A History and Update of Fluoride Dentifrices
Mechanism of Action of Fluoride

The development of newer dentifrice formulations has paralleled the increased understanding of the caries process and how fluoride works. The original belief of a continual dissolution of tooth surface has been replaced by the acceptance of an understanding of subsurface demineralization and the maintenance of a relatively intact surface layer (probably by remineralization).²⁰ Demineralization occurs when there is an imbalance between processes of mineral gain and loss. Fluoride may interact with these processes in several ways. It is now widely accepted that fluoride has both systemic and topical modes of action,²¹ although the topical benefits are generally considered to be the dominant factor. The interaction of fluoride with the mineral component of teeth produces a fluorohydroxyapatite (FHAP or FAP) mineral, by substitution of OH^- with F^-. This results in increased hydrogen bonding, a more dense crystal lattice, and an overall decrease in solubility. The incorporation of fluoride into the hydroxyapatite (HAP) lattice may occur while the tooth is forming or by ion exchange after it has erupted. A decrease in solubility increases with greater amounts of fluoride incorporation, but rarely do we exceed several thousand parts per million of fluoride in the outer enamel.²² Thus, only limited protection from fluoride substitution would be expected as compared to pure FAP that has 40,000 ppm fluoride. Another means of incorporating fluoride into the enamel is from topical applications and ion exchange. This surface oriented exchange could also affect the solubility of the bulk solid. The exception to limited protection may be the crystallite surface, where a thin coating of pure FAP would make the bulk solid appear to be less soluble than the degree of substitution would predict. Therefore, a limited incorporation of fluoride into the crystal lattice or on the surface may have a significant impact on solubility.²³ The systemic "solubility reduction effect" was thought to be the only mechanism of action until studies revealed a significant topical effect on mineralization as well as a bacterial effect.

Fluoride found in solution can also affect the dissolution rate without changing the solubility of tooth mineral. As little as 0.5 mg/L in acidic solutions causes a reduction in the dissolution rate of apatite.²⁵ This mechanism also involves absorption and/or ion exchange at the crystal surface. Thus, the surface may act more like FAP than HAP and have a different dissolution rate. When the enamel dissolves, it may also contribute fluoride to the surrounding solution. Under ‘sink’ conditions this would not have much of an effect, but the solutions normally bathing the teeth (i.e. saliva) are always partially saturated with respect to apatite. Extremely low fluoride levels have been shown to significantly reduce the dissolution rate of apatite.²⁶ Thus, both the concentration of fluoride at the crystal surfaces and the fluoride concentration in the liquid phase during a cariogenic challenge are important.²⁷

In addition to protecting against demineralization, another way in which fluoride interacts with enamel to reduce dissolution is through remineralization. This is a process in which partially dissolved enamel crystals act as a substrate for mineral deposition from the solution phase that enables partial repair of the damaged crystals. Therefore, remineralization helps counteract demineralization and an equilibrium then develops between the two processes. The carious lesion occurs when the demineralization process outweighs the remineralization process, and net damage occurs. One of the benefits of the demineralization/remineralization interplay is the creation of less soluble mineral in enamel.²⁸ This occurs by dissolution of the more soluble calcium deficient magnesium containing carbonated apatite which makes up enamel when first formed. The remineralization process results in formation of a less soluble form of apatite. When fluoride is also present, formation of fluorohydroxyapatite (FHAP or FAP) results in a mineral with an even greater level of acid resistance. The remineralization process is one controlled by the supersaturation of fluids bathing the teeth - plaque fluid or saliva. The degree of supersaturation will, in part, determine the rate of precipitation of minerals from the solution.²⁹ Too high of a supersaturation will result in the rapid formation of calcium phosphate and block the surface pores of enamel. This precipitation then limits the diffusion of calcium, phosphate and fluoride into the interior of the lesion, which can result in lesion arrestment rather than lesion repair.³⁰ The interior of the lesion is partially saturated with respect to HAP and can become supersaturated with respect to FAP, even if minimal levels of fluoride are present or diffuse into the lesion. The use of low concentration fluoride products, such as dentifrices on a daily basis, will help maintain this favorable saturation. Thus, remineralization of the lesion may result in the repair of the existing lesion with less soluble mineral and render this portion of the tooth less susceptible to future episodes of demineralization (Figure 2). This is probably one of the most important modes of action of fluoride.

Fluoride, at a relatively low concentration, may also interact with the oral bacteria to reduce plaque acid production. Several mechanisms have been proposed to account for this end result. One is the well-known interaction of fluoride with the enzyme enolase which could directly reduce the production of bacterial acids. There is also an indirect effect on the phosphotransferase system (PTS) pathway that decreases the amount of sugar entering the cell by limiting phosphoenolpyruvate (PEP).³² It is also likely that diffusion of fluoride into the cell occurs as hydrofluoric acid (HF) which then dissociates, lowering the intercellular pH and disrupting the cell. Fluoride may affect the ability of the cell to remove excess H+ and less acid production may result from cytoplasmic acidification. The overall effect is less acid and a less acidic environment that should reduce the driving force for dissolution.³³ If these less acidogenic conditions continue, the long-term ecology of the plaque may be altered. It is difficult to predict the long-term effects, since adaptation to the fluoride may occur. Importantly, some forms of fluoride may be better than others with respect to effects on oral bacteria. For example, stannous fluoride (SnF₂) provides antibacterial effects that are not delivered by other fluoride actives used in dentifrice formulations.