PERIODONTAL

MEDICINE

DR.K.Rekha Rani
Prof & HOD, Dept of
Periodontics
PMVIDS,HYDERABAD
INTRODUCTION
ETIOPATHOGENESIS OF
PERIODONTITIS

Page & Kornman

1997
•NOW THE BIG
QUESTION???
• Can the inflammatory response to
bacterial infection of the periodontium
have an effect remote from the oral
cavity???

• Is periodontal infection a risk factor

for systemic diseases or conditions
that affect human health???
 FOCAL INFECTION
CHANGING CONCEPTS
• Hippocrates (460-370BC) – noted a case of
rheumatism cured after infected tooth extraction.

• Benjamin Rush (1745-1813) – recognized relation

of oral infection to general health.

• W.D.Miller (1853-1907) – proposed oral infections

as the cause of many diseases.
• William Hunter (1861-1937) – indicated dental diseases
as a cause of what he called “oral sepsis” – that
caused rheumatic & other chronic diseases.

• For major infections oral focus was the periodontium

and not periapical disease.

• G.V.Black – important role of dental profession in

preserving general health.

• Frank Billings, Edward C. Rosenow, Charles H. Mayo –

interested in the same concept.
• Cecil.R (1938) – no improvement in rheumatoid
arthritis patients after teeth extraction &
tonsillectomy.
• Williams & Burkett – found no good scientific
evidence to support “focal infection theory”.
 Many patients with diseases presumably caused by foci
of infection have not been relieved by removal of foci
 Patients with same diseases may not have detectable
foci of infection
 Foci of infection can occur in healthy persons with no ill
effects. Journal of the American Medical
Association (1952)
• Concept of focal infection resurfaced with the work
by Mattila et al., 1989

Case-control study using a Dental Severity Index –

Dental health significantly worse in patients with MI
versus controls
Pathway for oral infection
Metastatic infection from
oral cavity via transient
bacteremia
Possible non oral diseases
Subacute infective endocarditis, acute bacterial
myocarditis, brain abscess, cavernous sinus
thrombosis,
sinusitis, lung abscess/infection, Ludwig's
angina, orbital cellulitis, skin ulcer,
osteomyelitis, prosthetic joint infection

Metastatic injury from Cerebral infarction, acute myocardial

circulation of oral microbial infarction,abnormal pregnancy outcome,
toxins persistent pyrexia,idiopathic trigeminal
neuralgia, toxic shock syndrome,
systemic granulocytic cell defects, chronic
meningitis

Metastatic inflammation Behcet's syndrome, chronic urticaria,

caused by immunological uveitis,inflammatory bowel disease, Crohn's
injury from oral organisms disease
Rams T E, Slots J. Systemic manifestations of oral infections. In: Slots J, Taubman M A,
editors. Contemporary oral microbiology and immunology. St. Louis, Mo: Mosby; 1992. pp. 500–
523.
Okuda K, Ebihara Y. Relationships between chronic oral infectious diseases and systemic
diseases. Bull Tokyo Dent Coll. 1998;39:165–174. [PubMed]
 Is Periodontitis unique ?
• Unusual anatomy of the tooth – The crown is exposed to
external environment,whereas the root is within the
connective tissues.

• Non-shedding outer layers of the tooth – facilitates diverse

microbial colonization held in proximity to soft tissues of
periodontium.

• Periodontitis is a Biofilm-induced disease – environment

very protective for colonizing organisms.

• Polymicrobial infection- Interplay of many putative

organisms
• It is asymptomatic most of the times and is a
longstanding chronic infection.

• Normal daily activities like chewing, brushing and flossing

can cause a transient bacteremia ( in the process,
cytokines and mediators are also pumped out into
systemic circulation).

• Complexity of treatment – As the disease is

polymicrobial treatment becomes complex.
Periodontitis disturbs systemic homeostasis

Chronic damage of epithelial tissues

due to periodontitis

may induce the periodontal pocket to

ulcerate that allows access to
the bloodstream

Bacteria and their toxins,

cytokines,mediators of inflammation
disrupt homeostasis when toxins
gain entry to the systemic circulation
PERIODONTAL MEDICINE
• The term “Periodontal Medicine” - first suggested
by Steven Offenbacher (1996)

• Definition

“Rapidly emerging branch of periodontology

focussing on the wealth of new data establishing
a strong relationship between periodontal
health or disease and systemic health or disease”
 PARADIGM SHIFT

