Tips to Boost Remineralization

Highly prevalent, dental caries is a significant public health issue.^1–5 The goal is to manage incipient carious lesions noninvasively while in their earliest stages using evidence-based measures, such as remineralization techniques.

The process of tooth remineralization is essential to prevent the progression of dental caries and to arrest incipient lesions. Tooth remineralization is a cost-effective way to regenerate damaged tooth structures. As oral health professionals with a strong focus on prevention, dental hygienists are charged with keeping up-to-date on available remineralization agents.

Dental enamel is a fairly stable structure characterized by a constant balance between demineralization and remineralization. Nevertheless, an interruption in this process can lead to demineralized lesions. Demineralization is the reversible process of losing mineral ions from hydroxyapatite crystals of tooth structures including enamel, dentin, or cementum. The demineralized hydroxyapatite crystal of teeth can be remineralized if exposed to an oral environment that supports mineralization.^1,2

Process of Remineralization

Remineralization is achieved when the oral plaque and mixed saliva are oversaturated with ions, such as calcium, phosphate, sodium, magnesium, chloride, fluoride, and hydroxide, similar to the structure of dental enamel. Replenishing these mineral ions to the hydroxyapatite crystals is known as remineralization.^2,3

A remineralized tooth surface is far more resistant to subsequent acid attacks. Demineralization must be stopped in order to prevent the risk of dental caries and the need for invasive dental procedures.^4–7 Therefore, remineralization therapies should be considered for patients exhibiting signs of demineralization.

The Role of Saliva

Saliva is an essential biological factor that acts as an antibacterial agent; it cleanses the teeth and neutralizes the acid in the mouth. Within normal physiological conditions of neutral pH, noncariogenic environment, and healthy salivary flow, saliva is a constant source of calcium and phosphate ions. These ions are required for remineralization when the pH in the mouth falls, and the promotion of remineralization when the pH neutralizes. The bioavailability of calcium and phosphate ions also ensures diffusion into an area of mineral deficiency, such as a white spot lesion.^2,6,8

The ability of saliva to neutralize the oral pH and remineralize tooth enamel is contingent on the capacity of three buffering systems:⁶

1. Carbonate/bicarbonate from parotid gland saliva as the primary regulator of pH
2. Phosphate buffer found mainly in non
3. Stimulated salivarotein system

However, natural remineralization from saliva alone is insufficient for two reasons. First, it is a slow process. Second, the low concentration of calcium and phosphate ions is only adequate to remineralize the surface of the lesion, not the entire lesion.

The subsurface of the white spot lesion remains demineralized during this natural remineralization process. Thus, extrinsic sources of stabilized calcium and phosphate ions should be added to the patients’ daily oral health regimen to amplify the natural remineralization potential of saliva and to produce faster and deeper subsurface remineralization.^9,10 Current remineralization agents include over-the-counter options and prescription-only products.

Fluoride

The role of fluoride in preventing and arresting dental caries is supported by multiple systematic reviews (the strongest level of evidence).^11,12 Fluoride interferes with the activity of acid-causing bacteria and promotes tooth remineralization. When bacterial acids break down the enamel, calcium and phosphate ions are released from the tooth surface. Fluoride ions bring these minerals back to the tooth surface and speed up the growth of the new fluorapatite.^4,11–13

Fluoride in saliva and plaque is key in preventing tooth demineralization and enhancing remineralization. The fluoride’s bioavailability depends on the fluoride content in dental plaque, fluoride formulation, saliva secretion, and salivary content.^2,14,15

Naumova et al¹⁴ demonstrated a rise in salivary fluoride concentration immediately after brushing with a dentifrice containing either sodium fluoride or amine fluoride. The surge in salivary fluoride was immediate and lasted for a minimum of 30 minutes, whereas the plaque fluoride concentration increased 30 minutes after brushing.

Fluoride in dental plaque is as essential as salivary fluoride because the acidogenic bacteria in plaque are the leading cause of dental caries.¹⁴ Fluoride is bacteriostatic in lower concentrations and bactericidal in higher concentrations. Dental plaque serves as a fluoride reservoir—it stores fluoride for some time and later delivers it to the tooth surface.

