How periodontal inflammation is connected to overall health -- you'd be surprised at the connection

1. In fla m m a tio n a n d
P e rio d o n ta l Dis e a s e s
A paradigm shift in periodontology and what it
means for patient care

2. Outline of Presentation
 All about inflammation: the paradigm shift in
periodontology
 Inflammation, periodontal disease and cardiovascular
disease
 Inflammation, periodontal disease and other disease
states
 Risk factors for periodontal disease
 Treatment of periodontal inflammation
 Five Things to Remember
 Future Directions and Questions
2

3. Media Coverage
 Re ce n t Ne w s Co ve r a g e
The Bos ton Globe
November 2, 2009 )Audience: 713,083)
We bMD
January 12, 2010 (Audience: 10,845,896)
Ea ting We ll
January 1, 2010 (Audience: 530,309)
Me n’s He a lth
January 1, 2010 (Audience: 7,438,572)
Me dica l Ne ws Toda y
February 20, 2010 (Audience: 1,800,000)
2

4. Periodontal Disease: A Quick
Overview
 Periodontal disease is a chronic
inflammatory disease that destroys
the bone and gum tissues that
support the teeth.
 The American Academy of Periodontology (AAP) estimates
that 3 out of 4 Americans are affected by periodontal
disease, ranging from mild gingivitis to more severe
periodontitis.
 If left untreated, mild cases of gingivitis can lead to
periodontitis.

5. Periodontal Disease
 However, the periodontal disease of
yesterday is not the periodontal disease of
today.
 Yesterday: researchers believed that
gum loss in periodontal disease was
caused by the bacteria in plaque.
 Today: researchers have determined that the
gum loss in periodontal disease is caused by
the inflammatory response to the bacteria in
plaque.
5

6. J Periodontol 2008;79:1560-1568.
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7. What is Inflammation?
 Inflammation is the body’s first response to an injury.
 The first phase (acute inflammation) includes redness, swelling, heat,
and altered function. It is self-perpetuating.
 There are several biological markers of inflammation in your blood,
including C-reactive protein (CRP).
 CRP is a protein found in the blood which can rise in response to
inflammation.
 Acute inflammation often causes elevated C-reactive protein.
 Elevated CRP is a risk factor for several chronic inflammatory diseases.
 Inflammation appears to be a common link between several common
diseases of aging.
 These diseases include heart disease, arthritis, and periodontitis.
6

8. Examples of Inflammation
 Sunburn
 Infection
 A cut on the skin
7

9. Inflammation’s Objective
 Inflammation tries to contain the injury to the local site.
 The body’s reaction is immediate (called the innate
response).
 Its ultimate purpose is to protect the body from further
damage.
8

10. Inflammation is Damaging when
Uncontrolled
 Though inflammation can be helpful under certain conditions,
uncontrolled inflammation, also called chronic inflammation, is
harmful and causes tissue loss.
 Chronic inflammation occurs when there is a sustained
infection, like periodontitis.
 Chronic inflammation involves more inflammatory mediators
than the immediate innate response.
9

11. Chronic Inflammation
 Chronic inflammation can negatively affect all organs and
tissues of the body.
 Chronic diseases of aging are connected through
common chronic inflammatory mechanisms.
10

12. Periodontal Paradigm Shift:
Because of this new focus on
inflammation, there has been a
shift in the way periodontists view
periodontal disease and its
relationship to other disease
states.
11

13. Periodontitis is a Chronic
Inflammatory Disease of Aging
 Periodontitis involves a microbial challenge to the gums which stimulates an
inflammatory response
 Genetic and acquired risk factors lead to immuno-inflammatory response
 A prolonged immuno-inflammatory response leads to destruction of
connective and bone tissues, which leads to the possible loss of teeth.
 Chronic inflammatory diseases, such as periodontitis, arise over decades.
 Periodontal disease is a significant contributor to the total inflammatory
burden on your body and can adversely affect your systemic health.
12

