Demineralization and remineralization of tooth surfaces
The physicochemical integrity of dental enamel in the oral environment is entirely dependent on the composition and chemical behavior of the surrounding fluids: saliva and plaque fluids. The main factors governing the stability of enamel apatite are pH and the free active concentrations of calcium, phosphate, and fluoride in solution, all of which can be derived from the saliva (see Box 12).
The development of a clinical carious lesion involves a complicated interplay between a number of factors in the oral environment and the dental hard tissues. The carious process is initiated by bacterial fermentation of carbohydrates, leading to the formation of a variety of organic acids and a fall in pH. Initially, H+ will be taken up by buffers in plaque and saliva; when the pH continues to fall (H+ increases), however, the fluid medium will be depleted of OH- and PO3 4-, which react with H+ to form H2O and HPO2 4-. On total depletion, the pH can fall below the critical value of 5.5, where the aqueous phase becomes undersaturated with respect to hydroxyapatite (HA). Therefore, whenever surface enamel is covered by a microbial deposit, the ongoing metabolic processes within this biomass result in fluctuations in pH and occasional steep falls in pH, which may result in dissolution of the mineralized surface. The role of the saliva in this process is highly dependent on accessibility, which is closely related to the thickness of the plaque (for review see Pearce, 1991; Tenovuo, 1997).
Caries versus erosion. As discussed earlier, dissolution of enamel can result in the development of either a carious lesion or an erosive lesion. Caries is defined as the result of chemical dissolution of the dental hard tissues, caused by bacterial degradation products, that is, acids produced by bacterial metabolism of lowmolecular weight sugars in the diet. Erosion is defined as chemical dissolution of tooth substance caused by any other acid-containing agent. Mixed lesions may well exist, particularly when the dentin has been exposed by erosion, causing hypersensitivity, which may lead to inadequate plaque control and, subsequently, to caries. This condition occurs frequently on exposed root surfaces.
The appearance of the two lesions differs. The carious lesion is characterized by a subsurface demineralized lesion body, covered by a rather well-mineralized surface layer. In erosion, the surface has been etched away layer by layer, and there is no subsurface demineralization. Under normal conditions, in the absence of thick undisturbed plaque and/or very high frequency of acidic dietary products, teeth do not dissolve in saliva, because it is supersaturated with calcium, phosphate, and hydroxyl ions, which constitute the mineral salts of the tooth. The degree of supersaturation is even greater in plaque, especially in its extracellular fluid phase, which is in direct contact with the tooth surface. In addition, in individuals who have a regular daily source of fluoride (eg, fluoride toothpaste), both the saliva and the plaque fluid should contain an abundance of fluoride ions. In the dynamic equilibrium of the carious process, the supersaturation of saliva provides a barrier for demineralization and a driving force for remineralization. This equilibrium is greatly affected by fluoride, which reduces demineralization and enhances remineralization. Salivary saturation is overcome only when the plaque pH falls so far that the hydroxyl and phosphate ion concentrations are reduced below a critical value (through conversion of PO4 3- to HPO4 2- and H2PO4 -).
In principle, dental enamel can be dissolved under two different chemical conditions.
When the surrounding aqueous phase is undersaturated with respect to hydroxyapatite
and supersaturated with respect to fluorapatite (FA), HA dissolves and FA is formed.
The resulting lesion is a carious lesion in which the dissolving HA originates from
subsurface enamel and FA is formed in the surface enamel layers. The higher the
supersaturation with respect to FA, the more fluoride is taken up in the enamel
surface, the better mineralized the surface enamel layer becomes, and the less
demineralized is the subsurface body of the lesion.
On the other hand, if there is undersaturation with respect to both HA and FA, both
apatites dissolve concurrently, and layer after layer is removed. This will result in an
erosive lesion. Fresh acidic fruit, fruit juices, acidic carbonated soft drinks, and some
champagnes are all unsaturated with respect to both apatites and are able to cause
erosive demineralization of the teeth. These mechanisms for enamel dissolution are
illustrated in Figure 100.
Role of calcium. In these processes, the most important inorganic ions are calcium,
phosphate, and fluoride. Calcium is a bivalent ion excreted, together with zymogen
proteins, into the lumen of the acinus. Therefore, the concentration of calcium found
in the saliva is dependent on the SSR. Going from an unstimulated state to a
“somewhat stimulated” state, the calcium concentration decreases somewhat.
However, the excretion pattern is complicated by the different calcium concentrations
found in the secretions from different glands: the concentration in the submandibular
or sublingual fluid is about twice as high as that in the parotid saliva. As the
proportion of parotid secretion in the total volume of saliva increases with
stimulation, the resulting flow pattern in whole saliva is a linear increase related to the
calcium concentration.
Depending on the pH, calcium is distributed in saliva in ionized and bound forms. The
free, ionized calcium is especially important in the carious process, because it
participates in establishing the equilibrium between the calcium phosphates of the
dental hard tissue and its surrounding liquid. At pH values close to normal, the
ionized calcium constitutes approximately 50% of the total calcium concentration, but
it increases if salivary pH is lowered. At pH values below 4, most of the salivary
calcium is in ionized form.
