1. H.K.E.S’s S.N. Dental College
Gulbarga

2. A paradigm shift in the
etiopathogenesis of periodontitis
Dr. Khushbu Mishra
Guided by:- Dr. Veena A Patil
H.O.D.
Dept. of Periodontia

3. Contents
 Introduction
 Rise of localist and local cause theory
 Generalist and the remote cause theory
 Rise of local cause hypothesis
 Fall of generalist
 Role of bacteria
 Role of susceptible host in periodontal tissue destruction
 Concepts of pathogenesis of periodontal disease
 Models of disease progression
 Conclusion

4. Introduction
 Periodontitis is a family of related diseases that differ in
etiology, natural history, disease progression and response
to therapy.
 But have a common underlying chain of events that are
influenced by disease modifiers.

5.  Clinical manifestations observed are a result of complex
interplay of these factors.
 It is well acknowledged that while etiology of periodontitis
is bacterial, pathogenesis is inflammatory.
khushbu mishra

6.  The understanding of regulation of inflammation is far
from complete.
 As the understanding of periodontal inflammation
increases, current understanding of the microbiology of
periodontitis becomes less clear.

7.  While we think we know that bacteria initiate the disease,
role of specific bacteria is still unknown.
 Proving the link between cause and effect of chronic
disease such as periodontal disease is not an easy task.

8.  Current knowledge of microbiology of periodontitis is
based on large cross-sectional and association studies.
 Periodontitis is seen as the direct consequence of bacterial
invasion and is regarded as an infectious disease.

9.  The foundation of our knowledge of periodontal disease is
not the product of a linear chronology of events, but rather
than bringing together of theories, discoveries and
advances that have occurred in parallel.
 Scientist and clinicians have been trying to understand and
treat periodontal disease for centuries.

10.  Loculosis
 Blennorrhea gingiva
 Periostitis
 Alveolodental periostitis
 Rigg’s disease
 Pyorrhea alveolaris
 Periodontal disease

11.  years ago periodontists were divided into 2 camps
 Localist Generalist
Cyril O. Enwonwu. 1972 – Orbans Periodontics a concept-
theory and practice

12.  The localists hypothesize that the primary causes of
periodontal disease are intra-oral and thus that intra-oral
interventions can, by themselves, prevent and successfully
treat periodontal disease.
.
khushbu mishra

13.  The generalists hypothesize that the primary causes of
periodontal disease are remote from the oral cavity and that
periodontal disease is only amenable to chronic disease
management unless the remote causes are pinpointed and
intervened upon.

14.  This local-cause paradigm became established before
comparative clinical research arose as a means by which to
objectively assess supporting evidence.
 One could say that a reasonable hypothesis (the plaque
hypothesis) evolved into accepted wisdom without going
through an intervening process of rigorous clinical and
epidemiologic investigation.

15. The rise of Localist & Local cause theory
 Pierre fauchard 1746 referred Periodontal disease as
different kind of scurvey which without involving other
parts of body attacks gums, alveoli & teeth.

16. i. Periodontal disease is independent of systemic disease
manifestations.
ii. Periodontal disease has local etiology.
iii. Local intraoral interventions can prevent & successfully
treat periodontal disease.
iv. Local treatment can provide systemic health benefits
4 axioms of localist theory

17. First axiom
 Periodontal disease is independent of systemic disease
manifestation.

18. Second axiom
 Periodontal disease has local etiology.
 Many authors suggested infection as local cause.
 Parasite – Gallipe 1888
 Amoeba
 Viruses- Baer PN 1962
 Mixed infections
 BANA +ve org.- Loesche WJ 1990
 Red cluster bacteria (Socransky 2000)
 Treponema pallidium (Riverie GR et al.)

19. Third axiom
 Fact that periodontal disease has local etiology, local
intraoral interventions can prevent and successfully
treat periodontal disease.
 Domino theory of Periodontal causation.
 Dental accretions gingivitis destructive
periodontal disease.
 Thus, removing causal factor resolves Periodontal disease.
 So, the concept evolved- periodontal disease is caused by
Dental plaque.

20.  Fauchard suggested no systemic treatment could lead to
cure for local disease.
 Rigg’s local cure (Dental calculus removal) was urged to
be forwarded by journal publication.
(Meritt AH 1921)
 Curability became almost unquestionable over subsequent
decades.

21. 4th axiom
 Local treatment can provide systemic health benefit.
 John Riggs made impressive claims for health giving
effects provided by his cure.
 G.V. Black supported it.

