The Continuum of Dental Caries--Evidence for a Dynamic Disease Process

Abstract

The eventual outcome of dental caries is determined by the dynamic balance between pathological factors that lead to demineralization and protective factors that lead to remineralization. Pathological factors include acidogenic bacteria, inhibition of salivary function, and frequency of ingestion of fermentable carbohydrates. Protective factors include salivary flow, numerous salivary components, antibacterials (both natural and applied), fluoride from extrinsic sources, and selected dietary components. Intervention in the caries process can occur at any stage, either naturally or by the insertion of some procedure or treatment. Dental caries covers the continuum from the first atomic level of demineralization, through the initial enamel or root lesion, through dentinal involvement, to eventual cavitation. The dynamic balance between demineralization and remineralization determines the end result. The disease is reversible, if detected early enough. Since demineralization can be quantified at early stages, before frank cavitation, intervention methods can be tested by short-term clinical trials.

Full text

INTRODUCTION
T
he process of dental caries is now well-understood, although there are many details
yet to be determined. Studies over approximately the last 20 to 30 years have
clarified the mechanisms of demineralization and remineralization and also elucidated
a great deal of the complex microbiology of the process (Loesche, 1986; ten Cate and
Featherstone, 1991). However, clinical trials are still conducted with the endpoint
being frank cavitation as measured and examined by standard criteria (Radike, 1972).
This endpoint of the caries process comes after months or years of decay progression
and is itself a rather crude measure. A great deal of time and effort has been spent in
modeling dental caries, both in the laboratory and utilizing the human mouth as a
laboratory, as well as in a range of animal models (ten Cate and Featherstone, 1991;
Featherstone, 1995; ten Cate and Mundorff-Shrestha, 1995; Zero, 1995). The
definitive proof, of course, of any product designed to intervene or reverse caries is the
so-called "clinical trial". With the in-depth understanding that we now have of the
dental caries process, it is possible to design measures for the detection of dental caries
at a much earlier stage and to assess the efficacy of therapeutic procedures to prevent
progression or, even better, reverse the process. However, there has been debate about
whether early caries turns into eventual cavitation, whether the different types of
caries are comparable, and whether the various modeling methods are predictive
(Featherstone, 1995). The purpose of the present paper is to present a brief review of
the continuum of dental caries and the evidence for caries being a dynamic disease
process.
CATEGORIES OF DENTAL CARIES
The categories of dental caries that are mostly considered by clinicians and researchers
are smooth-surface caries, pit and fissure caries, enamel caries, dentinal caries,
secondary caries, early childhood caries, and root caries. Other subdivisions may also
be considered and described clinically or histologically. The basic mechanism of dental
caries, as described in the next section, is the same for all of these so-called "types of
caries". Mineral is lost through attack by acid generated by bacteria. This is
demineralization. If demineralization continues, a cavity eventually occurs in whatever
form and in whatever position on the teeth in the mouth. The natural body repair
mechanism for dental caries is remineralization related primarily to minerals from
saliva diffusing back into the porous subsurface region of the caries lesion
(Featherstone, 2000). The physical treatment methodologies for restorative dentistry are
obviously different, depending on the location, extent, and seriousness of the decay.
However, the basic mechanistic principles are the same for all of the above-mentioned
categories of dental caries.
CARIES MECHANISM
Dental caries is a simple process in concept, but complicated in detail. In outline, the
caries mechanism can be described as follows (Featherstone, 2000):
(1) Acidogenic (acid-producing) oral plaque bacteria ferment carbohydrates that
are taken into the mouth, thereby producing organic acids, including lactic,
formic, acetic, and propionic.
(2) These acids diffuse into the enamel (Featherstone, 1983), dentin, or
cementum, partially dissolving the mineral crystals (composed of carbonated
hydroxyapatite (LeGeros, 1991) as they travel.
(3) Mineral (calcium and phosphate) diffuses out of the tooth, leading eventually
ABSTRACT
The eventual outcome of dental caries is determined by
the dynamic balance between pathological factors that
lead to demineralization and protective factors that lead
to remineralization. Pathological factors include
acidogenic bacteria, inhibition of salivary function, and
frequency of ingestion of fermentable carbohydrates.
Protective factors include salivary flow, numerous
salivary components, antibacterials (both natural and
applied), fluoride from extrinsic sources, and selected
dietary components. Intervention in the caries process
can occur at any stage, either naturally or by the
insertion of some procedure or treatment. Dental caries
covers the continuum from the first atomic level of
demineralization, through the initial enamel or root
lesion, through dentinal involvement, to eventual
cavitation. The dynamic balance between
demineralization and remineralization determines the
end result. The disease is reversible, if detected early
enough. Since demineralization can be quantified at
early stages, before frank cavitation, intervention
methods can be tested by short-term clinical trials.
KEY WORDS: dental caries, demineralization,
remineralization, acidogenic bacteria.
Presented at the International Consensus Workshop on
Caries Clinical Trials, Glasgow, Scotland, January 7-10,
2002
The Continuum of Dental Caries—
Evidence for a Dynamic
Disease Process
J.D.B. Featherstone
Department of Preventive and Restorative Dental Sciences,
School of Dentistry, University of California at San
Francisco, 707 Parnassus Avenue, San Francisco, CA
94143, USA; jdbf@itsa.ucsf.edu
J Dent Res
83(Spec Iss C):C39-C42, 2004
PROCEEDINGS
Clinical
C39

