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The Oral Health-Systemic
Health Relationship
Slide 1
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© Author / Presentation Reference
Oral sepsis theory :
a long-standing and fascinating story
Assyrians:
pains in head,
arms & feet
caused by teeth
2000 BC
1000 BC
Greeks:
tooth pain
associated with
disease in
reproductive
system
Hippocrates
finds arthritis
cured with
tooth
extraction
05/05/2017 09:12
Galen states head
is source of all
ills (teeth are the
result not the
cause of disease)
1 AD
Egyptians:
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Romans:
© Author / Presentation Reference
1500 AD
In the mid to late 1800’s,
Diseases were thought to be caused by:
Bad Blood
Bad Air
Evil Spirits
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Robert Koch
Introduced the
“germ” theory
of disease
in 1876
Louis Pasteur
Edward Jenner
Joseph Lister
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Willoughby
D. Miller
Graduated from
Penn Dental
School in 1879,
then on to
Berlin
and Koch’s new
Institute
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“The Human Mouth as a Focus of Infection”
Ostitis
Osteomyelitis
Pyaemia
Meningitis
Gangrene
Angina
Noma
Actinomycosis
Tuberculosis Syphilis
Septicemia
Pneumonia
Sinusitis
Diphtheria
Thrush
WD Miller, Dental Cosmos 33: 689-713,1891
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In 1899, William Hunter a young MD from
Edinburgh practicing in London attended a
talk by Miller:
“Oral infection as the cause of most
systemic diseases.”
From that time on, Hunter was a major
advocate for the concept that oral infection
was the cause of systemic diseases
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A century of progress in understanding
the nature of periodontal disease
• The role of the infectious burden and specific bacterial
types in disease causation
• The role of the susceptible host in periodontal tissue
destruction
• The incidence, prevalence and natural history of
periodontal disease
• The risk for periodontal disease
• Periodontal disease as a risk for systemic disease
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1912
The term “oral sepsis” replaced
with
“focal infection”
“The Era of Focal Infection”
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RHEUMATOLOGY
1938 RL Cecil, Ann Intern Med
200 patients with rheumatoid
arthritis studied; teeth removed;
no patient got better and 3 got
worse
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1952 Editorial, J Am Med Assoc 150:490
“…many patients with diseases
presumably caused by foci of infection
have not been relieved of their symptoms by
removal of foci such as teeth. Many patients
with these same diseases have no evident
focus of infection; also foci of infection are as
common in apparently healthy persons as
those with disease.”
JAMA 150: 490, 1952
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1952-1989
There is very little interest in the
relationship of periodontal disease to the
rest of the body
Exception for SBE
(Subacute Bacterial Endocarditis)
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1989
“A New Era”
Matilla,K, Niemeier,M,Valtonen, V et al,
Br Med Journal 298: 770-782, 1989
Association between dental health and
acute myocardial infarction
Patients presenting to the emergency room with a
heart attack had moderate to severe periodontal
disease. Age and gender matched subjects who
had no heart problems also had no or very little
periodontal disease
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1989, following Matilla’s
report
Dentistry begins to carefully re-look at
the relationship of periodontal disease to
systemic conditions
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World Health Organization
• WHO Executive Board Report on Oral Health,
January 27, 2007
• Platform accepted:
– “acknowledging of the intrinsic link between oral health, general
health and quality of life”
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What is the biological plausibility to
suggest that periodontitis may
contribute to a person’s risk for
having a heart attack or stroke?
