Advanceshttp://adr.sagepub.

com/
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

The online version of this article can be found at:

http://adr.sagepub.com/content/21/1/83

Published by:

http://www.sagepublications.com

On behalf of:
International and American Associations for Dental Research

Additional services and information for Advances in Dental Research can be found at:

Email Alerts: http://adr.sagepub.com/cgi/alerts

Subscriptions: http://adr.sagepub.com/subscriptions

Reprints: http://www.sagepub.com/journalsReprints.nav

Permissions: http://www.sagepub.com/journalsPermissions.nav

>> Version of Record - Aug 7, 2009

What is This?

Downloaded from adr.sagepub.com by guest on December 10, 2011 For personal use only. No other uses without permission.

Copyright 2009 by the International Association for Dental Research

 Remineralization/Desensitization:
What Is Known? What Is the Future?
N.B. Pitts1*,2, J.S. Wefel3,4
1
Centre for Clinical Innovations and 2Dental Health Services Research
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,
University of Iowa, Iowa City, USA; *corresponding author, n.b.pitts@
chs.dundee.ac.uk
Adv Dent Res 21:83-86, August, 2009
T he aim of this paper was to distill recommendations from
existing evidence and material on dental caries remineraliza-
tion/desensitization discussed at the ICNARA meeting within
the context of “modern” clinical management of the caries pro-
cess, aiming to prevent progression by promoting arrest and,
where possible, regression of pre-cavitation lesions. Since much
of the evidence reviewed has been published but not adopted for
decades, programs for more effective dissemination and imple-
mentation of research findings with educators, clinicians, and
patients are required. The broadly agreed research agenda rec-
ognized that the aim of remineralization therapy is to facilitate
caries control over a lifetime, using evidence-based, clinically
effective, multi-factorial prevention to keep the caries process
in balance. Over the coming years, the dental research commu-
nity in this field should continue to apply new knowledge and
methods from outside dentistry and develop a menu of caries
control strategies effective for individuals, groups, and popula-
tions using agreed, comparable protocols.
Introduction
The aim of this paper was to distill from the presentations and
discussions on caries remineralization and desensitization at the
International Conference on Novel Anti-Caries and Remineralizing
Agents (ICNARA) meeting and the existing evidence: What is
known now? What is the future? The purpose was to build a syn-
thesis and outline what the future research and development
agendas for the next 10 years should look like.
As an aid to structuring the discussions, the graphical structure
of the Collaboration for Improving Dentistry framework (Dental
Health Services Research Unit, 2007) was used (Fig. 1) to cover
all stages of the knowledge management process. This structure
links key elements which pertain to understanding and advancing
DOI: 10.1177/0895937409335644
Downloaded from adr.sagepub.com by guest on December 10, 2011 For personal use only. No other uses without permission.
Copyright 2009 by the International Association for Dental Research
research around the remineralization of dental caries. Although
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-
tine clinical practice in many (but not all) countries.
Synthesis and Discussion
Topics from the initial full panel session deemed important by
the meeting discussants included:
• the existence of several other novel remineralization
approaches not presented at the meeting, such as the use of
biomimetics and self-assembly proteins;
• the importance in clinical remineralization of assessing lesion
activity (determining the current state of a lesion at one spe-
cific point in time) as a complement to detecting lesions and
monitoring lesion behavior over time;
• the continuing need to explore and review technologies
developed outside of dentistry;
• the need to articulate a range of clinical goals for caries con-
trol appropriate for different groups with a range of caries
challenges; and
• the need to re-assess current guidelines for the types and num-
bers of clinical trials required for a product to be accepted by
various agencies and organizations, since these guidelines
were developed for agents assessed with frank carious cavita-
tion as an end-point, according to classic visuo-tactile criteria,
as opposed to remineralization seeking to achieve an end-
point prior to frank cavitation.
Issues from the Remineralization/
Desensitization Group Papers
It was believed (Featherstone, 2009) that there is a need in the
future for more in-depth understanding about the amount of car-
ies present in individuals and populations who need care. In the
future, this should be broken down by the stages of caries pres-
ent (at agreed detection thresholds) as well as, ideally, by the
level of activity of the caries.
The research community and all stakeholders should strive to
ensure that, in 20 years’ time, we are not re-stating the same
Key Words
Dental caries, remineralization, desensitization, activity, lesion behavior.
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.
83
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.