Infection Inflammation
Inflammation in Systemic Health and in Periodontal Disease. Anthony M. Iacopino, DMD,
PhD.Disclosures|April 07, 2011
ASSOCIATION
AND
CAUSALITY
 ASSOCIATION
Association is defined as the concurrence of
two variables more often than would be
expected by chance.
 CAUSALITY
Causality is defined as the relationship between
an event (cause) and a second event (effect)
where the second event is understood as a
consequence of the first.
 TYPES OF CAUSAL
RELATIONSHIPS
• Sufficient Cause

• Necessary Cause

• Risk Factor
 CRITERIA FOR
CAUSALITY
• Epidemiological association.

• Biological Plausibility.

• Impact of intervention / Reversibility.

• Relative risk measures the magnitude of an
association between an exposed and non-exposed
group. It describes the likelihood of developing
disease in an exposed group compared to a non-
exposed group.

• The Odds Ratio is a measure of association which

compares the odds of disease of those exposed to
the odds of disease of those unexposed.

• Hazard ratio is defined as the hazard in the

exposed groups divided by the hazard in the
unexposed groups.
 Is periodontitis a risk factor for
systemic diseases?
• Risk factor – distinctive characteristics/
exposures that increase the probability
of disease outcome (Albandar, 2002).

Bradford Hill’s criteria (1971)

Strength of association

Consistency of
Biological gradient the
 Strength of the association
• “Measures of association”
– used to quantify the strength of the association between an
exposure and outcome
– e.g. Relative risk, odds ratio

• Strong associations are more likely to be causal than

weak associations
– The larger the relative risk (RR) or odds ratio (OR), the
greater the likelihood that the relationship is causal

• Weak associations are more likely to be explained by

undetected biases or confounders
 Strength of the association
• How large must a relative risk or odds ratio be to be
considered ‘strong’:
– 2 ? 4 ? 20 ? …..?

• No universal agreement regarding what constitutes a

‘strong’ or ‘weak’ association
– An OR or RR > 2.0 is ‘moderately strong’
– An OR or RR > 5.0 is ‘strong’

• The relationship between smoking and lung cancer is

an excellent example of a ‘strong association’
– odds ratios and relative risks in different studies are in the 4
to 20 range
 Consistency of Findings
• Repeated observation of an association in studies conducted on
different populations under different circumstances
• If studies conducted by….
– different researchers
– at different times
– in different settings
– on different populations
– using different study designs
……all produce consistent results, this strengthens the argument for
causation

• e.g. The association between cigarette smoking and

Periodontitis has been consistently demonstrated in a number of
different types of epidemiological study (ecological, case-control,
cohort)
 Specificity of association
• According to Hill, associations are more likely to be
causal when they are specific, meaning the exposure
causes only one disease.

• While some examples of highly specific agent-

outcome associations exist, most exposure and
health concerns at the forefront of research today
centre around complex chemical mixtures and low-
dose environmental and occupational exposures
complicated by a variety of risk factors.
 Temporality
• This refers to the necessity for the exposure to precede the
outcome (effect) in time

• Any claim of causation must involve the cause preceding in time the
presumed effect

• Easier to establish in certain study designs

– Prospective cohort study.

Lack of temporality rules out causality

Normal Cancer
lung

Exposure Time Outcome

Easiest to establish in a cohort study

 Dose-response relationship
• Dose-response (‘biological gradient’)
– the relationship between the amount of exposure (dose) to a
substance and the resulting changes in outcome (response)

• If an increase in the level of exposure increases the risk

of the outcome
– this strengthens the argument for causality
R
R I
R I S
R I
I
S
S K
S
K K K
0 cigs/day < 5 cigs/day 5 - 20 cigs/day > 20 cigs/day
 Biological Plausibility
• Fundamental concepts of data integration
• The criterion implies that epidemiology and biology must
interact.
• Plausibility has historically been judged
based on the presence of existing biological or social
models that explain the association of interest

Fedak KM, Bernal A, Capshaw ZA, Gross S. Applying the Bradford Hill criteria in the
21st century: how data integration has changed causal inference in molecular
epidemiology. Emerging Themes in Epidemiology. 2015;12:14.
 STUDY DESIGN
Relative ability of different types of
study to ‘prove’ causation
NB: Assuming study well-designed & conducted & bias etc. minimised