C40 Featherstone
J Dent Res
83(Spec Iss C) 2004
to cavitation if the process continues.
(4) Demineralization can be reversed by calcium and phosphate,
together with fluoride, diffusing into the tooth and depositing a
new veneer on the crystal remnants in the non-cavitated lesion
(this is remineralization).
(5) The new mineral crystal surface is much more resistant to acid
as compared with the original carbonated hydroxyapatite
mineral.
(6) The process of demineralization and remineralization generally
occurs numerous times daily, leading either to cavitation, to
repair and reversal, or to maintenance of the status quo.
In root caries, the same mechanism occurs as outlined above,
initially causing demineralization and exposure of the collagen fibrils
(Wefel et al., 1985). Once the collagen is exposed, it is open to
breakdown by bacterially derived enzymes, leading to rapid cavitation
and breakdown of the dentin in the tooth root (Clarkson et al., 1986;
Kawasaki and Featherstone, 1997).
The bacteria that produce the acids fall into the category of
acidogenic bacteria and are also aciduric, which means that they can
live preferentially under acid conditions (Loesche, 1986). In normal
dental plaque, these acidogenic bacteria occupy less than 1% of the
total flora. As caries becomes progressive and more aggressive, the
environment in the plaque becomes more frequently acidic, and these
aciduric bacteria survive at the expense of the other benign bacteria.
The most important aspect for the current discussion is that all acids
produced by the bacteria—including lactic, acetic, formic, and
propionic acids—can readily dissolve tooth mineral (Featherstone and
Rodgers, 1981). Two major groups of bacteria produce such acids,
namely, the mutans streptococci (including Streptococcus mutans and
Streptococcus sobrinus) and the lactobacilli species (Loesche, 1986;
Leverett et al., 1993). There are undoubtedly other acidogenic
organisms involved in dental caries. Until fairly recently, it was
considered that early childhood caries, a particularly rampant form of
caries manifested in young children, had a different etiology. However,
it is now obvious that the same bacteria are involved, but the reasons
for the rapid progression of the disease in these children are still
uncertain (Alaluusua et al., 1987; Caufield et al., 1993). Pit and fissure
caries now occupies much of the caries seen in Western countries,
since it appears that common therapeutic measures such as fluoride in
the drinking water and in fluoride products is not as effective in these
surfaces.
Wherever bacteria have niches in which to live, these
acidogenic/aciduric bacteria preferentially survive well. Therefore,
orthodontic subjects who have brackets or bands are at high risk of
caries, because the bacteria live well in the surrounding edges of these
appliances (O'Reilly and Featherstone, 1987). The same applies to
restorations with poor margins and pits and fissures.
THE CARIES BALANCE
Remineralization has been demonstrated in the laboratory for all types
of caries listed above, but of course, the deeper the caries lesion, the
harder it is for remineralization to be effective (ten Cate and
Featherstone, 1991). Whether a lesion will progress, stay the same, or
reverse is determined by the balance between protective factors and
pathological factors (Featherstone, 2000). This balance is illustrated in
Fig. 1. If the pathological factors predominate, then caries progresses.
If the protective factors predominate, then caries is halted or reversed.
In simple terms, the pathological factors are cariogenic bacteria,
salivary dysfunction, and frequency of ingestion of fermentable
carbohydrates. Once established in a particular person's mouth, these
cariogenic bacteria are very difficult to manage. Protective factors
include most of the components in saliva (such as calcium), phosphate,
fluoride, protective proteins that form the pellicle, proteins that
maintain supersaturation of the mineral in saliva and plaque, and
antibacterial substances naturally in saliva but also supplied
extrinsically (e.g., chlorhexidine), salivary fluoride, fluoride from
external sources, and substances (e.g., chewing gum) that stimulate
salivary function. Fig. 1 conceptually summarizes the dynamic process
of dental caries as being a balance, or imbalance, between
demineralization and remineralization that occurs numerous times
daily in the mouths of most humans.
PREVENTION AND INTERVENTION
Prevention, intervention, and reversal of dental caries can be enhanced
by either reducing the pathological factors or enhancing the protective
factors.
Bacteria
Antibacterial therapy such as treatment by chlorhexidine gluconate
mouthrinse has been shown to be effective in reducing the cariogenic
bacteria (Krasse, 1988). If the bacterial challenge is reduced, then the
protective factors have a greater chance of taking over and halting or
reversing dental caries (Featherstone, 2000). The natural antibacterial
substances in saliva, such as lactoferrin and the immunoglobulins, are
obviously not sufficiently active in cases where caries progresses.
Fermentable Carbohydrates
One of the most significant contributions to dental caries is the
frequency of ingestion of fermentable carbohydrates. Reducing the
frequency of ingestion is a behavioral matter. However, substituting
non-cariogenic sweeteners such as xylitol for the fermentable
carbohydrates such as glucose, sucrose, and fructose has been shown
to be effective in reducing the pathological challenge (Hildebrandt and
Sparks, 2000; Söderling et al., 2000).
SALIVARY FUNCTION
In the case of reduced salivary function, there are fewer protective
factors provided by the saliva, and less ability for the saliva to enhance
remineralization, remove bacteria, or inhibit bacterial action.
Xerostomic patients have rampant caries if intervention strategies are
not put in place (Mandel, 1974, 1989). These subjects illustrate, in a
few months, the progression from smooth-surface caries to cavitation
and rapid breakdown of the teeth on all surfaces, related directly to the
lack of salivary function and the ability of the bacteria to take over and
produce mineral-destroying acids very rapidly (Dreizen et al., 1977).
FLUORIDE
It is very well-documented that, in clinical trials assessed by
conventional visual-tactile detection methods (Jenkins, 1985), fluoride
products such as toothpaste, mouthrinse, and office topicals have been
shown to reduce caries between 30 and 70% compared with no fluoride
therapy. Fluoride in the drinking water has also been shown, of course,
to be effective in reducing the severity of dental decay in entire
populations. However, it has become obvious that where the bacterial
Figure 1. Schematic diagram of the balance between pathological factors
and protective factors in the dental caries process. Reproduced with the
permission of the publisher, Munksgaard, from Featherstone (1999).

