As dental caries is one of the most common diseases worldwide, oral health care professionals are always looking to add new, effective instruments to their caries management armamentarium. The availability of calcium and phosphate in the remineralization process is essential. A variety of calcium phosphate technologies are currently available in professionally-dispensed and over-the-counter oral health care products that may help limit the progression of carious lesions and enhance the repair of early lesions already present.
THE ROLE OF FLUORIDE
Tooth enamel begins to demineralize in the presence of bacteria-produced acid once the oral cavity’s pH level drops below 5.5 and demineralization eliminates the calcium and phosphate ions that compose enamel’s hydroxyapatite. In the remineralization process, calcium and phosphate ions are redeposited into the tooth mineral. Fluoride contributes to the remineralization process in several ways. It accumulates on the surface of the enamel crystal, which creates a physical barrier that makes the tooth more acid resistant. The negatively charged fluoride ion attracts the positively charged calcium during this repair process, ultimately changing carbonated apatite to a fluorapatite- like form that is larger and stronger than the original hydroxyapatite.1,2 Fluoride may also provide antimicrobial effects through the inhibition of bacterial intracellular enzymes. Although fluoride serves as a catalyst for remineralization, remineralization will not occur unless adequate amounts of calcium and phosphate ions are available.3
For patients at risk of dental caries, the availability of calcium and phosphate ions is important. Calcium and phosphate from outside sources may be able to alter the cariogenic potential of dental plaque biofilm.4 Calcium phosphate products claim to enhance the bioavailability of calcium and phosphate ions. In theory, this aids in the enhancement of remineralization. Four types of calcium phosphate-based technologies are currently available in the United States: amorphous calcium phosphate (ACP), casein phosphopeptide amorphous calcium phosphate (CPP-ACP or Recaldent®), calcium sodium phosphosilicate (CSP or NovaMin®), and tri-calcium phosphate (TCP). Table 1 provides a list of products that contain these technologies. The use of calcium phosphate products in caries management is considered an “off-label” use because some of these products are accepted by the Food and Drug Administration (FDA) as tooth polishing or desensitizing ingredients only, rather than agents of remineralization.
AMORPHOUS CALCIUM PHOSPHATE
ACP technology was developed in 1991 by the American Dental Association’s (ADA) Paffenbarger Research Center. ACP contains the same minerals found in hydroxyapatite and aims, in the presence of fluoride, to speed up remineralization. ACP technology is considered unstablized because a calcium salt and a phosphate salt are delivered separately (eg, through a dual-barrel syringe). This delivery system allows for the precipitation of ACP at the tooth surface. Because it is not a premixed calcium phosphate compound, when ACP is introduced onto a tooth surface, a reservoir of calcium and phosphate ions forms. Rapid deposition of new mineral then may fill surface defects on the original tooth surface.5
ACP is available in a variety of products, including dentifrices, prophy pastes, fluoride varnish, fluoride gels, pit and fissure sealant materials, desensitizing agents, cements, and tooth whitening agents. In a dentifrice, ACP, with fluoride, enhances remineralization and forms a strong bond to the dentin, becoming an intrinsic part of the tooth.6-7 Sealants containing ACP promote in situ remineralization of artificially-induced carious lesions on smooth enamel surfaces, although not significantly more than sealants containing fluoride.8 Prophy paste with added calcium, phosphate, and fluoride has the potential to form ACP on the tooth surface.9 ACP-containing orthodontic com-posite resins may reduce enamel decalcification in patients with poor oral hygiene without dam-aging the cement’s shear bond strength.10,11 The addition of ACP in carbamide peroxide whitening agents may reduce transient tooth sensitivity caused by the whitening process.12
Most studies in support of ACP are animal model, in vitro, or in situ caries model studies. Although the use of ACP to assist in the remineralization process shows promise, more clinical trial research is needed. One clinical trial demonstrated a significant decrease in root caries among 44 high-risk head and neck radiation patients with the use of a dual phase ACP dentifrice containing 1,100 ppm sodium fluoride in comparison to a toothpaste containing 1,100 ppm sodium fluoride only.13
CASEIN PHOSPHOPEPTIDE AMORPHOUS CALCIUM PHOSPHATE OR RECALDENT
Casein (milk protein) was first investigated as a way to reduce caries as early as 1946.14 The University of Melbourne, Australia, and the Victorian Dairy Industry Authority, Abbotsford, Australia, are credited with the patent for the CPP-ACP complex and its trademark Recaldent. The FDA designated Recaldent as a “generally recognized as safe” (GRAS) ingredient to add to food products in 1999.15
CPP-ACP is referred to as stabilized ACP and is a complex of casein phosphopeptides that stabilize an amorphous form of calcium phosphate to maintain the calcium and phosphate ions, ensuring their delivery into the tooth structure before they precipitate or crystallize. CPP-ACP readily binds to the surface of the tooth as well as to the bacterial plaque surrounding the tooth.16,17 The CPP-ACP complex also acts as a reservoir of bioavailable calcium and phosphate. Under acidic conditions, CPP-ACP releases calcium and phosphate to enhance remineraliza- tion.18 Recently, CPP-ACP added to milk and hard candy (not available in United States) significantly remineralized enamel subsur- face carious lesions in situ.19,20
Products containing CPP-ACP that are currently on the market in the United States include one professionally-dispensed cream available with and without added fluoride and one chewing gum. The use of a CPPACP cream has demonstrated significant regression of white-spot lesions in postorthodontic populations.21,22 A recent in situ study using CPP-ACP combined with 900 ppm fluoride found that the combination offered a higher remineralization potential than CPP-ACP alone.23 Gum with added CPP-ACP demonstrated higher amounts of remineralization of enamel subsurface lesions in situ than sugar-free gum alone.24 A true milk allergy (casein) is a contraindication to using a product containing CPP-ACP.
