– Fluoride: How much is needed?

Few areas in health have seen such a dramatic change in the epidemiology of a disease as dentistry after the discovery of fluoride as an anticaries agent. The prevalence and severity of dental caries declined tremendously in many areas of the world after the introduction of fluoride in different manners: added to water or table salt for general consumption, formulated in oral health products for individual (toothpastes, rinses) or professional use (fluoride varnishes, fluoride gels). Despite this major public health accomplishment, untreated dental caries remains as the major burden of all oral conditions.1

Around a century ago, fluoride was identified as an anticaries agent by observations of mottled teeth in populations exposed to water with naturally high fluoride concentration.2,3 It was discovered that these populations experienced almost no caries lesions, but suffered from a side effect of chronic, systemic fluoride exposure at high levels: dental fluorosis. Therefore, since the beginning of the history of fluoride as an anticaries agent, balancing the anticaries benefit with the risk of developing dental fluorosis has always been of primary importance.

After some decades of dental caries prevalence decline, the disease is still highly prevalent, and current anti-caries strategies, which are mostly based on fluoride, seem to have reached an efficacy plateau.4 Meanwhile, there is a perceived increase in the prevalence of dental fluorosis, and some dental professionals have prompted discussions on the benefits and risks of fluoride, questioning the necessity of using fluoride to control caries.

This chapter aims to answer the question of how much fluoride is needed. With the main focus on individual and professional fluoride use, the best evidence currently available for the safe use of fluoride for caries control is presented and discussed.

Fluoride: the mode of action and why it is needed

In order to define the role of fluoride in caries control, it is necessary to describe the caries process itself. Dental caries is regarded as a multifactorial disease, with many factors affecting the appearance and severity of the disease. Two main conditions must be present for the disease to develop: biofilm accumulation on the tooth surface and its regular exposure to fermentable carbohydrates. Bacteria in the biofilm will metabolize the carbohydrates, generating organic acids that can dissolve enamel and dentin.5 Oral biofilms (or dental plaque) continuously form on teeth, starting immediately after effective tooth brushing or professional tooth cleaning. Additionally, sugars are omnipresent in the modern diet. With both necessary factors in place, caries lesions can develop in anyone’s mouth.

Fluoride is a unique agent for caries control, with significant impact on the balance of mineral loss/gain between tooth structure and the surrounding environment, favoring mineral gain even at very low concentrations (as low as 0.02 parts per million) in the oral cavity.6

Today’s understanding of fluoride as a modifier of the caries process,7 in contrast to earlier times when fluoride was thought to exert its action solely by being incorporated into the teeth, emphasizes that fluoride is needed in the oral fluids such as saliva or dental biofilm fluid to control the progression of caries. In the biofilm, fluoride will reduce the mineral loss during a cariogenic challenge (reduction of demineralization) or, after the challenge, induce regain of minerals that were previously lost, enhancing remineralization. When present in saliva, it can enhance remineralization of cleaned teeth. Therefore, all methods of fluoride used to control caries aim to increase fluoride concentrations in the oral fluids and maintain increased levels for as long as possible. This can be accomplished by different mechanisms, such as by drinking fluoridated water or eating food prepared with it, which will increase the fluoride concentration in the oral fluids during the ingestion8 and later, at a lower extent, return fluoride to the mouth via saliva secretion; by brushing with fluoride toothpaste; or by forming fluoride reservoirs on the surface of teeth by using professionally applied high concentration fluoride products (Table 3-1). All of these methods will slow down caries development by increasing the concentration of free fluoride in the oral fluids, thus affecting the balance of mineral loss, favoring mineral precipitation and reducing the mineral loss caused by the exposure of dental biofilm to sugars. Unless one has a very strict biofilm control, which is close to utopic in some tooth surfaces, and a very strict control of intake of fermentable carbohydrates, in particular sugars found in beverages and many between-meal snacks, he/she will need fluoride to help overcome the cariogenic challenges to which teeth are exposed on a daily basis.

