Review Article Int J Clin Prev Dent 2017;13(1):1-4ㆍhttps://doi.org/10.15236/ijcpd.2017.13.1.

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ISSN (Print) 1738-8546ㆍISSN (Online) 2287-6197

Remineralizing Agents: A Comprehensive Review

Rakesh Mittal, Nikhil Relhan, Tanya Tangri
Sudha Rustagi College of Dental Sciences and Research, Faridabad, India

Remineralizing agents are the most desirable means of early enamel caries management. There is a scope for such agents as
they prevent the progression of white spot lesions and reverse the process of demineralization. This need has redirected re-
search to develop novel preventive agents that can act as an adjunct to fluoride or independent of it.

Keywords: remineralization, fluoride, casein phosphopeptide-amorphous calcium phosphate, novamin, tricalcium phos-
phate, xylitol

Introduction the use of non-invasive treatment for these lesions [6-8].

Dental caries is an infectious microbiologic disease of the
teeth that results in localized dissolution and destruction of the
calcified tissues [1-3]. It is a worldwide public health problem,
affecting numerous urban and rural communities [4]. The proc-
ess of caries formation is a cycle of remineralization and de-
mineralization with various stages being either reversible or
irreversible. White spot lesions (WSLs) are manifestations of
the earliest stage of caries progression and are capable of being
reversible [5].
A surgical approach for the elimination of carious lesion was
developed only a century ago; this approach was necessary dur-
ing that time, because there was no valid alternative. The focus
on caries has recently shifted to the development of method-
ologies for the detection of the early stages of caries lesions and
Corresponding author Tanya Tangri
Sudha Rustagi College of Dental Sciences and Research,
Kheri More Sector-89, Gr Faridabad 121002, India. Tel:
+91-129-4230000, Fax: +91-129-4230010, E-mail:
tanyatangri@gmail.com
Received February 7, 2017, Revised March 14, 2017,
Accepted March 15, 2017
Prevention of initiation and interruption in progression of early
lesions are the desirable modes of caries management [1].
A variety of remineralizing agents like fluorides, casein cal-
cium phosphopeptides, bioactive glass etc, that aid in reminer-
alization of tooth structure are available commercially. This ar-
ticle provides an overview of the various available agents and
their roles in the remineralization of tooth tissue.
Flourides
Fluoride is the most commonly used remineralizing agent.
When the acid attacks the enamel surface, the pH begins to rise
and fluoride present in the microenvironment causes enamel
dissolution to stop. As the pH rises, new and larger fluoride crys-
tals containing fluorhydroxyapatite form, thereby, reducing the
enamel demineralization and enhancing remineralization [9,10].
Fluoride’s action in preventing dental caries is multi-
factorial. It promotes remineralisation of incipient lesions, in-
creases resistance to acid demineralization, interferes in the for-
mation and functioning of dental plaque micro-organisms, in-
creases the rate of post eruptive maturation; and alters tooth
morphology [11]. The various types of topical fluorides used
in dentistry are: Sodium fluoride (NaF), sodium mono-fluo-
rophosphate, stannous fluorides and acidulated phosphate fluo-

Copyright ⓒ 2017. Korean Academy of Preventive Dentistry. All rights reserved.