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Risk Factor:
an exposure that increases the
probability that disease will occur
e.g. obesity increases the likelihood
for hypertension
e.g. cigarette smoking and lung cancer
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Risk factors for periodontal disease
• Smoking
Drugs
• Age
Existing Bone Loss
• Diabetes Mellitus
Probing Depth > 5mm
• Bacterial Burden
Bleeding on Probing
• Specific bacterial
Root Form
• Inheritance
Pulpal Involvement
• Stress
Caries
• Race/Ethnicity
Types Furcation Involvement
• Phagocyte Dysfunction
Tooth Mobility
• HIV Infection
Crown to Root Ratio
• Gender (male)
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•Periodontal disease is an
inflammatory disease caused by
anaerobic and facultative bacteria
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Bacteria
Dental biofilm
Gingivitis
Periodontitis
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Bacteria
Dental biofilm
Inflammatory
reactions
Gingivitis
Periodontitis
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RISK FACTORS
Bacteria
Dental biofilm
Inflammatory
reactions
Gingivitis
Periodontitis
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• Diabetes mellitus
• Smoking
• Poor oral hygiene
• Male gender
• Race/ethnicity
• Low socioeconomic
status
RISK FACTORS
Bacteria
Dental biofilm
Inflammatory
reactions
Gingivitis
Periodontitis
DENTAL EFFECTS
• Connective tissue degradation
• Alveolar bone resorption
• Tooth mobility
• Abscess
• Tooth loss
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• Diabetes mellitus
• Smoking
• Poor oral hygiene
• Male gender
• Race/ethnicity
• Low socioeconomic
status
RISK FACTORS
Bacteria
Dental biofilm
Inflammatory
reactions
Gingivitis
Periodontitis
DENTAL EFFECTS
• Connective tissue degradation
• Alveolar bone resorption
• Tooth mobility
• Abscess
• Tooth loss
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• Diabetes mellitus
• Smoking
• Poor oral hygiene
• Male gender
• Race/ethnicity
• Low socioeconomic
status
ASSOCIATED MEDICAL
CONDITIONS
•
•
•
•
Diabetes
Cardiovascular diseases
Preterm Low birth weight
Respiratory Disease
Periodontal pocket - probed to 5mm depth
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Surface area of generalized moderate periodontitis
Waite, DE and Bradley, RE Oral infections JADA 71: 587-592, 1965
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2004
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Periodontal Disease as a risk factor
• Diabetes
• Cardiovascular Diseases
• Adverse Pregnancy Outcomes
• Pulmonary Diseases
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Periodontal Disease as a Risk
• Diabetes
• Cardiovascular Disease
• Adverse Pregnancy Outcomes
• Pulmonary Disease
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Review of different types of Diabetes
_______________________________________
•
Type 1 diabetes (10 – 15 % of all cases)
– also called insulin dependent diabetes mellitus (IDDM). The pancreas
undergoes an autoimmune attack by the body itself, and is rendered
incapable of making insulin. The patient with type 1 diabetes must rely on
insulin medication for survival.
• Type 2 diabetes (85 – 90 % of all cases)
– Patients can still produce insulin, but do so relatively inadequately for their
body’s needs. In many cases, the pancreas produces larger than normal
quantities of insulin, but there is a lack of sensitivity to insulin by the cells
of the body, it is called insulin resistance.
• Gestational diabetes:
– Blood sugar elevation during pregnancy is called gestational diabetes, it
usually resolves once the baby is born. However, 25-50 % of these
women will develop a Type II diabetes later in life.
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Diabetes and Periodontal Diseases:
A Two-Way Street
_______________________________________
• Patients with diabetes are at greater risk for
developing infections
• Periodontal infection may impair diabetes control
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Periodontitis and Diabetes
___________________________________
• May increase insulin resistance
• May aggravate glycemic control
– Severe periodontitis:
– prevalence of proteinuria
– number of cardiovascular
complications: stroke, angina, MI,
heart failure, intermittent claudication
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Periodontitis and Diabetes
________________________________________
• Diabetes mellitus has a significant impact on tissues
throughout the body, including the oral cavity
• Poorly controlled diabetes increases the risk of
periodontitis
• Periodontal infection and treatment may alter glycemic
control
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Diabetes increases the risk of developing
periodontitis
________________________________________
Ciancolla et al in 1982
• Type I diabetes was associated with a five-fold increased
prevalence of periodontitis in teenagers.
Lalla et al, 2006
• Periodontal destruction can start very early in life in diabetes
and becomes more prominent as children become
adolescents.
In addition, epidemiologic research supports an increased
prevalence and severity attachment loss and bone loss in
adults with diabetes*
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There is sufficient clinical evidence to
show that poor control of diabetes
increases the risk for developing a
number of oral manifestations of the
disease, including periodontitis.
Does treating periodontal infections have
a beneficial effect on glycemic control in
people with diabetes?
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Taylor GW et al
The effects of periodontal treatment on
diabetes
JADA 2003, Vol 134
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This review, consisted of MEDLINE research,
identified 12 studies
- 3 randomized clinical trials
- 9 non-randomized follow-up studies
-7 studies reported a beneficial effect of
periodontal treatment on glycemic control, with
either a reduction of HbA1c levels, or a reduction
in circulating TNF-alpha levels or finally a
reduction in insulin requirements.