Table 3-1 Overview of different methods of fluoride use and their mode of action

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The current understanding of the fluoride mode of action stresses the topical effect, and this has made the individual prescription of fluoride supplements questionable.6,7 The local enrichment of the oral fluids with fluoride is easily obtained by the use of fluoride toothpaste, even in areas where water fluoridation is not available. Water fluoridation continues to be considered important in many countries as a public health approach to fluoride use.9

Importantly, although fluoride is very effective in retaining minerals within the tooth structure during a cariogenic challenge, it is not enough to totally avoid mineral loss. The development of caries lesions over time, and their progression, will be a balance between the frequency of exposure of dental biofilm to sugar, and availability of fluoride to overcome part of the mineral loss (Fig 3-1).

Fig 3-1 The relationship between caries lesion development over time, under a low or high cariogenic challenge, in the presence or absence of fluoride. Fluoride is able to reduce mineral loss, but the clinical result (no new lesions or progression of lesions versus new lesions appearing and progressing) will depend on the level of the cariogenic challenge (biofilm + sugar interaction).

If the cariogenic challenge is not high, for instance if the biofilm is disorganized frequently by tooth brushing and/or the daily frequency of sugar exposure is not excessive, brushing with a fluoride toothpaste will be enough to maintain an individual free of clinically visible caries lesions (Fig 3-2). On the other hand, if the cariogenic challenge is high due to poor biofilm control and high frequency of daily sugar exposure, fluoride may not be enough to avoid the appearance of new lesions, or the progression of existing ones.

Figs 3-2a and b A 10-year-old boy who has been clinically caries free after using fluoride toothpaste (1,100 to 1,450 ppm F, twice/day), since the first tooth erupted, and moderate sugar consumption, including restraint on the frequency of sugary between-meal snacks (images courtesy of Line Staun Larsen).

In these individual cases, the dental practitioner could employ professional methods of fluoride delivery in order to increase the amount of available fluoride in the mouth. However, the clinical outcome will be the result of the interaction between the cariogenic challenge and the exposure to fluoride; even a combination of different methods of fluoride delivery may not be enough if the cariogenic challenge is high and not controlled (Fig 3-1).

Fluoride toothpaste: how much fluoride is enough?

Fluoride toothpaste is considered the most rational way of using fluoride, because it involves the removal of biofilm and the exposure of the oral cavity to fluoride. Not surprisingly, experts agree that fluoride toothpaste has significantly contributed to the worldwide decrease in dental caries that has been observed in the past decades.10,11

Although there is substantial evidence on the effectiveness of fluoride toothpaste for caries control,12,13 the recommendations are not straightforward. Evidence-based, clinical recommendations on which toothpaste formulation to use during the different stages of an individual’s life may be influenced by a number of factors; for example, the availability and affordability of the different fluoride toothpastes on the market, the professional assessment of the patient’s caries activity, and, in the case of children, fluorosis risk, the certainty of the evidence on the benefits and risks of toothpastes with different fluoride concentrations, and the preferences and values of the patient.

In this complex scenario, when discussing how much fluoride in toothpaste is enough, two main questions need to be answered:

  • What is the lowest concentration that shows (a clinically relevant) anticaries effect? Using the lowest effective concentration is especially important when recommendations for young children are made, aiming to reduce their exposure to fluoride and thereby lowering the risk of developing dental fluorosis.
  • Is more better? In patients that are no longer at risk of developing fluorosis, should higher concentration toothpastes be used?

In the next section, these two points are discussed, based on the best evidence currently available.