14. “Inflammation and Periodontal
Diseases: A Reappraisal”
 In January 2008 a workshop sponsored by the AAP
brought together more than 80 leading experts:
 Periodontists, cardiologists, diabetologists, geneticists,
gerontologists, inflammation researchers
 This was an opportunity to engage in collaborative thinking
and brainstorming across many different fields- using
inflammation as a common finding.
13

15. Workshop, cont.
 The workshop was developed to expand and advance our
understanding of inflammation and the role it plays in diseases of
aging.
 The experts from the diverse fields addressed topics of
inflammation:
 What is inflammation?
 What specific mechanisms constitute inflammation?
 What factors regulate inflammation?
 Why do individuals have different expression levels of inflammation?
 Is the inflammation in one disease common to the inflammation in
other diseases?
14

16. Workshop, cont.
 The experts engaged in discussion of the future of
inflammation therapies and how they may change the
future of periodontics.
 Proceedings from the Workshop were published in a
supplement to the Journal of Periodontology in August
2008.
(Available for free at: http://www.joponline.org/toc/jop/79/8s)
15

17. Workshop, cont.
 What we learned:
 Periodontal disease is a bacterially-induced chronic
inflammatory disease that does not resolve by itself.
 The inflammatory response is extremely complex .
 Environmental and genetic factors affect expression of
inflammation in individuals .
 The initiation and resolution of inflammation are well
controlled processes.
 Diabetes, CVD, and stroke all share common inflammatory
processes similar to periodontal inflammation.
 Resolution of any inflammation in the body is helpful for
overall health.
16

18. The Workshop helped highlight
the relationship between
various disease states, and
suggested that inflammation
may be the basis for these
relationships.
17

19. Perio-Cardio Link:
The relationship between periodontal
disease and cardiovascular disease (CVD)
18

20. Cardiovascular Disease: A
Quick Overview
 Cardiovascular disease
generally refers to conditions
that involve narrowed or
blocked blood vessels that
can lead to a heart attack,
chest pain (angina), or
stroke.
 The American Heart Association reports that cardiovascular
disease is the leading killer of men and women in the United
States.

21. Inflammation and CVD
 Inflammation contributes to heart attacks as much as
or more than cholesterol.*
 Atherosclerosis always begins with injury to the
endothelium of blood vessels.
 Periodontal pathogens have been found in
atherosclerotic lesions.
19
*Ridker PM, et al. N Engl J Med. 2005 Jan 6;352(1):20-8.

22. Periodontal Disease and
CVD
 Data derived from meta-analysis: meta-analysis combines the results of several
studies that address a set of related research
 Five prospective cohort studies hypotheses
 Five cross sectional studies Ability to control for between-study variation
 Five case control studies
 Subjects with periodontitis had a 1.14 - 1.59 fold greater risk for
developing CVD compared to those without periodontitis.
 Adjustments made for risk factors: smoking, diabetes, alcohol intake, obesity
and blood pressure
Bahekar AA, Singh S, et al. Am Heart J 154:830-837, 2007
19

23. C-Reactive Protein (CRP)
 CRP is a protein found in the blood that reflects the
amount of inflammation in your body.
 Periodontitis and other sources of inflammation elevate
CRP levels.
 Elevated CRP is a direct risk factor for CVD.
20

24. AJC-JOP Consensus Paper
 The American Journal of Cardiology contacted the AAP after
reading the August 2008 Journal of Periodontology supplement
from the Workshop on Inflammation.
 A consensus paper was developed in collaboration with the
American Academy of Periodontology and top cardiologists.
 The paper was published simultaneously in the Journal of
Periodontology and the American Journal of Cardiology in June
2009.
21

25. AJC-JOP Consensus Paper,
cont.
 The consensus paper is a summary of research that shows a
connection between periodontal disease and CVD.
 It explains the underlying biologic and inflammatory
mechanisms that may be the basis for the connection.
 Clinical recommendations for treating patients with
cardiovascular disease and periodontal disease are also
included.
22

