Periodontology 2000, Vol. 75, 2017, 723 2017 John Wiley & Sons A/S.
iley & Sons A/S. Published by John Wiley & Sons Ltd
Printed in Singapore. All rights reserved
Periodontitis: facts, fallacies and
the future
JRGEN SLOTS
The history of periodontology includes both progress
and detours, and a wide range of concepts regarding
periodontitis pathobiology and treatment. Periodon-
tology 2000 celebrates its 25th anniversary this year,
and the present volume uses the occasion to review
important developments in periodontology over the
past quarter-century. Renowned researchers and clin-
icians are assessing the current state of periodontol-
ogy and the challenges that remain.
Periodontitis etiopathogenesis
Periodontitis is a complex infectious disease with sev-
eral etiologic and contributory factors (146). The dis-
ease may begin in childhood or adolescence (26, 232)
but usually debuts in early adulthood (13, 103) and
occasionally in later years (131). Patients with peri-
odontitis reveal typically one or more risk factors for
the disease (70, 71, 112, 183), but individuals with
vastly different disease severity can show identical
risk factors. Some patients with severe disease, such
as localized aggressive (juvenile) periodontitis,
demonstrate none of the classical risk factors (7).
Aggregatibacter actinomycetemcomitans and Porphy-
romonas gingivalis are important pathogens of
aggressive periodontitis (40, 147, 235), but low levels
of the species can also inhabit disease-stable sites (28,
191). Periodontitis affects select teeth or tooth sur-
faces, and rarely the entire dentition, and may
approach the apex of one tooth while barely involving
a neighboring tooth sharing the same interdental
space. The site-specicity of periodontal breakdown
cannot be explained by mere dental plaque accumu-
lation, and not even by bacterial specicity or
immunopathology taken in isolation, but possibly by
a combined herpesvirusbacterial infection (205,
217). Disease-active periodontitis contains high loads
of reactivated herpesviruses (126, 191, 201, 237)
(Fig. 1), whereas chronic/quiescent periodontitis
PERIODONTOLOGY 2000
tends to be associated with latent herpesviruses (27)
and with high-titer cytomegalovirus IgG serum anti-
body (9, 125). An active herpesvirus infection may
induce immunosuppression and bacterial over-
growth, and potentially convert gingivitis to peri-
odontitis or stable periodontitis to progressive disease
(204, 214). In that scenario, herpesviruses are initia-
tors of periodontitis, analogous to an HIV infection
inducing oral candidiasis.
Herpesvirus-related periodontitis and classical her-
pesvirus infections, such as herpes labialis, may share
pathogenic characteristics, and that notion may help
to clarify the pathogenesis of destructive periodontal
disease. Herpes labialis occurs with a primary out-
break followed by a period of clinical health inter-
rupted by relapses, which decrease in frequency and
severity over time. Periodontitis tends to demonstrate
a similar pattern of disease activity with marked ini-
tial breakdown followed by a lengthy period of dis-
ease stability, which may be interrupted by one or
more relapses of reduced severity (72, 77, 226). Simi-
larly to the pathogenesis of herpes labialis, active
(aggressive) and non-progressive (chronic) periodon-
titis may basically be one and the same disease,
which exhibits relatively short episodes of exacerba-
tion and prolonged periods of remission, depending
on the intrinsic virulence of the herpesvirus infection
and the prevailing effectiveness of the anti-herpes-
virus host defense. Like other herpesvirus infections,
periodontal disease progression may recrudesce fol-
lowing immunosuppressive events or new infections
with immunologically unrelated herpesviruses. In
contrast to the clinical course of herpes labialis, peri-
odontitis-inactive sites exhibit continuing inamma-
tion, which, however, is attributable merely to the
presence of persistent subgingival bacteria. Disease-
stable periodontitis in that context basically com-
prises gingivitis in deep periodontal pockets. Also, the
term periodontitis refers literally to disease of all
four periodontal tissues, but nonprogressive disease
7
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Fig. 1. Viral particles in a subgingival sample of severe periodontitis (Sybr Gold nucleic acid stain; Life Technologies, Carls-
bad, CA, USA).
in deep pockets actively involves only gingiva and
may be labeled more appropriately as gingivitis.
Periodontal diagnostics and
classication
Periodontics is challenged with the question of
whether periodontitis is underdiagnosed, overdiag-
nosed, both or neither. The answer is usually both
but mostly overdiagnosis (161). The diagnosis of peri-
odontitis refers to pathologic loss of periodontal liga-
ment and alveolar bone. Aggressive periodontitis is
assigned to young individuals with evidence of recent
periodontal breakdown, but the current state of dis-
ease-activity and the timespan and pathophysiology
between the biological start and the initial clinical
signs of the disease are unknown. Chronic periodon-
titis is a general diagnosis for adult types of the dis-
ease, which may not progress for 56 years in 85% of
patients, even after only one-time scaling (180) or no
treatment at all (128). Also, the terms of aggressive
and chronic convey virtually no information on
specic etiologies or risk factors that may guide
preventive and curative therapies. Disease-stable
and disease-active periodontitis/peri-implantitis dif-
fer in virology (27, 100, 127), bacteriology (213) and
immunology (178), and also differ in clinical variables,
such as radiographic crestal lamina dura (176) and
pocket temperature (179, 239). These disease features
may help to identify stable but not progressive
periodontitis. The inability of current periodontal
variables to provide high-condence information on
present or future disease progression may result
in diagnostic misjudgment and overtreatment or
undertreatment. Rapid and cost-effective methods to
predict active periodontitis in clinical practice remain
an important research topic.
