Noninvasive Therapy: 12 Caries Management by Influencing Mineralization


Noninvasive Therapy: 12 Caries Management by Influencing Mineralization

Svante Twetman, Kim R Ekstrand

Fluoride has been proven to play a significant role in preventing and controlling the caries disease.1 Therefore, this chapter gives a thorough description of fluoride, how it works, its dangers, and side effects. The clinical use and caries-preventive effectiveness of fluoride are reviewed. A novel remineralization technology (CPP-ACP) is also described.

In detail this chapter will cover:

  • nature and occurrence of fluoride;

  • absorption and distribution of fluoride in humans;

  • safety aspects of fluoride at various ages;

  • mechanisms of fluoride action in the plaque–enamel interface;

  • population-based fluoride strategies;

  • fluoride in patient-based caries management; and

  • alternative methods for lesion repair.

What is Fluorine/Fluoride?

Fluorine is one of 118 chemical atomic elements in the periodic system. In its pure form, it is a poisonous pale yellowish brown gas. Fluorine is placed as number 9 in the periodic table, as it has 2 electrons in the inner shell and 7 electrons in the outer shell. Fluorine belongs to the group of chemical elements called halogens, which refers to their ability to form salts in union with a metal. Halogens, and in particular fluorine, are highly reactive being one electron short of a full outer shell. This electron can be gained by reacting with, for example, calcium, forming calcium fluoride (CaF2). Thus, fluoride is the term used when fluorine is combined with a positively charged counterpart. The complexes often consist of crystalline ionic salts such as fluorapatite (Ca10[PO4]6F2).


Fluorine is an atom with 7 electrons in the outer shell, thus it is very reactive to other atoms such as calcium and sodium.

Units of Measure

Fluoride content is commonly expressed in parts per million (ppm) ( Table 12.1 ), which is equivalent to 1 mg fluoride per kilogram or liter of water. Thus, 1 ppm fluoride in the water supply corresponds to 1 mg fluoride per liter of water. Similarly, 1450 ppm fluoride toothpaste corresponds to 1450 mg fluoride per kg toothpaste. We use about 1 g toothpaste for normal tooth brushing, which contains around 1.45 mg fluoride.2

When fluoride is combined with sodium, for example, in a 2% NaF solution, we have to include the molecular weight (mol wt) of Na+ and F to calculate the final concentration of fluoride in the solution. The mol wt of Na is about 23 g and for F it is 19 g; together, 42 g per mole. Thus, 2% NaF contains 19/42 × 2% F = 0.9047% F = 9047ppm F.

The concentration of fluoride in human enamel is also often expressed as ppm. However, a more relevant measure is how much of the hydroxyapatite (HAP) is replaced by fluorapatite (FAP) or fluorhydroxyapatite (FHAP) (see Chapter 2) when the enamel contains, for example, 2500 ppm F. This requires that we know the mol wt for HAP which is 500. The following formula can be used:

2500 ppm F x 500/19 × 106 = 0.0657

which corresponds to 6.57% of the enamel containing FAP/FHAP while 93.43% is HAP.

Fluoride in Our Surroundings

Fluoride occurs in nature as a constituent of natural minerals in the soil and more than 150 fluoride-containing minerals have been described.3 For example, cryolite contains aluminum fluoride and fluorspar contains calcium fluoride. As many of the minerals in the soil are soluble in water, fluoride is found in varying concentrations in the groundwater. Data from Denmark show that the concentration of fluoride in piped drinking water varies across the country between 1.4 ppm to 0.01 ppm with a mean value of 0.3 ppm.4 Values higher than 1.4 ppm are noted in local wells. Similar variations in fluoride concentration exist in many other countries around the world. The recommended upper limit of the World Health Organization (WHO) for fluoride in drinking water is 1.5 mg/L (1.5 ppm F) and a high probability of excessive concentrations is found in the mountainous regions of South America, the Middle East, and Central Asia. In Kenya and South Africa, the levels can exceed 25 ppm, and in India, concentrations up to 38.5 ppm have been reported. The concentration of fluoride in food varies ( Table 12.2 ) and is dependent on the water content of fluoride and the places where the dietary sources have originated.


