Remineralizing therapy as a non-invasive method of treating focal demineralization of enamel

An actual question for dentists is the treatment of initial dental caries using remineralizing therapy [1—3]. Remineralization of enamel is a natural process of restoration of pathological changes in the enamel of teeth that do not have a carious cavity, based on its saturation with mineral substances [4]. In the process of enamel mineralization, an important role is played by the oral fluid containing glycoproteins, the main function of which is absorption on the tooth surface and the creation of a protective film layer, which reduces the loss of minerals from the crystal lattice of tooth enamel under the action of acids [5].

However, resistant microflora of the oral cavity, lack of microelements in food, orthodontic treatment often used in modern dentistry, non-compliance with the rules for using systems for home teeth whitening, as well as the use of large amounts of high-carbohydrate food by patients violates the patient's hygienic status and contributes to the risk of initial caries [6— 9]. According to N.V. Bulkina et al. focal demineralization of enamel is characterized by an increase in pore-holes in the tooth enamel, which serves as an additional factor for the movement of microorganisms with the subsequent destruction of the enamel structure [10].

The main element of tooth enamel is enamel prisms. Their structural component is hydroxyapatite crystals, which are sensitive to the electrochemical composition of the intercellular and oral fluid, blood, which determines the processes of diffusion and ion substitution in the hard tissue of the tooth. This structural feature allows the use of methods of treatment and prevention of the initial stage of caries non-invasively [11]. The possibility of replenishing the mineral deficiency of trace elements and preserving the protein matrix in the enamel crystal lattice are the main indications for remineralizing therapy [12, 13].

Currently, the dental market offers many combinations of substances used in drugs to prevent the development and elimination of clinical manifestations of focal demineralization of enamel, which is of interest for their detailed study. Depending on the method of application of the funds, remineralizing therapy is divided into general and local. General remineralizing therapy is carried out with the use of oral drugs, and local — with the help of application gels, foams, creams, solutions and toothpastes [14—19]. We have reviewed in most detail the local remineralizing therapy and the drugs used.

The aim of this work is to review the data on the effectiveness of the use of local remineralizing therapy.

Modern remineralizing preparations must meet a number of requirements: long-term adhesion to tooth enamel, optimal content of fluoride ions, phosphates and calcium in the composition, which can increase the pH of the oral fluid and penetrate into the microspaces of demineralized areas of the enamel. The use of these dosage forms at the dental office and at home allows you to reduce time costs without involving complex and multi-stage methods [20].

A large group of drugs for remineralizing therapy are drugs based on calcium and phosphorus. In the study by O.V. Sysoeva et al. a comparative assessment of three gels was carried out: based on calcium glycerophosphate, Recaldent complex and individual calcium ions in combination with various microelements. The mechanism of action of the first gel is that hydrolysis of calcium glycerophosphate occurs under the action of enzymes with the release of calcium and phosphorus ions, as well as energy, which is used for the diffusion of ions into the enamel. The active ingredient of the second gel is casein protein, which includes phosphate and calcium ions associated with it. Casein phosphopeptides provide high adhesion between drug molecules and tooth enamel, pellicle, plaque surface and soft tissues of the oral cavity, and also allow phosphate and calcium to remain in a non-crystalline amorphous state. The complex of casein phosphopeptides with amorphous calcium phosphate (casein phosphopeptide — amorphous calcium phosphate, CPP—ACP), absorbed on the enamel of the teeth, releases part of the phosphate and calcium ions into the oral cavity, and part of the amorphous calcium phosphate bound to casein retains the activity of these ions. This creates a difference in the concentration of calcium and phosphate ions, which is a necessary condition for the transition of ions and their vapors to the focus of the initial stages of the enamel carious process. According to the results of the study, no statistically significant differences were found between the compared samples. This indicates that gels based on calcium and phosphorus have high clinical efficacy regardless of the compound in which they are presented, and also promote active mineralization of tooth enamel, increasing its resistance to acids [21—25].

In a research by M.A. Abbassy et al. the effectiveness of remineralizing therapy was assessed using a preparation based on bioactive glass 45S5, which is sodium calcium phosphosilicate. With the help of transverse microradiography, the authors obtained data that the use of bioactive glass significantly reduces the depth of damage to the enamel of the studied samples, and the results of research using infrared spectroscopy, X-ray diffraction and scanning electron microscopy showed that a layer of brushite crystals is formed on the surface of the enamel, which releases ions. calcium and fluorine for their further incorporation into the structure of enamel hydroxyapatite [26].