8
Periodontal classication undergoes periodic
updates to accommodate the changing views of
destructive periodontal disease. In this volume of Peri-
odontology 2000, van der Velden (239) provides a com-
prehensive overview of the history of periodontal
disease classication, and suggests bacterial invasion
of gingiva and elevated pocket temperature to be
important features of disease-active periodontitis. The
gingival invasion of bacterial pathogens may occur as
a sequel to herpesvirus-induced immunosuppression
(212). Past periodontal classications were based
almost exclusively on clinical characteristics and
offered high user-reproducibility (238) but very lim-
ited therapeutic guidance and little evidence of actu-
ally having helped to improve periodontal care or
clinical research. A classication system centered on
prognosis and treatment would incorporate etiology,
disease activity and degree of tissue damage (211) and
possibly include, as suggested by Papapanou & Susin
(161), variables capturing impaired function, esthetics
and impact on general health and quality of life.
Periodontal epidemiology
The prevalence estimate of periodontitis depends on
the case denition of periodontitis, the study popula-
tion and the method of screening for the disease (89).
Three US national surveys [the United States National
Health and Nutrition Examination Survey (NHANES)]
of adults from the past 25 years differ in study design
and in prevalence estimates of periodontitis (8, 54,
58). The 19881994 (8) and the 19992004 (54)
NHANES assessed periodontal disease at mesiofacial
and mid-facial sites of each fully erupted tooth,
excluding third molars, in one randomly selected
maxillary and mandibular quadrant, and found peri-
odontitis (clinical attachment loss 3 mm) to have a

population frequency of, respectively, 53.1% and
43.6%. Partial-mouth protocols underestimate the
prevalence of periodontitis (5, 6, 59), but well-selected
index teeth and tooth surfaces can minimize the inac-
curacy (109). The 2009-2012 NHANES examined six
sites per tooth of all teeth except for third molars and
identied clinical attachment loss of 3 mm in 37.4%
of all teeth, a probing pocket depth of 4 mm in
10.6% of all teeth and severe periodontitis in 8.9% of
US adults (58). Periodontitis occurred with particu-
larly high prevalence in low-income and older indi-
viduals (54, 60), and in Hispanic and non-Hispanic
Black populations (58).
A 2003 survey of 20- to 80-year-old Swedish individ-
uals found that 28% showed less than one-third bone
loss around most teeth (mild periodontitis), 11% had
more severe alveolar bone loss, 18% exhibited wide-
spread gingival bleeding on probing but normal bone
height and 44% were periodontally healthy with mini-
mal bleeding on probing (91). Studies in Germany
showed periodontitis, dened as clinical attachment
loss of 3 mm, to occur in 95.0% of adults and in
99.2% of seniors (90), and severe periodontitis to
occur in 16.948.0% of adults and seniors, depending
on the case denition (251). The average worldwide
prevalence of severe periodontitis has been estimated
to be 11%, including countries with relatively little
emphasis on periodontal health care (135). Some
countries in Africa show similarities in periodontal
pocket depth and attachment loss, and even a greater
retention of teeth, compared with countries in Eur-
ope and North America (14, 168).
Periodontal treatment needs for population-based
decisions is unclear because of uncertainty over the
prevalence of periodontitis and the risk of disease
progression. A one-time assessment of clinical attach-
ment loss and probing pocket depth overestimates
basic treatment needs, as an unknown percentage of
patients with periodontitis, in the absence of screen-
ing and subsequent treatment, would not experience
uncomfortable tooth mobility or tooth loss during a
normal lifetime. The periodontitis-active age peaks at
38 years (121, 161), and individuals in middle adult-
hood tend to encounter relatively little disease pro-
gression despite lack of thorough oral hygiene (58,
131, 167, 181). A signicant percentage of especially
older individuals may not either seek or want profes-
sional periodontal care (236). Furthermore, treatment
is less complex with localized periodontitis than with
generalized periodontitis, with mild and moderate
periodontitis than with advanced periodontitis, with
nonfurcation-involved teeth than with furcation-
involved teeth, and with missing molars being the
Review of periodontitis
most disease-prone teeth of the dentition (88, 129).
Health-care system strategies for periodontal disease
would need to consider the disease characteristics as
well as low-cost, high-impact types of therapy.
The struggle between periodontal
microbes and immunity
The early concept of a straight-line progression from
gingivitis or pulpitis to marginal and apical periodon-
titis implies a relatively simple pathophysiological
process of disease development. This notion has been
replaced by a highly complex understanding of the
etiopathogenesis of periodontal diseases (205, 212).
In this volume of Periodontology 2000, Ebersole et al.
(55) provide an extensive and highly informative over-
view of the encounter between virulence factors of
periodontal pathogens and tightly regulated immune
responses, which collectively contribute to the func-
tioning of the periodontal ecosystem. Periodontal
immunity includes overlapping innate and adaptive
cellular and humoral responses (5, 5557), which,
together with indigenous oral microbes (185), aim at
controlling invading pathogens. In turn, periodonto-
pathic bacteria (78, 215) and herpesviruses in mar-
ginal periodontitis (recent publications: 3, 15, 69, 85,
98, 104, 106, 108, 132, 139, 150, 163, 199, 212, 250, 253)
and apical periodontitis (recent publications: 84, 94,
95, 134, 157, 158, 172, 242, 247) elaborate a variety of
defense mechanisms to circumvent or disrupt protec-
tive host immune reactions (39, 212).