A meta-analysis by Walsh et al¹⁵ found that toothpaste with a minimum of 1,000 ppm to 1,250 ppm fluoride ions has an anticaries effect compared to nonfluoride toothpaste. Naumova’s study did not find any significant difference in bioavailability between sodium fluoride and amine fluoride in saliva or plaque.¹⁴ 

To remineralize enamel with fluoride, calcium and phosphate ions are required to promote the process. For every two fluoride ions, 10 calcium ions and six phosphate ions are necessary to form one unit cell of fluorapatite. During healthy physiological conditions, fluoride and saliva are often enough to remineralize incipient lesions. However, in a highly cariogenic or xerostomic oral environment, the presence of inadequate calcium and phosphate ions can impair the remineralization process.^2,9,10,13

The efficacy of fluoride to remineralize the tooth structure can be improved with additional strategies such as calcium-based boosters. The addition of extrinsic sources of stabilized calcium and phosphate ions to patients’ daily oral health regimens (ie, gel, toothpastes, mouthrinse) can amplify the natural remineralization potential of saliva and produce faster and deeper subsurface remineralization.^2,10

Silver Diamine Fluoride

Silver diamine fluoride (SDF) is a prescription-only translucent liquid used for topical fluoride application. This product is mainly available in 38% concentration, which is composed of 44,800 ppm of fluoride.¹⁶ SDF contains silver, which has antibacterial and antimicrobial properties, in addition to fluoride.¹⁷

A systematic review with meta-analysis by Oliveira et al¹⁸ found that the applications of 1% chlorhexidine, 5% sodium fluoride, and 38% silver diamine fluoride demonstrated preventive and remineralization effects on caries-susceptible root surfaces. SDF inhibited cariogenic bacteria, promoted demineralization, and prevented collagen degradation in dentin.

The authors further stated that the application of 38% SDF annually to elderly patients with exposed root surfaces is an efficient, economical, and effective way to halt tooth demineralization and progression of dental caries. SDF reduced new root caries by 50% and had a greater effect on preventing root caries with a longer duration.¹⁸ When comparing chlorhexidine varnish to SDF, applying 1% chlorhexidine varnish at quarterly intervals had a significantly higher preventative effect at 12 months over a yearly application of SDF, but there was no difference between the two products at 24 months.

The application of 1% chlorhexidine varnish or 5% fluoride varnish quarterly and the annual application of 38% SDF have similar effects in the long term.¹⁸ The annual application of SDF makes it more cost-effective, however the staining may impact patient compliance and satisfaction.^17,18 A new product that includes potassium iodide to be applied after the SDF may reduce staining while providing similar benefits.¹⁹

Calcium Phosphate Technologies

Calcium phosphate-based remineralization technologies are promising adjuncts to fluoride therapy in the management of incipient carious lesions.² Casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) is a bioactive material derived from the milk protein casein that increases calcium and phosphate bioavailability. Basically, CPP stabilizes ACP and delivers it to the tooth surface.²⁰

Dental plaque clusters of ACP, which prevent calcium phosphate precipitation, are formed through the combination of CPP with calcium phosphate. This CPP (milk protein) acts as a reservoir to precipitate these minerals onto the tooth surface.^2,13,21,22 This results in a supersaturated enamel that resists demineralization and improves remineralization.¹³

CPP-ACP can also inhibit bacterial adhesion to the tooth surface, thus slowing plaque formation. Furthermore, through the production of ammonia, the breakdown of the CPP buffers the oral environment by raising the oral pH.⁹ Research shows that CPP can be detected at low levels in those who consume dairy products.

The use of mouthrinses and chewing gum containing CPP-ACP significantly increased the availability of calcium and phosphate in plaque. In the chewing gum studies, this increase lasted for several hours after use. The use of CPP-ACP products increased calcium and phosphate levels in plaque biofilm and enhanced remineralization over unstabilized ACP or calcium added to products independently.²⁰

Dental products containing CPP-ACP in addition to fluoride are effective remineralizing agents.^2,13 A recent systematic review and meta-analysis by Ma et al²¹ assessed whether CPP-ACP effectively remineralizes white spot lesions compared to non-CPP-ACP pastes, fluoride toothpaste, or placebo. Results showed that CPP-ACP products produced a far better remineralization treatment effect on white spot lesions compared to non-CPP-ACP-containing products.

Similarly, Shen et al²³ compared various calcium phosphate and fluoride-containing varnishes to a placebo in preventing enamel demineralization. Results indicated that the fluoride-containing varnishes significantly inhibited demineralization in comparison to the placebo varnish. The varnish that included CPP-ACP and fluoride was deemed superior to the fluoride varnish in preventing enamel demineralization as it released the highest concentrations of calcium, phosphate, and fluoride ions. Hence, during the topical application of fluoride, calcium, and phosphate ions, availability is essential for enamel remineralization.^2,6,13

Remineralization of enamel can similarly be achieved by raising the salivary calcium/phosphate (Ca/P) to a ratio of 1.6.²⁴ In dental plaque, the Ca/P ratio is approximately 0.3, which is low; therefore, the use of calcium-containing products may promote tooth remineralization.^6,24

Research showed that the consumption of cheese and yogurt without any added sugar significantly improved calcium and phosphorus concentration in plaque biofilm, and is therefore a viable option to enhance tooth remineralization.²⁵