22. Generalist and the remote cause theory
 W.D. Miller (1853-1907)- first oral microbiologist
questioned infection as primary cause of Periodontal
disease.
 He remained unconvinced that local irritation be at all a
requisite to origination of this disease.
 There is often an inability to influence remote causes and
that as a result after treatment is necessary at intervals from
4-6 months in retarding progress of this disease.

23.  Miller hypothesized, potential remote cause
leads to
impaired resistance of periodontal tissue
suitable culture medium for bacteria
typical signs
suppuration, bleeding & oozing occurs
when periodontal tissues becomes infected.

24.  Bunting RW (1920) hypothesized
that in absence of infection,
remote causes
alveolar atrophy (degeneration of bone)
Atrophic shrinkage

25.  Periodontal disease compared to diabetic foot of leg.
 Several generalist-
periodontal disease as having a complex multi-factorial
and remote primary etiology.
 Miller Rachitic disease
 Maurice precocious senility
 Burchard (1894) Gout
 Ptaff tobacco smoking
 Price (1945), Cleave & Cheraskin nutrition factor

26. Rise of local-cause hypothesis
 So, the key point of debate was whether primary cause is
remote or local.
 Initially, Fauchard & G.V. Black recognized that for a
minority of patient, primary cause was remote.

27.  Clinical approach under this tolerant view
if local treatment results in cure, cause is local
if it fails cause is constitutional
 However, beginning in late 1960’s--- after arrival of model
of pathogenesis it became virtually sacrilegious to ascribe
genesis of inflammatory periodontal disease to factors
other than oral plaque.

28.  Role of leukemia in gingival bleeding-------not clearcut.
 Role of vitamin C deficiency in periodontal scurvey were
reinterpreted as periodontitis of bacterial causation.
khushbu mishra

29. Factors to establish dominance
 Periodontics became dental speciality.
* Chappin Harris
* John Riggs
 Dominance of germ theory.
 Simplicity versus complexity
 Clinical effectiveness of local therapies.

30. The fall of Generalists
 It can be said that periodontal textbooks are written by
winners--- those holding to local cause paradigm..
 Bergstrom– prominent in recognizing smoking
 Cheraskin– relationship between vitamin C, sucrose and
gingival bleeding. ----- Remained uncited
 Miller’s work, Koch’s disciple --- viewed through the lens
of localists
 Remote cause perspectives became largely ignored.

31.  Periodontal disease remains largely regarded as a locally
caused disease.

32. Role of Bacteria
 In the 1st part of 20th century, microbiologist used to rely
on culture methods.
 They believed that certain microorganisms such as
amoeba/ streptococci were primary etiologic agents.
 However, with each decade, data linking specific bacteria
to disease causation proved unreliable.

33.  Thus, by 1930s, it was generally believed that all bacteria
on teeth could cause periodontal disease.
 Amount of bacteria accumulated ∞ incidence and severity
of disease (Non specific plaque hypothesis).

34.  But clinician and investigators observed little disease in
some persons with poor oral hygiene over long periods.
 Large deposits were not related to subsequent destruction
of periodontal tissue.

35.  In 1964, Keyes and Jordan demonstrated
a. Periodontal disease could be transmitted from
hamsters with disease without disease.
b. or, by swabbing oral cavity of unaffected animals with
suspensions of A. viscous isolated from hamsters with
disease.
c. With demonstration of infectious and transmissible
component of periodontal disease in the hamster, the field
of periodontology changed substantially.

36.  Research efforts were renewed to determine whether
specific bacteria rather than all bacteria residing under
gingiva caused Periodontal disease.
 Socransky et al. undertook pioneering studies to examine
the bacteria in periodontal pocket of children with
localized juvenile periodontitis.

37.  Site of advanced bone loss adjacent site of no
and formation of deep pockets periodontal disease.
 Advanced bone loss--- anaerobic gram negative bacteria.
 Healthy site----- gram positive (facultative)

38.  -----Golden age of oral microbiology.
 1980s longitudinal trials provided further
evidence that specific bacteria are associated with sites of
active disease progression.
 1990s research findings indicated that out of 500
different types of bacteria, only few are responsible for
disease.