The nonionized calcium is distributed on a diversity of ligands with association
constants in a large range; that is, the calcium is more or less firmly bound to
inorganic ions such as inorganic phosphate, bicarbonate, and fluoride (10% to 20% of
the total calcium concentration, depending on pH and SSR), to small organic ions
(less than 10%) such as citrate, and to many macromolecules (10% to 30%). Some
salivary macromolecules have been attributed a special role in oral calcium
homeostasis.
The influence of SSR on the distribution of calcium on free and bound fractions is
complex. As already pointed out, the pH of saliva is strongly dependent on the SSR,
as are the concentrations of most of the calcium-complexing substances. At low SSR,
the bicarbonate concentration is very low, with a correspondingly low concentration
of the calcium bicarbonate complex.
The tooth is usually separated from the saliva by an intermediate layer of integuments,
in the form of a pellicle or a plaque. The total calcium concentration in these
compartments is slightly higher, sometimes much higher, than in the saliva, because
of a high concentration of binding sites for calcium and because of the presence of
precipitated calcium salts. There is a strong correlation between both total and ionized
calcium in saliva and dental plaque, showing a flow of calcium over the plaque-saliva
interface following existing diffusion gradients in ionized calcium. This gradient will
be large after sugar intake, liberating bound calcium; as the plaque pH slowly
increases, the concentrations of ionized calcium in saliva, pellicle, and plaque will
slowly reach an equilibrium.
Role of inorganic phosphate. The inorganic orthophosphate in saliva consists of
phosphoric acid (H3PO4) and the primary (H2PO4
-), secondary (HPO4
2-), and tertiary
(PO4
3-) inorganic phosphate ions. The concentrations of these ions are dependent on
the pH of the saliva. The sum of the ions and the molecule constitutes the total
phosphate concentration. The lower the pH, the less the concentration of the tertiary
ion, implying that the ion product of hydroxyapatite decreases considerably with
decreasing pH. This phenomenon is the main cause of demineralization of the teeth.
As with calcium, it is evident that the content of inorganic phosphate in saliva is a
prerequisite for the stability of the tooth mineral in the oral environment. The
concentration of total inorganic phosphate decreases with increasing SSR. As is the
case for calcium, the different glands differ in phosphate excretion: the phosphate
concentration in the submandibular glands is only about one third that in parotid
saliva, but is about six times higher than that in the minor mucous glands, the glands
nearest the tooth surfaces. Therefore, it may be assumed that the inorganic phosphate
concentration shows a large variation in the microenvironment.
About 10% to 25% of the inorganic phosphate, depending on pH, is complexed to
inorganic ions such as calcium or is bound to proteins. A small part, less than 10%, is
in the dimer form, pyrophosphate (H4P2O7), which is a potent inhibitor of the
precipitation of calcium phosphate and influences the formation of calculus. This is
the rationale for the inclusion of pyrophosphate in toothpastes intended to inhibit
calculus formation. However, the prevalence and incidence of caries in individuals
who exhibit rapid formation of salivary calculus tend to be less than average.
In a recent 3-year, longitudinal, double-blind study of fluoride toothpaste in more than
4,000 11 to 12 year olds, those with salivary-derived calculus developed significantly
fewer new carious surfaces than did the others (Stephan et al, 1994). Among adult
patients maintained for several years in a needs-related preventive program and with
very high standards of oral hygiene, a subselection of participants with very rapid
formation of salivary-derived calculus had more intact tooth surfaces than did patients
with little or no calculus formation (Axelsson et al, 1995, unpublished).
The inorganic phosphate of saliva has several important biologic functions, the most
important from a caries aspect being its contribution to solubility products with
respect to calcium phosphates and thus its role in the maintenance of the tooth
structure. Its minor role in salivary buffering has already been discussed.
Role of fluoride. Fluoride in the fluids surrounding the enamel crystals has been
shown to have the potential to reduce the rate of demineralization. When present in
the liquid phase of remineralization, fluoride will be incorporated into the enamel
crystals and the enamel will become more resistant to demineralization (Fig 103).
Fluoride has also been shown to reduce acid production in dental plaque. Therefore,
in caries-preventive programs, the aim of fluoride administration should be to ensure
that fluoride levels in the oral fluids are adequate to prevent and inhibit caries. The
fluid bathing a plaque-covered tooth surface consists of saliva, plaque fluid, and the
fluid surrounding the enamel crystals and is sometimes influenced by the crevicular
fluid. These fluids constitute a continuous system, and ions will diffuse according to
their concentration gradients. Fluoride introduced into the oral cavity will be
distributed in saliva and thus influence the fluoride concentration in plaque fluid and
enamel crystal fluid.
