The Science of Remineralization

Q. How does the demineralization process work?

CHOW: The most important premise for understanding remineralization and demineralization is to see them as two continuous reactions in opposite directions. Demineralization results from acids being produced by bacteria in plaque biofilm. Demineralization occurs almost immediately when we eat or drink fermentable carbohydrates. The process is dynamic and complex. When sugar (or other types of carbohydrates that can turn into sugar) gets into the plaque and is used by bacteria, this forms acids. At the same time, sugar can also come out of plaque. It may be washed away by saliva; the acids produced by the plaque can also be washed away into the saliva. At the same time, demineralization can occur (see Figure 1).

In plaque biofilm, there are a few processes going on simultaneously. The demineralization process occurs in an open system; it’s not like in a beaker where certain amounts of acid demineralize a tooth eventually. In the case of the caries process in the mouth, sugars are being added to the plaque and acids are being formed but both the sugar and acids in the plaque are also being rinsed away by saliva and eventually eliminated after we stop eating sweets. Before the acids are washed away into the saliva, some of the acids do some damage to the mineral by dissolving it.

WEFEL: From basic chemistry, we know that any time a solution is undersaturated with respect to a solid, the solid can start to dissolve. In this case, the enamel will begin to dissolve if the oral fluid is undersaturated with respect to tooth structure. If it’s saturated, then the enamel is at equilibrium with the solution and if it’s supersaturated then the opportunity exists for remineralization. An acidogenic microflora present in the mouth is fed by fermentable carbohydrates from the diet and the bacteria are masters at taking the fermentable carbohydrates and using them to produce organic acids. The organic acids then shift the pH of the oral or plaque fluid such that the pH, calcium, and phosphate present in the fluid can no longer keep the oral environment saturated with respect to the exposed tooth structure. So the fluid phase becomes undersaturated, and then the enamel or the tooth substance can begin to dissolve. This is the start of demineralization.

Demineralization is dissolution, just like when you put sugar in your coffee, it gets smaller and disappears. Teeth don’t simply dissolve from the outside in but tend to maintain their shape until the surface breaks down and a carious lesion is identified. When we look at the tooth histologically, we recognize that a unique type of demineralization has occurred. There is a subsurface demineralization and a relatively intact surface that remains until the demineralization has penetrated through the enamel and into the dentine. When the surface finally breaks down, a carious lesion is formed and the chance for additional remineralization is lost.

This process demonstrates some important points. One is that it takes a long time to go from the start of dissolution to cavitation, which also means that a chance for prevention exists. We can halt this process before it gets to the cavitation stage. The remineralization/ demineralization process is like a teeter totter going back and forth between demineralization and remineralization. In chemistry terms, this is an equilibrium situation where certain factors favor demineralization and other factors favor remineralization. Most of the time, the equilibrium situation is static and teeth are not harmed. When too many fermentable carbohydrates are consumed and the microflora produce a lot of acid too many times a day, then obviously we have a greater opportunity for demineralization and our disease and caries rates may go up.

Q. How does remineralization work?

WEFEL: The mineral part of the tooth is composed of calcium phosphate, which looks like hydroxyapatite, a calcium phosphate-containing solid. An entire series of solid calcium phosphates exist including fluorapatite, octocalcium phosphate, dicalcium phosphate, etc. The hydroxyapatite and fluorapatite are the most insoluble and thus are the preferred solid phase.

Enamel is like hydroxyapatite, or if it contains some fluoride, then a fluoridated hydroxyapatite. But enamel also contains many of the other contaminants that are present during the formation of enamel, like carbonate, sodium, potassium, and magnesium. Instead of a pure apatite, enamel is formed as a calcium deficient, carbonate-containing apatite. This is important to understand for several reasons. First, the solubility product that determines when a solution is saturated is different between enamel and hydroxyapatite. As you may surmise, enamel is more soluble than the apatites. Second, after demineralization dissolves the most soluble material, remineralization can replace the lost mineral with a less soluble apatite.

Remineralization is calcium phosphate penetrating into the tooth itself and crystallizing, making the crystals better and filling in the space that was left. The space is created by demineralization and then remineralization can follow. At the start of the demineralization process, we find that magnesium- and carbonate- containing enamel is most soluble and dissolves first. Remineralization can now occur on the remaining mineral if calcium, phosphate, and fluoride are present in the fluid phase surrounding the crystals. The forming of better crystals through remineralization also creates a less soluble apatite.

Remineralization also occurs as demineralization continues much farther, going into the middle of the enamel to the dentine. Solution conditions can be changed to make them more favorable toward remineralization vs demineralization, providing a chance for remineralization. Some of the same issues encountered with demineralization in terms of saturation or undersaturation, diffusion of dissolved product, and maintenance of undersaturation, are very similar in remineralization. In remineralization, a diffusion of the right solution, which includes calcium and phosphate to make more mineral, is necessary for the process. Fluoride is a catalyst that speeds this process up. But a super saturated condition is necessary for remineralization to occur.