39.  1996 World Workshop in periodontics --- agreed on four
bacterial types that had supported their involvement in
etiology of periodontal disease.
 These included – Aggregatibacter actinomycetemcomitans
P.gingivalis
T. forsythia
T. denticola

40.  Recently, field of oral microbiology has focused on oral
Biofilms.
 a biofilms confers certain properties to bacteria that are
not seen in Planktonic state.
 cell-cell communication
 gene transfer
 antimicrobial resistance
 regulation of gene expression etc.
Which explains the importance of recognizing plaque as a
biofilm not as bacteria in the planktonic state

41.  Oral microbial plaque communities composed of numerous
genetically distinct types of bacteria, that live in close
juxtaposition on host surface.
(Kolenbrander PE 2000)
As our concepts of etiology of periodontal disease changed
so, is the pathogenesis.
khushbu mishra

42. Concepts of pathogenesis of periodontal
disease
 The modern era of the pathogenesis, prevention and
treatment of periodontal disease began in mid 1960s with
experiments demonstrating critical role of bacteria in the
initiation of gingivitis and periodontitis.
 Clear concept in 1960s-
Bacteria causes periodontitis

43. 1960s model tenent
Microbial
challenge
Clinical signs of
disease initiation
and progression

44.  As this model implicated bacterial plaque deposits as the
primary direct factor in development of periodontitis,
resulted in abandonment of former concepts that involved
non-bacterial factors such as
Trauma from occlusion
systemic conditions
& diet.

45.  Research and scientific discussions based on simple
concept of bacterial causation led to great advances in
knowledge during the 1970s.

46. 1970s model tenent
Bacterial
plaque
Calculus
formation
Periodontal
pocket
formation
Bone loss
Occlusal
trauma
• All bacteria on tooth surface are harmful.
• Untreated periodontitis progresses slowly, steadily in
a linear fashion overtime.

47. Role of susceptible host in periodontal
tissue destruction
 20th century brought exceptional years of discovery.
 Most of the 1900s– focused on periodontal pockets.
 Histologic specimen from human autopsy.
 Numerous and diverse theories ---explain why a healthy
gingival sulcus ‘‘shifted’’ to a deepening periodontal
pocket.
 A review by Glickman (1964) summarized the state of the
knowledge within this area of research.

48.  Around 1970, a major shift in emphasis occurred in how
the pathogenesis of periodontal disease was studied.
 study of pocket formation per se to a study of cells,
enzymes, and mediators that might explain the host
response in the progression of periodontitis.

49.  Ivanyi and Lehner (1970)
that peripheral blood lymphocytes isolated from
subjects with periodontitis >> lymphocytes from healthy
subjects.
 Klein and Raisz--- prostaglandins were potent stimulators
of bone resorption in tissue culture.
 Goodson (1972)--- prostaglandins were in the periodontal
tissues and were likely important in the alveolar bone
destruction of periodontal disease.

50.  Horton et al. (1972)--- human peripheral blood leukocytes
from subjects with periodontitis produced a substance,
termed osteoclast activating factor, which induced bone
resorption.
 Clark et al. (1977) discovered that subjects with
aggressive periodontitis had a neutrophil chemotactic
defect.
 In 1976, Page and Schroeder summarized what was known
about the pathogenesis of periodontitis with regard to the
major histopathologic events that occurred from health to
advanced disease.

51.  These investigators used histology and evidence from
biochemical studies that linked cell types and immune
mediators to help elucidate why certain individuals have
periodontal disease.
 In most of the models of the late 1980s, specific bacteria
initiated the disease process by activating host responses,
which were protective and destructive.

52.  As immunologic and molecular techniques improved, the
roles of cytokines and inflammatory cell mediators came to
the forefront of the periodontal literature.
 The actual destruction of connective tissue and bone
resulted primarily from activated tissue mechanisms such
as MMPs, IL-1 & prostaglandins.

53. 1980s model tenent
Microbial
challenge
Host
immunoinflammatory
response
Clinical signs
of disease
initiation &
progress

54. From 1985-1995
 Despite a strong and reproducible association between
plaque accumulation and the development of gingivitis,
these associations were less clear on a patient-to-patient
analysis and were confusing on an individual site analysis
within the same patient.

55.  In a classic study in beagle dogs, plaque accumulation was
associated with a progression to periodontitis, but two of
eight dogs failed to develop periodontitis, despite
substantial plaque and calculus accumulations and
extensive gingivitis.
(Lindhe J, Hamp SE, Loe H. 1975)
khushbu mishra

56.  Longitudinal studies of tea plantation workers in Sri
Lanka.
 As first reported, a failure to clean teeth regularly resulted
in the development of extensive gingivitis and in early and
severe periodontitis.
 However, further analysis determined that there were three
distinct subsets of the population relative to the
development of periodontitis in response to bacterial
accumulations.
(Loe H et al. 1986)

57.  one group that had poor oral hygiene and gingivitis but
developed minimal to no periodontitis.
 The extensive research started for risk factors modifying
clinical expression of disease.