Type of Study Ability to ‘prove’ causation

1) Randomised Controlled STRONG

Trial
2) Cohort Study Moderate
3) Case-control study Moderate
4) Cross-sectional study WEAK
5) Ecological study WEAK
 IS PERIODONTITIS A RISK
FACTOR
FOR………….??
• Cardiovascular disease
• Diabetes mellitus
• Adverse pregnancy outcomes
• Respiratory infections
• Rheumatoid arthritis
• Osteoporosis
• Renal dysfunction
• Alzheimer’s disease
CARDIOVASCULAR DISEASE&
PERIODONTITIS
• 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.
• Atherosclerosis : Disease of
large and medium-sized
arteries characterized by
endothelial dysfunction,
vascular inflammation and
accumulation of lipids,
cholesterol, calcium and
cellular debris within the intima
of the vessel wall.
Mechanism of Atheroma formation
http://www.pathophys.org/
Specific pathways linking
Periodontitis and CVD
• 1. Direct Bacterial effect on platelets:
Two oral bacteria Porphyromonas gingivalis and
Streptococcus sanguis have been found to express
virulence factor, collagen like platelet aggregation
associated proteins (PAAP) that
induce platelet aggregation in vitro and in vivo.

• Herzberg ME & Meyer MW. Dental plaque, platelets and cardiovascular

disease. Ann Periodontol1998;3:152-60.
• 2.Invasion and/or uptake of bacteria in
endothelial cells and macrophages -
Porphyromonas gingivalis which is one
amongst the most putative periodontal
pathogens can invade aortic and heart
endothelial cells via its fimbriae.

• Deshpande RG, Khan MB, Genco CA. Invasion of aortic and heart
endothelial cells by Porphyromonas gingivalis. Infect Immun
1998;66:5337-43.
• 3. Endocrine-like effects of pro
inflammatory mediators:
• There is an upregulation of mediators in the
vascular tissues. C Reactive protein and
fibrinogen levels are elevated.

• Slade GD, Offenbacher S, Beck JD, Heiss G, PankowJS. Acute-phase

inflammatory response to periodontal disease in the US population. J Dent
Res 2000;79:
49-57.
• 4. Macrophages incubated in vitro with
Porphyromonas gingivalis and low density
lipoprotein take up bacteria intracellularly and
are capable of transforming into
foam cells

• Giacona MB, Papapanou PN, Lamster IB, Rong LL,D’Agati VD, Schmidt
AM et al. Porphyromonas gingivalis induces uptake by human
macrophages and promotes foam cell formation in vitro. FEMS
Microbiology Letters 2004;241:95-101.
• 5. Autoimmune response:
Antibodies cross-react with periodontal bacteria and
human Heat Shock Proteins (HSPs). Antibodies
developed against Porphyromonas gingivalis HSP
60 cross react with human HSP because of the
structural homology that exists between the two.
(Hinode et al,1998, Sims et al, 2002)
• 6. MMP’S:
• MMPs, including the collagenases, likely play an
important role in periodontal tissue breakdown as
well as destabilization of atheromas leading to heart
failure and the deleterious changes in extracellular
matrix in the myocardium. (Lee et al., 2004,
Matsumara et al., 2005)
Biological plausibility of the relationship between the development of athero-thrombotic
lesions and periodontal infection.
Bacteria entering the circulation as a
result of periodontal infection, dental
procedures, and routine tooth care
result in varying levels of bacteremia.
This may enhance the progression of
atherosclerotic cardiovascular disease
(red arrow).
Inflammatory mediators produced in
infected gingival tissues or as part of
the hepatic response to periodontal
infection may enhance the progression
of atherosclerotic cardiovascular
disease (blue arrow).
Dyslipidemia modulated by periodontal
infection primarily affecting the hepatic
response may enhance the progression
of atherosclerotic cardiovascular
disease (green arrow).
 Summary of association
between oral conditions
and CVD in longitudinal
studies with positive finding

Dhadse P, Gattani D, Mishra R. The link between periodontal disease

and cardiovascular disease: How far we have come in last two decades ?.
J Indian Soc Periodontol 2010;14:148-54
Source, year, Country Exposure Outcome Measure of Adjusted for
total no. of (follow-up association potential
subjects period) confounders
Mattila and Finland (7 Total dental New Age, sex,
+ $
colleagues, years) index myocardial HR =1.2 race,
1995, infarction or education,
214 (182 death from poverty,
males, 32 CHD marital status,
**
females) SBP , BMI,
Cholesterol
level,
diabetes,
physical
activity,
alcohol use,
smoking