According to I.L. Gorbunova et al. the most effective method of remineralizing therapy is deep fluoridation. This method is based on the step-by-step use of solutions of fluoride silicates of magnesium, copper and suspensions of highly dispersed calcium hydroxide. As a result of a chemical reaction, a fluorosilicate complex is formed, which dissociates into microcrystals of polymerized silicic acid, copper, magnesium and calcium fluoride. The formed CaF₂ nanocrystals actively move into microspaces in the crystal lattice of tooth enamel. Silicic acid gel is a protective shell for fluorine ions, preventing them from leaving the enamel crystal lattice and creating conditions for their long-term release (from 0.5 to 2 years) in sufficient quantities for the remineralization process. These processes lead to the formation of fluorapatite, the main function of which is to restore the structure of the enamel in the lesion. The authors concluded that the number of preventive dental visits in caries-resistant patients should be increased up to 4 times a year [27, 28].

In a research of E.Yu. Leontyeva et al. a comparative assessment of the remineralizing activity of preparations based on the Recaldent complex containing CPP—ACP and this complex with the addition of fluorine ions (CPP—ACPF) was carried out. Fluorides penetrate into the crystal structure of the tooth enamel, giving it acid resistance and contributing to its remineralization. The study made it possible to conclude that the most effective is a fluorine-containing agent, since its use allows to achieve a longer and more stable demineralization of the enamel [29—30].

Currently, therapeutic and prophylactic fluoride foams are of great interest. Their active ingredient is 1.23% sodium fluoride acidified with phosphoric acid, which causes fluoride to be absorbed within one minute from the moment of its application. According to the manufacturer, the main function of the phosphate ion found in phosphoric acid is to prevent further development of the initial caries. However, there is no scientific data on the effectiveness of the use of foams with sodium fluoride in clinical practice [31].

Currently, a drug has appeared on the dental market that has only one active component — a synthetic analogue of the amelogenin protein; its main function is to directly actively participate in the formation of enamel in the process of odontogenesis. The formed tooth after eruption loses amelogenin from the crystal lattice, therefore this material is the most biocompatible for remineralizing therapy. This protein is able to stop the formation of foci of enamel demineralization by stimulating biomimetic regeneration. It was found that when the pH of the oral cavity changes, the correct crystal lattice of the enamel hydroxyapatite is formed. It is a three-dimensional biological matrix around which phosphorus and calcium minerals from human saliva accumulate. But the basis of this lattice is the "regeneration" of hydroxyapatite crystals, of which enamel prisms are composed. The described process is identical to the natural mineralization of enamel during odontogenesis, which determines its physiology and determines the advantage over other drugs that are used in dental practice today [32, 33].

According to M.M. Tusupbekov et al. a preparation based on synthetic amelogenin has a high remineralizing ability, which is confirmed by a high percentage of recovery of the organic matrix of demineralized enamel due to the incorporation of minerals from saliva [34].

In research of Z. Solovyeva et al. a comparative analysis of the effectiveness of remineralizing therapy by the method of deep fluorination by two different agents was carried out: a drug based on amelogenin and a light-cured hybrid material of prolonged action, which releases large amounts of fluorine, calcium and phosphorus ions in the first 24 hours after application. The active ingredient of the first agent for deep fluorination is a high molecular weight polymer of silicic acid, the second is a fluorosilicate complex. The results of a study using laser fluorescence of enamel and its vital staining showed that the index of enamel resistance 3 months after remineralizing therapy significantly decreased in all studied groups, which allows us to conclude about the high clinical efficacy of these drugs [35].

The development of new drugs in recent decades for the non-invasive treatment of focal demineralization of enamel can significantly increase the effectiveness of preventive measures, reducing the risk of caries in different age groups. Knowledge and understanding of the processes occurring in violation of the structural organization of enamel and its restoration is of great importance in pediatric dentistry, which is directly related to the active spread of the carious process in children. It is important to take into account that not only the composition of drugs for remineralizing therapy affects the result, but also their effect on the elements contained in the oral fluid that take part in mineral metabolism [36, 37].