As with ACP, the majority of investigations of CPP-ACP are animal model, in vitro, and in situ caries model studies. Although lower level evidence, published case reports are growing. A recent 2-year clinical trial conducted on 2,000 children demonstrated that CPP-ACP in a sugar-free chewing gum slowed progression and enhanced regression of approximal caries compared to a sugar-free control gum.25 To achieve this benefit, participants in the study chewed the gum for 10 minutes, three times a day. More clinical trial research is needed to quantify that CPP-ACP can prevent or reverse carious lesions or the dental caries process.
Calcium Sodium Phosphosilicate or Novamin
CSP belongs to a class of compounds called bioactive glass that have been available since the late 1960s to help regenerate bone.26 CSP reacts in an aqueous environment, so when exposed to saliva, ions of calcium, phosphate, and sodium are released. The sodium helps buffer the acid and then with time, the calcium and phosphate ions are available to assist in remineralization. Originally developed for the treatment of dentinal hypersensitivity,27 a series of in vitro and in situ studies suggest that CSP has the ability to prevent dentin demineralization, remineralize root carious lesions, heal white spot lesions, and fill demineralized lesions.28
Most products available with CSP claim a reduction in tooth sensitivity and include toothpastes, desensitizing toothpastes, one prophy paste, and one air polishing powder. Added to a commercially available dentifrice containing strontium chloride (SrCl2), the CSP-containing paste was superior in reducing pain from air and cold water stimulus compared with the SrCl2 and placebo group.29 This reduction in pain was confirmed in a recent 6-week clinical trial where a 5% CSP paste reduced the visual analog scale score more than a toothpaste containing 5% potassium nitrate or a placebo.30
The use of CSP in an air polishing powder demonstrated a significant reduction in cold pain stimulus compared with sodium bicarbonate air polishing powder at a 10-day recall.31 An in vitro study suggested teeth polished with a prophy paste and an air polishing powder both containing CSP were effective in reducing the dentin permeability of acid-treated dentin, with the air polishing powder being the most effective.32 High fluoride toothpaste (2,800 ppm and 5,000 ppm) promoted remineralization and inhibited demineralization more effectively than a CSP toothpaste.33 No published data are available yet about the combination of high fluoride toothpaste (5,000 ppm) and CSP.
Much of the research conducted about CSP has looked at its role as a desensitizing agent rather than its ability to enhance remineralization and prevent demineralization. At this time, there are no published animal model or clinical studies supporting its anticariogenic effects. One published report details a series of in vitro studies and one in situ caries model study.
TCP is a new hybrid material created with a milling technique that fuses beta tricalcium phosphate (ß-TCP) and sodium lauryl sulfate or fumaric acid. This blending results in a “functionalized” calcium and a “free” phosphate, designed to increase the efficacy of fluoride remineralization.34,35 ß-TCP, which is commonly used in FDA-approved orthopedic applications to boost bone growth, is similar to apatite structure and possesses unique calcium environments capable of reacting with fluoride and enamel. While the phosphate floats free, these exposed calcium environments are protected, preventing the calcium from prematurely interacting with fluoride.35 TCP provides catalytic amounts of calcium to boost fluoride efficacy and may be welldesigned to coexist with fluoride in a mouthrinse or dentifrice because it will not react before reaching the tooth surface.36 When TCP finally comes into contact with the tooth surface and is moistened by saliva, the protective barrier breaks down, making the calcium, phosphate, and fluoride ions available to the teeth. The fluoride and calcium then react with weakened enamel to provide a seed for enhanced mineral growth relative to fluoride alone.
