Australian Dental Journal 2008; 53: 268273

SYMPOSIUM REPORT

doi: 10.1111/j.1834-7819.2008.00061.x

Calcium phosphate-based remineralization systems:

scientific evidence?
EC Reynolds*
*Centre for Oral Health Science, School of Dental Science, The University of Melbourne, Victoria.

ABSTRACT
Dental caries remains a major public health problem in most communities even though the prevalence of disease has
decreased since the introduction of fluorides. The focus in caries research has recently shifted to the development of
methodologies for the detection of the early stages of caries lesions and the non-invasive treatment of these lesions. Topical
fluoride ions, in the presence of calcium and phosphate ions, promote the formation of fluorapatite in tooth enamel by a
process referred to as remineralization. The non-invasive treatment of early caries lesions by remineralization has the
potential to be a major advance in the clinical management of the disease. However, for net remineralization to occur
adequate levels of calcium and phosphate ions must be available and this process is normally calcium phosphate limited. In
recent times three calcium phosphate-based remineralization systems have been developed and are now commercially
available: a casein phosphopeptide stabilized amorphous calcium phosphate (RecaldentTM (CPP-ACP), CASRN691364-49-5),
an unstabilized amorphous calcium phosphate (ACP or EnamelonTM) and a bioactive glass containing calcium sodium
phosphosilicate (NovaMinTM). The purpose of this review was to determine the scientific evidence to support a role for these
remineralization systems in the non-invasive treatment of early caries lesions. The review has revealed that there is evidence
for an anticariogenic efficacy of the EnamelonTM technology for root caries and for the RecaldentTM technology in
significantly slowing the progression of coronal caries and promoting the regression of lesions in randomized, controlled
clinical trials. Hence the calcium phosphate-based remineralization technologies show promise as adjunctive treatments to
fluoride therapy in the non-invasive management of early caries lesions.
Key words: Enamel remineralization, CPP-ACP, ACP, scientific evidence.
Abbreviations and acronyms: ACP = amorphous calcium phosphate; ACFP = amorphous calcium fluoride phosphate; CPP = casein
phosphopeptides; FA = fluorapatite.
(Accepted for publication 24 April 2008.)

INTRODUCTION
Dental caries is a pathological process of localized
destruction of tooth tissue by micro-organisms. The
disease is initiated via the demineralization of tooth
hard tissue by organic acids produced from fermentable
carbohydrate by dental plaque cariogenic bacteria.
Even though in most developed countries the prevalence of dental caries has decreased through the use of
fluorides, the disease remains a major public health
problem.1
Fluoride ions promote the formation of fluorapatite
in enamel in the presence of calcium and phosphate
ions produced during enamel demineralization by
plaque bacterial organic acids.2 This is now believed
to be the major mechanism of fluoride ions action in
preventing enamel demineralization.2,3 Fluoride ions
268

can also drive the remineralization of previously

demineralized enamel if enough salivary or plaque
calcium and phosphate ions are available when the
fluoride is applied. The non-invasive treatment of early
caries lesions by remineralization has the potential to
be a major advance in the clinical management of
the disease. However, for every two fluoride ions, 10
calcium ions and six phosphate ions are required to
form one unit cell of fluorapatite (Ca10(PO4)6F2).
Hence on topical application of fluoride ions, the
availability of calcium and phosphate ions can be
the limiting factor for net enamel remineralization to
occur and this is highly exacerbated under xerostomic
conditions.
The clinical use of calcium and phosphate ions for
remineralization has not been successful in the past due
to the low solubility of calcium phosphates, particularly
2008 Australian Dental Association