In a research by N.A. Naronova et al. the assessment of the content of phosphorus and calcium in the oral fluid in children was carried out and the change in their values after a while under the influence of remineralizing drugs was analyzed. The first preparation was a long-acting gel containing calcium, phosphorus, chlorine, potassium, sodium, magnesium and a small amount of fluorine. After applying the agent to the enamel of the teeth, a film is formed, which ensures the duration of the effect of the remineralizing components of the drug. From it, the ions of mineral substances are gradually released and enter the microspaces of demineralized enamel foci. The second study drug is a gel based on the Mineralin compound. The main substance in this complex is calcium glycerophosphate, which is actively decomposed when interacting with acidic and alkaline phosphatase of the oral fluid. During the chemical reaction of the decomposition of calcium glycerophosphate, phosphorus and calcium ions are diffused into the crystal lattice of the tooth enamel, which provides a mineralizing effect. The inclusion of magnesium chloride in the composition increases the effectiveness of the product. Its main function is to ensure the work of phosphatases involved in the hydrolysis of calcium glycerophosphate. Xylitol increases the mineralizing effect of this agent, and also has an antibacterial effect against cariogenic microorganisms. This compound does not require saliva isolation trays to use, which is an advantage. The research results showed that an increase in the content of calcium in the oral fluid in children is observed when using a gel with calcium glycerophosphate, and an increase in the concentration of phosphorus is facilitated by the appointment of the first gel, which has a complex composition [8, 38].

The opinion of researchers about the effect of remineralizing agents containing fluorides or CPP—ACP on the strength of adhesion of bracket systems and the surface of tooth enamel is quite contradictory. According to S.B. Cehreli et al. the surface treatment of teeth before orthodontic treatment with fluorine-containing CPP—ACP does not affect the bonding strength, however, the use of CPP—ACP without fluoride as a remineralizing agent significantly affects the adhesion of the orthodontic construction to the tooth enamel [39]. However, the results of the S.Y. Park et al. showed that the CPP—ACP complex is an effective tool for the prevention of initial caries during orthodontic treatment, and the etching technique chosen by the doctor has the greatest effect on the bonding strength during the installation of bracket systems [40].

The use of a laser to increase the preventive effect of means for remineralization of teeth was evaluated by H. Ghadirian et al. As noted above, the enamel consists of hydroxyapatite crystals that can resist the effects of acids, but due to risk factors for caries, the phosphate group is replaced by carbonate ions with the formation of carbonate hydroxyapatite, which is more susceptible to acidic factors. As a result of laser action in carbonate hydroxyapatite, the carbonate bond in the molecule is broken, which allows reverse substitution with phosphate groups. The authors of the study concluded that no statically significant results were found between the groups of samples to which the remineralizing agent was applied with and without further laser treatment [41].

The use of highly concentrated peroxide compounds in teeth whitening can cause destructive changes in the hard tissues of the tooth and lead to a change in the biochemical composition of the oral fluid [42—45]. A number of authors believe that the above changes are due to an increase in enamel permeability. In a study by Z.A. Bichikaeva, using scanned electron microscopy, it was revealed that after office teeth whitening, changes in the structure of the enamel in the form of foci of destruction and depressions, exposure of areas of enamel prisms were observed, which indicates the occurrence of focal demineralization of the enamel of the teeth. The use of a preparation based on amorphous calcium phosphate contributes to the closure of the open surfaces of enamel prisms and aligns its structure, as well as obturation of the lumen of dentinal tubules, which is probably associated with deep penetration of calcium ions.

According to O.V. Ganicheva et al. after office teeth whitening, the concentration of calcium ions in the oral fluid increases, which indicates the release of this ion from the structure of tooth enamel [46]. As remineralizing therapy, deep fluorination, a gel based on zinc-substituted hydroxyapatite carbonate with and without laser phoresis was chosen. The most effective method turned out to be lasertophoresis with a preparation based on zinc-substituted hydroxyapatite carbonate: after 2 weeks of use, patients showed the most pronounced decrease in the level of calcium in the oral fluid, which is due to the diffusion of ions into the enamel crystal lattice.

Conclusion

Thanks to the use of non-invasive technologies, remineralizing therapy is the most effective method of treating focal demineralization of enamel, which avoids the preparation of hard tooth tissues. This approach reduces common patient fears about surgical treatments for dental caries, which include pain relief and dental hard tissue excision. The safety, simplicity, availability and convenience for the use of modern remineralizing agents allow reaching the vast majority of the population and reducing the overall prevalence of the carious process.

Analysis of the literature showed that the choice of a remedy for remineralizing therapy depends on many factors, the most important of which are the patient's age, the resistance of the enamel of the teeth, as well as the content of electrolytes in the oral fluid, which are involved in mineral metabolism.

In our opinion, an important aspect of remineralizing therapy is taking into account the calcium-phosphorus ratio, which will allow you to choose the most appropriate drug in a specific clinical situation. It should also be noted that the use of fluorides in combination with preparations based on calcium and phosphorus will provide the best result in restoring the structural organization of tooth enamel, increasing the efficiency of the procedure.