- However 5 studies reported no beneficial effect.
Taylor et al, 2003
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Periodontitis and Diabetes - Conclusions
Despite the variation and limitations of the
evidence, it can be concluded that:
- periodontal diseases may contribute to
poorer glycemic control in people with
diabetes
- treating periodontal infections could have
a beneficial effect on glycemic control in
patients with either type 1 or type 2
diabetes.
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Periodontal Disease as a risk factor
• Diabetes
• Cardiovascular Diseases
• Adverse Pregnancy Outcomes
• Pulmonary Diseases
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Review Cardiovascular Terms
Atherosclerosis:
Progressive disease process through which atheroma are
formed; involves large to medium sized muscular and large
elastic arteries
Atheroma:
Elevated intimal fibrolipid plaque
Coronary Heart Disease:
Clinical diagnosis made by physician based on tests, signs
and symptoms
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What is the biological plausibility to
suggest that periodontitis may
contribute to a person’s risk for
having a heart attack or stroke?
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Infection-inflammation have been linked to
the risk for coronary heart disease for
several years
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Bacteria and soluble bacterial products,
such as LPS, can enter the bloodstream
and can reach distant sites, e.g. the
endothelium of a blood vessel, where it
can initiate a local inflammatory
response and resultant injury
Dave S et al, Compendium July 2004
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• The local inflammatory response to bacterial biofilm in the
periodontal pocket may cause or amplify systemic
inflammatory events.
• Inflammatory cells, such as monocytes and leukocytes,
“stick” to and activate the endothelial cells lining the
arteries
• The monocytes are converted to macrophages which start
to accumulate lipids to become “foam cells”, a hallmark of
atherosclerosis, proliferate and thicken the walls of the
arteries.
Dave S et al, Compendium July 2004
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Mast cells in the area produce proteases
which can be implicated in plaque
remodeling and rupture, thus creating a
thrombus.
Libby P et al, circulation 2007
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Epidemiological Evidence
Epidemiological data have been
analyzed to examine for a possible
relationship between exposure
(periodontitis) and the outcome
(cardiovascular disease)
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Available Data
1. NHANES 1 Follow-up Study
2. VA Normative Aging Study
3. Health Professions Follow-up Study
4. Nutrition Canada Study
5. Physician’s Health Study
6. Mini-Finland Health Survey
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Up to 2007 there are 16 studies of the 6 existing data
sets
DeStefano F et al, 1993
Mattila K et al, 1995
Beck JD et al, 1996
Joshipura K et al, 1996, 2003
Mendez et al, 1998
Morrison et al, 1999
Wu et al, 2000
Hujoel P et al, 2000, 2001,2002
Jansson et al, 2001
Howell TH et al, 2001
Hung et al, 2003
Ajwani et al, 2003
Tuominen et al, 2003
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DeStefano F et al
From NHANES 1 follow up study
Dental disease and risk of coronary
heart disease and mortality
Br Med J 1993;306: 688-691.
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20,749 subjects initially studied
9760 subjects included in this study of
Periodontitis-CHD
Subjects with periodontitis had a 24%
increased risk of coronary heart disease
relative to those who had minimal periodontal
disease
DeStefano et al, 1993
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Beck JD et al
From VA Normative aging study
Periodontal disease and
cardiovascular disease
J Periodontol 1996; 67: 1123-1137.
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Age-adjusted and multivariate incidence
odds ratios for total coronary heart disease,
fatal coronary heart disease and stroke
according to bone loss at baseline
Total
CHD
Fatal
CHD
Stroke
N cases
203
58
40
Odds ratios
1.5
1.9
2.8
Beck at al, 1996
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Morisson HI et al
From Nutrition Canada Study
Periodontal disease and risk of fatal
coronary heart and cerebrovascular
diseases.
J Cardiovasc Risk. 1999; 6(1): 7-11
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A statistically significant association between
periodontal disease and risk of fatal coronary
heart disease was observed with a rate ratio
of 2.15 for severe gingivitis.
Non-statistically significantly increased rate
ratio (1.81) was observed for severe gingivitis
and cerebrovascular disease.
These data suggested that poor dental health
is associated with an increased risk of fatal
CHD.
Morisson et al, 1999
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Joshipura K et al
From Health Professions Follow-up Study
Poor oral health and coronary heart
disease
J Dental Research 1996; vol 75, 1631-1636
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Health status monitoring of 44,119 males
participating in the Health Professionals Followup Study over a 6-year period.