 Tricalcium phosphate (TCP) is designed to accelerate enamel fluoride uptake.^23,26,27 When TCP contacts a saliva-moistened tooth surface, it is believed that the protective barrier breaks down, making calcium, phosphate, and fluoride ions available that accelerate the remineralization process.^23,26

Research shows that TCP products improved remineralization and enhanced anticavity resistance in in vitro and in situ studies, however, their clinical efficacy remains unknown.^5,23,28,29 Studies indicated that TCP improved the fluoride uptake of permanent enamel treated with fluoride toothpaste and increased the mineralization of dentin in bovine teeth.^24,28,30

Alamoudi et al²⁹ found that combining TCP with fluoride varnish significantly inhibited demineralization on primary teeth in vitro. In enamel subsurface lesions, Hamba et al⁵ observed increased remineralization in samples exposed to fluoride toothpaste containing TCP.

Arginine

An amino acid made up of proteins and peptides, arginine has been shown to reduce both biofilm accumulation and dental caries.^31,32 Particularly when combined with fluoride, arginine can help boost remineralization, especially among patients at high risk for caries.

Research demonstrates that the addition of 2% arginine to a fluoride dentifrice significantly improved the remineralization efficacy of the dentifrice.³³

Xylitol

Xylitol is a five-carbon natural sugar alcohol with a similar dietary sweetening property to sucrose. Research shows that xylitol is safe, noncariogenic, and has a dose-/frequency-dependent effect on the cariogenic bacteria mutans streptococci in dental plaque.^34–36

Habitual consumption of xylitol is defined as the daily intake of 5 grams to 7 grams of xylitol three times per day; the recommended consumption dose for caries prevention is 6 grams to 10 grams/day (~6 pieces to 10 pieces of a xylitol product such as chewing gum).³⁴

Systematic reviews have concluded that the habitual consumption of sucrose-free xylitol/polyol-combination chewing gum or lozenges is effective in preventing coronal caries.³⁵ Additionally, research studies cite that xylitol significantly reduced dental caries when used in combination with fluoride toothpaste.^35–37 In a systematic review, Mickenautsch and Yengopal³⁷ recommended the combination of xylitol to existing fluoride treatments to prevent dental caries.

Future Remineralizing Agents

Titanium tetrafluoride (TiF4) is a fluoridated compound that reduces demineralization through the creation of an acid-stable surface layer on the tooth.^23,38,39 It provides mechanical protection and enhances fluoride uptake due to the fluoride binding to the metal ions. When a varnish containing TiF4 is applied to the tooth surface, it is believed that the titanium ions react with dental apatite to a layer containing titanium phosphate and titanium dioxide, which inhibits the microorganism adhesion and viability, as well as hinders subsequent plaque growth.³⁹

Comar et al³⁹ reported that varnish containing TiF4 generates a higher calcium and fluoride deposition than sodium fluoride varnish on both healthy and demineralized enamel surfaces. This is possible due to its viscosity, which increases the contact time with enamel, therefore improving the reaction of titanium with the tooth apatite. Varnish containing TiF4 also has a low pH and can augment the enamel fluoride uptake compared to sodium fluoride varnish.^39,40

Polat and Ilday²² found that TiF4 combined with Er: YAG laser produced an even higher remineralization effect. They assessed various remineralization agents including TCP, TiF4, CPP-ACP, and bioactive glass individually and in combination with Er: YAG laser. This study evaluated the effects of each on microhardness values of 150 extracted third molars and found statistically significant differences among all the groups.

Except for the CPP/ACP/Er: YAG laser combination, each agent combined with the Er: YAG laser produced microhardness values that were significantly higher than any agent alone. The TiF4 /Er: YAG laser combination generated a far better resistance to demineralization and demonstrated the most effective remineralization.

A systematic review by Wahengbam et al⁴¹ reported that TiF4 is a viable option for tooth remineralization because of its formation of an acid-resistant coating in addition to higher uptake, greater penetration, and longer retention of fluoride. Despite the various studies supporting the effects and the beneficial properties of TiF4, the performance of the product is still unclear and its chemistry is not completely understood.⁴¹

Conclusion

The battle between demineralization and remineralization processes is constant in the oral cavity. Minerals available in saliva and plaque determine which action wins the fight. Thus, maintaining an oral environment that inhibits demineralization and promotes remineralization is critical.

In addition to dietary counseling, oral hygiene instruction, recommendation and application of preventive agents, dental hygienists must be aware of the current remineralization strategies available to prevent or arrest dental caries. Incorporating evidence-based remineralization agents into patients’ oral hygiene education is an important step to reduce caries risk and to avoid invasive restorative treatment.

References

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From Dimensions of Dental Hygiene. April 2023; 21(4):18-21.