Dysregulation of the innate and adaptive immune
systems may play an important role in the etiology of
periodontal disease (55). Briey, the initiation of peri-
odontitis involves attachment of bacterial antigens
and viral DNA/RNA and peptides to toll-like pattern-
recognition receptors on immune cells. Toll-like
receptors activate signaling transduction pathways,
which launch immune and inammatory responses
to eliminate invading pathogens. Nuclear factor-kap-
paB is a particularly important transduction pathway
that regulates proliferation and differentiation of
macrophages and lymphocytes, and its aberrant acti-
vation, potentially induced by herpesviruses (31),
may trigger chronic inammation and autoimmunity.
Activated lymphocytes differentiate into a number of
subtypes, including cytotoxic T-cells (which recognize
and destroy herpesvirus-infected cells) and T-helper-
2 cells (which communicate with and cause B-cells to
proliferate, differentiate and synthesize antibodies
against pathogenic antigens). However, besides com-
batting pathogens, the inammatory response, and
9
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especially long-standing inammation in older indi-
viduals, may induce T- or B-cell dysregulation, DNA
damage, cellular senescence and oxidative stress,
potentially causing immunodeciency and oppor-
tunistic infections. Prolonged gingival inammation
also promotes the ingress of herpesviruses, which are
imbedded in macrophages, T- and B-cells and poly-
morphonuclear leukocytes (42, 186), and activation of
the herpesviruses can produce direct cytopathogenic
effects and immunopathology (212). To control and
counteract host-destructive immune reactions, regu-
latory T-cells and noncoding RNA regulation seek to
restrain or abrogate excessive inammation, T- and
B-cell activation, autoimmunity and immunopathol-
ogy (107). Cytomegalovirus encodes microRNAs to
prevent the vigorous immune response from cytome-
galovirus reactivation, thereby prolonging virus
latency and viral persistence (65).
In 1976, Page & Schroeder (159) outlined the
histopathology of periodontal disease development,
and Hajishengallis & Korostoff (79), in this volume of
Periodontology 2000, present the current concept of
induction, regulation and effector functions of peri-
odontal immune/inammatory responses, including
cytokines. Cytokines regulate interactions and cellular
networks among macrophages, natural killer cells,
neutrophils, T-cells, B-cells, broblasts, epithelial cells
and other cell types (118). Proinammatory cytokines
(e.g. interferon-gamma, interleukin-17 and tumor
necrosis factor) activate M1 (killer) macrophages in
the immune defense against infectious agents, but
prolonged release or overproduction of proinamma-
tory cytokines may also activate osteoclasts (cells of
the monocyte/macrophage lineage) and matrix met-
alloproteinases (collagenases). Anti-inammatory
cytokines (e.g. interleukin-4, interleukin-10 and inter-
leukin-13) promote activation of macrophages into
M2 (repair) cells and participate in B-cell matura-
tion, proliferation and isotype switching, and thus in
antibody production and control of periodontopathic
bacteria. Transforming growth factor-beta regulates
immune function and cell proliferation (deactivates
macrophages) and is involved in cell adhesion, apop-
totic regulation and wound healing, as well as in
developmental processes. The increased knowledge
on molecular interactions among innate and adaptive
leukocytes, and among the immune system and local
regulatory mechanisms, has provided important
insights into the pathogenesis of periodontitis and
suggested new types of therapy.
Treatment of severe periodontitis may not always
ensure disease resolution (19, 211), and immunother-
apy may serve as an adjunct or alternative to traditional
10
therapy (173). Hyperactive, as well as insufcient,
immune responses are parts of the complex etiopathol-
ogy of periodontitis (212) and may constitute potential
therapeutic targets (35, 248). Immunopharmaceutical
agents can be used to suppress overloads of proinam-
matory cytokines (82) or to suppress hyper-responsive
and poorly regulated polymorphonuclear neutrophils
(87, 153). Low-dose interleukin-2 (110), anti-tumor
necrosis factor-alpha (173) and adoptive T-cell
immunotherapy (34) have the potential to modulate
dysregulated immunity in autoimmune and inamma-
tory diseases. Bartold & Van Dyke (19), in this volume
of Periodontology 2000, describe opportunities for
immunotherapy in the management of periodontal
disease. Their concept is that the inammatory
response modies the subgingival microenvironment
to change from a commensal to a pathogenic micro-
biota, and that a pharmacotherapeutic suppression of
the inammatory process can control periodontal
infections. For example, herpesvirus infections trigger
the release of an abundance of proinammatory
cytokines, which suppress anti-inammatory cytokines
and facilitate up-growth of periodontopathic bacteria
(207, 214). Interventional immunology may help to
treat atypical types of periodontal disease, but long-
term immunosuppressive therapy of chronic periodon-
titis seems problematic (173, 189). It is unknown
whether immunomodulation therapy can reduce
destructive host responses without compromising pro-
tective immunity in a combined periodontal infection
of herpesviruses (controlled by proinammatory
cytokines/cytotoxic T-cells) and bacteria (controlled by
anti-inammatory cytokines/antibodies).
Periodontal causative therapy
Periodontitis has an excellent prognosis if intercepted
early but can cause severe damage to the dentition
with delay in therapy. However, most of our knowl-
edge on therapeutic effectiveness pertains to chronic
periodontitis and not necessarily to disease-active
periodontitis. In any case, all types of inammatory
periodontal disease may need to be controlled in
order to prevent colonization and propagation of her-
pesviruses and bacterial pathogens.