Products available with TCP include a 5,000 ppm sodium fluoride dentifrice and a 5% sodium fluoride varnish. One study that investigated the toothpaste found that it delivered more high-quality mineral above the surface and deep in the carious lesions, and provided superior surface and subsurface remineralization compared to a 5,000 ppm fluoride product alone.37 Another study found that the TCP toothpaste showed better subsurface remineralization when compared to a CPP-ACP-containing product.38 There are no published studies yet about TCP added to fluoride varnish.
All published studies supporting this material have been in vitro studies. The potential of TCP is promising, but more studies are needed, including clinical trials supporting its efficacy in boosting remineral ization.
Dental caries remains a complex, multifactorial, and infectious bacterial biofilm disease that involves two continuous processes—demineralization and remineralization of the tooth surface. The goal of remineralization therapy should be to strengthen teeth. Along with an under-standing of the patient’s caries risk and an adequate anti-plaque self-care program, successful management of the dental caries infection over a lifetime can be accomplished using evidence-based, clinically effective methods and products. Calcium phosphate products may offer patients added protection against the progression or repair of carious lesions, but more in vivo clinical trials are needed to determine their short-term and long-term effects and to establish their clinical relevance.
Despite their growing popularity, calcium phosphate products are not for every patient and should not be used as a substitute for fluoride. For patients with normal salivary flow and composition, sufficient calcium and phosphate ions are already present to assist the body in the remineralization process, thus making the need for additional calcium and phosphate unnecessary. In this case, the use of low level fluoride should be recommended. In patients with salivary hypofunction including low flow, low pH, and poor buffering capacity, the use of agents containing bioavailable calcium and phosphate may be beneficial.
- ten Cate JM, Featherstone JDB. Mechanistic aspects of the interactions between fluoride and dental enamel. Crit Rev Oral Biol Med. 1991;2:283-296.
- Featherstone JDB. Dental caries: a dynamic process. Aus Dent J. 2008;53:286-291.
- Featherstone JDB. Prevention and reversal of dental caries: role of low level fluoride. Comm Dent Oral Epidemiol. 1999;27:31-40.
- Garcia-Gody F, Hick MJ. Maintaining the integrity of the enamel surface: the role of dental biofilm, saliva, and preventive agents in enamel demineralization and remineralization. J Am Dent Assoc. 2008;139:25S-34S.
- Tung MS, Eichmiller FC. Amorphous calcium phosphates for tooth remineralization. Compend Contin Educ Dent. 2004;25(9 Suppl 1):9-13.
- Schemehorn BR, Orban JC, Wood GD, Fischer GM, Winston AE. Remineralization by fluoride enhanced with calcium and phosphate ingredients. J Clin Dent. 1999;10(1 Spec No):13-16.
- Schemehorn BR, Wood GD, Winston AE. Laboratory enamel solubility reduction and fluoride uptake from enamelon dentifrice. J Clin Dent. 1999;10(1 Spec No):9-12.
- Silva KG, Pedrini D, Delbem ACB, Ferreira L, Cannon M. In situ evaluation of the remineralizing capacity of pit and fissure sealants containing amorphous calcium phosphate and/or fluoride. Acta Odontol Scand. 2010;68:11-18.
- Tung MS, Malerman R, Huang S, McHale WA. Reactivity of prophylaxis paste containing calcium, phosphate and fluoride salts. J Dent Res. 2005;84:Special Issue A.
- Uysal T, Amasyali M, Koyuturk AE, Ozcan S, Sagdic D. Amorphous calcium phosphate-containing orthodontic composites. Do they prevent demineralisation around orthodontic brackets? Aust Orthod J. 2010;26:10-15.
- Uysal T, Yilmaz E, Ramoglu SI. Amorphous calcium phosphate-containing orthodontic cement for band fixation: an in vitro study. World J Orthod. 2010;11:129-134.
- Giniger M, MacDonald J, Ziemba S, Felix, H. The clinical performance of professionally dispensed bleaching gel with added amorphous calcium phosphate. J Am Dent Assoc. 2005;136:383-392.
- Papas A, Russell D, Singh M, Kent R, Triol C, Winston A. Caries clinical trial of a remineralising toothpaste in radiation patients. Gerodontology. 2008;25:76-88.
- Schweigert BS, Shaw JH, Zepplen M, Elvehiem CA. Dental caries in the cotton rat. VI. The effect of the amount of protein, fat and carbohydrate in the diet on the incidence and extent of carious lesions. J Nutr. 1946;32:405-412.
- Azarpazhooh A, Limeback H. Clinical efficacy of casein derivatives. A systematic review of the literature. J Am Dent Assoc. 2008;139:915-924.