Fluoride is present in saliva in concentrations that depend on fluoride in the
environment, especially in drinking water. Other important sources are fluoride
toothpastes and other fluoride products used for caries prevention and control. In
areas with low concentrations of fluoride in the drinking water (below 10 umol [0.2
ppm]), the basal concentration of fluoride in whole saliva is usually less than 1 uM.
The concentration may be much higher in areas with higher water fluoride
concentrations.
After an intake of fluoride, the levels of fluoride in the blood increase, reaching a
peak after 30 minutes to 1 hour. The fluoride enters the saliva by simple diffusion
over the membranes of the acinar cells. The concentration of fluoride in the duct
saliva will therefore follow the plasma values, at a 30% to 40% lower level. This
results in an increase of fluoride concentration in whole saliva, although only 0.1% to
0.2% of the ingested fluoride is excreted via the salivary glands.
In some foods and beverages, the fluoride is mainly in ionized form, which readily
dissolves in the saliva; in others, fluoride may be firmly bound, making it difficult to
predict the resulting fluoride concentration after exposure. This variable should be
taken into account in the formulation of caries-preventive topical agents: For example,
fluoride tablets and fluoride chewing gum have very different solubility rates. In
addition, some slow-release fluoride agents, such as fluoride varnish, may contain up
to 2% to 5% fluoride; glass-ionomer cements may be intermittently reloaded with
fluoride, and as a consequence, release fluctuating amounts of fluoride.
Because the oral cavity contains only a small volume of saliva in a thin film, even if
only very small amounts of fluoride dissolve in the residual saliva, the resulting
concentration may be very high. For example, if a fluoride tablet of 0.25 mg is
dissolved in 1 mL of saliva, the resulting fluoride concentration is about 13 mol
(about 200 ppm), more than 10,000 times higher than the basal fluoride concentration.
Even higher fluoride concentrations could be expected in loci close to the fluoride
source. For example, if a fluoride tablet is placed on one side of the oral cavity, very
large differences in salivary fluoride concentration are found between the exposed and
unexposed sides of the mouth (Sjogren et al, 1993). Therefore, slowly dissolving
fluoride tablets and fluoride chewing gum should be moved around the mouth
continuously to distribute fluoride to as many microenvironments as possible, and
slow-release fluoride agents should be applied to key-risk teeth and key-risk surfaces.
The high initial fluoride concentration in the salivary film after fluoride exposure will
establish a concentration gradient between the dental integuments and the plaque.
Fluoride will diffuse from saliva into the pellicle and the plaque, rapidly elevating the
concentration of fluoride in the plaque fluid. Mineral calcium fluoride (CaF2) may
form in saliva, in the pellicle, and in plaque fluid (see Fig 101) (Ogaard et al, 1983a,
b).
The limiting factor for the formation of CaF2 is the calcium content of the oral fluids.
Therefore, the use of fluoride chewing gum after every meal as a combined salivastimulating
and fluoride agent, resulting in increased calcium release from the saliva,
fluoride release, and increased buffering effect, offers a rational, self-administered
measure for caries control during or just after the fall in pH. Calcium fluoride releases
fluoride slowly (Fig 102). Fluoride diffusing into microorganisms also prevents
participation of the enzyme enolase in the glycolytic pathway by binding magnesium,
essential for optimal function of the enzyme. However, this will not occur on plaquefree
tooth surfaces.
After the initial exposure to fluoride, the salivary concentration of fluoride decreases
rapidly, by the same mechanisms involved in sugar clearance. The most important
factor for the fluoride clearance rate is, as for sugar, the salivary secretion rate, which
is dependent on the degree of stimulation. Fortunately, fluoride clearance is
significantly slower in patients with hyposalivation than in individuals with normal
SSR. Clearance varies markedly at different sites in the oral cavity, is generally more
rapid from lingual than from buccal sites, and is most rapid beneath the tongue.
However, there are some important differences between salivary fluoride clearance
and salivary sugar clearance. The saliva contains a certain basal level of fluoride,
which results in a gradual, theoretically asymptomatic decrease of fluoride to the
basal level. This slow adaptation is often prolonged for several reasons. First,
swallowed fluoride will partly reenter the saliva, increasing the amount of fluoride,
but the effect on the fluoride concentration is probably minor. Second, after a few
minutes, the fluoride concentration in pellicle and plaque fluids is higher than it is in
the saliva, causing the concentration gradient to reverse direction. Some fluoride will
therefore diffuse back from the pellicle into the saliva. Third, after the fluoride
concentration in the pellicle has fallen to a level that makes the fluid undersaturated
with respect to calcium fluoride, this salt may start to dissolve slowly, increasing the
ionized fluoride concentration.
This last factor is complicated by its dependency on the pH of the pellicle, because at
pH values in the normal range, calcium fluoride dissolution is inhibited by adsorbed
phosphate ions. When pH approaches 5, this coating of the calcium fluoride particles
vanishes (see Fig 102). When pH rises again, phosphate and protein-coated CaF2 is
re-formed in the pellicle (Fig 103).
