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Year : 2012  |  Volume : 30  |  Issue : 1  |  Page : 2-6

Latest developments in non-fluoridated remineralizing technologies

1 Department of Pediatric and Preventive Dentistry, Kothiwal Dental College and Research Centre, Moradabad, Uttar Pradesh, India
2 Department of Pediatric and Preventive Dentistry, Sardar Patel Post Graduate Institute of Dental and Medical Sciences, Raibareili Road, Lucknow, Uttar Pradesh, India

Date of Web Publication3-May-2012

Correspondence Address:
M Goswami
Kothiwal Dental College and Research Centre, Kanth Road, Moradabad 244 001, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-4388.95561

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The goal of modern dentistry is to manage non-cavitated carious lesions non-invasively through remineralization in an attempt to prevent disease progression, and to improve strength, esthetics, and function of teeth. The emphasis currently is being given to new technologies for enamel remineralization which suggest the changes in the understanding of dental caries. The aim of this paper is to review the contemporary non-fluoridated systems available for remineralization therapy and ideas for their implementation into clinical practice. A search of articles from "Pubmed" and "Medline" with the keywords Remineralization-demineralization, Casein derivatives, Non-fluoridated remineralizing agents was conducted. A total of 526 abstracts were collected, out of which 172 articles that discussed current technologies of non-fluoridated remineralizing agents were read and 33 most relevant articles were included in this paper. Casein phosphopeptide based technology has been established as a strong non-fluoridated remineralizing agent fulfilling all the criteria of an ideal remineralizing material.

Keywords: Casein derivatives, non-fluoridated remineralizing agents, remineralization-demineralization

How to cite this article:
Goswami M, Saha S, Chaitra T R. Latest developments in non-fluoridated remineralizing technologies. J Indian Soc Pedod Prev Dent 2012;30:2-6

How to cite this URL:
Goswami M, Saha S, Chaitra T R. Latest developments in non-fluoridated remineralizing technologies. J Indian Soc Pedod Prev Dent [serial online] 2012 [cited 2023 Jan 27];30:2-6. Available from: http://www.jisppd.com/text.asp?2012/30/1/2/95561

   Introduction Top

Dental caries remains the major public health problem in most countries. In the last decade, the focus in caries research has shifted to the development of methodologies for remineralization of carious lesion. Demineralization begins at the atomic level on the crystal surface inside the enamel or dentin and can continue unless halted with the end point being cavitation. [1]

Remineralization is defined as the process whereby calcium and phosphate ions are supplied from a source external to the tooth to promote ion deposition into crystal voids in demineralized enamel to produce net mineral gain. [2] Fluoride is known to promote remineralization, but is dependent on calcium and phosphate ions from saliva to accomplish this. Recent investigations have primarily focused on various calcium phosphate based technologies which are designed to supplement and enhance fluoride's ability to restore tooth mineral. [3]

A search of articles from "Pubmed" and "Medline," with the keywords Remineralization-demineralization, Casein derivatives, Non-fluoridated remineralizing agents, was conducted. A total of 526 abstracts were retrieved, out of which 172 articles that discussed current technologies of non-fluoridated remineralizing agents were read and 33 most relevant articles were included in this paper.

Reasons to seek alternatives to fluorides

  1. Fluoride is highly effective on smooth-surface caries; its effect would seem to be more limited on pit and fissure caries.
  2. A high-fluoride strategy cannot be followed to avoid the potential for adverse effects (e.g., fluorosis) due to overexposure to fluoride.
  3. Although fluoride presents no problems when used properly, among certain parts of the world, there has been the suggestion that fluoride exposure should be limited. [4]

Requirements of an ideal remineralization material

  • Diffuses into the subsurface or delivers calcium and phosphate into the subsurface
  • Does not deliver an excess of calcium
  • Does not favor calculus formation
  • Works at an acidic pH
  • Works in xerostomic patients
  • Boosts the remineralizing properties of saliva
  • For novel materials, shows a benefit over fluoride [5]

Non-fluoride remineralizing agents

Complex of casein phosphopeptides-amorphous calcium phosphate

CPP-ACP is the acronym for a complex of casein phosphopeptides (CPPs) and amorphous calcium phosphate (ACP). Caseins are a heterogeneous family of proteins predominated by alpha 1 and 2 and b-caseins. CPPs are phosphorylated casein-derived peptides produced by tryptic digestion of casein.