J Dent Res
83(Spec Iss C) 2004 The Continuum of Dental Caries C41
challenge is too high, it is not possible for fluoride to overcome this
challenge completely. Again, this is an illustration of the continuum of
dental caries and the ability or inability to balance the outcome
according to the schematic diagram in Fig. 1.
THE CONTINUUM OF DENTAL CARIES
As described above, demineralization and remineralization occur in the
mouth several times daily as a dynamic process, with progression or
reversal of dental caries being the end result. The site at which the
caries occurs is determined by the acidogenic bacteria at that site and
access to either pathological factors and/or protective factors. Caries
begins to manifest itself at the atomic level as soon as a diffusing
molecule of organic acid reaches a susceptible site on a crystal surface
of carbonated hydroxyapatite down inside the tooth (Featherstone,
1983). This has been shown, by laboratory experiments, to cause
preferential loss of calcium, phosphate, and carbonate from specific
sites in the crystal. This process was visualized by Featherstone and
co-workers approximately 20 years ago (Featherstone et al., 1979,
1981). The reversal of demineralization also occurs at the atomic level
when calcium, phosphate, and fluoride come together to build a new
surface onto the existing crystal remnants that have remained
following demineralization. This again has been visualized at the
atomic level, at the ultrastructural level, and in chemical experiments
by numerous researchers (Featherstone et al., 1981; ten Cate and
Duijsters, 1983; ten Cate and Featherstone, 1991; ten Cate and
Mundorff-Shrestha, 1995).
The process of dental decay can be modeled in the laboratory in
chemical or microbiological systems to produce the early
manifestation of caries, namely, the white spot lesion, decay around
orthodontic brackets, secondary decay around restorations, decay on
smooth surfaces or on occlusal surfaces, root caries, and dentinal
caries. In general, in the mouth, the process takes much longer than in
the laboratory models. The advantage of the models is that much can
be learned about processes involved in a much shorter period of time
(Featherstone, 1995; ten Cate and Mundorff-Shrestha, 1995). The
thousands of experiments that have been conducted and reported in
the literature for both in vitro and in vivo experiments readily confirm
that the caries lesion is formed by a continuous process starting at the
atomic level on the crystal surface in the subsurface of the tooth, and
progressing deeper and deeper into the enamel, or, in the case of root
caries ,starting in the cementum and eventually ending up in the
dentin.
The dynamic nature of the process has been modeled in numerous
laboratories by various pH cycling models (ten Cate and Duijsters,
1982; Featherstone et al., 1990). To review these studies is beyond the
scope of the space of the present article. Suffice it to summarize that
these models can produce a continuum of the dental decay process
with end results ranging from an almost imperceptible white spot to a
cavity. For example, a recent study (unpublished) in our laboratory
examined pH cycling (alternating demineralization/remineralization)
over a period of 3 wks with 6 hrs of demineralization daily in a pH 4.3
partially saturated calcium and phosphate demineralizing solution and
17 hours of remineralization during every 24 hours, according to
methods reported previously (Featherstone et al., 1990). In between
each of the de- and remineralization steps, the crowns were subjected
to treatment in dentifrice slurries made from a range of products
containing, respectively, 2800 ppm F, 1100 ppm F, 250 ppm F as NaF,
and a placebo product with no added fluoride. At the end of the
experimental time, the teeth were hemi-sectioned and assessed by
cross-sectional micro-hardness (Featherstone et al., 1990). The relative
mineral loss (volume % x ␮m) as ⌬Z was linearly related to the
negative logarithm of the fluoride content of the products (p < 0.01).
The lesion profiles are shown in Fig. 2. The placebo product contained
less than 1 ppm F. In the case of the treatment by the placebo,
