J Periodontol • August 2008 (Suppl.
Clinical Innovations in Managing
Inflammation and Periodontal Diseases:
The Workshop on Inflammation
and Periodontal Diseases
Robert J. Genco*
T
his summary will highlight the clinical impli-
cations of the Workshop on Inflammation and
Periodontal Diseases reported in this supple-
ment of the Journal of Periodontology. In selecting
clinical innovations, the objective criteria of present
or potential clinical utility have been applied, as well
as the context of these innovations in light of recent
and past literature. However, in any such endeavor,
there is likely to be unintentional selectivity based upon
judgment about future developments and relevance.
Clinical innovations will be discussed relative to a
timeline of implementation with three categories dis-
cussed: those that may be applied in the short term (1
to 2 years), medium term (5 to 10 years), and long
term (‡10 years). The medium-term innovations will
require further research and development, whereas
the long-term innovations will likely require extensive
translation of science and technology to apply them to
useful clinical practice. The risk/benefit ratios and
cost/benefit ratios will be important considerations
in final decisions to implement these innovations.
INNOVATIONS THAT APPEAR TO BE
READY FOR SHORT-TERM APPLICATION
(1 TO 2 YEARS)
1) Development and use of risk profiles for periodon-
tal disease and for diabetes that can be self-reported and
used in dental and medical practices (King, p. 1527).
2) Assessment of risk for future atherothrombotic
vascular events in dental patients, especially those
with periodontal disease using the traditional markers
of risk as well as C-reactive protein (CRP) in the Reyn-
olds Risk Score (Ridker and Silvertown, p. 1544).
3) Management of periodontal disease in patients
with diabetes and cardiovascular disease to improve
oral health as well as overall health (King, p. 1527).
4) Use of nutraceutical and drug combinations
such as omega-3 fatty acid and aspirin to control in-
flammation associated with periodontal infections
(Van Dyke, p. 1601).
* Department of Oral Biology, School of Dental Medicine, State University of
New York at Buffalo, Amherst, NY.
5) Use of inhibitors of matrix metalloproteinase
(MMP)-2, -8 and -9 for adjunctive management of
periodontal disease to assist in surgical and non-sur-
gical therapy (Giannobile, p. 1592).
INITIATIVES FOR APPLICATION IN THE
MEDIUM TERM (5 TO 10 YEARS)
1) Diagnosis of active bone loss by measuring the ra-
tio of receptor activator of nuclear factor-kappa B ligand
(RANKL)/osteoprotegerin (OPG) (Cochran, p. 1569).
2) Use of diet rich in omega-3-fatty acids to reduce
genetic predilection to metabolic syndrome; applica-
tion of nutragenomics (Ordovas and Shen, p. 1508).
3) Use of a new class of anti-inflammatory agents,
the endogenous resolvins and protectins. These mol-
ecules possess potent anti-inflammatory, proresolv-
ing, and anti-fibrotic activity to moderate excessive
inflammation in chronic diseases such as inflammatory
bowel disease and periodontitis (Serhan, p. 1520 and
Van Dyke, p. 1601). Resolvins will resolve inflamma-
tion by an active, well-orchestrated, agonist-mediated
return to tissue homeostasis (Van Dyke, p. 1601).
4) Use of tests for MMP-8 in saliva, and fragments of
bone collagen in tissue fluids for monitoring periodon-
tal disease (Giannobile, p. 1592).
5) Use of bone sparing agents such as bisphospho-
nates that inhibit osteoclast recruitment and limit
bone loss while minimizing osteonecrosis of the jaw
(Giannobile, p. 1592).
6) Use of statins and targeted anti-inflammatory
therapies in patients with periodontal disease to mod-
ulate inflammation and, hence, lower risk for sys-
temic conditions such as atherosclerosis (Ridker and
Silvertown, p. 1544).