The CPP containing the amino acid cluster sequence -Ser (P)-Ser (P)-Ser (P)-Glu-Glu- has the ability to bind and stabilize calcium and phosphate in solution, as well as to bind dental plaque and tooth enamel. Through their multiple phosphoryl residues, the CPPs bind to form clusters of ACP in metastable solution, preventing their growth to the critical size required for nucleation and precipitation. The proposed mechanism of anticariogenicity for the CPP-ACP is that it localizes ACP in dental plaque, which buffers the free calcium and phosphate ion activities, thereby helping to maintain a state of supersaturation with respect to tooth enamel depressing demineralization and enhancing remineralization. The CPPs have been shown to keep fluoride ions in solution, thereby enhancing the efficacy of the fluoride as a remineralizing agent. [6],[7]

Effect of CPP-ACP on erosive lesions

CPP-ACP paste may enhance the remineralization after an erosive challenge, and thus offers some protection for patients who are at risk for erosion. [8]

Adding CPP-ACP to soft drinks and sports drinks reduced their erosive potential on enamel when compared to those without. [9],[10]

CPP inhibits adherence of oral bacteria to saliva-coated hydroxyapatite beads (S-HA). By selectively inhibiting streptococcal adhesion to teeth, it can modulate the microbial composition of dental plaque and favor establishment of less cariogenic species such as oral actinomyces. This could also control acid formation (buffering) in dental plaque, in turn reducing hydroxyapatite dissolution from tooth enamel. [11],[12]

It can be incorporated into the pellicle in exchange for albumin, and thus inhibits the adherence of Streptrococcus mutans and Streptococcus sobrinus, causing both neutralization and enhancement of remineralization. [13]

Though casein derivatives have been investigated as a remineralizing agent, some authors have reported insufficient clinical trial evidence to make a recommendation regarding the long-term effectiveness of casein derivatives in preventing caries in vivo. [14]

The Recaldent technology was developed by Prof. Eric Reynolds of the University of Melbourne. CPP-ACP has been trademarked Recaldent and has been launched in sugarless chewing gum and confectionery. More recently, a sugar-free, water-based cream containing RECALDENT (CPP-ACP) (GC Tooth Mousse/Prospec MI Paste) has been made available to dental professionals. [15]

Amorphous calcium phosphate

The ACP technology requires a two-phase delivery system to keep the calcium and phosphorous components from reacting with each other before use. The current sources of calcium and phosphorous are two salts, calcium sulfate and dipotassium phosphate. When the two salts are mixed, they rapidly form ACP that can precipitate onto the tooth surface. This precipitated ACP can then readily dissolve into the saliva and can be available for tooth remineralization. [16]

It can be considered a useful adjuvant for the control of caries in orthodontic applications. Experimental ACP composite has shown to efficiently establish mineral ion transfer throughout the body of the lesion and restore the mineral lost due to acid attack. [17]

The ACP technology was developed by Dr. Ming S. Tung. In 1999, ACP was incorporated into toothpaste called Enamelon and later reintroduced in 2004 in Enamel Care toothpaste by Church and Dwight. It is also available as Discus Dental's Nite White Bleaching Gel and Premier Dental's Enamel Pro Polishing Paste. It is also used in the Aegis product line, such as Aegis Pit and Fissure Sealant, produced by Bosworth. [18]

Sodium calciumphosphosilicate (bioactive glass)

When bioactive glass comes in contact with saliva, it rapidly releases sodium, calcium, and phosphorous ions into the saliva that are available for remineralization of the tooth surface. The ions released form hydroxycarbonate apatite (HCA) directly. They also attach to the tooth surface and continue to release ions and remineralize the tooth surface after the initial application. These particles have been shown to release ions and transform into HCA for up to 2 weeks. Ultimately, these particles will completely transform into HCA. [19]

Novamin adheres to exposed dentin surface and forms a mineralized layer that is mechanically strong and resistant to acid. There is continuous release of calcium over time, which maintains the protective effects on dentin. [20]

The NovaMin Technology was developed by Dr. Len Litkowski and Dr. Gary Hack. Currently available products in the market are NovaMin: SootheRx, DenShield, NuCare-Root Conditioner with NovaMin, NuCare-Prophylaxis Paste with NovaMin, and Oravive. [21],[22]

Calcium carbonate carrier - SensiStat

The SensiStat technology is made of arginine bicarbonate, an amino acid complex, and particles of calcium carbonate, a common abrasive in toothpaste. The arginine complex is responsible for adhering the calcium carbonate particles to the dentin or enamel surface and allows the calcium carbonate to slowly dissolve and release calcium that is then available to remineralize the tooth surface. [23]