Morrison and Canada (23 Mild, severe Fatal CHD RR at age Age, sex,
colleagues years) gingivitis and stroke 35–69 years; cholesterol
1999 periodontitis mild level, smoking,
gingivitis diabetes,
$
=3.6 ; hypertension,
$
severe=6.9 p province of
eriodontitis= residence
Source, Country Exposure Outcome Measure of Adjusted for
year, total (follow-up association potential
no. of period) confounders
subjects
Beck and Age, sex, cholesterol
++ $
colleagues,1 United Whole- New CHD OR =1.5 O level, smoking,
$
996, States (18 mouth bone Fatal CHD R=1.9 OR=2 diabetes, blood
$
921 (men) years) level Stroke .8 pressure, family
history, education.

Wu and United Gingivitis Incident RR: Sex, age, race,

colleagues, States and non- Gingivitis=1. education, poverty
$
2000, 9962 (NHANES-I: periodontitis hemorrhagi 2; index, diabetes, HT,
adults 21 years) (>4 mm c stroke periodontitis smoking status,
$
pockets); =2.1 alcohol use, BMI,
edentulous cholesterol level,
by Russell’s sample design
periodontal
index
* # ++
CHD = Coronary heart disease ,RR = Relative risk; HR = Hazard Ratio OR =
**
Odds ratio,SBP = Systolic blood pressure
$
= Statistically significant adjusted measure of association;
 Summary of association
between oral conditions and
CVD in longitudinal studies
with negative
findings
Dhadse P, Gattani D, Mishra R. The link between periodontal disease
and cardiovascular disease: How far we have come in last two decades ?.
J Indian Soc Periodontol 2010;14:148-54
Source, year, Country Exposure Outcome Measure of Adjusted for
total no. of (follow-up association potential
subjects period) confounder
s

**
Age, BMI ,
*
Joshipura and United States Reported Fatal and RR =1.04 exercise,
colleagues, (6 years) history of PD non-fatal smoking,
alcohol
1996, in men myocardial
consumption,
44,119 (male infarction and vitamin E use,
health sudden death family history
professionals) of MI before
age 60 years

Age, age
Hujoel and United Gingivitis Death or Gingivitis squared, sex,
% #
colleagues, States and hospitalizati HR =NS ; race, poverty
2000. (National periodontiti on due to periodontitis index, marital
$ status,
8032 dentate Health and s (>1-mm CHD or HR=1.14
education,
adults Nutrition pockets) by revasculariza marital
Examination Russel’s tion +
status/sex ,
++
Survey I: 21 periodontal log
years) index smoking
duration.
Effect of Periodontal treatment
on CVD Outcomes
Title Outcome Number of Overall Level
RCT’s of evidence
met criteria
Effects of periodontal therapy on lipids Lipids (multiple) 7 Moderate
Effects of periodontal therapy on blood pressure Systolic, diastolic 4 Limited

Effects of periodontal therapy on endothelial Endothelial Function 3 Moderate

function
Effects of periodontal therapy on white cell WBC’s 2 Limited
counts
Effects of periodontal therapy on acute-phase Acute-phase reactions 3 Limited
reactants
Effects of periodontal therapy on interleukins, Multiple cytokines 6 for interleukin-6 Moderate
/tumour necrosis factor-alpha, CD40/monocyte and others
chemoattractant
protein-1 and soluble adhesion molecules

Effects of periodontal therapy on haemostatic Multiple factors 2 Limited

factors
Effects of periodontal therapy on matrix Multiple MMPs 1 Limited
metalloproteinases
Effects of periodontal therapy on oxidative Multiple oxidative stress 2 Limited
stress CRP
Effects of periodontal therapy on CRP Paraskevas et al. Moderate
2008
D’Aiuto F, Orlandi M, Gunsolley JC. Evidence that periodontal treatment improves
biomarkers and CVD outcomes. J Clin Periodontol 2013; 40 (Suppl. 14): S85–S105
 Periodontitis and
atherosclerotic
cardiovascular disease:
consensus report of the
Joint EFP/AAP Workshop
on Periodontitis and
Systemic Diseases.
 “There is consistent and strong epidemiologic
evidence that periodontitis imparts increased risk for
future cardiovascular disease;
While in vitro, animal and clinical studies do support
the interaction and biological mechanism,
intervention trials to date are not adequate to draw
further conclusions.
Well-designed intervention trials on the impact of
periodontal treatment on prevention of ACVD hard
clinical outcomes are needed.”