7) New classification system for periodontal dis-
ease defining ‘‘disease resistant,’’ ‘‘disease aggressive,’’
and ‘‘treatment resistant subjects.’’ This will likely be
based on subgingival microbial composition, clinical
features, systemic risk factors such as diabetes and
smoking, inflammatory molecule profiles, and ge-
netic background including classic genetic features
doi: 10.1902/jop.2008.080305
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Summary of Workshop on Inflammation and Periodontal Disease Volume 79 • Number 8 (Suppl.)

based upon DNA sequences and epigenetic and mi- terest regarding the role of anti-inflammatory therapy
cro-RNA features (Offenbacher et al., p. 1577). in managing periodontal disease. It is well accepted
INITIATIVES FOR APPLICATION IN THE LONG that periodontal tissue destruction is a result of infec-
TERM ( >10 YEARS) tion with oral biofilm organisms, setting into motion a
wide variety of inflammatory reactions that result in
1) Regulation of RANK/RANKL/OPG axis to pre-
epithelial, connective tissue, and bony tissue destruc-
vent bone loss (Cochran, p. 1569).
tion. There are key questions that remain to be
2) Regulation of apoptosis to minimize bone loss
answered: What is the long-term effect of this inflam-
(Cochran, p. 1569).
matory response? Does it persist? Does it alter the tis-
3) Application of knowledge of dietary modulation
sue’s susceptibility to secondary infection, or is it
of genetic influence on phenotype in pathogenic path-
merely transient with no long-term effects on host sus-
ways, e.g., cholesterol levels and obesity, likely lead-
ceptibility and subsequent infection? There are at
ing to personalized genetic-based approaches for
least four possibilities:
prevention and treatment of cardiovascular diseases
1. The inflammation is self-perpetuating. Somehow
and other complex inflammatory disease such as peri-
the inflammatory response persists after an initiating
odontal disease (Ordovas and Shen, p. 1508).
event. This appears to be the case in many autoimmune
4) Determination of genetic risk profiles for periodon-
diseases where there is an adaptive or innate immune
tal disease based upon: a) genome-wide association
response to altered tissue antigens which perpetuates
studies of genetic changes encoded in DNA (SNPs, in-
the disease, even for a lifetime. So far, studies have
sertion, deletion, and inversions); and/or b) epigenetics
not found clear evidence for an autoimmune response
(changes in meiotic or mitotic inherited change in gene
in periodontal disease; however, antibodies to bacterial
expression not included in DNA itself). These epigenetic
antigens which cross-react with tissues have been
changes involve posttranslational methylation of DNA
found in patients who have periodontal disease. The
or modification of histone proteins in the chromatin.
role of these antibodies remains unclear.
They are influenced by environmental factors including
The inflammation may also be self-perpetuating
diet, infection and inflammation, aging, and other fac-
because of a persistent antigen, such as intracellular
tors (Wilson, p. 1514 and Offenbacher et al., p. 1577);
organisms, or an antigen that is not effectively re-
and/or c) based on micro-RNAs, the small non-coding
moved. Clearly, there is a persistence of the infecting
RNAs that regulate expression of many genes (Wilson,
agents and the antigens in untreated periodontal dis-
p. 1514).
ease; however, rigorous study of this is also needed.
5) Use of tests for genetic links between CRP or other
Why do the pathogens emerge and persist in some in-
inflammatory mediators, periodontal disease, diabetes,
dividuals, but others who harbor the same organisms
and premature atherothrombosis to assess risk for de-
seem to be resistant to pathogen emergence?
velopment of these conditions (Ridker and Silvertown,
If the inflammation were truly self-perpetuating,
p. 1544).
long-term anti-inflammatory therapy may be indi-
6) New understanding of periodontal disease where
cated. There is no evidence that this is the case
disease pathogenesis may be modeled by incorporating
because significant resolution of periodontal inflam-
gene, protein, and metabolite data into dynamic biologic
mation most often occurs after removing the causa-
networks. The key nodal points in these networks may
tive microflora, but recurrence of disease is high
be targets for disease management (Kornman, p. 1560).
