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in Dental Research

Remineralization/Desensitization: What Is Known? What Is the Future?


N.B. Pitts and J.S. Wefel
ADR 2009 21: 83
DOI: 10.1177/0895937409335644

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Remineralization/Desensitization:
What Is Known? What Is the Future?

research around the remineralization of dental caries. Although


N.B. Pitts1*,2, J.S. Wefel3,4 much of the evidence base for some of this field has been in exis-
tence for more than two decades, it has yet to be adopted as rou-
1
Centre for Clinical Innovations and 2Dental Health Services Research tine clinical practice in many (but not all) countries.
Unit, University of Dundee, The Mackenzie Building, Kirsty Semple
Way, Dundee, DD2 4BF, Scotland, UK; and 3Department of Pediatric
Dentistry and 4Dows Institute for Dental Research College of Dentistry, Synthesis and Discussion
University of Iowa, Iowa City, USA; *corresponding author, n.b.pitts@
chs.dundee.ac.uk
Topics from the initial full panel session deemed important by
the meeting discussants included:
Adv Dent Res 21:83-86, August, 2009
• the existence of several other novel remineralization
approaches not presented at the meeting, such as the use of
biomimetics and self-assembly proteins;

T he aim of this paper was to distill recommendations from • the importance in clinical remineralization of assessing lesion
existing evidence and material on dental caries remineraliza- activity (determining the current state of a lesion at one spe-
tion/desensitization discussed at the ICNARA meeting within cific point in time) as a complement to detecting lesions and
the context of “modern” clinical management of the caries pro- monitoring lesion behavior over time;
cess, aiming to prevent progression by promoting arrest and, • the continuing need to explore and review technologies
where possible, regression of pre-cavitation lesions. Since much developed outside of dentistry;
of the evidence reviewed has been published but not adopted for • the need to articulate a range of clinical goals for caries con-
decades, programs for more effective dissemination and imple- trol appropriate for different groups with a range of caries
mentation of research findings with educators, clinicians, and challenges; and
patients are required. The broadly agreed research agenda rec- • the need to re-assess current guidelines for the types and num-
ognized that the aim of remineralization therapy is to facilitate bers of clinical trials required for a product to be accepted by
caries control over a lifetime, using evidence-based, clinically various agencies and organizations, since these guidelines
effective, multi-factorial prevention to keep the caries process were developed for agents assessed with frank carious cavita-
in balance. Over the coming years, the dental research commu- tion as an end-point, according to classic visuo-tactile criteria,
nity in this field should continue to apply new knowledge and as opposed to remineralization seeking to achieve an end-
methods from outside dentistry and develop a menu of caries point prior to frank cavitation.
control strategies effective for individuals, groups, and popula-
tions using agreed, comparable protocols. Issues from the Remineralization/
Desensitization Group Papers
Introduction
It was believed (Featherstone, 2009) that there is a need in the
The aim of this paper was to distill from the presentations and future for more in-depth understanding about the amount of car-
discussions on caries remineralization and desensitization at the ies present in individuals and populations who need care. In the
International Conference on Novel Anti-Caries and Remineralizing future, this should be broken down by the stages of caries pres-
Agents (ICNARA) meeting and the existing evidence: What is ent (at agreed detection thresholds) as well as, ideally, by the
known now? What is the future? The purpose was to build a syn- level of activity of the caries.
thesis and outline what the future research and development The research community and all stakeholders should strive to
agendas for the next 10 years should look like. ensure that, in 20 years’ time, we are not re-stating the same
As an aid to structuring the discussions, the graphical structure
of the Collaboration for Improving Dentistry framework (Dental Key Words
Health Services Research Unit, 2007) was used (Fig. 1) to cover
Dental caries, remineralization, desensitization, activity, lesion behavior.
all stages of the knowledge management process. This structure
links key elements which pertain to understanding and advancing Presented at the International Conference on Novel Anti-caries and
Remineralizing Agents, held in Vina del Mar, Chile, January 10-12,
2008

The authors declare no conflict of interest.


