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
- Carbonate/bicarbonate from parotid gland saliva as the primary regulator of pH
- Phosphate buffer found mainly in non
- 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.
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.
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 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
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.
- Ehrlich H, Koutsoukos PG, Demadis KD, Pokrovsky OS. Principles of demineralization: modern strategies for the isolation of organic frameworks. Part II. Decalcification. Micron. 2009;40:169–193.
- Abou Neel EA, Aljabo A, Strange A, et al. Demineralization-remineralization dynamics in teeth and bone. Int J Nanomedicine. 2016;11:4743–4763.
- Li X, Wang J, Joiner A, Chang J. The remineralization of enamel: a review of the literature. J Dent. 2014;42 Suppl 1:S12–20.
- Ten Cate JM, Buzalaf MAR. Fluoride mode of action: once there was an observant dentist. J Dent Res. 2019;98:725–730.
- Hamba H, Nakamura K, Nikaido T, Tagami J, Muramatsu T. Remineralization of enamel subsurface lesions using toothpaste containing tricalcium phosphate and fluoride: an in vitro µCT analysis. BMC Oral Health. 2020;20:1–9.
- Farooq I, Bugshan A. The role of salivary contents and modern technologies in the remineralization of dental enamel: a narrative review. F1000Res. 2020;9:171.
- Meyer-Lueckel H, Paris S. When and how to intervene in the caries process. Oper Dent. 2016;41:S35–47.
- Cummins D. The development and validation of a new technology, based upon 1.5% arginine, an insoluble calcium compound and fluoride, for everyday use in the prevention and treatment of dental caries. J Dent. 2013;41:S1–S11.
- Cochrane NJ, Cai F, Huq NL, Burrow MF, Reynolds EC. New approaches to enhanced remineralization of tooth enamel. J Dent Res. 2010;89:118–1197.
- Philip N. State of the art enamel remineralization systems: The next frontier in caries management. Caries Res. 2019;53:284–295.
- Benson PE, Parkin N, Dyer F, Millett DT, Furness S, Germain P. Fluorides for the prevention of early tooth decay (demineralised white lesions) during fixed brace treatment. Cochrane Database Syst Rev. 2013;12:CD003809.
- Shahid M. Regular supervised fluoride mouthrinse use by children and adolescents associated with caries reduction. Evid Based Dent. 2017;18:11–12.
- Reynolds EC. Calcium phosphate-based remineralization systems: scientific evidence? Aust Dent J. 2008;53:268–273.
- Naumova EA, Kuehnl P, Hertenstein P, et al. Fluoride bioavailability in saliva and plaque. BMC Oral Health. 2012 Jan 9;12:3.
- Walsh T, Worthington HV, Glenny AM, Marinho VC, Jeroncic A. Fluoride toothpastes of different concentrations for preventing dental caries. Cochrane Database Syst Rev. 2019;3:CD007868.
- Yu OY, Mei ML, Zhao IS, Li QL, Lo EC, Chu CH. Remineralisation of enamel with silver diamine fluoride and sodium fluoride. Dent Mater. 2018;34:e344–e352.
- Hendrick L, Suedbeck J, Claiborne D. Using silver diamine fluoride to improve the oral health of older adults. Dimensions of Dental Hygiene. 2021;19(4):32–35.
- Oliveira BH, Cunha-Cruz J, Rajendra A, Niederman R. Controlling caries in exposed root surfaces with silver diamine fluoride: A systematic review with meta-analysis. J Am Dent Assoc. 2018;149:671–679.
- Haiat A, Ngo HC, Samaranayake LP, Fakhruddin KS. The effect of the combined use of silver diamine fluoride and potassium iodide in disrupting the plaque biofilm microbiome and alleviating tooth discoloration: A systematic review. PLoS One. 2021;16:e0252734
- Reynolds EC, Cai F, Shen P, Walker GD. Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum. J Dent Res. 2003;82:206–211.
- Ma X, Lin X, Zhong T, Xie F. Evaluation of the efficacy of casein phosphopeptide-amorphous calcium phosphate on remineralization of white spot lesions in vitro and clinical research: a systematic review and meta-analysis. BMC Oral Health. 2019;19:295.