26. CVD-PD Clinical Recommendations
 Examples of the clinical recommendations:
 Dentists are asked to consider their patients’ heart
health and risk for CVD.
 Assess risk factors for CVD such as smoking and family
history of CVD
 Physicians are asked to consider their patients’
periodontal health and risk for periodontal disease.
 Assess symptoms such as tooth loss or bleeding and
swollen gum tissue
 All health professionals are asked to educate patients
on chronic inflammatory diseases and how they are
related.
 Health professionals are also asked to work together
to ensure patients are in best health.
23

27. The Relationship of Periodontal Disease to
Other Inflammatory Diseases
 Inflammation appears to be the basis for the association between
oral and systemic disease.
 One chronic inflammatory disease potentially influences the
expression of other diseases:
 Tissue destruction is caused by prolonged inflammation.
 Moderate/severe periodontitis increases systemic inflammation.
 Systemic inflammation is associated with most chronic diseases of
aging.
 For example, periodontal disease influences diabetes and diabetes
influences periodontal disease.
24

28. The Relationship of Periodontal
Disease to other Chronic Inflammatory
Diseases of Aging
 Cardiovascular disease
 Arthritis
 Diabetes
 Alzheimer’s Disease
 Cancers
25

29. Arthritis
 Arthritis (Rheumatoid arthritis
and osteoarthritis) is an inflammation
of the joints.
 Patients with arthritis have a higher
incidence of periodontal disease
compared to healthy controls.*
Source: National Institutes of Health
 Periodontal treatment decreases arthritis parameters:**
 Patients’ number of swollen and tender joints decreased following
periodontal treatment.
 Patients’ assessment of pain also decreased following periodontal
treatment.
*Pischon N, et al. J Periodontol. 2008 Jun;79(6):979-86.
**Ortiz P, et al. J Periodontol. 2009 Apr;80(4):535-40. 26

30. Diabetes
 Worldwide incidence is expected to increase with increased
prevalence of obesity.
 Major public health burden because of serious microvascular
sequelae.
 nephropathy
 retinopathy
 neuropathy
 cardiovascular disease
 periodontitis
 Total annual costs exceed $132 billion in US alone
28

31. Risk Factors for Diabetes
 Genetics
 Diet
 Sedentary lifestyle
 Perinatal environment
 Age
 Obesity
 Chronic Inflammation
 Type I and Type II Diabetes
28

32. Diabetes
 Type I Diabetes
 Adolescents and young adults
 Autoimmune destruction of pancreatic islet cells that produce
insulin
 Increased CRP in patients with long termed type I diabetes
 Type II Diabetes
 Occurs mainly in adults but prevalence among young people
increasing due increase in childhood obesity
 Characterized by increased cellular non responsiveness to
insulin (insulin resistance)
 Pancreatic beta cells do not secrete sufficient insulin
28

33. Diabetes
 Hyperglycemia inhibits the resolution of inflammation.
 High CRP and IL-6 promotes insulin resistance.
 Patients with diabetes are three
times more likely to have periodontal
disease.
 Controlling periodontal disease helps
control blood sugar levels.
Insulin
28

34. Obesity
 Patients with a higher body mass index (BMI) tend to have
higher levels of CRP.
 Calorie reduction leads to decreased gingival bleeding and
rate of periodontal disease progression.*
*Branch-Mays GL, et al. J Periodontol. 2008
Jul;79(7):1184-91.
30

35. Alzheimer’s Disease
 Progressive intellectual failure and a major cause of dementia
 Pathologic hallmarks:
 amyloid plaques and neurofibrillary tangles which are distributed in the
frontal neocortex and limbic system
 Alzheimer’s Dz is an innate inflammatory response in an attempt to
remove the amyloid deposits from the brain
27