  • Fluoride is a natural mineral in soil and water.

  • The fluoride concentration is commonly expressed as parts per million (ppm).

Fluoride in Humans

Acute Toxicity

The normal daily intake of fluoride is rather low and estimated to be 1–3 mg per day in adults.5 The intake in newborns is much less at about 0.32 mg F per day, but increases rapidly to 1.23 mg at the age of 4–6 months.5 Intake of high amounts of fluoride can be toxic, however, although very rarely lethal. The probably toxic dose (PTD) sufficient to produce severe poisoning (including death, in some individuals) in humans is estimated to be around 5mg F/kg body weight. Thus, for a 1-year-old child with a weight of 8 kg, eating 8 g of 5000 ppm F toothpaste (~ 1/6 of the content of the tube containing 51 ml) on an empty stomach could be critical. The symptoms of acute toxicity occur rapidly, with diffuse abdominal pain, diarrhea, vomiting, excess saliva, and thirst. The immediate treatment when a toxic dose is suspected is to induce vomiting. Second, milk should be swallowed to reduce fluoride absorption. Then, without delay the person should be referred to medical/toxicological attendance. Chronic toxicity due to high intakes of fluoride over an extended period of time will be covered later in this chapter.

Fluoride products for oral use


F content (ppm)


Toothpaste < 0.05% F

< 500

Self-administered daily procedure

Toothpaste 0.1% F


Self-administered daily procedure

Toothpaste 0.15% F


Self-administered daily procedure

Toothpaste 2.8 mg F/g


High-risk patients

Toothpaste 5.0 mg F/g


High-risk patients

0.05% NaF solution*


Home-based, daily rinsing

0.2% NaF solution*


Home-based, weekly rinsing

0.1% Fluor Protector


For professional application

2% NaF solution*


For professional application

5% Duraphat-varnish (NaF, 2.26% F)


For professional application

6% Bifluoride-varnish (NaF/CaF2, ~2.8% F)


For professional application

Chewing gum 0.1–0.25 mg F/unit


High-risk patients

Gels for trays 0.2%–1% F


High-risk patients

Tablets 0.25, 0.50 and 0.75 mg F pr. Tablet


For children at risk

Salt (table salt, 90–250mg F/kg)


Population approach

Drinking water: 0–1.4mg F/L

From 0 to 1.4

Population approach

* Sometimes F is present with Na, sometimes alone. If present with Na halve the concentration because the mol weight of fluoride and Na is nearly the same

Fluoride content in different food products

Dietary source

F content (ppm)

Human milk


Cow′s milk






Fish and shellfish








Fluoride Absorption and Distribution

The major route of fluoride absorption in the human body is via the gastrointestinal tract. The compound′s physical and chemical properties will influence the amount that eventually enters the systemic circulation. The level of fluoride in the blood plasma averages between 0.01 and 0.05 ppm, but the concentration increases considerably after an intake of compounds with high fluoride content. Let us use ingested fluoride-containing toothpaste as an example. The degree of absorption of fluoride from toothpaste is almost 100% for sodium fluoride (NaF)-containing dentifrices and somewhat less for monofluorophosphate (MFP) toothpaste when ingested on the fasting stomach,6 where the peak concentration is reached within 30 minutes ( Fig. 12.1 ). When fluoride is ingested after a meal this peak is reduced, delayed, and extended ( Fig. 12.1 ). This knowledge is important in particular for young children who swallow a great proportion of the toothpaste used because they are unable to spit. Therefore, in young children a limited amount of toothpaste should be used (pea size) and tooth brushing should be performed after a meal to reduce the chance of developing dental fluorosis (see below).

Fig. 12.1 Mean plasma fluoride concentration after swallowing 3mg of MFP-toothpaste on the fasting stomach and 15 minutes after breakfast (modified after Ekstrand and Ehrnebo6).