Calcium phosphate-based remineralization

in the presence of fluoride ions. Insoluble calcium
phosphates are not easily applied, do not localize
effectively at the tooth surface and require acid for
solubility to produce ions capable of diffusing into
enamel subsurface lesions. On the other hand, soluble
calcium and phosphate ions can only be used at very
low concentrations due to the intrinsic insolubility of
the calcium phosphates, in particular the calcium
fluoride phosphates. Soluble calcium and phosphate
ions do not substantially incorporate into dental plaque
or localize at the tooth surface to produce effective
concentration gradients to drive diffusion into the
subsurface enamel. Three calcium phosphate-based
remineralization systems have now been commercialized where the manufacturers claim the specific form of
the calcium phosphate helps overcome the limited
bioavailability of calcium and phosphate ions for the
remineralization process (Table 1).
The first technology involves casein phosphopeptide
stabilized amorphous calcium phosphate (RecaldentTM
(CPP-ACP), CASRN691364-49-5) where it is claimed
that the casein phosphopeptides (CPP) stabilize high
concentrations of calcium and phosphate ions, together
with fluoride ions, at the tooth surface by binding to
pellicle and plaque. Although the calcium, phosphate
and fluoride ions are stabilized by the CPP from
promoting dental calculus, the ions are freely bioavailable to diffuse down concentration gradients into
enamel subsurface lesions thereby effectively promoting
remineralization in vivo.
The second technology is an unstabilized amorphous calcium phosphate (ACP or EnamelonTM). This
technology applies calcium ions (e.g., calcium sulphate) and phosphate ions (e.g., ammonium phosphate, sometimes in the presence of fluoride ions)
separately (e.g., from a dual chamber device) so that
amorphous calcium phosphate or amorphous calcium
fluoride phosphate forms intra-orally. More recently,
this technology is also being used in bleach-based
whitening products (Table 1). The manufacturers
claim that the formation of amorphous calcium
phosphate intra-orally helps rebuild tooth enamel
through remineralization.

The third technology is a bioactive glass containing

calcium sodium phosphosilicate (NovaMinTM) where
the manufacturers claim that the glass particles release
calcium and phosphate ions intra-orally to promote
remineralization (Table 1).
In this paper the scientific evidence for each technology is reviewed. The scientific evidence was based on
published original studies (papers and abstracts) reporting the testing of the technologies in various caries
model systems and in randomized, controlled caries
trials (Table 2).
NovaMinTM technology
The NovaMinTM technology is based on calcium
sodium phosphosilicate bioactive glass which is claimed
to release calcium and phosphate ions intra-orally to
help the self-repair process of teeth. As shown in
Table 2, no published studies could be found supporting the remineralization of enamel subsurface lesions
in vitro or in situ. Furthermore, no published studies
could be found showing an anticariogenic efficacy of
NovaMinTM in animal models or other caries model
systems or randomized, controlled caries clinical trials.
This technology appears to be at a very early stage of
development.
EnamelonTM (ACP) technology
The EnamelonTM technology is based on unstabilized
ACP, where a calcium salt (e.g., calcium sulphate) and a
phosphate salt (e.g., ammonium phosphate) are delivered separately (e.g., from a dual chamber device) intraorally. As the salts mix with saliva they dissolve
releasing calcium and phosphate ions. The mixing of
calcium ions with phosphate ions to produce an ion
activity product for ACP which exceeds its solubility
product results in the immediate precipitation of ACP
or in the presence of fluoride ions, amorphous calcium
fluoride phosphate (ACFP). In the intra-oral environment these phases (ACP and ACFP) are very unstable
and rapidly transform to a more thermodynamically
stable, insoluble crystalline phase (e.g., hydroxyapatite

Table 1. Commercially available calcium phosphate-based remineralization technologies

Technology

Commercial product

Remineralization claim
TM

Casein phosphopeptide stabilized

calcium phosphate
(RecaldentTM, CPP-ACP)

Trident White sugar-free gum,

Recaldent sugar-free gum, Tooth
Mousse, MI paste

Recaldent
(CPP-ACP) a remineralizing
ingredient that strengthens teeth by delivering
calcium and phosphate to the tooths surface.