Ramfjord et al. (175), in a classic study, compared
four types of conventional (mechanical) periodontal
therapy and found similar clinical outcome, but 18%
of the treated deep-pocket sites experienced addi-
tional breakdown, a rate of disease progression equiv-
alent to that of untreated periodontitis (128). The
ndings of Ramfjord et al. (175) question the efcacy

of pure mechanical surgical and nonsurgical peri-
odontal therapy. Deas et al. (50) recently outlined
guidelines for treatment of chronic periodontitis.
Mild-to-moderate periodontitis is best managed by
nonsurgical therapy and instruction in effective self-
care. Nonsurgical therapy employs ultrasonic scalers
or hand instruments and adjunctive antimicrobial
agents to eliminate dental calculus and subgingival
biolms (116). Sodium hypochlorite, povidone-iodine
and chlorhexidine (184, 246), and properly selected
systemic antibiotics (62), can decrease the numbers
of periodontal pathogens to levels below those found
in disease-active periodontitis (28, 116, 213). Sodium
hypochlorite oral rinse is particularly efcient in
reducing gingival and postoperative bleeding (29, 73).
Severe types of periodontitis are traditionally man-
aged surgically, but the value of periodontal surgery is
generally overestimated. Even if surgical treatment of
deep periodontal lesions might yield more gain of
clinical attachment than nonsurgical therapy (83), the
difference seems too small (and is probably nonexis-
tent after employing antimicrobial agents) to justify
the higher cost and discomfort of surgery. Moreover,
in accordance with a modern concept of best-practice
dental care, an alleged superior outcome of periodon-
tal surgery needs to be demonstrated in well-
designed randomized controlled trials, not only in
observational studies or in other forms of minimally
controlled research. In this volume of Periodontology
2000, Graziani and colleagues (75) review various sur-
gical and nonsurgical periodontal treatments and
offer a wealth of valuable insights. They conclude that
current treatments yield essentially similar outcome
and that systemic antibiotics can help arrest aggres-
sive/disease-active periodontitis (75).
Laser treatment has been promoted as a supple-
ment or substitute to conventional periodontal ther-
apy. The neodymium-doped yttrium aluminium
garnet (Nd:YAG) laser has shown efcacy against
periodontopathic bacteria (115) and subgingival her-
pesviruses (136), but the utility of laser treatment ver-
sus other types of periodontal therapy remains
unresolved (10, 149, 164). In this volume of Periodon-
tology 2000, Cobb (37) provides a comprehensive nar-
rative review of 118 human studies on laser treatment
of periodontitis. Most studies were found to suffer
from design weaknesses and were underpowered sta-
tistically, thus precluding a denite conclusion on the
utility of periodontal lasers. At any rate, the average
clinical improvement reported from laser treatment
seems too small to be of clinical signicance (37).
Large, well-executed randomized controlled trials
with adequate description of study design, methods
Review of periodontitis
and results are needed to clarify the potential role of
lasers in periodontal treatment (37, 149).
Periodontal plastic therapy
Periodontists are performing an increasing number of
plastic surgery treatments around teeth and implants
to correct anatomic, developmental, traumatic or dis-
ease-induced defects of gingiva, mucosa and bone
(148, 255). Periodontal plastic surgery is carried out
for cosmetic reasons, to assist with prosthetic treat-
ment, to obtain keratinized tissue around teeth, to
treat dentin hypersensitivity and to prevent root-sur-
face caries (20, 32, 144, 197, 254). Plastic surgery is
also used to eliminate excessive gingival display
caused by altered passive eruption, drug-induced gin-
gival enlargement, a high lip line or vertical maxillary
overdevelopment (97, 143). Traditional periodontal
resective surgery, by contrast, results in exposed root
surfaces with risk of poor esthetics and root-surface
caries. However, the premise and promise of peri-
odontal plastic therapy are still evolving, and different
preferences among dentists for resective therapy vs.
reparative therapy can create confusion. One dentist
may treat periodontitis with apically positioned ap
surgery, only to have another dentist proposing gingi-
val grafting to cover the exposed root surfaces. Peri-
odontal therapy has also evolved from accepting a
moderate retraction of interdental gingiva to facilitate
interdental cleaning, to attempting a challenging
restoration of lost papillae (80).
Infections can severely compromise periodontal-
regenerative therapy. Guided tissue regeneration
therapy to produce new periodontal attachment (i.e.
restoration of the normal architecture of cementum,
alveolar bone and periodontal ligament), rather than
long junctional epithelial attachment, has been bur-
dened with unpredictable results (44, 231), but sup-
pression of periodontal herpesviruses (190, 230) and
P. gingivalis (222) can signicantly improve the out-
come of mucogingival therapy (21, 86, 169, 224). Vala-
cyclovir is effective in management of periodontal
herpesvirus infections (230), and application of 0.1%
sodium hypochlorite for 10 minutes to a periodontal
surgical wound may help to promote new attachment
formation (166).
In this volume of Periodontology 2000, Cairo (32)
reviews predisposing factors for gingival recession and
provides valuable guidelines for gingival grafting of
recessions around single and multiple teeth. Gingival
grafting, in addition to esthetic improvement, may pre-
vent further progression of gingival recession (32, 187,
11
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254). Cairo (32) evaluates the use of coronally advanced
ap, laterally sliding ap, free gingival graft, tunnel
grafting technique, barrier membranes, enamel matrix
derivative, collagen matrix and acellular dermal matrix,
and concludes that the most complete root coverage is
achieved by using a coronally advanced ap with an
underlying connective tissue graft. Greater insights into
the cellular and molecular biology of periodontal
wound healing (12, 188, 196, 198, 225), and rapid pro-
gress in tissue engineering, biofabrication and three-
dimensional bioprinting (162), may further advance
periodontal plastic therapy.