The SensiStat Technology was developed by Dr. Israel Kleinberg of New York. The technology was first incorporated into Ortek's Proclude desensitizing prophy paste and later in Denclude. [24]

Xylitol carrier

The use of chewing gum carrying xylitol increases salivary flow rate and enhances the protective properties of saliva. This is because the concentration of bicarbonate and phosphate is higher in stimulated saliva, and the resultant increase in plaque pH and salivary buffering capacity prevents demineralization of tooth structure. Moreover, the higher concentration of calcium, phosphate, and hydroxyl ions in such saliva also enhances remineralization. [25]

Miake et al. observed that xylitol can induce remineralization of deeper layers of demineralized enamel by facilitating Ca 2+ movement and accessibility. [26]


A study was done to determine the effect of nano-hydroxyapatite concentrations on initial enamel lesions under dynamic pH-cycling conditions. It was concluded that nano-hydroxyapatite had the potential to remineralize initial enamel lesions. A concentration of 10% nano-hydroxyapatite may be optimal for remineralization of early enamel caries. [27]

The trimetaphosphate ion

The potential mode of action of trimetaphosphate ion (TMP) is likely to involve in adsorption of the agent to the enamel surface, causing a barrier coating that is effective in preventing or retarding reactions of the crystal surface with its fluid environment, and hence reducing demineralization during acid challenge. [28]

Gu highlighted the role of sodium TMP as a templating analog of dentin matrix phosphoproteins for inducing intrafibrillar remineralization of apatite nanocrystals within the collagen matrix of incompletely resin infiltrated dentin. [29]

Alpha-tricalcium phosphate

It is used in products such as Cerasorb, Bio-Resorb, and Biovision. Tricalcium phosphate (TCP) has also been considered as one possible means for enhancing the levels of calcium in plaque and saliva. Some small effects on free calcium and phosphate levels in plaque fluid and in saliva have been found when an experimental gum with 2.5% alpha-TCP by weight was chewed, when compared to a control gum without added TCP. [30]

Dicalcium phosphate dihydrate

Inclusion of dicalcium phosphate dehydrate (DCPD) in a dentifrice increases the levels of free calcium ions in plaque fluid, and these remain elevated for up to 12 hours after brushing, when compared to conventional silica dentifrices. [5]

Calcium from DCPD was incorporated into enamel and detected in plaque 18 hours post-treatment after brushing with a DCPD dentrifice which fosters improved remineralization of teeth in combination with fluoride. [31]

The reaction of DCPD and fluoride forming fluorapatite may provide a potentially promising treatment for remineralization of caries lesions in vivo. [32]

Challenges of implementing new remineralization technology

Therapeutic benefits of calcium phosphates or other calcium salts is via increased levels of calcium in dental plaque or increased levels of bioavailable fluoride. However, few studies have confirmed that the calcium-based agent actually reached the target tissue and resulted in anti-caries benefits.

Formulation challenges typically involve ingredient compatibility issues. Products are designed to deliver a new agent (i.e., calcium ions) and fluoride simultaneously from single-phase products and may present formulation challenges such as long-term fluoride compatibility.

Pre-clinical models may not necessarily be predictive of clinical performance for these non-fluoride agents and that new agents still require direct clinical validation to ensure efficacy. [33]

   Conclusion Top

In the last few decades, advances in technologies, changes in lifestyle, modifications in the diet, and longer life expectancy are some of the many factors which have affected the health and esthetics of tooth enamel and dentin. With a clearer understanding of the implementation of these remineralizing agents and new technologies accessible to dentists, we can create a more favorable relationship in which remineralization occurs more often than demineralization.