When the fluoride has reached the blood plasma it is circulated around in the body and distributed to the various organs before it is eliminated (about 50% is eliminated) from the body. The major route for the removal of fluoride is via the kidneys. The distribution of fluoride that is not eliminated within the different organs is related to the blood supply of the individual organs. Organs with high blood flow accumulate more fluoride than organs with low blood flow. However, 99% of the fluoride in the body is eventually accumulated in the bones. This is related to the fact that mineralized tissues consist of hydroxyapatite (HAP) and fluoride has, due to its size and negative charge, a high affinity to replace the hydroxyl ion and to form fluorhydroxyapatite (FHAP) (see Chapter 2). It is important to understand that fluoride is not irreversibly bound to the bone. If the plasma concentration drops over a long time, for example, when a person moves from a place with high concentration of fluoride in the water supply to a place with no or low concentration of fluoride in the water, fluoride will leave the bone.


  • Fluoride is absorbed via the gastrointestinal tract and accumulated in the bones.

  • The probable toxic dose in humans is about 5 mg/kg body weight.

  • Acute overdose symptoms are abdominal pain, diarrhea, vomiting, and thirst.

Fluoride in Teeth

In the dental hard tissues, fluoride is distributed in a very characteristic way. In surface enamel, the concentration of fluoride is quite high, about 2500 ppm, and as mentioned earlier, about 7% of the surface enamel consists of FAP/FHAP. This is in sharp contrast to the subsurface enamel which contains only around 50–100 ppm. In the dentin, especially in the pulpal part, the fluoride levels are higher than in the enamel. The highest concentration is seen in the cementum. The explanation is that dentin and cementum form during one′s entire lifetime in contrast to enamel (see Chapter 1). The elevated levels of fluoride in the surface enamel are related to the following facts:

  • Access to fluoride (in plasma) is greater at the surface of the enamel compared with the deeper layers during the entire mineralization process (pre-eruptive period).

  • Fluoride can further accumulate in the surface enamel during and after eruption due to maturation and in particular remineralization (post-eruptive period).

Fluoride in Saliva and in Plaque

The fluoride concentration in resting whole saliva is low, ranging between 0.005 and 0.05 ppm. The fluoride concentration in the secreted saliva is, however, influenced by the amount of fluoride in the environment. One important factor is the systemic ingestion of fluoride. A study from Sweden7 showed that people living in an area with 1.2 ppm fluoride in the drinking supply had a three-times-higher concentration of fluoride (mean 0.02 ppm F) in their saliva during the whole day compared with those living in areas with low fluoride levels in the water. In plaque, the fluoride concentration is much higher than in saliva (5–10 ppm), but the major part is bound in complexes, for example as CaF2.8

Fluoride concentrations in whole saliva and in plaque are significantly elevated after, for example, tooth brushing with fluoride toothpaste or after topical applications of fluoride.9,10 Concerning toothpaste, the peak concentration and the clearance time are related to the amount of fluoride in the formula. For example, during tooth brushing with 1500 ppm toothpaste, a peak concentration of 150ppm can be seen that rapidly drops to 0.2ppm after 20–40 minutes. If 500 ppm toothpaste is used, the peak concentration is limited to 60 ppm.


Regular use of fluoride toothpaste or other vehicles for fluoride provides elevated fluoride concentrations in saliva as well as in plaque, with a clear dose–response relationship.

From Mottled Enamel (Colorado Stained Teeth) to Dental Fluorosis

The dentist F. S. McKay from Colorado discovered in 1901 that many of his patients had permanent stains on their teeth ( Fig. 12.2 ). He termed it “Colorado stain” or “stain mottled enamel.” The visual appearance varied between “minute white flecks, yellow or brown spots or areas, scattered irregularly over the surface of a tooth, or it may be a condition where the entire tooth surface is of a dead paper-white, like the color of a china dish.” G. W. Black (the “father of dentistry”) examined the teeth histologically and stated that there was an “endemic imperfection of the enamel (hypocalcification) of the teeth heretofore unknown in the literature of dentistry”.11 Some of the conclusions concerning mottled enamel were:

  • Not related to class of people

  • Also seen in parts of the world other than Colorado

  • Restricted to localized areas

  • Only natives from the area had mottle enamel

  • Newcomers older than 10 years did not have it

  • Families, whether rich or poor, were affected

F. S. McKay in 191612 stated “that mottled conditions, in itself, does not seem to increase the susceptibility of teeth to caries, which is perhaps contrary to what might be expected, because the enamel surface is much more corrugated and rougher than normal enamel.”