Dental implant treatment
Implant treatment to replace severely diseased or
missing teeth is an important part of dentistry (30,
174, 223) and can be successful also in elderly
patients (18, 194). Molars are the teeth most affected
by periodontitis and caries, and are most frequently
missing (88). Implant placement in the maxillary pos-
terior region may require horizontal and vertical alve-
olar ridge augmentation and/or sinus oor elevation
to build support for the implant xture (170). Implant
placement in mandibular molar sites carries risks of
severe hemorrhage and injury to the inferior alveolar
nerve (92). In sites with limited bone volume, short
(154) or narrow (111) implants and computer-assisted
surgery (52, 240) may help alleviate surgical trauma
and morbidity (194). Peri-implantitis is another com-
plication that affects disproportionately more smok-
ers and individuals with poor oral hygiene (48, 223).
Peri-implantitis and periodontitis show similar infec-
tious agents (212, 241, 242) but treatment of peri-
implantitis has a lower success rate (63, 182), proba-
bly because implants lack the host defenses provided
by the blood supply of the periodontal ligament (211).
Furthermore, effective long-term supportive care
commands a cost three- to ve times higher per unit
implant than per unit natural tooth (140). Risk of
adverse surgical events, peri-implantitis and high cost
of implant therapy may lead patients with unsalvage-
able or missing molars to choose traditional
prosthodontic therapy or accept an empty space in
the molar region, which still can provide acceptable
functionality and esthetics according to the concept
of the shortened dental arch therapy (105). A miss-
ing molar is generally not a major patient concern,
but treatment is encouraged by implant manufactur-
ers and dental professionals. Overuse of dental
implants is not just unnecessary and wasteful but, as
described above, also potentially harmful. However,
12
implant placement in the molar area may be indi-
cated in the case of anterior bite collapse and tem-
poromandibular dysfunction or with unopposed
(maxillary) molars at risk of super-erupting and caus-
ing a locked bite. Complex implant cases can benet
from a multidisciplinary approach to planning and
treatment (133).
Patient self-care
Patient self-care seeks to remove dental biolms in
order to maintain periodontal health and reduce the
need for professional intervention. However, current
methods of biolm removal are cumbersome, largely
ineffective and have essentially remained unchanged
for the past 50 years (53). Despite yielding better sta-
tistical outcome than placebo controls, the absolute
effectiveness of oral hygiene products is not satisfac-
tory (210). Oral hygiene studies also tend to have a
duration of 12 months or less, and whether common
self-care products actually save teeth long term is
unknown. Another concern is that self-care products
are typically tested in individuals with gingivitis or
mild periodontitis, diseases that are most likely to
respond favorably but are not representative of most
adult types of periodontal disease. Furthermore, oral
hygiene studies are usually performed in the USA or
Europe, which may limit their global validity and
applicability. The slow development of oral hygiene
products may be attributed to overestimation of the
benets of current cleansing methodologies, the ago-
nizingly long process from discovery to clinical trans-
lation to effective commercialization and a crowded
and highly competitive marketplace. Lack of afford-
able media channels for oral-health promotion also
hampers the introduction of new self-care products
(101), but the Internet and teledentistry offer promis-
ing new venues to inform the public about periodon-
tal disease prevention (152, 209). Google Trends
reports that, in 2016, most Internet requests for peri-
odontal information originated from Latin America.
To conclude, development of oral hygiene products
involves an amalgamation of signicant scientic
complexity, costly business processes and economic
risks, which combined may stie inventiveness.
Sodium hypochlorite oral rinse constitutes an
important new development in periodontal (119, 184)
and peri-implant (74) self-care, and most likely also
in caries prevention (67). Oral rinsing twice-weekly
for 3 months with 0.25% sodium hypochlorite
(sourced from Clorox Regular Bleach; The Clorox
Company, Oakland, CA, USA), together with

conventional oral hygiene, yielded improvements of
94% in plaque-free facial surfaces, 195% in plaque-
free lingual surfaces and 421% in the number of teeth
showing no bleeding on probing; the same clinical
variables improved by 29-30% in control subjects
(67). The dilute bleach oral rinse also reduced subgin-
gival levels of periodontopathic bacteria (33, 67). The
clinical and microbiological improvements occurred
in unscaled periodontal pockets with probing depth
as much as 7-9 mm (73). These data reported for
sodium hypochlorite rinsing question the absolute
necessity of highly meticulous scaling and root plan-
ing to obtain acceptable periodontal healing (4) and
of surgical reduction of pockets > 5 mm to prevent
periodontal disease recurrence (76). Shah et al. (200)
found similar decreases in dental plaque level and
bleeding on probing after twice-weekly rinsing with
0.10% sodium hypochlorite, and early studies (1, 29,
130) showed sodium hypochlorite rinse to be effective
in cleansing the mouth and in controlling gingival
bleeding. These striking outcomes are related to the
strong anti-plaque (67) and anti-inammatory (124)
properties of sodium hypochlorite. Twice-weekly oral
rinsing with 0.1-0.25% sodium hypochlorite caused
no visual staining of teeth in a 3-month study (67),
but a higher concentration or a more frequent and
longer usage of sodium hypochlorite may yield extrin-
sic tooth staining and slight supragingival calculus
formation (29, 49). Sodium hypochlorite kills a broad
spectrum of oral pathogens and therefore does not
induce pathogenic superinfections. Rapid post-treat-
ment repopulation of indigenous/low-virulent bacte-
ria relative to pathogenic species may even promote a
healthier oral microbiota. To sum up, sodium
hypochlorite oral rinse simplies and augments peri-
odontal self-care and is safe and readily available as
inexpensive household beach.