DOI: 10.1177/0895937409335644

83
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Copyright 2009 by the International Association for Dental Research


84  Pitts & Wefel Adv Dent Res 21: 2009

dental caries, research in this


Effective area is in its infancy. There is an
Dissemination acute need for better and stan-
of Research dardized tools for assessing the
Systematic Findings
prevalence of erosion and for
Reviews assessing changes over time.
Stakeholder It should be appreciated that
Groups remineralization products and the

for
Critical biofilm are linked to both sensitiv-

Im
Appraisal ity problems and solutions (Wolff,

pr
Education
2009), but although several caries

ov
Providers
ion

ing
remineralization technologies
ra t
Primary have evolved from attempts to
bo

Research control sensitivity, the mechanisms


lla

involved are very different, and


Co

Dentistry
outcomes may differ.

Discussion session 1
Compliance issues are consid-
Pursuing an ered to be a very important, but
Effective
informed Patients Clinicians often neglected, topic for devel-
Implementation
Research oping strategies for products and
of
Agenda for clinical trials. The aims of
Research Findings
care may be to bring individuals
Figure 1. The Dental Health Services Research Unit (DHSRU) Collaboration for Improving Dentistry to the dental office and have
Reutersvärd Triangle, relating the disparate processes of Pursuing an Informed Research Agenda, mounting long-lasting “treatments” involv-
Effective Dissemination of Research Findings, and seeking Effective Implementation of the Research Findings
ing caries lesions and/or the bio-
by clinicians to help their patients.
film, but a parallel approach that
evidence on remineralization as we had in the late 1980s. All par- provides alternatives to or complements office-based treatments
ties should strive to ensure that previous evidence will now get is the development of more effective home-use agents. It was
into practice and products, and that new studies will incrementally agreed that a multi-channel approach is needed, especially for
build into unbiased synthesized reviews of rational caries man- “high risk” groups. Society needs both office-based solutions
agement. The challenge was made to Industry to meet the need for for those who can and will attend, as well as alternative and low-
effective products with sustained slow release of fluoride. cost solutions for use in different settings.
A key and important issue was identified (ten Cate, 2009) in It was agreed that the presence of saliva was an important
effectively and honestly communicating to patients and all influence on caries control, and that this can work on both sides
stakeholders the true and complex nature of dental caries. After of the caries balance. This was well-demonstrated from existing
much debate, there was support for the wording recognizing that evidence at the two extremes:
“Caries is a multi-factorial disease process involving the biofilm
which can be controlled by combination strategies addressing • in xerostomic situations, when caries progression is pro-
the aetiological factors”. This was preferred to the more sim- moted; and
plistic statement that “Caries is an infectious disease”, which • where saliva is stimulated, as in chewing, when caries remin-
seems to be misunderstood in many countries and among stake- eralization is promoted.
holder groups. This view was reinforced by arguments including:
(i) the organisms concerned are commensals in the oral flora, Consideration of the “Recaldent” papers (Reynolds, 2009;
rather than invading pathogens; (ii) cariogenic organisms, as Zero, 2009) led to an appreciation of the extended process of
part of the normal flora, will recolonize if they are temporarily development. Moving forward, it was noted that more studies
removed; (iii) the oral biofilm (as others) will normally have a from different centers are now being published and are desir-
healthy interaction with the host; (iv) caries is not a typical able. Looking to the future, continuing research could explore
medical infectious disease; and (v) appendicitis would not be improving remineralization still further, if possible. The use of
classified as an infectious disease. There was support for a range so-called ‘transition matrices’, pioneered in the 1970s and
of new studies needed in the area of caries risk assessment and the 1980s, which consider the behavior of individual lesions in
early detection of disease across a wide range of age groups (not terms of both progression and regression, is attracting increasing
just for children). attention with ICDAS datasets (Ismail et al., 2007) and should
Erosion is multi-factorial and fundamentally different from be explored further in remineralization studies.
the caries process (Lussi, 2009). There is a great need to under- Other future items for the wider research agenda include:
stand erosion better in the next 10 years, since, compared with exploring further the use of calcium agents in combination with