58.  Smoking as a risk factor
Preber H et al. 1984, 1986
Haber 1993
Bergstrom 2006
 Diabetes as risk factors
Bissada et al. 1982
Emrich LJ 1991
Genco 1996

59.  Genetics
Michalowicz et al., 2000
Dowsett et al., 2001
Ronderos et al., 2001
 Age
Grossi et al., 1994; Grossi et al., 1995
 Psychological factors(Hugoson et al., 2002; Mawhorter
and Lauer, 2001; Pistorius et al.,2002; Wimmer et
al., 2002).

60. Risk factors identified
Innate
•race
•Sex
•Genetics
•Congenital
immunodeficiencies
•Phagocyte dysfunction
•Down’s syndrome
•Papillon-lefevre
syndrome
•Ehlers-danlos syndrome
Acquired & environmental
•Poor oral hygiene
•Medications
•Tobacco/smoking
•Stress
•Acquired immune defects
•Acquired endocrine
disease
•Acquired inflammatory
disease
•Nutritional deficiencies

61.  With new knowledge of the various factors contributing to
periodontal disease came recognition that clinical
phenotype is not simply the microbial challenge translated
by a standard host response.
 Laboratory and clinical research demonstrated that these
risk factors were most likely influencing disease
expression by altering host protective and destructive
mechanisms.

62.  According to Emrich LJ 1991, risk of developing
destructive periodontitis increases threefold in people with
diabetes.

63.  Thorstenseon et al. 1996
 Alba Loureiro et al. 2007
 Lalla et al. 2001
 Salvi et al. 1998
 Iacopimo 1995

64. Andersen et al. 2007

65. Smoking
 Eichel and shehrik 1969
 Kennya et al. 1977
 Haffajee et al. 1997
 Soder B 1999

67.  In the absence of disease-modifying risk factors, it seems
that the host responds appropriately to the bacterial
accumulations by attempting to protect against bacterial
invasion.
 Evidence began to accumulate that disease modifiers, such
as smoking, in the presence of bacterial accumulations on
the teeth, shifted the immunoinflammatory responses
outside of the normal boundaries of host response and
repair processes.

68.  In the presence of modifying factors, such as smoking, an
exuberant host response and/or impaired repair
mechanisms seem to lead to more destructive
periodontitis..

69.  The basic conceptual model of periodontitis was revised in
1997, in great part to acknowledge that various risk
factors operated by modifying host responses led to
changes in disease expression.
khushbu mishra

70. End of
session 1
Thank you

71. Models of disease progression
 Continuous model -- Slow, steady, progressive disease
process .
 Episodic burst theory(1982,1986)---Irregular periods of
exacerbation and remission
 Synchronous burst theory(1984)---Periods of exacerbation
and remission during a defined period.

72.  Epidemiologic model(1988)--- Consistent with continuous
disease aging process that depends only on duration of the
process.
 Brownian motion or stochastic model(1989)---Random
periods of sharp bursts and/or remission can occur, but
underlying disease activity remains constant.

73.  Random walking model(1989)---When observed at regular
intervals, model is similar to Brownian motion model.
 Fractural model(1991)---Multifactorial model simulates
disease advancing with age in bursts and remission.
khushbu mishra

74. 1997 model (Page and kornman)

75.  The primary conceptual change in the 1997 model was that
it explicitly acknowledged the role of a number of
environmental and acquired risk factors, including
genetics, as modifiers of the immunoinflammatory
response and in resulting connective tissue and bone
metabolism.

76.  Simply put, modifying factors such as exposure to
cigarette smoke and/or inherent genetic risk factors may
alter the nature of the immunoinflammatory response to
shift the balance to more severe periodontal destruction.
khushbu mishra

77. Advances in knowledge of the pathogenesis
of periodontitis
1. Microbial periodontal pathogens are found in ecologic
complexes, and an ecologic shift can lead to emergence of
a specific set of microbial pathogens.
2. A number of studies confirmed that a small group of
disease modifiers, including diabetes, genotype, and
smoking, contribute strongly to individual patient
differences in the susceptibility to periodontitis.

78. 3. Many studies Beck JD 2000,
Offenbacher S 1998,
Taylor GW 2000
described associations between periodontitis and other
diseases, such as cardiovascular disease, and potentially
explained such associations through bacterial seeding,
common inflammatory mechanisms, and/or common
modifying factors.

79. 4. There was an extension of knowledge about specific
bacterial mechanisms and immunoinflammatory
mechanisms in periodontitis.