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

Downloaded from adr.sagepub.com by guest on December 10, 2011 For personal use only. No other uses without permission.

Copyright 2009 by the International Association for Dental Research

Adv Dent Res 21: 2009 Remineralization/Desensitization: What is Known?   85
fluoride to see if synergies can be achieved; further validation of
methods and models for remineralization studies; knowing more
about the natural history of initial caries in different age groups;
understanding more about the hierarchy of preventive interven-
tions as more non-fluoride remineralization research is done;
and ascertaining more about the long-term impact of the remin-
eralization effects on individual lesions followed up over years.
Consideration of the “Novamin” papers (Burwell et al.,
2009; Wefel, 2009) revealed an interesting technology with a
history of other uses, but at an early stage of development in the
caries remineralization application. This example exemplifies
the useful work in this area to evaluate materials developed
primarily for use elsewhere, making a transition from uses in
sensitivity to explorations of caries remineralization.
It was believed that the research community needs to con-
struct separate research agendas for dentin and enamel reminer-
alization and avoid confusion between the two. The future
direction should be to optimize interactions with fluoride where
possible, and the need to have standardized assessment methods
and clinical trial designs was highlighted, as they have been
previously at the International Consensus Workshop for Caries
Clinical Trials: ICW-CCT (Pitts and Stamm, 2004) and the
Indiana Caries Conferences.
Consideration of the “xylitol” papers (Milgrom et al., 2009;
Twetman, 2009) raised a range of important issues. There is a
need to better understand the validity of surrogate markers and
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
poor-quality evidence in the literature mean that new, carefully
conducted, modern-design studies are required in the most
promising areas.
Data were presented where the results of the same trial were
analyzed with two caries cut-offs producing two different results.
This served to reinforce the need to standardize the diagnostic
thresholds used in caries examinations to combat the danger of
confusion among some stakeholders. Consensus has already
been reached on these issues (Pitts and Stamm, 2004), and stan-
dardized open systems (ICDAS, 2008) are now available.
The research agenda for the future should also include con-
siderations of economic and cost-effectiveness issues. In the
future, this analysis must be based on a full understanding of the
disease process and long-term health. There is also a clear need
for Randomized Controlled Trials to be conducted and reported
to CONSORT standards.
Discussion session 2
A very powerful observation was made that the traditional mea-
sure of caries, the simple dmf/DMF index, has now “had its day
in research in this area”, and there is a need in the future for the
use of carefully applied and validated new technologies. A fur-
ther key point for the future research agenda is that lesion arrest
is a good outcome—treatments and products should be aiming
to either arrest or reverse a lesion, and both outcomes are good
clinically. The point was also made strongly that remineraliza-
tion, which has been shown to be possible when objectively
monitored in vivo, is a very desirable way of controlling the car-
ies process in the future.
Downloaded from adr.sagepub.com by guest on December 10, 2011 For personal use only. No other uses without permission.
Copyright 2009 by the International Association for Dental Research
Reviews of the Current Evidence
As documented clearly elsewhere (National Institutes of Health,
2001), a review of many areas of study reveals that the quality
of previously published work in this field is highly variable,
with some studies appearing methodologically poor when
judged by contemporary quality standards.
It was acknowledged that there is a need for:
• further, unbiased, systematic reviews in the key and promising
areas (increasingly essential for many stakeholders);
• systematic reviews to be updated and maintained (this work
needs to be funded);
• recognition that remineralization is a natural repair process in
cariology;
• dissemination more widely of authoritative reviews on the
caries process, lesion behaviour, and the desirability/possi-
bility to stop lesion progression and to promote long-term
remineralization of lesions;
• finding strategies for dealing with and managing the growing
amount of information and misinformation on remineraliza-
tion that is already on the World Wide Web; and
• better understanding of the reasons for the failure of both
dissemination and implementation of the current knowledge
base in this area and the impact of equitable remuneration for
delivering clinical prevention (National Institutes of Health,
2001).
What Is Known Now?
The following were broadly agreed:
• It is important to differentiate between remineralization of a
caries lesion that has previously been demineralized, as
opposed to precipitation of mineral onto a surface that has
not been previously demineralized.
• The aim of remineralization therapies in caries management
for enamel lesions is to:
— do no harm, but achieve a health benefit.
— put mineral back into a lesion, ideally penetrating to the
subsurface areas of the lesion, as well as the surface, and
— ideally, achieve an area more resistant to subsequent car-
ies attack than the original tissue
To slow lesion progression, promote lesion arrest, and,
ideally, achieve lesion regression.
• Other forms of precipitation/mineralization on surfaces have
clinical applications in the management of sensitivity and
erosion, but should be considered separately.
• There is a range of clinical applications and outcomes, and it
is unlikely that one research design or one product will be
optimal for all situations.
• The clinical outcomes relevant to the research agenda in this
field for the next 10 years can be considered as a matrix
including enamel caries, dentin caries, root-surface caries,
orthodontic treatment-related caries; this framework has an
overlap with the related, but separate, areas of erosion and
sensitivity research.
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