Chlorhexidine gluconate/digluconate is an impor-
tant anti-plaque agent but shows extrinsic tooth-
staining (2) and reduced anti-plaque effectiveness
after 6 months of usage (96). The declining effective-
ness may be the result of overgrowth of chlorhexi-
dine-resistant microorganisms (102, 142, 187, 219,
233). Chlorhexidine also eliminates pre-existing pla-
que less efciently than hypochlorite (51, 99). In
apparent contrast to sodium hypochlorite rinse, oral
rinsing for 4 months with chlorhexidine failed to
resolve gingival inammation in pockets deeper than
3 mm (64), supragingival rinsing with chlorhexidine
did not decrease the pathogenicity of monkey subgin-
gival microbiota (137) and subgingival placement of
chlorhexidine chips plus scaling yielded no more sup-
pression of periodontal pathogens than did scaling
Review of periodontitis
alone (47). Triclosan [5-chloro-2-(2,4-dichlorophe-
noxy)phenol] is an antimicrobial agent of some tooth-
pastes but poses a risk of inducing bacterial
resistance and hormonal changes (61). Alcohol in
mouthwashes may also constitute health risks, espe-
cially in smokers (141), although adverse effects have
been difcult to establish in epidemiological studies
(38).
Periodontal recall
Periodontal post-treatment supportive care includes
assessment of the periodontal health status, scaling,
depuration and counseling on proper oral hygiene.
The frequency of recall appointments depends on the
past history of periodontal disease, the level of risk
factors for periodontitis and the effectiveness of
patient self-care (11). Because major bacterial patho-
gens in deep pockets predispose to recurrent disease
(177) and have a repopulation time of 36 months
after treatment (218), recalls are typically scheduled
every 6 months. More closely scheduled recalls may
be warranted for individuals in the periodontitis-
active age from 30 to 45 years (121) and for patients
of advanced age (140).
Gingival bleeding on probing increases the risk of
periodontal breakdown and may prompt more fre-
quent recalls. In a 3-month study of patients with
untreated periodontitis, Gonzalez et al. (73) found
disease progression (dened as an increase in prob-
ing depth of 2 mm) in twice as many sites that bled
on probing at two occasions vs. one occasion, and in
ve times as many sites that showed one-time bleed-
ing on probing vs. never bleeding (P < 0.001). Probing
pocket depth increased in 4.5% (decreased in 1.0%;
possibly measurement error) of sites that bled on
probing at baseline and increased in 1.4% (decreased
in 1.0%) of sites that revealed no baseline bleeding on
probing (73). Lang et al. (122, 123) suggested to
shorten the recall interval by 1 month if bleeding on
probing scores of the full dentition exceeded 16-25%
and to increase the recall interval by 1 month if the
bleeding on probing score was below 10%. Self-care
methods that are effective in reducing bleeding on
probing, such as twice-weekly oral rinsing with
sodium hypochlorite (73, 200), may signicantly
extend the recall interval and reduce the need for
professional intervention.
Laleman and colleagues (120) have evaluated the
efcacy of various types of subgingival debridement,
dened as elimination of biolms without intention-
ally removing root cementum or subgingival calculus.
13
Slots
Their main conclusion is that debridement by hand
instrumentation, ultrasonic scaling, laser treatment,
photodynamic therapy or air-polishing devices do
not differ markedly in terms of clinical and antimicro-
bial efcacy, but therapeutic discomfort is less with
laser treatment, photodynamic therapy and air-
polishing. No evidential-based conclusion can be
drawn as to the optimal interval between subgingival
debridements.
McCracken et al. (140) conclude, in this volume of
Periodontology 2000, that the principal goals of sup-
portive periodontal care are to achieve a high stan-
dard of plaque control, to minimize bleeding on
probing and to maintain pocket depths of 5 mm.
The goals of supportive implant care are less clear,
but may include probing depths of no greater than
5 mm, absence of bleeding on probing and absence
of implant-surrounding continuous radiolucency
(140). However, studies on conventional oral hygiene
techniques reveal that 30-60% of health information
is forgotten within 1 hour and 50% of health recom-
mendations are not followed (246), and plaque scores
tend to return to pretreatment levels within 1 year
after oral hygiene instruction (229). When supportive
periodontal care shows, or is anticipated to show, dis-
appointing results, despite diligent attempts to mod-
ify predictive (e.g. smoking and poorly controlled
diabetes) and behavioral factors, antimicrobial
chemotherapy and more frequent recall visits are
warranted (140).
Periodontitis and systemic disease
Epidemiologic research has provided evidence of a
link between severe periodontitis and at least 43 sys-
temic diseases (17, 45, 193, 203). The majority of stud-
ies have found relatively modest odds ratios between
periodontitis and specic systemic diseases. How-
ever, the high prevalence of periodontitis may trans-
late into numerous cases of medical pathosis, and the
potential involvement of periodontitis in several med-
ical illnesses may render the aggregate systemic dis-
ease risk highly signicant.
Studies on the systemic impact of periodontitis
struggle with residual confounders (249) and have
shown associations and not causation (202, 216).