Tonetti MS, Van Dyke TE; working group 1 of the joint EFP/AAP workshop..
J Periodontol. 2013 Apr;84(4 Suppl):S24-9
Stroke/ Ischaemic Cerebral
Infarction &Periodontitis
Etiology of Stroke
Periodontitis as a risk factor for
stroke
 Indirect Systemic effects
• Elevated production of fibrinogen and CRP

Atheroma formation
 Platelet aggregation
• Platelets selectively bind with some strains of
Streptococcus Sanguis and Porphyromonas
Gingivalis.
• Aggregation of platelets is induced by Platelet
aggregation associated protein (PAAP) expressed
on some strains of these bacteria
• Thrombus formation
• Thromboembolism
• Stroke
Prospective studies. The risk of stroke in the periodontitis group is 1.47 times (95%
confidence interval [CI], 1.13-1.92) the risk of the non periodontitis group. RR, Relative
risk.
Retrospective studies. The odds of stroke of the periodontitis group are 2.63 (95%
confidence interval [CI] 1.59-4.34) times the odds of the non periodontitis group. OR,
Odds ratio.
• Association between periodontal disease and
stroke
George S. Sfyroeras, MD, PhD,a Nikolaos Roussas, MD,b Vassileios G. Saleptsis, MD,b
Christos Argyriou, MD,b and Athanasios D. Giannoukas, MSc, MD, PhD, FEBVS,b
Athens and Larissa, Greece

• Conclusions: There is evidence that periodontitis is

associated with increased risk of stroke. However, the
results of this meta-analysis should be interpreted with
caution because of the heterogeneity of the studies as well
as the differences in periodontitis definition. ( J Vasc Surg
2012;55:1178-84)
 Potential mechanisms
involved in the pathogenesis
of periodontitis in diabetes
Taylor JJ, Preshaw PM, Lalla E. A review of the evidence for pathogenic mechanisms
that may link periodontitis and diabetes. J Clin Periodontol. 2013;40(Suppl 14):129.
 Effect of Diabetes on periodontium
Poor periodontal outcomes result from hyperglycemia in
diabetes due to changes in :

Micro-organisms

Host response

Wound healing

Blood vessels
 Change in oral Microorganisms

SALIVARY HIGH GLUCOSE

FLUX CONC IN SALIVA
REDUCTION & GCF

DEVELOPMENT OF
PERIODONTOGENIC FLORA

Thus susceptibility of diabetics to periodontal disease is

increased
 Changes in Immune response
Function of neutrophils and
monocytes altered
Neutrophil
adherence,chemotaxis &
phagocytosis impaired.
Thus periodontitis is
aggravated
Monocytes &
Macrophages often
exhibit elevated
production of
inflammatory mediators,
and this hyperesponsive
state increases host
tissue
destruction
 Altered wound healing

a)The fibroblast, does not function properly in high-glucose

environments.

b) The collagen produced by these fibroblasts is susceptible to

rapid degradation by MMP enzymes which are elevated in
diabetes.

Wound healing responses to chronic microbial insult may be

altered in those with sustained hyperglycemia, resulting in
increased bone loss and attachment loss.
Change in microvascular Integrity
Effect of Diabetes on
Periodontitis
Cianciola et al 1982 In children with Type I diabetes, the prevalence of gingivitis was
greater than in non diabetic children with similar plaque levels

Sastrowijot oS 1990 Improvement in glycemic control may be associated with

et al decreased gingival inflammation

Papapanou PN 1996 Majority of the studies demonstrate a more severe periodontal

condition in diabetic adults than in adults without diabetes.

Tsai C et al 2002 In a large epidemiological study in the united states,adults with

poorly controlled diabetes had a 2.9 fold increased risk of having
periodontitis compared to non-diabetic adult subjects: Conversely
well controlled diabetic subjects had no significant increase in the
risk of periodontitis.

Salvi GE et al 2005 Rapid and pronounced development of gingival inflammation

in relatively well controlled type I diabetic patients than in
non-diabetic controls, despite similar levels of plaque
accumulation and similar bacterial composition of plaque,
suggesting a hyper inflammatory gingival response in
diabetes.
 MECHANISM BY WHICH PERIODONTAL
DISEASE MAY INFLUENCE DIABETES

• Acute Bacterial and Viral Infections

1
• Chronic gram -negative periodontal infections, have
significantly higher serum markers of inflammation,
2 such as CRP,IL6 and Fibrinogen than subjects without
periodontitis.

