilean population can access fluoridated water at the moment, this fluoride application is hardly used in caries preventive programmes. Also, given the risk of ingestion and possible fluoride overdose (Ripa, 1990), MINSAL has contraindicated the use of such gels in children under 6 years old (MINSAL, 2008). Fluoride mouthwashes contain 0.2% sodium fluoride. Such a solution is used in Chile in supervised weekly rinsing programmes in non-fluoridated school communities, due to the positive effect found in the literature in which a pooled estimate by Marinho et al. (2016) resulted in D(M)FT prevention fraction of 23% (95% CI, 18 to 29; p < 0.0001). However, given the risk of accidental intake, MINSAL has stated that its use is contraindicated for children under the age of 6 years (MINSAL, 2008;MINSAL, 2009b).
Despite the positive effects on caries reduction for some highly concentrated topical fluoride applications such as fluoride pastes, gels, and mouthwashes, the American Dental Association in their updated clinical recommendations on topical fluoride for caries prevention (Weyant et al., 2013) concluded that only 2.26% FV is recommended for children younger than 6 years of age. This was based on the high risk of nausea and vomiting associated with gel and mouthwashes, as well as the risk of fluorosis due to the ingestion of fluoride.
Fluoride varnish
Fluoride varnish (FV) was initially developed in 1964 with the objective of prolonging the contact time between fluoride and dental enamel (Seppa, 2004). FV contains a highly- concentrated fluoride active ingredient (i.e., a high concentration of fluoride ions), in a base that allows the product to adhere to the tooth surface even in presence of saliva. The fluoride ion can form fluorapatite crystals during the remineralisation process and interact with saliva, forming calcium fluoride (CaF2) that releases fluoride ions when the pH drops.
The oldest and best studied product is Duraphat (Colgate Oral Pharmaceuticals by Pharbil Waltrop GmbH, Waltrop, Germany), which contains sodium fluoride at 50 mg/ml or 22,600 ppm of fluoride ion in a natural colophony base. Others product based on the same active ingredient at the same concentration include, amongst others, Fluoridin, Durofluor, and Cavity Shield. Another product, Fluor Protector, has a different composition containing fluorsilane in a polyurethane polymer. No matter the brand of the product, FV must be applied on teeth surfaced using a microbrush, probe, or swab. There are two methods of administration, single and multiple-doses.
Efficacy
Several systematic reviews and meta-analyses have been performed in order to determine the effect of FV on the preschool population, among them, Carvalho et al. (2010) who included randomized, controlled clinical trials, and quasi-randomized studies. They compared FV application and no intervention or placebo and calculated the prevention fraction (PF) of dmfs. The target population were preschool aged children (up to 6 years old). They concluded that the studies analysed in this systematic review suggest that FV can reduce caries incidence, but they did not find conclusive scientific evidence to support this.
In another Cochrane systematic review, Marinho et al. (2013) compared FV application versus either no intervention or placebo. This review included randomised and quasi-randomised controlled trials with blind outcome assessment used or indicated; in children with primary dentition aged 1 to 8 years. They found that FV caused a significant reduction in caries (37%; 95% CI, 24 to 51) at the surface level (dmfs); however, at an individual level, despite finding a caries reduction (RR = 0.81), the difference was not statistically significant in the meta-analysis (95% CI, 0.62 to 1.06). Despite the fact that there is evidence to suggest that FV has a positive effect on primary dentition, this finding must be taken into consideration carefully because the
target population included children with mixed dentitions, which is beyond the objective of this thesis.
There are no systematic reviews that analyse the effect of FV on caries prevalence in a caries- free preschool population; there are only two studies that were designed to evaluate this question, the studies of Weintraub et al. (2006) and Tickle et al. (2011). Recently, the results of the latter one, the Northern Ireland Caries Prevention in Practice Trial or NIC-PIP (see 3.6.4), which was ongoing during the development of this thesis, have recently been published (O'Neill et al., 2017;Tickle et al., 2017).
Few studies can be found about the cost-effectiveness of FV, for instance, Quinonez et al. (2006), evaluated the cost-effectiveness of FV during attendance at a Medicaid well-child appointment in North Carolina, USA. In this programme, FV was applied by physicians to children aged 9 to 42 months. The study included clinical data only and used the number of months without cavities per child as the outcome. The authors concluded that FV is not cost saving in the 42 first months of life. Unfortunately, given both the difficulties of measurement and the lack of clinical significance, the outcome is very difficult to apply in a public health programme.
The pilot study (NIC-PIP), published at the beginning of 2017 (O’Neill et al.) found no statistically significant difference (p = 0.81) in caries prevalence (at dmft>0 or caries-free level) between intervention group (FV) and control group (no FV). However, Tickle et al. (2017) found statistically significant differences (p = 0.007) between both groups at surface level (dmfs level), where the intervention group had in average 1.3 fewer carious surfaces than control group. The mean cost per carious surface avoided after a follow-up of 3-years was £251 (95% CI from £ 79.52 to £ 454.39).
In summary, very little is known about the cost-effectiveness of FV and, even less is known about the effect on caries-free populations. Therefore, this thesis will enhance our understanding of the effect of FV on such population.
Furthemore, information related to both the efficacy and costs of FV on caries-free populations would be extremely useful to evaluate MINSAL’s goal of increasing the caries-free population by 2020. Due to the importance of determining the correct value of efficacy of FV for this thesis,
a systematic review of the effects of FV on caries prevalence in preschool populations was performed and is presented in Chapter 9.
Safety
Related to safety, Duraphat (Colgate-Palmolive, 2014) is contraindicated when the patient is allergic to one of its ingredients (sodium fluoride, colophony, or other ingredients) or when the patient has stomatitis, mouth ulcers, gum disease, or asthma. Unfortunately, the systematic review performed by Marinho et al. (2013) did not provide information about the side effects and acceptability.
However, Milgrom et al. (2014) who studied the pharmacokinetics of FV application in young children, concluded that sporadic application of FV is safe for young children. They measured urinary fluoride levels of children aged 12 to 15 months five hours after application of FV, following guidance by the American Academy of Paediatrics. These findings are consistent with Weintraub et al. (2006) and Salazar (2008) whose studies reported no adverse effects.
Clinical procedure
In general, the procedure of application is very simple and requires a dose up to 0.25 ml (or 5.65 mg fluoride) for primary dentition (Colgate-Palmolive, 2014). The following sequence of application is based on the Chilean protocol of FV application (MINSAL, 2012c).
Toothbrushing without toothpaste must be supervised by professional or an assistant (educator or technical). Given the age of the children, there is a need for the professional or an assistant to double-check the molar sector, where there is greater accumulation of plaque and caries risk.
Ask the child to swallow saliva and then open the mouth.
Use gauze to remove excess saliva and to keep teeth partially isolated and dry. It is not advisable to use cotton wool because it adheres to FV.
Apply a thin coat of varnish on all tooth surfaces, thicker layers do not protect more and only lead to a loss of material. Apply the varnish by quadrants.
It is desirable to wait at least 3 hours from the application of varnish before the child eats food, and the child should also try to avoid hard foods or hot liquids after application. Only if it is critical, after a half an hour has elapsed, children can drink water, cold milk, or yogurt.
Do not brush your child's teeth during the rest of the day.
To summarise, FV intervention is safe for use in preschool children, easy to apply, and highly effective. However, the evidence about the efficacy of FV on caries-free populations is scarce. It could be the option of choice for public health programmes, but more studies are required.