36. Alzheimer’s Disease
 Antibodies and immune cells cross the blood brain barrier.
 Exposure to chronic periodontal
disease quadruples an individual's
risk of developing Alzheimer's
disease.*
*Watts A, et al. Neuropsychiatr Dis Treat.
2008 Oct;4(5):865-76.
© 2000 - 2009 American Health Assistance Foundation
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37. Cancers
 Pancreatic cancer
 Men with a history of gum disease are 54% more likely to
develop pancreatic cancer than men with healthy gums.*
 Head and neck cancers
 Chronic periodontitis is independently associated with the
incidence of head and neck cancers.**
 Smoking increases this association.
*Michaud DS, et al. Lancet Oncol. 2008 Jun;9(6):550-8. Epub 2008 May 5.
**Tezal M, et al. Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2406-12.
29

38. Other Inflammatory Diseases
 Asthma and other chronic respiratory diseases
 Osteoporosis
 Kidney disease
 Metabolic syndrome
31

39. Risk Factors for Periodontal
Disease
 Genetic risk factors
 Can be minimized with proper diet, exercise, and oral hygiene.
 Biological risk factors
 Other systemic diseases of inflammation may increase the risk of
periodontal disease.
 Predisposition to inflammatory conditions such as obesity,
diabetes, or CVD
32

40. Risk Factors for Periodontal Disease,
cont.
 Behavioral risk factors Biologic Risk Factors
 Poor oral hygiene
 Smoking (specifically, nicotine intake)
 Smokers have higher levels of CRP.
 Stress
 Sleep deprivation
 Poor diet
Behavioral Risk
Genetic Risk Factors
Factors
33

41. Treatment of Periodontitis
 Reduction of tissue inflammation
 Reducing one type of inflammation may reduce another:
 Patients with periodontitis and rheumatoid arthritis who received
periodontal treatment:
 Reduced inflammation in periodontal tissues.
 Reduced severity of RA symptoms.*
* Ortiz P, et al. J Periodontol. 2009 Apr;80(4):535-40.
35

42. The good news is that inflammation
levels can be reduced.
When chronic inflammation is
controlled, the associated chronic
inflammatory diseases may be
controlled.
36

43. How to Reduce Inflammation:
What does this mean for patients?
 Reduce direct sources of inflammation:
 Visceral fat
 Exercise
 Reduce calories
 Chronic infections
 Periodontists can help reduce inflammation in the oral cavity.
 Have your teeth professionally examined and cleaned
regularly.
 Stop smoking.
 Activate inflammation resolution systems:
 Add Omega-3 fatty acids to your diet.
 Take a daily low-dose aspirin.
37

44. J Periodontol 2008;79:1601- 1608.
43

45. Inflammation:
5 things to remember
1. There has been a paradigm shift in the field of
periodontology.
Periodontal disease today is defined by the
inflammatory response to the biologic
components of plaque.
38

46. Inflammation:
5 things to remember
2. The relationship between periodontal disease and
other chronic inflammatory diseases of aging is better
understood.
These diseases include cardiovascular disease,
respiratory diseases, diabetes and arthritis.
39

47. Inflammation:
5 things to remember
3. Treatment of chronic oral inflammation
should be done by trained dental
professionals.
Co-management with periodontal
specialists to help in evaluating,
diagnosing, and treating periodontal
inflammation and disease.
40

48. Inflammation:
5 things to remember
4. Reducing inflammation in the body can reduce
the occurrence and severity of chronic
inflammatory diseases.
41

49. Inflammation:
5 things to remember
5. Dentists and physicians need to work together to
ensure the best health of their patients.
42

50. Conclusions: Future Directions
 A paradigm shift is occurring in both medicine and dentistry in our
understanding of preventing many of today’s systemic diseases.
 The incidence and amount of inflammation that patients
experience may be critical to the onset and progression of certain
systemic diseases.
 Prospective treatment studies are needed that define whether or
not periodontal treatment makes a substantial difference in the
expression of certain diseases.
 As we wait for such studies, we should educate our patients
about what is known and to help them manage their own health
by assisting in the reduction of inflammation.
43

51. Future Directions
 Significant clinical limitation in diagnosing and monitoring periodontal
inflammation
 gingival inflammation and bleeding
 periodontal pocket depth
 gingival attachment level
 Classical approaches to controlling periodontal inflammation rely on
attempts to suppress bacteria that incite inflammatory response
 Mechanical (SC/RP, flap surgery)
 Chemical (antimicrobials, antibiotics)
 Emerging and future approaches need to rely more on
 Modifying the inflammatory response itself
 Limiting the activities of pro-inflammatory pathways, effector cells and
mediators
43