Examine the incidence of coronary heart disease
in relation to number of teeth present and
periodontal disease.
Overall, no significant association between tooth
loss and coronary heart disease (RR = 1.04)
However, men with 10 or fewer teeth were at
increased risk of CHD compared with men with
25 or more teeth (RR = 1,67)
Joshipura et al, 1996
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Periodontitis and Cardiovascular Disease –
Conclusions
There is clearly an association between
periodontal disease and cardiovascular
disease.
Further research is required to better
understand its nature.
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Periodontal Disease as a Risk
• Diabetes
• Cardiovascular Disease
• Adverse Pregnancy outcomes
•Preterm low birth weight infants (PLBW)
•Preeclampsia
• Pulmonary Disease
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Definitions
Preterm Birth:
A birth that occurs before 37 weeks of gestation (WHO
1977)
Low Birth Weight:
Birth weight under 2500 grams or 5 lbs.
Preeclampsia
It is a disorder that affects at least 5-8% of all
pregnancies.
Characterized by high blood pressure, protein in the
urine, swelling, headaches and sudden weight gain.
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Known Risk Factors for Preterm Low
Birth-weight







Maternal Age.
Drug, Alcohol and Tobacco usage
Intake of medicine
Genetic History
Acute infection and inflammation of the genital organs
Diabetes and hypertension
25-50% occur without any known etiology
Biochemical Mediators of Prematurity
LPS, PGE2, IL-1β, TNFα, IL-6
Can induce:
 uterine contraction
 cervical dilation
 labor or abortion
 inhibit fetal growth
which mediate preterm delivery, low birth weight
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Adverse Pregnancy Outcomes
• PLBW may be associated with sub clinical genitourinary
or other infections.
• A variety of biologically active molecules such as
prostaglandin E2 (PGE2) and TNF, which are normally
involved in normal parturition, are raised to artificially
high levels by the infection process, which may foster
premature labor.
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Adverse Pregnancy Outcomes
• Periodontal infection
– Release of LPS and endotoxins by oral bacteria
trigger release of immune modulators such as
PGE2 and TNF in gingival crevicular fluid
– Bacteria, bacterial by-products and mediators
may enter the circulation
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2 Possible mechanisms
Periodontitis
Systemic challenge
Systemic challenge
PGE2, IL-1ß, TNF
Bacteria, LPS
Direct
Maternal response
PLBW
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IL-1, IL-6,TNF,PGE2
Offenbacher, S et al
Periodontal infection as a possible
risk factor for pre-term low birth-weight
J Periodontol 1996; 67: 1103
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Case-control study of 124 pregnant or postpartum
mothers
Women with periodontal disease were
seven times more likely to have preterm
low birth (PLBW) weight babies than
women not affected by the disease.
Offenbacher et al, 1996
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Periodontitis & Pre-term, low birth-weight infants
Multivariate Logistic Regression Model of All PLBW
Periodontitis
Alcohol
Afro-American
Age
Parity
Treated BV
0
1
Offenbacher et al, 1996
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2
3
4
5
ODDS Ratio
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6
7
8
Lopez, NJ et al
Periodontal therapy may reduce the risk
of preterm low birth weight in women
with periodontal disease : a randomized
controlled trial
J. Periodontology. 2002 Aug;73(8):911-924
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400 pregnant women with periodontal disease
randomly assigned to either experimental
group (n=200, periodontal treatment before 28
weeks of gestation) or a control group (n=200,
periodontal treatment after delivery)
Periodontal disease appears to be an
independent risk factor for PLBR.
Periodontal therapy significantly reduces
the rates of PLBR in this population of
women with periodontal disease.
Lopez et al, 2002
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Offenbacher, S et al
Progressive Periodontal Disease and Risk
of Very Preterm Delivery
Obstetrics & Gynecology 2006;107:29-36
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Prospective study of obstetric outcomes, entitled
Oral Conditions and Pregnancy (OCAP) was
conducted with 1,020 pregnant women who
received both an antepartum and postpartum
periodontal examination.
This study demonstrated that maternal
periodontal disease increases relative risk of
preterm birth.
In addition, women with progressing periodontal
disease during pregnancy are more likely to
have very preterm deliveries compared with
women whose disease does not progress.