Unstabilized amorphous calcium

phosphate (ACP, EnamelonTM)

Enamel Care with liquid calcium,

Nite White ACP, Day White ACP,
Mentadent replenishing white

Rebuilds enamel. The deposition of hydroxyapatite

onto teeth rebuilds enamel through a process
called remineralization.

Bioactive glass containing calcium

sodium phosphosilicate (NovaMinTM)

Oravive toothpaste

Nourishes the teeth with essential calcium and

phosphorous ions needed for the natural self-repair
process of the teeth.

2008 Australian Dental Association

269

270

Faller RV, Pfarrer AM. Effects on remineralization and acid resistance from conventional and remineralizing toothpastes. J Dent Res Sp Iss Abstract 1998;77:188.

No references found
No references found
No references found
No references found
No references found
NovaMinTM

No
(Eversole et al., 1998)
No
(Landrigan et al., 1998)
(Best et al., 1998)

No
(Eversole et al., 1998)
(Faller and Pfarrer, 1998)

Yes
(Schemehorn et al., 1999b)7
(Hicks and Flaitz, 2000)8
Yes
(Mundorff-Shrestha
et al., 1999)4
(Grant et al., 1999)20
ACP EnamelonTM

Yes
(Schemehorn et al.,
1999a)6

No references found

No
(Faller et al., 1998)

No references found

Yes
Inhibition of root caries
in a radiation therapy
population but no
reduction in coronal
caries relative to control
(1150 ppmF) (Papas
et al., 1999)9

Yes
(Morgan et al., 2008)19
Yes
(Shen et al., 2001)16
(Iijima et al., 2004)15
Yes
(Reynolds, 1998)23
(Reynolds, 1987)21
Yes
(Reynolds, 1998)23
(Yamaguchi et al., 2006)24
Yes
(Reynolds et al., 1995)11
RecaldentTM CPP-ACP

Yes
(Reynolds, 1997)22

Inhibition of
enamel
demineralization
in situ
Promotion of enamel
subsurface lesion
remineralization
in vitro
Inhibition of
enamel
demineralization
in vitro
Inhibition of
caries in an
animal model
Technology

Table 2. Scientific evidence for anticaries activity and enamel subsurface lesion remineralization

Promotion
of enamel
subsurface lesion
remineralization
in situ

Inhibition of caries
progression and
promotion of
regression of caries
in a randomized
controlled clinical trial

EC Reynolds
and fluorhydroxyapatite). However, before the phases
transform calcium and phosphate ions should be
transiently bioavailable to inhibit demineralization
of enamel and promote enamel subsurface lesion
remineralization.
Several papers have been published providing some
evidence of efficacy of the EnamelonTM technology in
model systems (Table 2). Two studies using the rat caries
model have shown a superior efficacy of a dentifrice
containing the EnamelonTM technology plus fluoride
over a standard fluoride-alone dentifrice.4,5 However,
two other reports (abstracts) suggest that the
EnamelonTM technology plus fluoride was in fact
inferior to the standard fluoride-alone dentifrice in
the rat caries model.* This discrepancy may relate to
how the EnamelonTM technology was delivered to the
teeth of the animals as once the calcium salts and
phosphate salts are mixed from the dual chamber
device the ACP would immediately start to transform
to an insoluble phase with little efficacy. Hence, a
greater time between mixing the salts and the application to the teeth would result in a lower potential
efficacy. Further, efficacy would be model sensitive and
these different outcomes reported could also relate to
differences in diet, particularly the level of calcium,
phosphate and fluoride of the cariogenic diet.
A superior efficacy of the EnamelonTM technology
plus fluoride over fluoride alone has also been suggested
from in vitro cyclic demineralization assays by Schemehorn et al.,6,7 and by Hicks and Flaitz.8 However, two
other reports (abstracts) from Eversole et al. and Faller
et al. indicated that the EnamelonTM technology plus
fluoride was in fact inferior to a standard fluoride
dentifrice in in vitro cyclic demineralization assays.
These authors suggested that the fluoride was less
available in the EnamelonTM product. Only one in situ
study on the EnamelonTM technology could be found.
This study by Faller et al. compared the EnamelonTM
technology plus fluoride with fluoride alone in an in situ
remineralization model and concluded that the fluoride
alone was superior to the EnamelonTM technology plus
fluoride in promoting fluoride uptake into enamel
subsurface lesions in situ. However, in this study
subsurface remineralization using microradiography
was not determined.
*Best JM, Eversole SL, Faller RV. Remineralization potential of
conventional and novel toothpastes: rat model testing. J Dent Res Sp
Iss Abstract 1998;77:246.
Landrigan WF, Eversole SL, Best JM, Faller RV. Animal caries
efficacy of conventional and remineralizing toothpastes. J Dent Res
Sp Iss Abstract 1998;77:843.
Eversole SL, Faller RV, Bitten ER, Featherstone JDB. Conventional
and remineralizing toothpastes compared in two pH cycling models.
J Dent Res Sp Iss Abstract 1998;77:843.
Faller RV, Eversole SL, Kelly SA, Lukantsova L, Dunipace AJ. In situ
comparison of conventional fluoride and remineralizing toothpastes.
J Dent Res Sp Iss Abstract 1998;77:1017.
2008 Australian Dental Association