cavitation occurred in some parts of some lesions, the lesions were
deep (⌬Z approximately 4000) for the period of treatment, and the
mineral content remaining in the outer portion of the lesion was on the
order of 30% volume mineral (Fig. 2). On the other hand, the group
treated with the 2800-ppm-F product produced lesions that were barely
visibly perceptible as white spots, with a low ⌬Z value (approximately
500). This model clearly illustrates the continuum from almost no
effect of the strong acid challenge when treated with the high-F
product, to major demineralization and cavitation with the placebo
dentifrice. These results parallel those of clinical trials involving
similar products.
Similarly, the caries process can be modeled in the mouth with in
situ studies, as demonstrated over the last 30 years by numerous
laboratories, as reviewed in a recent conference (Featherstone, 1995).
Several models have been used, and these have been reported in many
papers. Most of the models involve utilizing extracted teeth and
placing enamel and/or dentin samples in the mouth and observing
subsequent demineralization or remineralization. Again, these models
have produced product efficacy indications similar to those found in
laboratory in vitro pH cycling studies. A model that is one step closer
to what might be considered 'natural caries' is one that uses orthodontic
appliances. In this case, true caries occurs on the smooth surfaces
surrounding these orthodontic appliances. For example, O'Reilly and
Featherstone (1987) reported such a model and based the development
of a pH cycling model on the results that they found in the human
mouth. Øgaard and co-workers have used orthodontic models,
particularly banding, to show severe caries challenge and rapid
progression of lesions in the mouth in a high-challenge situation with
poor access for remineralization (Øgaard and Rølla, 1992). There is no
reason to believe that caries around orthodontic brackets is any
different from any other of the forms of caries described above.
Since it has been established that the caries process is a
continuum, albeit one that is interrupted numerous times daily, it is
therefore possible to intervene at any stage with a therapeutic product
or an intervention methodology. If detection methods are accurate and
objective enough, then the disease can be followed over time, the rate
of progress measured, or the rate of reversal measured (Stookey,
1999).
In summary, dental caries covers the continuum from the first
atomic level of demineralization, through the initial white spot (or its
equivalent in the tooth root), often through dentinal involvement, to
eventual cavitation. All of the steps can be modeled in the laboratory
or in the mouth. The dynamic balance between demineralization and
remineralization, as determined by pathological factors and protective
Figure 2. Plot of volume % mineral
vs.
depth from the surface for 4
groups in a pH cycling study. Each group was treated between
demineralization and remineralization by a dentifrice containing,
respectively, (a) no added fluoride, (b) 250 ppm F, (c) 1100 ppm F, and
(d) 2800 ppm F each as NaF. Error bars are standard deviations for the
data at each depth from the surface. Each group is statistically
significantly different from every other group (p < 0.05).

C42 Featherstone
J Dent Res
83(Spec Iss C) 2004
factors, determines the end result. The disease of dental caries is
reversible, if detected early enough. It may be necessary to use
antibacterial methods as well as methods that enhance remineralization
or inhibit demineralization. With the sophisticated knowledge we now
have of the dental caries mechanism and our ability to quantify
demineralization at early stages, rather than wait for frank cavitation,
intervention methods can be tested by short-term clinical trials.
ACKNOWLEDGMENTS
The contributions of many people to the studies reviewed here are
acknowledged sincerely. The space restriction of this limited review
makes it impossible to refer to all the relevant studies. The support of
numerous grants from commercial sources and from the National
Institutes of Health is also acknowledged with thanks.
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