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Adv Dent Res 21: 2009 Remineralization/Desensitization: What is Known?   85

fluoride to see if synergies can be achieved; further validation of Reviews of the Current Evidence
methods and models for remineralization studies; knowing more
about the natural history of initial caries in different age groups; As documented clearly elsewhere (National Institutes of Health,
understanding more about the hierarchy of preventive interven- 2001), a review of many areas of study reveals that the quality
tions as more non-fluoride remineralization research is done; of previously published work in this field is highly variable,
and ascertaining more about the long-term impact of the remin- with some studies appearing methodologically poor when
eralization effects on individual lesions followed up over years. judged by contemporary quality standards.
Consideration of the “Novamin” papers (Burwell et al., It was acknowledged that there is a need for:
2009; Wefel, 2009) revealed an interesting technology with a
• further, unbiased, systematic reviews in the key and promising
history of other uses, but at an early stage of development in the
areas (increasingly essential for many stakeholders);
caries remineralization application. This example exemplifies
• systematic reviews to be updated and maintained (this work
the useful work in this area to evaluate materials developed
needs to be funded);
primarily for use elsewhere, making a transition from uses in
• recognition that remineralization is a natural repair process in
sensitivity to explorations of caries remineralization.
cariology;
It was believed that the research community needs to con-
• dissemination more widely of authoritative reviews on the
struct separate research agendas for dentin and enamel reminer-
caries process, lesion behaviour, and the desirability/possi-
alization and avoid confusion between the two. The future
bility to stop lesion progression and to promote long-term
direction should be to optimize interactions with fluoride where
remineralization of lesions;
possible, and the need to have standardized assessment methods
• finding strategies for dealing with and managing the growing
and clinical trial designs was highlighted, as they have been
amount of information and misinformation on remineraliza-
previously at the International Consensus Workshop for Caries
tion that is already on the World Wide Web; and
Clinical Trials: ICW-CCT (Pitts and Stamm, 2004) and the
• better understanding of the reasons for the failure of both
Indiana Caries Conferences.
dissemination and implementation of the current knowledge
Consideration of the “xylitol” papers (Milgrom et al., 2009;
base in this area and the impact of equitable remuneration for
Twetman, 2009) raised a range of important issues. There is a
delivering clinical prevention (National Institutes of Health,
need to better understand the validity of surrogate markers and
2001).
a debate as to the link between a decrease in mutans streptococci
counts and a change in clinical caries outcomes. The challenges
of there often being few studies in novel areas and a history of What Is Known Now?
poor-quality evidence in the literature mean that new, carefully
The following were broadly agreed:
conducted, modern-design studies are required in the most
promising areas.
Data were presented where the results of the same trial were • It is important to differentiate between remineralization of a
analyzed with two caries cut-offs producing two different results. caries lesion that has previously been demineralized, as
This served to reinforce the need to standardize the diagnostic opposed to precipitation of mineral onto a surface that has
thresholds used in caries examinations to combat the danger of not been previously demineralized.
confusion among some stakeholders. Consensus has already • The aim of remineralization therapies in caries management
been reached on these issues (Pitts and Stamm, 2004), and stan- for enamel lesions is to:
dardized open systems (ICDAS, 2008) are now available. — do no harm, but achieve a health benefit.
The research agenda for the future should also include con- — put mineral back into a lesion, ideally penetrating to the
siderations of economic and cost-effectiveness issues. In the subsurface areas of the lesion, as well as the surface, and
future, this analysis must be based on a full understanding of the — ideally, achieve an area more resistant to subsequent car-
disease process and long-term health. There is also a clear need ies attack than the original tissue
for Randomized Controlled Trials to be conducted and reported
to CONSORT standards. To slow lesion progression, promote lesion arrest, and,
ideally, achieve lesion regression.
Discussion session 2
• Other forms of precipitation/mineralization on surfaces have
A very powerful observation was made that the traditional mea- clinical applications in the management of sensitivity and
sure of caries, the simple dmf/DMF index, has now “had its day erosion, but should be considered separately.
in research in this area”, and there is a need in the future for the • There is a range of clinical applications and outcomes, and it
use of carefully applied and validated new technologies. A fur- is unlikely that one research design or one product will be
ther key point for the future research agenda is that lesion arrest optimal for all situations.
is a good outcome—treatments and products should be aiming • The clinical outcomes relevant to the research agenda in this
to either arrest or reverse a lesion, and both outcomes are good field for the next 10 years can be considered as a matrix
clinically. The point was also made strongly that remineraliza- including enamel caries, dentin caries, root-surface caries,
tion, which has been shown to be possible when objectively orthodontic treatment-related caries; this framework has an
monitored in vivo, is a very desirable way of controlling the car- overlap with the related, but separate, areas of erosion and
ies process in the future. sensitivity research.