52. Pathogenesis of Periodontal Disease
P in k, He a lth y Tis s u e , No
Clin ic a l S ig n s o f Dis e a s e
Go o d Ora l Hyg ie n e
Lo w S u s c e p tib ility
He a lth
No S ys te m ic Ris k Fa c to rs
Na tu ra l En zym e In h ib ito rs Tis s u e De s tru c tive En zym e s
Balance of Tissue Destruction
in the Periodontium

53. J Periodontol 2008;79:1592-1600.
43

54. Pathogenesis of Periodontal Disease
P o o r Ora l Hyg ie n e
Dis e a s e S ys Hig hicSRisckeFatibto rs
te m
u s p ility
c
Na tu ra l En zym e In h ib ito rs
• S m o kin g
• Ge n e tic s
• Dia b e te s
Ove rp ro d u c tio n
Tis s u e De s tru c tive En zym e s
Imbalance of Tissue Destruction
in the Periodontium

55. Pathogenesis of Periodontal Disease
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Dis e a s e
Ch ro n ic Ove rp ro d u c tio n
Tis s u e De s tru c tive En zym e s
S tudie s s how s moke rs (Bo n e Lo s s , De e p e r P o c ke ts Are
ha ve a le s s fa vora ble Gre a tly Affe c te d )
re s pons e to tra ditiona l
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mode s of pe riodonta l
the ra py
Imbalance of Tissue Destruction
in the Periodontium

56. Pathogenesis of Periodontal
Disease
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57. The Future of Periodontal
Diagnosis
 Traditional diagnostic (i.e. PD, AL, BOP, etc.) measures are
informative to evaluate disease severity.
 We need diagnostic determinants of disease activity.
 Extensive research has been ongoing in this area since the
1990’s
 Presence of biomarkers of measured with the gingival crevicular
fluid (GCF)
 Presence of biomarkers present within saliva
43

58. Gingival Crevicular Fluid
 Most appropriate analytical fluid of choice because it was
specific to the periodontal tissues
 The three most promising biomarkers for predicting future
disease activity
 Beta-glucuronidase
 Alkaline phosphatase
 Cathepsin B
 Many diagnostic kits emerged based, many of which
demonstrated high levels of sensitivity and specificity
demonstrating disease activity at site level.
43

59. Gingival Crevicular Fluid
 Problems
 Too time consuming to perform
 Site specific - the choice of site was problematic
 168 potential sites within the mouth to examine
 Too costly for routine use
 Results did not translate to changes in therapeutic
intervention
43

60. Saliva
 Medium of choice in the 21st Century.
 Contains microbial and host response mediators.
 Simple to collect using non-invasive techniques.
 Provides whole mouth summary analysis.
 Already used as a diagnostic fluid for:
 Determining hormone levels
 Drug detection
 Presence of HIV or Hep C virus
43

61. Saliva
 Problems
 Assays need to be highly sensitive.
 Biochemistry varies with its origin (whole saliva or specific
gland secretions)
 Not possible to fully quantify markers within saliva using
chairside technologies. Qualitative analysis may be all that
can be achieved
 Saliva contains mucins and cell debris making it
challenging to work with.
43

62. Saliva
 Identify the biomarkers for periodontitis - aid in diagnosis and
therapeutic monitoring of disease activity.
 Difficult due to the complex nature op periodontal disease - no
single etiology with multiple risk factors.
 Periodontal researchers do not fully understand the
pathogenesis of periodontitis.
 However, identification of biomarkers the characterize
periodontal tissue destruction will be attainable
43

63. Question?
 Can salivary testing for inflammatory
biomarkers be a way for medical profession
to screen patients for periodontal disease and
the dental profession to screen patients for
cardiovascular disease, diabetes and
systemic diseases?
43

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