- Polat YK, Ilday NO. The effects of different anticavity agents and Er:YAG laser usage on enamel surface microhardness. Oral Health Prev Dent. 2020;18:601–606.
- Shen P, McKeever A, Walker G, et al. Remineralization and fluoride uptake of white spot lesions under dental varnishes. Aust Dent J. 2020;65:278.
- Arifa MK, Ephraim R, Rajamani T. Recent advances in dental hard tissue remineralization: a review of literature. Int J Clin Pediatr Dent. 2019;12:139–144.
- Ravishankar TL, Yadav V, Tangade PS, Tirth A, Chaitra TR. Effect of consuming different dairy products on calcium, phosphorus and pH levels of human dental plaque: a comparative study. Eur Arch Paediatr Dent. 2012;13:144–148.
- Juntavee A, Juntavee N, Hirunmoon P. Remineralization potential of nanohydroxyapatite toothpaste compared with tricalcium phosphate and fluoride toothpaste on artificial carious lesions. Int J Dent. 2021;2021:5588832.
- Karlinsey RL, Mackey AC, Walker ER, Frederick KE. Preparation, characterization and in vitro efficacy of an acid-modified beta-TCP material for dental hard-tissue remineralization. Acta Biomater. 2010;6:969–978.
- Karlinsey RL, Mackey AC, Stookey GK, Pfarrer AM. In vitro assessments of experimental NaF dentifrices containing a prospective calcium phosphate technology. Am J Dent. 2009;22:180–184.
- Alamoudi SA, Pani SC, Alomari M. The effect of the addition of tricalcium phosphate to 5% sodium fluoride varnishes on the microhardness of enamel of primary teeth. Int J Dent. 2013;2013:486358.
- Karlinsey RL, Mackey AC, Schwandt CS. Effects on dentin treated with eluted multi-mineral varnish in vitro. Open Dent J. 2012;6:157–163.
- Nancy V, Carr J, Derrick L, Kabani F, MalloneeL. The oral and systemic health benefits of arginine. Dimensions of Dental Hygiene. 2019;17(10):40—43.
- Li J, Huang Z, Mei L, et al. Anti-caries effect of arginine-containing formulations in vivo: a systematic review and meta-analysis. Caries Res. 2015;49:606–617.
- Bijle M, Manikandan E, Edward L, et al. The combined enamel remineralization potential of arginine and fluoride toothpaste. J Dent. 2018;76:75–82.
- Milgrom P, Ly KA, Rothen M. Xylitol and its vehicles for public health needs. Adv Dent Res. 2009;21:44–47.
- Fontana M. Enhancing fluoride: Clinical human studies of alternatives or boosters for caries management. Caries Res. 2016;50 Suppl 1:22–37.
- Nayak PA, Nayak UA, Khandelwal V. The effect of xylitol on dental caries and oral flora. Clin Cosmet Investig Dent. 2014;6:8994.
- Mickenautsch S, Yengopal V. Anticariogenic effect of xylitol versus fluoride—a quantitative systematic review of clinical trials. Int Dent J. 2012;62:6–20.
- Dos Santos DMS, Pires JG, Silva AB, Salomão PMA, Buzalaf MAR, Magalhães AC. Protective effect of 4% titanium tetrafluoride varnish on dentin demineralization using a microcosm biofilm model. Caries Res. 2019;53:576–583.
- Comar LP, Souza BM, Al-Ahj LP, et al. Mechanism of action of TiF4 on dental enamel surface:SEM/EDX, KOH-Soluble F, and X-Ray diffraction analysis. Caries Res. 2017;51:554–567.
- Souza BM, Santos DMS, Braga AS, et al. Effect of a titanium tetrafluoride varnish in the prevention and treatment of carious lesions in the permanent teeth of children living in a fluoridated region: Protocol for a randomized controlled trial. JMIR Res Protoc. 2018;7:e26.
- Wahengbam P, Tikku AP, Lee WB. Role of titanium tetrafluoride (TiF(4)) in conservative dentistry: A systematic review. J Conserv Dent. 2011;14:98–102.
From Dimensions of Dental Hygiene. April 2023; 21(4):18-21.