80. Advances in knowledge of complex diseases
 First, inflammatory mechanisms were recognized as
common to many chronic diseases of aging, such as
cardiovascular disease.
 Second, periodontitis and other chronic diseases are now
seen as complex in character. This means that the overall
biologic system has a distinct behavior that is more than
the sum of its parts.
khushbu mishra

81.  Third, although the biology is complex, the integrated
behavior of the entire system can be studied using new
simulation tools. For example, molecular networks of
specific biologic components, eg. the immuno-
inflammatory response, can be studied as a functional
module.

82.  Combinations of modules can be integrated to study the
overall system behavior that translates into clinical
outcomes.
4. The fourth is the result of a larger appreciation for the
effects of environmental factors. For example, smoking or
nutrition may affect gene expression in numerous ways,
some of which may persist. Additionally, genetic
variations from person to person may create different
responses to a specific environmental context.

83. Elements of a new model of pathogenesis of
periodontal disease
 The principle of system biology is the use of multiple
levels to provide a framework for defining the interactions
between the cellular and molecular processes occurring at
the lowest levels to the clinical presentation of disease at
the uppermost level.

85. Biologic system model (Kornman 2008)
 This model represents that the pathogenesis of
periodontitis may be defined by the bacterial components,
environmental factors and host-genetic variations
associated with disease.
 Within this framework, discrete modules of genetic,
environmental and other modifying factors are combined
together to define molecular to clinical expression patterns
that are responsible for health or disease.

87.  Ultimately, the goal will be to define expression patterns in
the tissues with respect to each set of environmental and
genetic conditions and to understand the corresponding
clinical parameters and profiles.
 Such information will allow construction of system
biology model that includes the state of key parameters at
the basic biology level, which is critical in defining the
regulatory status of tissue at any point of time.
khushbu mishra

88.  Although, even partial information should improve the
ability to identify an individual’s susceptibility to disease
and a likely response to treatment, complete expression of
these networks should be a valuable tool for determining
new preventive and therapeutic approaches.

89. Biologic system model (Offenbacher S Barros SP
and Beck JD 2008)
 A biologic system approach provides a framework for
viewing the contributions and relative importance of all the
components that contribute to the clinical presentation of
disease.
 Thus, in the context of periodontal disease such a system
would include a person level, a genetic/epigenetic level,
the biologic phenotype and ultimately the clinical
phenotype.

91.  The model depicts the different biologic factors that
underpin the development of periodontal disease in
different individuals and ultimately may be used to classify
disease according to the contribution provided to the
clinical phenotype at each level.
khushbu mishra

92. Conclusion
 Periodontal diseases are highly complex, evidencing
variations at multiple levels ranging from molecular to
clinical.
 New information and technical capabilities are helping
improve our understanding of these disease.
 An improved idea of pathogenesis of disease may facilitate
periodontal disease therapy that is better customized to
each patient’s need.

93. References
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notable past, a promising future. J Periodontol. 2008; 79:1552-1559.
2. Kornman KS. Mapping the pathogenesis of perio - dontitis: a new
look. J Periodontol. 2008;79:1560-1568.
3. Offenbacher S, Barros SP, Beck JD. Rethinking perio - dontal
inflammation. J Periodontol. 2008; 79:1577-1584.
4. Lindhe J, Haffajee AD, Socransky SS. Progression of periodontal
disease in adult subjects in the absence of periodontal therapy. J Clin
Periodontol. 1983; 10:433-442.
5. Beck JD. Methods of assessing risk for periodontitis and developing
multifactorial models. J Periodontol. 1994; 65(5 Suppl):468-478.
6. Page RC, Marting JA. Quantification of periodontal risk and disease
severity and extent using the Oral Health Information Suite
(OHIS). Periodontal Practice Today. 2007;4:163-180.

94.  7. Keyes PH, Jordan HV. Periodontal lesions in the Syrian hamster. III.
Findings related to an infectious and trans - missible component. Arch
Oral Biol. 1964;32:377-400.
9. Clark RA, Page RC, Wilde G. Defective neutrophil chemotaxis in
juvenile periodontitis. Infect Immun. 1977;18:694-700.
16. Ximenez-Fyvie LA, Haffajee AD, Socransky SS. Com -parison of
the microbiota of supra- and sub gin gival plaque in health and
periodontitis. J Clin Periodontol. 2000;27:648-57.
20. Armitage GC. Periodontal diagnoses and classifi cation of
periodontal diseases. Periodontol 2000. 2004; 34:9-21.
21. Offenbacher S, Barros SP, Singer RE, Moss K, Williams RC, Beck
JD. Periodontal disease at the biofilm-gingival interface. J Periodontol.
2007;78:1911-1925.

95. Thank you