Calcium phosphate-based remineralization

No published papers could be found demonstrating
that the EnamelonTM technology could slow progression of coronal caries or promote regression of coronal
caries in a randomized, controlled caries clinical trial.
However, one small clinical trial of the technology in a
group of high caries risk, head and neck radiation
patients has been published.9 In this study no significant
difference was found in coronal caries increment with
the EnamelonTM plus fluoride dentifrice compared with
that of the standard fluoride dentifrice. However,
a significant difference in root caries increment was
observed with the EnamelonTM plus fluoride dentifrice
producing a lower increment than the standard fluoride
dentifrice.
Although some of these published papers suggest
that the EnamelonTM technology may have efficacy in
preventing caries progression several authors have
expressed concern with the unstabilized nature of
the ACP that forms intra-orally with this technology.
The unstabilized ACP rapidly transforms to crystalline
phases in the mouth and in so doing may act to promote
dental calculus. In the presence of fluoride ions the
unstabilized ACP may produce fluorapatite. The formation of fluorapatite intra-orally would sequester
available fluoride ions thereby reducing their ability
to remineralize subsurface enamel during acid
challenge.
Casein phosphopeptide amorphous calcium phosphate
technology
Casein phosphopeptide amorphous calcium phosphate
nanocomplexes (RecaldentTM (CPP-ACP)) is a technology based on ACP stabilized by casein phosphopeptides
(CPP). CPP containing the cluster sequence Ser(P)Ser(P)-Ser(P)-Glu-Glu- stabilize ACP in metastable
solution.10 Through the cluster sequence the CPP bind
to forming nanoclusters of ACP preventing their
growth to the critical size required for nucleation and
phase transformation.10 The CPP-ACP technology has
been demonstrated to have anticariogenic activity in
laboratory, animal and human in situ experiments as
well as a randomized, controlled caries clinical trial
(Table 2).
The CPP-ACP nanocomplexes have been shown to
reduce caries activity in the rat caries model.11 Solutions (100 ll) containing different concentrations of
CPP-ACP were applied to the animals molar teeth
twice daily. Other groups of animals received 100 ll of
either 500 ppm fluoride ions (positive control) or
distilled water (negative control). The animals consumed a highly cariogenic sucrose gluten diet that did
not contain dairy products. The CPP-ACP significantly
reduced caries activity in a dose-response fashion with
0.1% w v CPP-ACP producing a 14% reduction and
1.0 % w v CPP-ACP a 55% reduction relative to the
2008 Australian Dental Association