Dental fluorosis

Fluorosis is the only scientifically proven side-effect of chronic exposure to fluoride. Dental fluorosis occurs during amelogenesis when teeth are exposed to elevated fluoride doses for a prolonged period of time. The level of fluorosis is dependent on the dose and duration of the exposure, and permanent teeth take years to complete their mineralization. Considering the probably most important esthetic teeth, the maxillary permanent central incisors, the overall duration of fluoride exposure is thought to be more important than short specific risk periods for the development of dental fluorosis.14 Accordingly, children with a history of long exposure (> 2 years during the first 4 years of life) have been shown to be 5.8 times more likely to develop dental fluorosis than children with < 2 years of exposure during the same period of life. Therefore, only methods used daily, like water fluoridation, fluoride tablets, and the overdosing of fluoride toothpaste, have been associated with fluorosis development.15

It should be emphasized that the level of fluorosis currently observed in populations exposed to fluoridated water and toothpaste is mainly restricted to the very mild or mild levels (Fig 3-3).16,17 At these levels, the clinical appearance is seldom regarded as disfiguring by the patients themselves and people around them. Even so, the balance of benefits versus risks of fluoride toothpaste use by children in the first years of their lives, when they are not yet capable of spitting out the toothpaste slurry and may ingest most of it, has been debated, especially in areas with water fluoridation. Therefore, in the last few years researchers have been summarizing the evidence on the benefits and risks of fluoride toothpaste use by young children, as discussed in the next section.

Fig 3-3 Mild fluorosis typical of regions where water fluoridation has been implemented and fluoride toothpaste use is widespread. Given the superficial nature of mild fluorosis, the whitish aspect observed in the incisal areas tend to fade away as the patient ages, as a result of enamel wear.

Evidence-based recommendations for fluoride toothpaste use throughout life

The evidence behind the use of fluoride toothpaste for caries prevention, and the risks associated with its use, have been summarized in a number of systematic reviews and meta-analyses in recent years.12,13,1821 Although in some instances the evidence from clinical trials is not abundant, these reviews have served as an important resource to guide professionals on the best available evidence. Table 3-2 describes the most common effect measures used in clinical trials and how they are usually presented in these reviews.

Table 3-2 Common effect measures used in clinical trials on fluoride toothpaste*

Term

Interpretation

Prevented fraction (PF)

Difference in mean caries increment between treatment and control groups, expressed as the percentage of mean caries increment in the control group. This is the relative difference in caries increment. It is also called the percentage reduction in caries increment.

Absolute risk (AR) or risk difference (RD)

Proportion of subjects developing new caries lesions in the untreated group or the group treated with a placebo (caries incidence in the control group) minus the proportion of subjects developing new caries lesions in the group treated with fluoride (caries incidence in the test group). The absolute risk reduction (ARR) is usually presented as counts (eg, 1 out of 100).

Number needed to treat (NNT)

Number of people who need to receive the experimental rather than the comparator intervention for one additional person to either have or avoid an event in a given time frame (eg, one subject with new caries lesion[s]/one new carious tooth or surface). The NNT is derived from the risk difference.

Relative risk (RR)

Proportion of subjects developing new caries lesions in the untreated group or the group treated with a placebo (caries incidence in the control group) divided by the proportion of subjects developing new caries lesions in the group treated with fluoride (caries incidence in the test group). The relative reduction in caries incidence is usually presented as a percentage reduction: RRR = 100% × (1 – RR).

*In meta-analysis the results of individual trials with similar study designs are pooled. Thus, the combined effects are presented, for example, as pooled RR and pooled PF with their respective confidence intervals (CI). NNTs cannot be pooled but pooled RRs may be converted to NNTs.

The first comprehensive review with meta-analyses on the effect of fluoride toothpaste for caries prevention in children and adolescents was published in 2003.12 This review found a mean 24% (prevented fraction; decayed, missing, or filled surfaces [DMFS]) decrease in caries severity in the permanent dentition of children who brushed with fluoride toothpaste in comparison to children who brushed with nonfluoride toothpaste for a period of 3 years. When considering a lifetime exposure to fluoride toothpaste, this would represent a remarkable anticaries effect. Also, an increased anticaries effect was observed in populations with higher caries levels, higher frequency of tooth brushing, and supervised tooth brushing. However, these last findings should be interpreted with caution because they were obtained through subgroup analyses and meta-regression, which are subject to the limitations of any observational investigation.