During the 1920s, analyses of the water in some areas where mottled enamel was prevalent showed very high levels of fluorine, between 2.0 and 13.7 ppm.13 Through findings from histological studies on rats and humans14 it was finally possible in the beginning of the 1930s to establish that fluoride was the reason for mottled enamel and the term “dental fluorosis” was introduced.

H. T. Dean developed a six-step clinical classification system for dental fluorosis in the beginning of the 1940s: no fluorosis, questionable, very mild, mild, moderate, and severe fluorisis.15 Later, in 1978, Thylstrup and Fejerskov16 suggested a new classification based on histological examinations and operated with 10 classifications (the TF-index, Fig. 12.2 ). This refined system contributed strongly to the understanding of the pathogenesis of dental fluorosis. The tooth surface index of fluorosis is yet another index,17 focusing more on the esthetic aspects of tooth surfaces. In one study from Brazil,18 data indicated that the three fluorosis indices mentioned above found similar prevalences when the same measuring methods for clinical examination were used. For further reading on this subject we refer to the review by Rozier.19

Numerous investigations have tried to explore and establish a threshold level for the development of dental fluorosis in humans,20,21 but without conclusive results. In fact, any level over zero milligrams of fluoride per kilogram body weight per day can induce dental fluorosis, but an intake exceeding 0.04 mg/kg per day increases the risk for the mild forms of fluorosis significantly (TF-index 1–2). An intake above 0.1 mg/kg per day would almost certainly result in more severe (TF-index ≥ 3) and esthetically compromising forms of the condition.2 The risk for developing dental fluorosis that is visible on the permanent incisors is greatest during the first three years of life.


  • Dental fluorosis can affect both dentitions.

  • There is a linear dose–response relationship between fluoride ingestion and dental fluorosis.

  • There is only a risk of developing dental fluorosis when the dentitions are developing.

  • Dental fluorosis is an impairment of mineral acquisition into the enamel during the long-lasting and complex process of maturation. This results in increasing enamel porosity along the striae of Retzius and along the entire tooth surface.22

Prevalence of Dental Fluorosis

Numerous epidemiological studies have been performed around the world over the years to investigate the prevalence and severity of dental fluorosis and its relation to the use of fluoride in any form. The prevalence of dental fluorosis (TF-index ≥ 1) among 8-year-olds from 7 different European study sites was found to be between 51% and 89%.23 However, fewer than 5% had stages of dental fluorosis where professionals regarded it as a cosmetic problem (TF-index ≥ 3). The prevalence of fluorosis has increased in some countries during the later years of the last century. In the United States, for example, an increase in prevalence of definite stages of dental fluorosis (corresponding to TF-index ≥ 3) in children from North America from 1% in 1938–44 to 5% for 1982–88 was reported.24 In Germany an increase in prevalence of dental fluorosis in 12-year-old children from 7% in 1993 to 15% in 1997 was reported; however, the majority of cases were of very mild degree (TF-index 1 and 2).25 In some parts of Australia the prevalence of dental fluorosis has dropped during recent years from about 35% (TF-index ≥ 1) of children born in 1989/90 to 22% of children born in 1993/94.26 This reduction was, according to the authors, a result of implementing a new policy in South Australia in 1992/93 which focused on a reduction in exposure to fluoride, particularly from fluoride toothpaste.

Figure 12.3 shows data from Denmark on the prevalence of dental fluorosis in 12-year-olds related to areas with different fluoride concentration in the water supply. It appears that hardly anyone had dental fluorosis of TF-index ≥ 3. Furthermore, around 80% had no dental fluorosis, or fluorosis which required air drying (TF-index 1) in order to be diagnosed. The fluoride politics in Denmark has been to maximize the benefit of fluoride on caries and to minimize the risk of getting dental fluorosis. As the natural level of fluoride in the water supply is low in Denmark (average 0.3 ppm3) and no other systemic fluoride supplements are offered, the focus of attention has been on fluoride toothpaste: 1050–1100 ppm is recommended from the time when the first tooth erupts (~8 months, see Chapters 1 and 21). With increasing age (> 3 years) the parents are recommended to use 1450–1500 ppm fluoride toothpaste for their children. The amount of toothpaste used for young children should correspond to the size of the fingernail of the child. If tooth brushing is performed twice a day the amount of toothpaste should correspond to one-half of the child′s fingernail. In contrast, local application of fluoride has been undertaken by professionals when they found indications for doing so (active caries or risk of active caries).27