- Reynolds EC. The prevention of sub-surface demineralization of bovine enamel and change in plaque composition by casein in an intra-oral model. J Dent Res. 1987;66:1120-1127.
- Reynolds EC. Remineralization of enamel subsurface lesions by casein phosphopeptide – stabilized calcium phosphate solutions. J Dental Res. 1997;76:1587-1595.
- Reynolds EC. Casein phosphopeptide- amorphous calcium phosphate: the scientific evidence. Adv Dent Res. 2009;21:25-29.
- Walker GD, Cai F, Shen P, Adams GG, Reynolds C, Reynolds EC. Casein phosphopeptide-amorphous calcium phosphate incorporated into sugar confections inhibits the progression of enamel subsurface lesions in situ. Caries Res. 2010;44:33-40.
- Walker GD, Cai F, Shen P, et al. Consumption of milk with added casein phosphopeptide- amorphous calcium phosphate remineralizes enamel subsurface lesions in situ. Aust Dent J. 2009;54:245-249.
- Andersson A, Skold-Larsson K, Hallgren A, Petersson LG, Twetman S. Effect of a dental cream containing amorphous calcium phosphate complexes on white spot lesion regression assessed by laser fluorescence. Oral Health Prev Dent. 2007;5:229-233.
- Bailey DL, Adams GG, Tsao CE, et al. Regression of post-orthodontic lesions by a remineralizing cream. J Dent Res. 2009;88:1148-1153.
- Srinivasan N, Kavitha M, Loganathan SC. Comparison of the remineralization potential of CPP-ACP and CPP-ACP with 900 ppm fluoride on eroded human enamel: An in situ study. Arch Oral Biol. 2010;55:541-544.
- Shen P, Cai F, Nowicki A, Vincent J, Reynolds EC. Remineralization of enamel subsurface lesions by sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate. J Dent Res. 2001;80:2066-2070.
- Morgan MV, Adams GG, Bailey DL, Tsao CE, Fischman SL, Reynolds EC. The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography. Caries Res. 2008;42:171-184.
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- Andersson OH, Kangasniemi I. Calcium phosphate formation at the surface of bioactive glass in vitro. J Biomed Mater Res. 1991;25:1019- 1030.
- Burwell AK, Litkowski LJ, Greenspan DC. Calcium sodium phosphosilicate (NovaMin): reminerali zation potential. Adv Dent Res. 2009;21:35-39.
- Du Min Q, Bian Z, Jiang H, et al. Clinical evaluation of a dentifrice containing calcium sodium phosphosilicate (NovaMin) for the treatment of dentin hypersensitivity. Am J Dent. 2008;21:210- 214.
- Pradeep AR, Sharma A. Comparison of clinical efficacy of a dentifrice containing calcium sodium phosphosilicate to a dentifrice containing potassium nitrate and to a placebo on dentinal hypersensitivity: a randomized clinical trial. J Periodontol. 2010;81:1167-1173.
- Banerjee A, Hajatdoost-Sani M, Farrell S, Thompson I. A clinical evaluation and comparison of bioactive glass and sodium bicarbonate air- polishing powders. J Dent. 2010;38:475-482.
- Sauro S, Watson TF, Thompson I. Dentine desensitization induced by prophylactic and air- polishing procedures: An in vitro dentine permeability and confocal microscopy study. J Dent. 2010;38:411-422.
- Diamenti I, Koletsi-Kounari H, Mamai-Homata E,Vougiouklakis G. Effect of fluoride and of calcium sodium phosphosilicate toothpastes on pre-softened dentin demineralization and remineralization in vitro. J Dent. 2010;38:671-677.
- Karlinsey RL, Mackey AC. Solid-state preparation and dental application of an organically modified calcium phosphate. J Mater Sci. 2009;44:346-349.
- Karlinsey RL, Mackey AC, Walker ER, Frederick KE. Preparation, characterization, and in vitro efficacy of an acid-modified ß-TCP material for dental hard-tissue remineralization. Acta Biomater. 2010;6:969-978.
- Karlinsey RL, Mackey AC, Walker ER, Frederick KE. Surfactant-modified ß-TCP: structure, properties, and in vitro remineralization of subsurface enamel lesions. J Mater Sci. 2010;21:2009-2020.
- Karlinsey RL, Mackey AC, Walker ER, et al. Remineralization potential of 5000 ppm fluoride dentifrices evaluated in a pH cycling model. J Dent Oral Hyg. 2010;2:1-6.
- Karlinsey RL, Mackey AC, Stookey GK, PfarrerAM. In vitro assessments of experimental NaF dentifrices containing a prospective calcium phosphate technology. Am J Dent. 2009;22:180-184.
From Dimensions of Dental Hygiene. October 2010; 8(10): 40, 42, 44-46.