Proving a causative effect of periodontitis on a variety
of systemic diseases constitutes an immense scientic
challenge and may not be fully accomplished in the
foreseeable future, if ever, but denitive proof of cau-
sation is probably not necessary to make meaningful
clinical decisions. Despite the tobacco industrys
14
contention of mere correlations had been demon-
strated between cigarette smoking and lung cancer
and other systemic diseases, the US Surgeon General
decided, in 1964/1965, that the quality of the evidence
and the strength of the associations, together with the
seriousness of the diseases, were sufcient reasons to
issue a warning label on tobacco products. Similarly,
it may be unduly restrictive and even ill-considered
to require complex interventional studies before
starting periodontal treatment for medical reasons in
patients at high risk for systemic diseases (22). Also, if
performed based on wrongly deducing a systemic
impact of periodontitis, periodontal treatment would
at least improve the periodontal health status and the
negative effect would be merely monetary.
Periodontal bacteria or their antigens enter the cir-
culatory system in relatively small amounts at any
given time, and are routinely eliminated by the
immune defense within minutes (160), making it dif-
cult, if not implausible, to argue for a causative link
between periodontal bacteria and a wide range of sys-
temic diseases. Moreover, bacterial pathogenicity has
not been linked conclusively to the etiologic pathway
of most systemic diseases. Herpesviruses, on the
other hand, can reside in millions of copies in inam-
matory cells within gingiva (41, 42, 104, 117, 191), and
can enter saliva (190) and circulate in the blood-
stream for extended periods of time (145). Her-
pesviruses are major causes of health-care-associated
infections and have been linked to diseases in virtu-
ally every organ of the body, including kidney, liver,
pancreas, heart, brain, lungs, stomach, adrenals, gen-
italia, eye, blood vessels, intestines, joints, skin and
salivary glands (165). For example, cytomegalovirus
can pass through placenta to the fetus and cause sev-
ere birth defects and may, together with herpes sim-
plex virus, contribute to atherosclerosis (212).
EpsteinBarr virus is a direct carcinogen in nasopha-
ryngeal carcinoma, gastric carcinoma, Burkitt lym-
phoma, Hodgkin lymphoma, immune-suppression-
related non-Hodgkin lymphoma and extranodal nat-
ural killer/T-cell lymphoma (nasal type) (155), and in
oral tumorigenesis (206). Herpesvirus-induced release
of proinammatory cytokines may also aggravate sys-
temic diseases (212). In addition, the ability of a peri-
odontal herpesvirus infection to cause bacterial
overgrowth may explain, at least in part, the statistical
relationship between periodontopathic bacteria and
systemic diseases (207).
Varicella zoster disease may serve as a model to
illustrate the link between periodontal herpesviruses
and systemic diseases. The varicella zoster her-
pesvirus causes chickenpox in unvaccinated children,

followed by a lifelong replicational latency in cranial
or dorsal root ganglia, from which the virus may reac-
tivate during times of suppressed cellular immunity
(e.g. psychosocial stress, old age) and travel along
sensory nerves to produce shingles in distant der-
matomes (245). Likewise, periodontal cytomegalo-
virus and EpsteinBarr virus may reactivate during
immunosuppressive events and disseminate via the
circulatory system to nonoral sites (39). These her-
pesviruses, unlike the herpes zoster virus, demon-
strate no distinct clinical manifestations and usually
go unnoticed. Herpesvirus age-related reactivation
and morbidity is expected to assume increased medi-
cal importance with the longer life expectancy of
most populations.
Taken together, periodontal herpesviruses have
ready access to the systemic circulation and can
infect numerous extra-oral sites, making her-
pesviruses the most likely periodontal candidate for
systemic diseases and a target of prophylactic ther-
apy. Periodontal depuration, anti-herpesvirus
chemotherapy and regular oral rinsing with sodium
hypochlorite may provide adequate and long-lasting
suppression of periodontal herpesviruses (212), but
traditional oral hygiene methods may not ensure
healthy periodontal conditions and removal of her-
pesviruses (23). However, proper periodontal treat-
ment or even extraction of the entire dentition may
not prevent disease in body sites already infected
with herpesviruses, implying that periodontal her-
pesvirus-preventive measures may have to be insti-
tuted with signs of spontaneous gingival bleeding.
The research-based future of
periodontology
The future of periodontology is closely connected to
progress in biological sciences. Periodontal research
over the past quarter-century has explored integrative
biology to gain better insights into the pathogenesis
of periodontitis. Modern molecular technologies have
signicantly improved studies on periodontal patho-
genic agents, virulence genes and haplotype aberra-
tions, and genomic data analysis is becoming user-
friendly and scalable. Real-time PCR is a robust tech-
nology for quantitation of periodontal herpesviruses
and bacteria (212). PCR arrays can be used to monitor
the gene-expression level of cytokines and other
inammatory mediators. Next-generation sequencing
combined with metagenomic analysis has the poten-
tial for rapid identication of collective communities
of periodontal viruses, bacteria, fungi and parasites,
Review of periodontitis
and is cost-efcient when processing higher numbers
of samples (46). Metagenomic and metabolomic
functional proling of periodontal microbial commu-
nities are used in longitudinal comparisons of patient
cases and control groups (25, 33, 244). Disease-related
shifts in the composition of the periodontal micro-
biome parallel changes in immune responses, and
studies that use omics technologies have begun to
provide a molecular-level understanding of the suc-
cessional dynamics, stability and perturbation of the
periodontal ecosystem. Such knowledge might foster
innovative methods of ecosystem management to
prevent and control periodontal disease.
Research on periodontal therapy in the near term
may focus on personalized and more effective pre-
ventive treatments to improve outcome and cost-
effectiveness. Disease-related biomarkers in oral
biouids may assist in risk stratication, prognostica-
tion, early disease detection, treatment planning, pre-
diction of treatment response and therapeutic
monitoring. Salivary biomarkers are nding use in
managing periodontitis (93, 114, 151, 192, 221, 227),
dental caries (68) and systemic diseases (43, 171, 252).