Fig 1. The incorporation of the CPP-ACP nanocomplexes into

supragingival plaque from a mouthrinse.
(Reproduced with permission from 12.)

distilled water control. CPP-ACP at 0.5% w v produced a reduction in caries activity similar to that
of 500 ppm fluoride. A solution containing both
0.5% w v CPP-ACP and 500 ppm fluoride produced
a significantly greater reduction in caries activity
than either CPP-ACP or fluoride alone at the same
concentrations.
The CPP-ACP technology has also been demonstrated to significantly increase the levels of calcium and
phosphate ions in supragingival plaque when delivered
in a mouthrinse and to promote the remineralization
of enamel subsurface lesions in situ.12 In fact, in a
mouthrinse clinical study, the CPP-ACP technology was
shown to be superior to other forms of calcium
phosphate including unstabilized ACP.12 These studies
highlight the importance of the CPP in stabilizing the
high levels of calcium and phosphate ions but also in
delivering the ions to the tooth surface. Electron
microscopic analysis of immunocytochemically stained
thin sections of supragingival plaque samples12 showed
that the CPP-ACP nanocomplexes were localized in the
plaque matrix and on the surface of bacterial cells
(Fig 1) confirming the work of Rose13,14 who showed
the CPP-ACP nanocomplexes bound tightly to Streptococcus mutans and model plaque to produce a reservoir
of bioavailable calcium ions.
The ability of the CPP-ACP technology added to
sugar-free chewing gum to remineralize enamel subsurface lesions has been demonstrated in several
randomized, controlled, double-blind in situ clinical
studies.12,15,16 The sugar-free gums (control and
CPP-ACP containing gums) were chewed for either 20minute periods, four times a day or for 5-minute periods,
seven times a day. Microradiography and computerassisted densitometric image analysis demonstrated
that, independent of gum type and chewing duration
(e.g., 20 minutes or 5 minutes), the CPP-ACP nanocomplexes produced a dose-related remineralization of
enamel subsurface lesions in situ. Gum containing
18.8 mg and 56.4 mg of the CPP-ACP nanocomplexes,
271

EC Reynolds
chewed for 20 minutes, four times per day for 14 days,
increased enamel subsurface remineralization by 101
per cent and 151 per cent, respectively, relative to the
control sugar-free gum. Microradiographs of the enamel
lesions before and after remineralization showed that
the CPP-ACP nanocomplexes promoted remineralization throughout the body of the lesion. Electron
microprobe wavelength dispersive spectrometric analyses of sections of the remineralized enamel indicated that
the mineral deposited was hydroxyapatite with a higher
Ca:P ratio than normal apatite. Acid challenge of the
enamel remineralized by the CPP-ACP nanocomplexes
in situ showed that the remineralized apatite was more
resistant to acid challenge than the normal calciumdeficient carbonated tooth enamel.15
It has been reported that the CPP-ACP nanocomplexes interact with fluoride ions to produce a novel
ACFP phase.17,18 The identification of this novel ACFP
phase is consistent with the observed additive anticariogenic effect of the CPP-ACP nanocomplexes and
F.11,18 The anticariogenic mechanism of fluoride is the
localization of the fluoride ion at the tooth surface,
particularly in plaque in the presence of calcium and
phosphate ions. This localization increases the degree
of saturation with respect to fluorapatite (FA), thus
promoting remineralization of enamel with FA during
an acid challenge. It is clear that for the formation of
FA (Ca10(PO4)6F2), calcium and phosphate ions must
also be present with the fluoride ions. The reported
additive anticariogenic effect of the CPP-ACP nanocomplexes and F therefore may be attributable to the
localization of ACFP at the tooth surface by the CPP,
which co-localizes calcium, phosphate and fluoride as
bioavailable ions in the correct molar ratio to form
fluorapatite. In a randomized, controlled, mouthrinse
trial, a rinse containing 2.0% CPP-ACP nanocomplexes
plus 450 ppm fluoride significantly increased supragingival plaque fluoride ion content to 33.0 17.6 nM
F mg dry wt of plaque when compared to 14.4
6.7 nM F mg dry wt of plaque attained by use of
a rinse containing the equivalent concentration of
fluoride ions as sodium fluoride.18 Although marked
increases in plaque calcium, phosphate and fluoride
were found, calculus was not observed in any of the
subjects, indicating that the plaque calcium fluoride
phosphate remained stabilized at the tooth surface by
the CPP as bioavailable ions and did not transform into a
crystalline phase. These results indicate that the CPP act
as a delivery vehicle to co-localize bioavailable calcium,
fluoride and phosphate ions at the tooth surface.
A dentifrice formulation containing 2% CPP-ACP
nanocomplexes plus 1100 ppm F has been shown to
be superior (2.6 times) to a dentifrice containing only
1100 ppm F in remineralization of enamel subsurface
lesions with mineral that was more resistant to acid
challenge (Fig 2).18 The CPP-ACP nanocomplexes plus
272