Offenbacher et al, 2006
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Michalowicz, BS et al
Periodontal treatment in pregnant women
improves periodontal diseases but does
not alter rates of preterm birth
Evidence-Based Dentistry, 2007; 8, 5-6
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Multicentre randomized controlled trial
2 groups:
Treatment group n=413 (scaling and root planing before 21
weeks’ gestation)
Control group n=410 (following delivery)
Treatment of periodontitis in pregnant women
improves periodontal disease and is safe but
does not significantly alter rates of preterm
birth, low birth weight or foetal growth
restrictions.
Michalowicz et al, 2007
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Xiong, X et al
Periodontal Disease and Adverse
Pregnancy Outcomes : A systemic Review
British Journal of Obstetrics and Gynecology, 2006 Feb;
113(2):135-143
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In this review, 25 studies were identified:
• 13 case control studies
• 9 cohort studies (prospective)
• 3 controlled trials (2 were randomized)
18 studies suggested an association between
periodontal disease and an increased risk of
adverse pregnancy outcomes (odds ratio
ranged from 1.10 to 20.0)
7 other studies yielded no evidence of such an
association.
Xiong et al, 2006
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Conclusion of this systemic review :
Periodontal disease may be associated
with an increased risk of adverse
pregnancy outcome. However, more
methodologically rigorous studies are
needed for confirmation.
Xiong et al, 2006
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Periodontitis and Preeclampsia
Most studies have been focused on the role of
periodontal disease in pre-term birth.
Recent investigations suggested that periodontal
disease is more prevalent in pre-eclampsia
(Contreras et al, 2006,Cota et al, 2006, Kunnen et
al, 2007, Herrera et al, 2007)
Although most of studies to date indicate a positive
correlation between Periodontitis and
Preeclampsie, it is still too early to attribute a
cause-and-effect relationship.
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Periodontitis and Adverse Pregnancy Outcomes
- Conclusions
There is an association between periodontal
disease and increased risk for adverse
pregnancy outcomes
In addition, the balance of evidence suggests
that periodontal intervention may reduce the
incidence of adverse pregnancy outcomes
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Periodontal Disease as a Risk
Diabetes
• Cardiovascular diseases
• Preterm Low Birth Weight Infants
• Pulmonary Disease
•
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Oral bacteria,
cytokines and
the lower airway
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Potential Mechanisms
• Periodontal infection and respiratory pathogens in plaque
have been linked to an increased risk for aspiration
pneumonia and chronic obstructive pulmonary disease.
• In hospitalized patients and those in nursing homes,
bacteria that colonize teeth can potentially be aspirated
into the lung and can lead to pneumonia.
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NHANES III – Pulmonary disease
Patients with a history of chronic obstructive pulmonary
disease have significantly more periodontal attachment
loss than subjects without COPD
Scannapieco, 2001, 2003
Azarpazhooh and Leake, 2006
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Yoneyama T et al
Oral care reduces pneumonia in older
patients in nursing home
J Am Geriatr Soc, 2002 Mar;50(3):430-3
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11 nursing homes in Japan
417 patients randomly assigned to an oral care group or no
oral care group
During follow-up, pneumonia, febrile days and death from
pneumonia decreased significantly in patients with oral
care.
Oral care must be useful in preventing pneumonia in
older patients in nursing home.
Yoneyama et al, 2002
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Azarpazhooh A et al
Systemic review of the association
between respiratory diseases and oral
health
J Periodontol 2006 Sep;77(9):1465-82
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19 studies selected.
Conclusions :
•Fair evidence of an association of pneumonia with
oral health (level II-2, grade B)
•Poor evidence supporting a weak association (level
II-2/3, grade C)
•Good evidence (level I, grade A) that oropharyngeal
decontamination with different antimicrobial
interventions reduces the progression or occurrence
of respiratory diseases.
Azarpazhooh et al, 2006
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Oral Health and Pulmonary disease - Conclusions
•Some evidence exists that poor oral hygiene and
periodontal disease may increase the risk of developing
community-acquired pneumonia.
•However, stronger evidence exists to support the
relationship between poor oral hygiene and bacterial
pneumonia in special-care populations.
•Health professionals need to become more involved in the
care of hospitalized and nursing home populations.
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The question in 2007 is :
Should dentists and physicians be
doing more to ensure greater awareness
of the influence that oral diseases can
have on systemic conditions?
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The Oral Health-Systemic Health
Relationship
A New Partnership Between Dentistry
and Medicine ?
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