g
and Disclaimer
bo

of Clinical under-graduate
lla

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
tocols be developed for each type of application.
International Caries Detection and Assessment System (ICDAS): an
integrated system for measuring dental caries. Community Dent Oral
Epidemiol 35:170-178.
What Is the Future? Lussi A (2009). Dental erosion—novel remineralizing agents in prevention
or repair. Adv Dent Res 21:13-16.
The following were broadly agreed: Milgrom P, Ly KA, Rothen M (2009). Xylitol and its vehicles for public
health needs. Adv Dent Res 21:44-47.
• The aim of remineralization therapy is to facilitate caries control National Institutes of Health (2001). The diagnosis and management of
over a lifetime using evidence-based, clinically effective, multi- dental caries throughout life. National Institutes of Health Consensus
Development Conference, Washington, DC, March 26th-28th, 2001.
factorial prevention to keep the caries process in balance. J Dent Educ 65:1162-1168.
• A menu of caries control strategies/methods/products, which Pitts NB, Stamm J (2004). International Consensus Workshop on Caries
are effective for individuals, subgroups, and populations, is Clinical Trials: ICW-CCT Statements. J Dent Res 83(Spec Iss C):
needed. C125-C128.
• A corresponding menu of standardized, agreed, comparable Reynolds EC (2009). Cacein phosphopeptide-amorphous calcium phos-
phate: the scientific evidence. Adv Dent Res 21:25-29.
protocols is also needed to allow for meaningful comparisons ten Cate JM (2009). The need for antibacterial approaches to improve caries
across studies. control. Adv Dent Res 21:8-12.
• Over the coming years, the dental research community in this Twetman S (2009). Current controversies—Is there merit? Adv Dent Res
field should continue to apply new knowledge and methods 21:48-52.
Wefel JS (2009). NovaMin®: likely clinical successes. Adv Dent Res 21:40-43.
from outside dentistry.
Wolff MS (2009). Dentin hypersensitivity, the biofilm, and remineralization:
what is the connection? Adv Dent Res 21:21-24.
The key elements of the Future Agenda which were agreed Zero DT (2009). Recaldent™—evidence for clinical activity. Adv Dent Res
appear at the macro-level in Fig. 2. This includes important and 21:30-34.

Downloaded from adr.sagepub.com by guest on December 10, 2011 For personal use only. No other uses without permission.

Copyright 2009 by the International Association for Dental Research