• Periodontal treatment may reduce inflammation locally

and also decrease the serum levels of the inflammatory
3 mediators,that cause insulin resistance, thereby
positively affecting glycemic control
Effect of Periodontal treatment
on HbA1C Levels
Williams RC Jr., 1960 Type I Diabetic patients with periodontitis had a reduction
MahamCJ in required insulin doses, following scaling and root
planing , localised gingivectomy and selective tooth
extraction combined with systemic procaine penicillin G
and Streptomycin

Taylor GW et al 1996 In a 2 year longitudinal trial,, diabetic subjects with

severe periodontitis at baseline had a six fold increased
risk of worsening of glycemic control over
time,compared to diabetic subjects without periodontitis.

Rodrigues DC et 2003 Better improvement in glycemic control in a diabetic

al group treated with scaling and root planing alone
compared to diabetic subjects treated with scaling and
root planing plus systemic amoxycillin/Clauvalanic acid

In older poorly controlled type 2 diabetic subjects

Promsudthi A et 2005 who received scaling and root planing plus
al adjunctive doxycycline showed a significant
improvement in periodontal health but only a non
significant improvement in HBAIC Values.
Jones et al 2007 No significant benefit was found for
periodontal therapy after 4 months in
this study; trends in some results
were in favour of periodontal
treatment.
Janket et al 2005 Following mechanical debridement
HbA1c levels decreased on average
by 0.38% for all studies. Not
statistically significant.
 Diabetes and periodontal
diseases: consensus report of
the Joint EFP/AAP Workshop on
Periodontitis and Systemic
Diseases
“Overall, there is consistent and robust evidence that
severe periodontitis, adversely affects blood
glucose levels expressed as HbA1C in individuals
with and without diabetes.
Moderate-to-severe periodontitis is associated with
an increased risk for the development of
diabetes.Evidence supports a dose-dependent
role for periodontitis and diabetes complications.”

• Chapple ILC, Genco R, and on behalf of working group 2 of the joint

EFP/AAPworkshop. Diabetes and periodontal diseases: consensus report of the
Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin
Periodontol 2013;40 (Suppl. 14): S106–S112.
Periodontitis and Adverse
Pregnancy Outcome
PERIODONTITIS & ADVERSE PREGNANCY
OUTCOMES
• Preterm birth – one of the most complicated and
challenging issues in perinatal medicine

• Spontaneous preterm birth – social (maternal

race/ethnicity, poverty) and individual risk factors
(underweight, tobacco use, maternal infection).

• Periodontal disease occurs in 40% of pregnant

women (Lieff et al.,2004)
PRE-TERM BIRTH birth <37wks gestational age

birth at 34-36wks gestational age

LATE PRE-TERM BIRTH

VERY PRE-TERM Birth <32wks of gestational age

(Martin et al.,2007)

EXTREMELY PRE-TERM (Martin et Birth <28wks gestational age

al.,2007)

LOW BIRTH WEIGHT (WHO 2005) <2500g

VERY LOW BIRTH WEIGHT (WHO <1500g

2005)
PHYSIOLOGY OF NORMAL LABOUR
ABNORMAL LABOUR
 Psychosocial factors
Socio-economical factors
S
Demographic factors c
h
Infections Disorganization of placentation n
•Urinary passage •Preeclampsia e
•Systemic •Placenta praevia i
•Ascending •Abruptio placentae d
Chrionammionitis e
r

e
t

al
Preterm labour
Premature rupture of membranes 2
Medical induced interruption 0
0
Uterus pathology 6
Fetal pathology
•Deformities
•Deformities Multiple •Myoma
•Chromosomal abnormalities pregnancies •Cervix insufficiency
•Allo-immunopathies
 Landmark study
• Greg Collins (1994) conducted series of experiments
in pregnant hamster animal model. Demonstrated that
chronic exposure to oral pathogens like
Porphyromonas gingivalis in a chamber model
amplifies enhanced fetal-placental toxicity of exposure
during pregnancy.