   References Top

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2.Cochrane NJ, Cai F, Huq NL, Burrow MF, Reynolds EC. New approach to enhance remineralization of tooth enamel. J Dent Res 2010;89:1187-97.  Back to cited text no. 2
3.Fejerskov O. Changing paradigms in concepts on dental caries: Consequences for oral health care. Caries Res 2004;38:182-91.  Back to cited text no. 3
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5.Walsh LJ. Contemporary technologies for remineralization therapies: A review. Int Dent SA 2009;11:6-16.  Back to cited text no. 5
6.Rose RK. Effects of an anticariogenic casein phosphopeptide on Ca diffusion in streptococcal model dental plaques. Arch Oral Biol 2000;45:569-75.  Back to cited text no. 6
7.Reynolds EC. Calcium phosphate-based remineralization systems: Scientific evidence? Aust Dent J 2008;53:268-73.  Back to cited text no. 7
8.Ranjitkar S, Rodriguez JM, Kaidonis JA, Richards LC, Townsend GC, Bartlett DW. The effect of caseinphosphopeptide- amorphous calcium phosphate on erosive enamel and dentin wear by toothbrush abrasion. J Dent 2009;37:250-4.  Back to cited text no. 8
9.Manton DJ, Cai F, Yuan Y, Walker GD, Cochrane NJ, Reynolds C, et al. Effect of casein phospeptide -amorphous calcium phosphate added to acidic beverages on enamel erosion in vitro. Aust Dent J 2010;55:275-9.  Back to cited text no. 9
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12.Rose RK. Binding characteristics of Streptococcus mutans for calcium and casein phosphopeptide. Caries Res 2000;34:427-31.  Back to cited text no. 12
13.Schupbach P, Neeser JR, Golliard M, Rouvet M, Guggenheim B. incorporation of caseinoglycomacropeptide and caseinophosphopeptide into the salivary pellicle inhibits adherence of mutans streptococci. J Dent Res 1996;75:1779-88.  Back to cited text no. 13
14.Azarpazhooh A, Limeback H. Clinical efficacy of casein derivatives: A systematic review of the literature. J Am Dent Assoc 2008;139:915-24.  Back to cited text no. 14
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16.Tung MS, Eichmiller FC. Dental Applications of Amorphous Calcium Phosphates. J Clin Dent 2003;10:1-6.  Back to cited text no. 16
17.Langhorst SE, O'Donnell JN, Skrtic D. Invitro remineralization of enamel by polymeric amorphous calcium phosphate composite: Quantitative microradiographic study. Dent Mater 2009;25:884-91.  Back to cited text no. 17
18.Sullivan RJ, Charig A, Haskins JP, Zhang YP, Miller SM, Strannick M, et al. In vivo detection of calcium from dicalcium phosphate dihydrate dentrifrice in demineralized human enamel and plaque. Adv Dent Res 1997;11:380-7.  Back to cited text no. 18
19.Du M, Tai BJ, Jiang H, Zhong J, Greenspan D, Clark A. Efficacy of dentifrice containing bioactive glass (NovaMin) on dentine hypersensitivity. J Dent Res 2004;83:13-5.  Back to cited text no. 19
20.Burwell A, Jennings D, Muscle D, Greenspan DC. Novamin and dentin hypersensitivity- invitro evidence of efficacy. J Clin Dent 2010;21:66-71.  Back to cited text no. 20
21.Tai BJ, Bian Z, Jiang H. Anti-gingivitis effect of a dentifrice containing bioactive glass (NovaMin) particulate. J Clin Periodontol 2006;33:86-91.  Back to cited text no. 21
22.Iijima Y, Cai F, Shen P, Walker G, Reynolds C, Reynolds EC. Acid resistance of enamel sub surface lesions remineralized by a sugar free chewing gum containing amorphous calcium phosphate. Caries Res 2004;38:551-6.  Back to cited text no. 22
23.Nizel AE, Harris RS. The Effects of Phosphates on Experimental Dental Caries: A Literature Review. J Dent Res 1964;43:1123-35.  Back to cited text no. 23
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27.Huang SB, Gao SS, Yu HY. Effect of nano-hydroxyapatite concentration on remineralization of initial enamel lesion in vitro. Biomed Mater 2009;4:55-9.  Back to cited text no. 27
28.Gonzalez M. Effect of Trimetaphosphate Ions on the process of Mineralization. J Dent Res 1971;50:1055-60.  Back to cited text no. 28
29.Gu LS, Kim J, Kim YK, Liu Y, Dickens SH, Pashley DH, et al. A chemical phosphorylation-inspired design for Type I collagen biomimetic remineralization. Dent Mater 2010;26:1077-89.  Back to cited text no. 29
30.Vogel GL, Zhang Z, Carey CM, Chow LC, Proskin HM. Composition of plaque and saliva following a sucrose challenge and use of an alpha-tricalcium-phosphate-containing chewing gum. J Dent Res 1998;77:518-24.  Back to cited text no. 30
31.Sullivan RJ, Masters J, Cantore R, Roberson A, Petrou I, Stranick M, et al. Development of an enhanced anticaries efficacy dual component dentifrice containing sodium fluoride and dicalcium phosphate dihydrate. Am J Dent 2001;14 Spec No:3A-11A.  Back to cited text no. 31
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33.Clarkson BH, Rafter ME. Emerging Methods Used in the Prevention and Repair of Carious Tissues. J Dent Educ 2000;61:1114-20.  Back to cited text no. 33

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