The only data on adverse effects available in the primary studies that were included in this review12 were tooth staining in children brushing with stannous fluoride toothpaste; the pooled risk difference between placebo and fluoride toothpaste was significant. This problem seems to be solved in the current toothpaste formulations based on stannous fluoride.22

In 2010, a systematic review with the objective of assessing whether the anticaries effect of fluoride toothpastes in children and adolescents differs according to their fluoride concentration was published.23 The updated 2019 version13 also assessed the benefits of fluoride toothpastes in adults. The results of these reviews confirmed the expressive caries preventive effect of fluoride toothpastes with 1,000 ppm F and above for both children and adults, and showed a dose-response effect for DMFS in children and adolescents. However, moderate-certainty evidence was not capable of showing a difference in caries increment when comparing 1,700 to 2,800 ppm F toothpaste to 1,450 to 1,500 ppm F.

Low-fluoride toothpastes (< 600 ppm F) have been developed as an alternative to standard fluoride toothpastes (1,000 to 1500 ppm F) in order to deliver fluoride during tooth brushing to the oral environment while reducing the risk of fluorosis. They are targeted at children 6 years of age and younger who are more likely to swallow toothpaste while brushing teeth, therefore at risk of developing dental fluorosis.

Regarding the balance of benefits versus risks of the use of low fluoride toothpastes observed in clinical trials, a systematic review published in 201020 investigated the role of individual and professional use of fluoride as a cause of dental fluorosis. The use of fluoride toothpaste with 1,000 ppm F or more was found to be associated with an increased risk of any fluorosis. The authors of this review recommended the fluoride level of toothpaste for young children to be lower than 1,000 ppm if the risk of fluorosis was of concern. However, another systematic review published in 201319 was designed to answer specifically the question of whether low-fluoride toothpastes (< 600 ppm F) in comparison to standard fluoride toothpastes (1,000 to 1,500 ppm F) would prevent dental caries in children younger than 8 years and, at the same time, would protect them against esthetically objectionable fluorosis in permanent teeth. Low-fluoride toothpastes were shown to increase by 13% the risk of developing new dentin caries in the primary dentition (relative risk [RR] = 1.13; 95% confidence interval [CI] 1.07 to 1.20; three studies). Among 1,968 children analyzed in two studies, there were only 34 cases (11 in the low-fluoride group and 23 in the standard-fluoride group) of esthetically objectionable fluorosis in the maxillary permanent incisors, and the risk of developing fluorosis between the “< 600 ppm F” and “> 1,000 ppm F” groups was not significantly different. Another systematic review21 addressed the caries protective effect of 1,055 to 1,450 ppm F toothpastes versus 250 to 550 ppm F toothpastes in preschoolers at high risk of developing dental caries. In the head-to-head comparisons, the differences in pooled mean decayed, missing, and filled teeth (dmft) and dmfs between the two groups favored the higher concentration toothpastes, but only the dmft difference reached statistical significance. With respect to the indirect comparisons, the pooled estimates of dmfs and dmft increments with toothpastes with 500 ppm F or more in comparison to nonfluoride toothpastes produced statistically significant lower mean caries, whereas the pooled estimates regarding toothpastes with less than 500 ppm F failed to produce statistically significant differences. The same review found that there was a tendency for fluorosis to decrease with the use of toothpaste containing lower fluoride concentrations, but the pooled effect was not significant.

The body of evidence on low-fluoride toothpastes (< 600 ppm) appears to indicate that they confer no significant protection against dental caries in primary teeth and fluorosis in permanent teeth. Thus, in order to gain maximum anticaries benefit with minimum fluorosis risk, most professional and research associations in dentistry advise caretakers of young children to brush their children’s teeth twice a day with small amounts of standard fluoride toothpaste (≥ 1,000 ppm, Fig 3-4).

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Jan 3, 2022 | Posted by in General Dentistry | Comments Off on – Fluoride: How much is needed?
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