Fig 2. Representative microradiographs of enamel subsurface lesions

after remineralization in situ by various dentifrice formulations and
acid challenge (AC) in vitro. The percentage enamel remineralization
is shown in each panel as %R.
(Modified from 18 and reproduced with permission.)

fluoride dentifrice resulted in significantly greater incorporation of the fluoride into the subsurface enamel as
fluorapatite as shown by electron microprobe wavelength dispersive spectrometry.18
A randomized, controlled caries clinical trial of CPPACP-containing sugar-free chewing gum demonstrated
that the CPP-ACP gum significantly slowed progression
of caries and enhanced regression of caries compared
with the control sugar-free gum.19 In the two-year
study, 2720 school children were randomly assigned to
either a test or control sugar-free gum. All subjects
received accepted preventive procedures, including
fluoridated water, fluoridated dentifrice and access to
professional care. Subjects were instructed to chew their
assigned gum for 10 minutes, three times per day, with
one session supervised on school days. Standardized
digital radiographs were taken at baseline and at the
completion of the trial. The radiographs, scored by a
single examiner, were assessed for approximal caries at
both the enamel and dentine level. Analysis of caries
progression or regression was undertaken using a
transition matrix. The CPP-ACP gum effected a significant 18 per cent reduction in caries progression after
24 months at the subject level and a 53 per cent greater
regression (remineralization) of baseline lesions when
compared with the control gum.19 These results are
consistent with the proposed anticariogenic mechanism
of the CPP-ACP technology being the inhibition of
enamel demineralization and enhancement of remineralization through the localization of bioavailable
calcium and phosphate ions at the tooth surface.
CONCLUSIONS
The RecaldentTM (CPP-ACP) technology has been
shown to remineralize enamel subsurface lesions in situ
and to significantly slow the progression of coronal
2008 Australian Dental Association