Gingival crevicular uid biomarkers can help deter-
mine risk and severity of periodontal disease (16,
227). Computerized algorithms may enhance peri-
odontal diagnosis, therapy and prognosis and struc-
ture clinical decision making. In the long term, novel
diagnostic and therapeutic methodologies may per-
mit patients to self-detect and arrest mild-to-moder-
ate periodontitis, and herpesvirus vaccines developed
for medical purposes may prevent severe types of
periodontitis.
The future role of the specialty of periodontics is an
important theme of the article by Kornman et al.
(113). These authors foresee a greater collaboration
with medicine as periodontitis becomes recognized
as an independent risk factor in the initiation, pro-
gression and complications of several chronic inam-
matory diseases and preterm births. Kornman et al.
(113) also envision a different, and perhaps greater,
interaction between the periodontal specialty and
segments of general dentistry. Treatment of mild-to-
moderate periodontitis with 1 validated risk factor
would be the responsibility of dental hygienists and
general dentists. Generalized moderate-to-severe
periodontitis or mild-to-moderate localized peri-
odontitis with > 1 validated risk factor are envisioned
to be best treated and monitored by periodontists
using established protocols and dened end points.
Controlled trials may help to determine the difference
in clinical outcome and nancial costs between
a skill-based therapeutic template and a more
15
Slots
universal chemotherapeutic model (210) of periodon-
tal treatment.
The changing face of periodontics
Herpesviruses have emerged as important periodon-
tal pathogens that deserve serious attention (208).
Severe periodontitis is closely associated with her-
pesvirus active infection, specic bacterial species
and destructive immune responses (212). Periapical
lesions of endodontic origin exhibit a similar
etiopathogenesis (81, 220). It is hypothesized that
periodontal herpesviruses are required for the onset
of rapidly advancing periodontitis and that the
absence of periodontal herpesviruses precludes
development of severe periodontitis. It is also con-
ceivable that herpesviruses cooperate with periodon-
topathic bacteria to produce severe periodontitis and
may cause little or no periodontal breakdown in the
absence of such bacteria. The notion of a key role of
herpesviruses in periodontitis, if correct, will pro-
foundly change the current concepts of the pathogen-
esis and management of periodontal disease.
The diversity in genetic, infectious and immuno-
logic subtypes of periodontal disease argues for per-
sonalized therapy (195). Periodontics of the past did
not assess specic etiologies, probably because of
cumbersome and expensive testing methodologies,
but molecular technologies have advanced the con-
cept of precision periodontics (234). Multiplex nucleic
acid-based tests and ELISAs are rapid methods used
to quantify markers in biological samples and are par-
ticularly well suited for development of user-friendly
diagnostics. Early disease detection and targeted
treatments are expected to improve periodontal
health status and yield signicant cost savings, and
become an important part of future dentistry (66).
Treatment of periodontal disease is important in its
own right, but the nding of comorbidity between
periodontitis and various medical diseases raises
periodontal treatment to a new level of importance.
Low-income populations are those most affected by
periodontitis and cannot afford to disburse funds on
unproven or minimally effective treatments (24, 156).
A recent study found that 35% of households world-
wide receiving dental treatment incurred catas-
trophic dental health expenditures (138). Traditional
periodontal surgery provides, at best, only minor clin-
ical benets compared with lower-cost nonsurgical
therapy, and the role of surgery in periodontal treat-
ment is becoming increasingly unclear. Dental expen-
ditures can be contained by avoiding overtreatment
16
and managing periodontitis by ultrasonic scaling,
antiseptic rinses and systemic antibiotics in severe
cases, followed by efcacious and affordable self-care
(210, 228). Even if such simplied therapy leads to a
slightly higher number of therapeutic failures, which
is unproven, it may constitute the best, and most
realistic, option for controlling periodontal disease in
the general population. It is obviously a challenge to
deliver high-quality periodontal health care and
reduce cost at the same time, but a greater use of
cost-benet, cost-effectiveness and cost-minimiza-
tion analyses would help to avoid low-value and
overly expensive treatments (243).
Patient self-care is the cornerstone of periodontal
health care. Even after proper professional treatment,
the long-term outcome is unsatisfactory in patients
who fail to perform adequate oral hygiene. However,
current anti-plaque methods are difcult to adminis-
ter effectively and new means of oral self-care are
clearly needed (212). Antiseptics were used routinely
in dentistry in the early part of the 20th century, and
sodium hypochlorite (dilute household bleach) and
iodine have once again become important parts of
periodontal health care (212). Sodium hypochlorite
oral rinse exhibits both preventive and curative prop-
erties (73) and may represent a rst step in changing
treatment of mild and moderate periodontitis from a
professional responsibility to patient self-care.
Finally, the observation of a link between severe
periodontitis and several systemic diseases may sig-
nicantly expand the scope and appreciation of
periodontal practice. The public needs to be
informed about the role of periodontal disease in
overall health care and the treatment options avail-
able to modern periodontics. Following a general
acceptance of an etiopathogenic relationship
between periodontitis and various systemic diseases,
patients with severe periodontal disease may be
referred to medical professionals for screening for
systemic diseases, and medical patients prone to
certain systemic diseases may be referred to dentists
for evaluation and treatment of periodontal disease
(36). Close collaboration with the medical profession
to reduce the incidence and severity of systemic dis-
eases is poised to create new exciting opportunities
for dentistry.
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