• Offenbacher et al., (1996) (human study) conducted

a case-control study on 124 pregnant or postpartum
women. Significant association between periodontal
disease and low birth weight.
 Proposed hypothetical model of the association between
periodontal disease and adverse pregnancy outcomes (Ann
Acad Med Singapore 2005)
Infection (bacterial vaginosis, Periodontitis)

Endotoxin/microbiological products

Inflammation

Pro-inflammatory mediator activation

IL-1,TNF-alpha,MMPs

Fetal toxicity
Pre-term low birth weight
Fetal growth restriction
 Systematic reviews
AUTHOR CONCLUSION
Scannapieco et al., (2003) •Periodontal disease may be a risk factor
for PTB/LBW.
•Unclear if PD has a casual role in APO.
•Additional studies needed.

Xiong et al., (2006) •Periodontal disease may be associated

with increased risk of APO

Vettore et al., (2006) •Methodological limitations of studies did

not allow conclusions concerning the
effects of PD on APO.
 Systematic review on periodontal disease & pre-
eclampsia (Alina Kunnen et al.,2010)

• A generalized inflammatory response plays an important role in

the pathogenesis of pre-eclampsia; periodontal disease might
contribute to its pathogenesis.

• Questionable role of periodontal disease

• None of RCTs till date reported reductions in pre-eclamptic rate

after periodontal therapy during pregnancy.

• Larger RCTs – required to explore causuality and biologic

mechanism.
 Meta-analysis
AUTHOR CONCLUSION
Khader & Taani (2005) Periodontal disease in pregnant mother
significantly increases the risk of subsequent
PTB/LBW

Vergnes & Sixou (2007) Likely association of periodontal disease and

APO

Xiong et al., (2007) Periodontal disease may be associated with

increased risk of APO

Meta analysis of RCTs to determine if

Polyzos et al., (2009) periodontal treatment during pregnancy
reduced preterm birth – significantly lower PTB
Effect of Periodontal therapy
on Adverse Pregnancy
outcome
Significant Effect of
Periodontal
Treatment on APO
Lopez et al 2002,2005)
Offenbacher et al., (2006)
Sadatmansouri et al., (2006)
Tarannum & Faizuddin
(2007)
No Significant Effect of
Periodontal treatment on
APO
Michalowicz et al., (2013)
Alcione Maria Soares Dutra
Oliveira (2010)
Nikolaos P Polyzos
(2010)
Jeffcoat et al (2003)
 Periodontitis and adverse pregnancy
outcomes: consensus report of the Joint
EFP/AAP Workshop on Periodontitis and
Systemic Diseases.
“Although periodontal therapy has been shown
to be safe and leads to improved periodontal
conditions in pregnant women, case-related
periodontal therapy, with or without systemic
antibiotics does not reduce overall rates of
pre-term birth and low birthweight.”

Sanz M, Kornman K; Working group 3 of joint EFP/AAP workshop. Periodontitis

and adverse pregnancy outcomes: consensus report of the Joint EFP/AAP
Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol. 2013
Apr;40 Suppl 14:S164-9.
Periodontitis and Respiratory
diseases
• Pneumonia is the inflammation of lung tissues
followed by the accumulation of blood cells, fibrin &
exudates in the alveoli
• COPD is characterized by chronic obstruction to
airflow with excess production of sputum resulting
from chronic bronchitis (CB) and or emphysema.
•Chronic bronchitis is defined as a condition
associated with excessive tracheo-bronchial
mucus production to cause cough with
expectoration for at least 3 months of the year, for
more than 2 consecutive years.
•Emphysema is defined as the distention of the air
spaces distal to the terminal bronchiole with
destruction of the alveolar septa
• VAP – pneumonia developing in 48hrs or more after
initiation of mechanical ventilation

• HAP – pneumonia with an onset 48hrs or more after

admission to the hospital

• Scannapieco’s report (1992) – oral and/or

periodontal infection may increase the risk for
bacterial pneumonia or COPD
Etiopathogenesis
• Four important mechanisms have been
proposed to explain, how oral bacteria can
participate in the pathogenesis of respiratory
infection.
• 1. Oral pathogens may be aspirated into the
lung.
• 2. Enzymes in the saliva, which are
associated with periodontal disease, may
modify mucosal surfaces to promote adhesion
and colonization by respiratory pathogens.
 • 3. Periodontal disease associated enzymes
may destroy salivary pellicles on pathogenic
bacteria.