Calcium phosphate-based remineralization

caries and promote the regression of caries in a
randomized, controlled clinical trial. Furthermore, the
EnamelonTM (ACP) technology has been shown to
decrease root caries increment in a clinical trial of high
caries risk, head and neck radiation patients. Hence the
new calcium phosphate-based remineralization technologies look promising as adjunctive treatments to
topical fluorides in the non-invasive management of
early caries lesions.
REFERENCES
1. Armfield J, Roberts-Thomson K, Spencer A. Australias Health
2000: the seventh biennial health report of the Australian Institute of Health and Welfare. AIHW cat. no. AUS 19. Canberra:
AIHW, 2000.
2. ten Cate JM. Current concepts on the theories of the mechanism
of action of fluoride. Acta Odontol Scand 1999;57:325329.
3. Lynch RJ, Navada R, Walia R. Low-levels of fluoride in plaque
and saliva and their effects on the demineralisation and remineralisation of enamel; role of fluoride toothpastes. Int Dent J
2004;54(5 Suppl):304309.
4. Mundorff-Shrestha SA, Proskin HM, Winston AE, Triol CW,
Cornell G, Sharpe T. Cariostatic effect of a two-part fluoride
dentifrice in rats. J Clin Dent 1999;10:2629.
5. Thompson A, Grant LP, Tanzer JM. Model for assessment of
carious lesion remineralization, and remineralization by a novel
toothpaste. J Clin Dent 1999;10:3439.
6. Schemehorn BR, Orban JC, Wood GD, Fischer GM, Winston AE.
Remineralization by fluoride enhanced with calcium and phosphate ingredients. J Clin Dent 1999;10:1316.
7. Schemehorn BR, Wood GD, Winston AE. Laboratory enamel
solubility reduction and fluoride uptake from enamelon dentifrice. J Clin Dent 1999;10:912.
8. Hicks MJ, Flaitz CM. Enamel caries formation and lesion progression with a fluoride dentifrice and a calcium-phosphate containing fluoride dentifrice: a polarized light microscopic study.
ASDC J Dent Child 2000;67:2128.
9. Papas A, Russell D, Singh M, et al. Double blind clinical trial of a
remineralizing dentifrice in the prevention of caries in a radiation
therapy population. Gerodontology 1999;16:210.
10. Cross KJ, Huq NL, Palamara JE, Perich JW, Reynolds EC.
Physicochemical characterization of casein phosphopeptideamorphous calcium phosphate nanocomplexes. J Biol Chem
2005;280:1536215369.
11. Reynolds EC, Cain CJ, Webber FL, et al. Anticariogenicity of
calcium phosphate complexes of tryptic casein phosphopeptides
in the rat. J Dent Res 1995;74:12721279.
12. 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;82:206211.

2008 Australian Dental Association

13. Rose RK. Binding characteristics of Streptococcus mutans for

calcium and casein phosphopeptide. Caries Res 2000;34:427
431.
14. Rose RK. Effects of an anticariogenic casein phosphopeptide on
calcium diffusion in streptococcal model dental plaques. Arch
Oral Biol 2000;45:569575.
15. Iijima Y, Cai F, Shen P, Walker G, Reynolds C, Reynolds EC.
Acid resistance of enamel subsurface lesions remineralized
by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate. Caries Res 2004;38:551
556.
16. 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;80:20662070.
17. Cross KJ, Huq NL, Stanton DP, Sum M, Reynolds EC.
NMR studies of a novel calcium, phosphate and fluoride delivery
vehicle-a(S1)-casein(59-79) by stabilized amorphous calcium
fluoride phosphate nanocomplexes. Biomaterials 2004;25:5061
5069.
18. Reynolds EC, Cai F, Cochrane NJ, et al. Fluoride and casein
phosphopeptide-amorphous calcium phosphate. J Dent Res
2008;87:344348.
19. 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;42:171184.
20. Grant LP, Thompson A, Tanzer JM. Caries inhibition in rats by a
remineralizing toothpaste. J Clin Dent 1999;10:3033.
21. 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;66:11201127.
22. Reynolds EC. Remineralization of enamel subsurface lesions by
casein phosphopeptide-stabilized calcium phosphate solutions.
J Dent Res 1997;76:15871595.
23. Reynolds EC. Anticariogenic complexes of amorphous calcium
phosphate stabilised by casein phosphopeptides: a review. Spec
Care Dentist 1998;18:816.
24. Yamaguchi K, Miyazaki M, Takamizawa T, Inage H, Moore BK.
Effect of CPP-ACP paste on mechanical properties of bovine
enamel as determined by an ultrasonic device. J Dent 2006;
34:230236.

Address for correspondence:

Professor EC Reynolds
Centre for Oral Health Science
School of Dental Science
The University of Melbourne
720 Swanston Street
Melbourne, Victoria 3010
Email: e.reynolds@unimelb.edu.au

273