Fig. 12.2 Illustration of the associations between the clinical and histological stages of the first eight of the 10 stages in the Thylstrup–-Fejerskov index.16

The effect of fluoride on teeth is cumulative, meaning that the longer the teeth undergo mineralization, the more likely that severe dental fluorosis will appear following a constant dose of fluoride.28 Posterior teeth are therefore more severely attacked by dental fluorosis than anterior teeth.16

Prevalence and severity of dental fluorosis in 12-year-old Danes in 2006 in relation to fluoride concentration in the water supply. The colors indicate the stages of TF-index.
Fig. 12.4 The relation between DMFT, fluoride concentration in the water supply, and severity of dental fluorosis (very mild to severe).29


  • Dental fluorosis is impaired mineral acquisition that occurs during tooth development.

  • There is a linear dose–response relationship between fluoride ingestion and fluorosis but there is no safe threshold level.

  • The mild forms of fluorosis display increasing prevalence in many countries, albeit cosmetic problems are rare.

Effects of Water Fluoridation on Caries and Dental Fluorosis: Pre- or Posteruption?

In the beginning of the 1940s H. T. Dean and his coworkers15,29,30 mapped the caries data of various communities (n = 21) with regard to their respective concentration of fluoride in the water supply as well as with prevalence of dental fluorosis ( Fig. 12.4 ). Under conditions at that time, when no fluoride toothpaste or fluoridated tablets, etc. were available, it was concluded that an optimal caries reduction would be seen at around 1 ppm fluoride, a level at which the harmful effects (dental fluorosis) were still considered to be acceptable.

The original data were collected from cross-sectional study designs for which cause–effect relationships cannot be established. During the 1940s, several prospective intervention studies were performed to investigate the influence of water fluoride on the prevalence of dental caries. In general, it was established that fluoride in the water supply at a level of 1 ppm versus no fluoride reduced the number of decayed, missing, and filled teeth by 50%.31,32 These studies resulted in some communities artificially adding fluoride to their water supply. WHO has several times stated that “fluoridation of communal water supplies, where feasible, should be the cornerstone of any national programme of dental caries prevention.”33

From the early water fluoridation studies done in the 1940s, it was assumed, notably by McKay in 1952, that the preventive effect of fluoride on caries was related to a preeruptive action.34,35 The theory was that incorporation of fluoride into the enamel during enamel formation increased the size of the apatite crystals and made them more well-formed, which was supposed to decrease their solubility.36 The concept of pre-eruptive effect of fluoride led to the development of fluoride tablets and fluoride drops intended for infant use. Histological examinations, however, revealed a very small difference (1%) in the fluoride content of surface enamel from persons raised in areas with high fluoride content in the water (1 ppm) compared with persons that had grown up in low-fluoride areas (0.2 ppm).37 Furthermore, clinical observations showed that children who were raised in a low-fluoride area and moved to areas with higher fluoride content experienced a significant reduction in dental caries prevalence.38 This was confirmed by findings that children exposed to naturally fluoridated water since birth had significantly less caries than children from areas with no fluoridated water (control group), also as adolescents.39 Moreover it was found that children of the same age who only had consumed fluoridated water for the last two years had less DMFS (decayed, missing, fillings in the tooth surfaces; see also Chapter 8) than the control group ( Fig. 12.5 ). Today, it is generally accepted that the preeruptive effect of fluoride is of little importance compared with the more significant post-eruptive effect.4043


The main beneficial effect of fluorides on caries is post-eruptive.

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May 23, 2020 | Posted by in General Dentistry | Comments Off on Noninvasive Therapy: 12 Caries Management by Influencing Mineralization
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