The normal vehicle for calcium phosphate is saliva. Saliva has enough calcium phosphate in it to keep the oral environment saturated if not super saturated. But it doesn’t cause extra remineralization or crystallization to occur because there are also inhibitors in the saliva that stop the unwanted precipitation. So what changes the most in saliva is the pH, not the calcium and phosphate concentration. When the enamel pH is allowed to drop below 5.6 or 5.4, a point of undersaturation is reached and demineralization begins. When the pH level rises above this point, the chance for saturation or supersaturation is realized so that some remineralization can occur if the conditions are appropriate.

Q. How can we reduce demineralization?

CHOW: In the absence of a challenge (the presence of acid), saliva is a continuous factor in the mouth that can reduce demineralization. Demineralization is more likely to occur in areas that saliva can’t reach, like the occlusal fissures, proximal surfaces, and cervical areas around the gingiva. It is also more difficult to remove plaque from these areas with daily oral hygiene procedures. Because there is more plaque present and these are not open areas that are exposed to saliva in large volumes, they are the sites where demineralization will occur.

Other factors come into play with secondary caries. The saliva is able to wash away the sugars and the acids being produced in the plaque biofilm more readily in primary caries. If decay is present in the lesion underneath the filling, the situation becomes even worse. If bacteria can enter the space between the filling and cavity wall, then the risk for decay is very high. This is why in secondary caries, manufacturers are working on restorative materials that can release some calcium, phosphate, and fluoride. This may be beneficial if the material is alkaline in nature so it can neutralize some of the acids.

Q. How does a product that contains calcium phosphate work?

WEFEL: Most of the products containing calcium phosphate are what I refer to as salivary enhancers. They are designed to provide more calcium phosphate, which normally comes from saliva. These products work best in people with poor salivary flow who don’t maintain the right calcium phosphate levels. This is common in people with some sort of xerostomic condition, whether it’s from head and neck cancer treatment that shuts down the salivary glands, the taking of hypertensive drugs that dry out the mouth, or diseases like Sjogren’s syndrome that decrease salivary flow. If salivary flow is restricted, calcium phosphate products can be quite useful in supplying calcium phosphate that is lacking from the oral environment. In normal patients with a normal salivary flow, a system is necessary that delivers calcium phosphate to the site in which it’s needed and then remains around long enough to be used when conditions are favorable.

The oral cavity goes through episodes of demineralization and remineralization where additional calcium phosphate is needed not so much when saturated or supersaturated conditions exist as much as when demineralizing conditions exist. If calcium phosphate is present during demineralization conditions, then it could act as a common ion and stop or inhibit part of the demineralization that is going to occur when the acid is formed.

Calcium phosphate comes in a variety of products including dentifrice, hypersensitivity products, varnishes, chewing gum, sealants, and prophy pastes. Different types of calcium phosphate technologies also exist: amorphous calcium phosphate, calcium sodium phosphosilicate, and casein phosphopeptide-amorphous calcium phosphate (see Table 1).

Calcium phosphate products don’t only remineralize. The process of demineralization and remineralization are not separated. These products may well be effective because they inhibit demineralization as much as they help remineralization. I think this is often forgotten. For instance, in a product designed to bind calcium phosphate in a greater concentration than normal, if it is delivered and stays at the site of demineralization, then an acidic pH change may release the bound calcium and phosphate. When this happens, the calcium phosphate is in the right spot in the oral environment to increase the concentration and decrease demineralization. This has nothing to do with remineralization yet. If the calcium and phosphate are able to diffuse into the tooth when in abundance, they may be used for remineralization when the acidic conditions are neutralized.

It is difficult to separate the processes of remineralization and demineralization because between the starting mineral content and the ending mineral content, the process has moved back and forth between remineralization and demineralization. The end result may be a healthier tooth with less mineral loss or more mineral gain.

CHOW: Chewing gum itself is also very effective especially if it’s used after a cariogenic challenge. Any kind of sugarless gum will have some beneficial effect if it’s used after eating or drinking something sweet, mainly because chewing stimulates salivary flow so a greater amount of saliva is available to rinse away the sugar in the plaque biofilm or the acids being produced by the plaque. Chewing gum also stimulates the saliva to have a higher pH than natural saliva so it produces a greater source of buffering effect to neutralize some of the acid.

Calcium phosphate-releasing gum or candy can produce a beneficial effect even if it’s used before a challenge by building the reservoir of calcium phosphate in the plaque. Calcium phosphate- containing tooth whitening products seem to reduce dentinal hypersensitivity caused by the whitening process because whenever there is calcium phosphate in the solution gel or paste, it prevents or reduces demineralization. Calcium phosphate-containing products work because they reduce or prevent demineralization and allow saliva the opportunity to produce remineralization. If we can eliminate or reduce demineralization, we will have remineralization as the result.

From Dimensions of Dental Hygiene. February 2009; 7(2): 42, 44, 46.