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International Journal of Clinical Preventive Dentistry
ride (APF). All these fluorides are inorganic in nature and are
available in the form of solutions, varnishes, foam, gels, denti-
frices, etc [12,13].
Fluoride dentrifices are considered as most effective agents
of preventing enamel demineralization. The efficacy of con-
ventional toothpastes containing 1,000 ppm fluoride have been
documented in many studies, but evidence suggests that tooth-
paste containing 5,000 ppm fluoride can further reduce de-
mineralization and enhance remineralization [14].
Dental professionals typically recommend 5,000 ppm fluo-
ride dentifrices for high caries riskpatients, including those with
orthodontic brackets, prostheses and restorations, those with
xerostomia, or those genetically susceptible to tooth decay. One
of the highly recommended 5,000 ppm fluoride dentifrice is
Colgate’s PreviDentⓇ Booster 5000. This fluidic or gel-like for-
mulation has been reported to provide faster dispersion in saliva
and higher fluoride uptake into enamel saliva [15].
Casein Phosphopeptide-Amorphous
Calcium Phosphate (CPP-ACP)
Casein Phosphopeptide-Amorphous Calcium Phosphate
(CPP-ACP), (Tooth Mousse, GC India) was introduced as a re-
mineralizing agent in the year 1998 [16,17]. The anticariogenic
properties of milk and milk products,such as cheese, have been
studied previously in animal model [17-19]. This activity has
been attributed to the direct chemical effects of phosphoprotein
casein and calcium phosphate components in cheese [20].
Caseins are a heterogeneous family of proteins predominated
by alpha 1 and 2 and b-caseins. Casein phosphopeptides (CPPs)
are phosphorylated casein-derived peptides produced by tryp-
tic digestion of casein. The CPP component, which contains 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 [21,22]. CPP can also bind to dental plaque and tooth
enamel. Each molecule of CPP can bind upto 25 calcium ions,
15 phosphate ions, and 5 fluoride ions. The calcium phosphate
in these complexes is biologically available for remineraliza-
tion of subsurface lesions in tooth enamel [22].
The multiphosphoseryl sequences in CPP have ability to sta-
bilize calcium phosphate in nanocomplexes in solutions like
amorphous calcium phosphate (ACP) [9]. Through these se-
quences, CPP binds to ACP in metastable solution preventing
the dissolution of calcium and phosphate ions. The ACP-CPP
also acts as reservoir of bio-available calcium and phosphate
and maintains the solution supersaturated, thus facilitating re-
mineralization [23].
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Casein Phosphopeptide-Amorphous
Calcium Fluoride Phosphate
(CPP-ACFP)
Casein phosphopeptides are used alone as CPP-ACP, or the
CPP-ACP is further complexed with fluoride, CPP-ACFP
(casein phosphopeptides with amorphous calcium fluoride
phosphate). With respect to its interaction with fiuoride, the
CPPs have been shown to keep fluoride ions in solution, thereby
enhancing the efficacy of the fluoride as a remineralizing agent,
with the end result being the formation of fluoroapatite [14].
Jayarajan et al. [24] in an in vitro study found that the efficacy
TM
of CPP-ACPF containing paste (Tooth Mousse Plus ) was
TM
more than CPP-ACP containing paste (Tooth Mousse ) paste
in remineralization of artificial caries lesion.
Bioactive Glass
Bioactive glass materials have been introduced in many
fields of dentistry and are considered as a break through in re-
Ⓡ
mineralizing technology [22,25]. NovaMin is the brand name
Ⓡ
of a particulate bioactive glass. NovaMin is technically de-
scribed as an inorganic amorphous calcium sodium phosphosi-
licate (CSPS) material that was designed based on a class of ma-
terials known as bioactive glasses. It comprises SiO2 (45%),
Na2O (24.5%), CaO (24.5%) and P2O5 (6%) [26]. NovaMin is
claimed to release calcium and phosphate ions intraorally to
help the self-repair process of enamel. A silica-rich surface layer
forms through polycondensation of hydrated silica groups on
which precipitation of ions happens which crystallizes over
time to form a hydroxyl-carbonate apatite. Although it is used
extensively as a desensitizing agent reports also claim that the
chemical reactions that promote apatite formation may enhance
the remineralization [27]. A recent investigation examined the
potential remineralization effect of topical NovaMin and so-
dium fluoride gel on caries-like lesions in permanent teeth.
NovaMin dentifrice (Oravive revitalizing toothpaste contain-
ing NovaMin) appeared to have a greater effect on remineraliza-
tion of carious-like lesions in permanent teeth when compared
to that of a fiuoride-containing dentifrice (Topex” Take Home
Care’ 1.1% neutral sodium fluoride gel [Sultan Healthcare])
containing 0.5% fluoride ion (which is equal to 5,000 ppm fluo-
ride) [22].
Functionalized Tricalcium
Phosphate (fTCP)
Functionalized tricalcium phosphateis produced by milling
TCP with sodium lauryl sulfate. fTCP stabilizes fluoride in sol-

ution and maintains high concentration of calcium, phosphate
and fluoride in white spot lesions [12]. Inclusion of the function-
alized TCP ingredient in NaF formulations has been shown to
produce stronger, more acid-resistant mineral relative to fluo-
ride alone in laboratory and clinical evaluations [28]. A novel
5,000 ppm fluoride dentifrice,ClinproⓇ 5000, was recently in-
troduced by 3 M ESPE. This 1.1% NaFsilica-containing paste
containing an innovative functionalized tricalcium phosphate
(fTCP) ingredient that, when evaluated in development for-
mulations, has been shown to boost remineralization perform-
ance relative to fluoride-only systems [15].
Xylitol
Xylitol is believed to be a “tooth-friendly”, non-fermentable
sugar alcohol. The main properties of this sweetener is that it
is not fermented to acids, forms less of plaque and reduces the
number of Mutans streptococci in saliva [29,30].
Some researchers indidcated that xylitol might be involved
in the enamel demineralization and remineralizing process by
acting as a ca2+ carrier required for remineralization [31].
A novel method of delivering remineralizing ions (calcium
and phosphate) in combination with xylitol has been developed
using a NaF varnish (Embrace Varnish, Pulpdent).The xylitol
coating prevents early reaction and produces a sustained release
of the remineralizing ions. Saliva exposure dissolves the xylitol
and frees the calcium and phosphate ions. They then react with
the fluoride in the varnish to form protective fluorapatite on the
teeth [32].
Conclusion
A goal of modern dentistry is to manage non-cavitated caries
lesions non-invasively through remineralization in an attempt
to prevent disease progression and improve aesthetics, strength,
and function.With a clearer understanding of the implemen-
tation of these remineralizing agents, we can create a more fa-
vorable relationship in which remineralization can occur. It is
important for dental professionals to be aware that it takes sig-
nificant time to establish the bonafides of a new technology.
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