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86  Pitts & Wefel Adv Dent Res 21: 2009

clearly identified subcategories


Effective
Systematic in the continuing and inter-
Dissemination
Reviews: of Research
related processes of Pursuing an
• Randomised trials Findings Informed Research Agenda, then
• Other Designs mounting Effective Dissemination
• Where little evidence Researchers & Associations
of Research Findings, and taking
Research Funders
active steps to achieve Effective
Critical Oral Health Industry
Care Providers
Implementation of the Research
Appraisal

fo
Care Funders Findings by clinicians to help

rI
for Quality and
their patients.

mp
Relevance Professional Associations

ro
ion
Education

vin
Primary
Research
rat
Providers: Acknowledgments

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and Disclaimer
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of Clinical under-graduate
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Relevance post-graduate
Dentistry
Co

Industry support The active and engaged partici-


C.P.D. pation of ICNARA speakers
and delegates is gratefully
acknowledged. The views
expressed above are those of
Pursuing an Awareness of Uptake of synthesized Effective the authors, and not necessarily
informed synthesized and research findings Implementation of any Health Department,
Research updated evidence by by of Company or Research Funding
Agenda Patients Clinicians Research Organization.
Findings

Figure 2. An expanded version of the DHSRU Reutersvärd Triangle, identifying the specific areas which References
need to be addressed in a cyclical way over the coming years in the field of remineralization research and
development, by: Pursuing an Informed Research Agenda, then mounting Effective Dissemination of Research Burwell AK, Litkowski D, Greenspan
Findings to key groups, and, in addition, taking active steps to achieve Effective Implementation of the DC (2009). Calcium sodium phos-
Research Findings by enabled clinicians to help informed patients (which will then, in turn, be re-evaluated). phosilicate (NovaMin®): remineral-
isation potential. Adv Dent Res
21:35-39.
• The matrix should also include anatomical sites/caries predi- Dental Health Services Research Unit (2007). Dental Health Services
lection areas (occlusal, free, smooth-surface, and approxi- Research Unit—Annual Report 2007, Director’s Overview, p3-11,
mal), age group (e.g., pre-school, primary dentition, University of Dundee. DHSRU Web site: http://www.dundee.ac.uk/
dhsru/docs/anrep07_summary.pdf (accessed Feb 19, 2009)
adolescent, adult, and senior), and also specific high-risk Featherstone JDB (2009). Remineralization, the natural caries repair
groups and populations. process—the need for new approaches. Adv Dent Res 21:4-7.
• There is a range of clinical strategies that are in use and in International Caries Detection and Assessment System (2008). ICDAS Web
development for cells in this matrix; it is desirable that pro- site: www.icdas.org/ (accessed Feb 19, 2009).
Ismail AI, Sohn W, Tellez M, Amaya A, Sen A, Hasson H, et al. (2007). The
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