unless there is regular control of the microflora, and
7) Vaccination with periodontal pathogens to pro-
not all gingivitis progresses to periodontitis. Is varia-
tect against periodontal infection. For example, vac-
tion in individual inflammatory response the key?
cination against periodontal pathogens such as
2. It is possible that inflammatory changes alter sus-
Porphyromonas gingivalis may protect against peri-
ceptibility of the periodontium to reinfection. That is,
odontal bone loss based on experiments in rats and
changes do not lead to persistence of an inflammatory
monkeys. Also, vaccines for dogs and cats are al-
response in the periodontium after removing the in-
ready on the market directed to canine and feline Por-
fectious insult but do alter susceptibility to reinfection.
phyromonas species including P. gulae.
The inflammation resulting from periodontal infection
8) Strategies to prevent uncoupling of bone depo-
changes the tissue in some way so that it is more sus-
sition and bone resorption, possibly by inhibiting tu-
ceptible to another bout of infection with oral biofilm.
mor necrosis factor-alpha (Graves, p. 1585).
The possibility raised in this symposium is that this oc-
THE ROLE OF ANTI-INFLAMMATORY curs through epigenetic changes in DNA or histones
THERAPY IN MANAGING PERIODONTAL by methylation. It is hypothesized that these changes
DISEASES: AN OVERARCHING THEME? then persist in the tissue and increase the susceptibility
In addition to the short-, medium-, and long-term ini- to reinfection (Offenbacher et al., p. 1577); in this in-
tiatives described above, there was an overarching in- stance, long-term tissue changes that might increase

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J Periodontol • August 2008 (Suppl.)
susceptibility to reinfection but directly do not cause in-
flammation. If this were the case, an approach to ther-
apy would be to not only remove the infection but also
to treat the tissue somehow to mitigate, modulate, or
eliminate the posttranscriptionally altered DNA and
histones resulting from epigenetic changes.
3. It is possible that inflammation is transient and ex-
ists only during active periodontal infection. Once this
infection is resolved, the tissue goes back to the original
state of homeostasis. In this case, the inflammation is
not perpetuated and is not long lasting, and the tissue
shows no increased susceptibility to reinfection. The
therapeutic approach would be to remove the infecting
organism and prevent their recurrence. Anti-inflamma-
tory agents may assist in the initial resolution of inflam-
mation but may not be essential for long-term therapy
or prevention of recurrence of periodontal disease.
4. It is possible that the individual inflammatory re-
sponse is genetically programmed to be hyperreac-
tive or resolution deficient. The initial inflammatory
response to the biofilm sets up the environment for
overgrowth of pathogens and development of peri-
odontitis. This would require long-term therapeutic
management of the inflammatory response, either
continuous or intermittent.
Based on present evidence, a strong case can be
made for the third and perhaps the fourth possibility,
Genco
i.e., resolution of inflammation after effective removal
of the periodontal infection. However, it remains to be
investigated to what extent prior periodontal disease
increases the susceptibility of the host to subsequent
bouts of infection and whether, once diseased, it is
possible to restore tissue homeostasis. There is ample
evidence that the anatomic changes resulting from
periodontal disease, such as residual periodontal
pockets and angular bony defects, predispose individ-
uals to further periodontal infection and destruction.
The old adage is still extant: the best predictor of future
periodontal breakdown is past periodontal breakdown.
The conference speakers, moderators, and those in
the audience who asked critical questions challenged
our thinking on the role of inflammation in periodontal
diseases and those systemic conditions linked to
periodontal disease. From this constructive confron-
tation comes new insight into these complex relation-
ships and hopefully innovations that will benefit our
patients.
Correspondence: Dr. Robert J. Genco, School of Dental
Medicine, State University of New York at Buffalo, Baird
Research Park, 1576 Sweet Home Rd., Suite 103, Amherst,
NY 14228. Fax: 716/636-5921; e-mail: rjgenco@buffalo.edu.
Submitted June 4, 2008; accepted for publication June 19,
2008.
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