• 4. Cytokines released during periodontal

disease process may alter respiratory
epithelium to promote infection by respiratory
pathogens

Scannapieco FA ,Role of Oral Bacteria in Respiratory Infection, J Periodontol 70, 1999,

793-802 .
 Aspiration of bacteria from oral cavity

Entry into upper airway & lungs

Failure of host defense to clear bacteria

Lung infection

VAP Bacteria adhere to endotracheal

tube surface

Growth of biofilm

Biofilm dislodged & embolize distally to set up foci of infection

Interventional Studies
AUTHOR ORAL RESULT
INTERVENTION

DeRiso et al., (1996) 0.12%CHX with ventilator 69% reduction in total

WP respiratory tract infections

Houston et al., 0.12% CHX versus 52% reduction in overall rate

(2002) Listerine of pneumonia in CHX group

Flanders et al., 0.12% CHX gel 3times a Did not reduce nosocomial
(2006) day infections

Scannapieco Oral topical 0.12% CHX CHX reduced the number of

etal.,(2009) or placebo S.aureus but not enterics.
Non-significant reduction in
pneumonia rate noted in CHX
group
 Systematic reviews
AUTHOR FINDING

Scannapieco et al., (2003) No sufficient evidence to say

there is an association between
periodontal disease and COPD

Azarpazhooh & Leake (2006) No sufficient evidence to say

there is an association between
periodontal disease and COPD
 Periodontitis and systemic
diseases: a record of discussions
of working group 4 of the Joint
EFP/AAP Workshop on
Periodontitis and Systemic
Diseases
 COPD
• “An association with periodontitis is suggested based
on analyses of the NHANES data sets. There
appears to be a dose effect, whereby greater
periodontal disease is associated with
increasing loss of lung function.
• The primary aetiological factor is smoking as
modified by underlying inflammation.
• Studies of the association between periodontal
disease and exacerbations of COPD would be
valuable.”
 Pneumonia
“The association between dental plaque and
pneumonia appears to be stronger than for plaque
and COPD. That improved oral hygiene reduces the
risk of health care-associated
pneumonia is suggested by several meta-analyses.
The relationship with periodontitis however is not
known.”

Linden JG ,Herzberg MC, Periodontitis and systemic diseases:a record of

discussion of working group 4 of the Joint EFP/AAP Workshop on Periodontitis
.
and Systemic Diseases , J Periodontol , 84(4 suppl.), 2013, S20-3
Periodontitis & Rheumatoid
arthritis
The area of lavendar overlap indicates similarities in clinical and pathological features
between Rheumatoid arthritis and periodontitis.

Dimensions of dental hygiene March 2008

 Periodontitis Intervention Studies in
Rheumatoid Arthritis Patients
Study No of Design/Duration Main systemic
patients/Periodontal findings
treatment
Ribeiro et al. RA Control: n = 16, Randomization not
(2005) OHI + Supragingival specified ↓ ESR in experimental
Cleaning − 3 months group; No change in
RA Experimental: n = 26, RF or HAQ
OHI + Supragingival
Cleaning + SR

Al-Katma et al. RA Control: n = 12, no Randomized ↓ ESR and DAS28 in

(2007) treatment − No intent-to-treat experimental group
RA Experimental: n = 17, analysis (i.e., compared with control
OHI + SRP dropouts not included group; No change in
in analysis) swollen or tender joint
− 8 weeks count, global well-
being or morning
stiffness
 Periodontitis Intervention Studies in Rheumatoid
Arthritis Patients
Study No of
patients/Periodontal
treatment
Pinho et al.(2009) RA Control: n = 15, no
periodontal treatment
RA Control: n = 15, full
mouth extraction, no
follow-up visit
RA Experimental: n = 15,
SRP
2 additional groups, n = 15
each, without RA
Ortiz et al.(2009) RA Control: n = 20, no
periodontal treatment, half
on anti-TNF-α
RA Experimental: n = 20,
SRP + OHI + half on anti-
TNF-α
Design/Duration Main systemic
findings
Non-randomized No differences at 6
− 6 months months between RA
groups in ESR or
other acute phase
reactants or DAS28
Randomized ↓ DAS28, swollen and
− 6 weeks tender joints, global
well-being, and TNF-α
in group receiving
periodontal treatment
Study No of Design/Duration Main systemic
patients/Periodontal findings
treatment
Erciyas et al. RA patients with 3 months ↓ DAS28, ESR, CRP
(2013) moderate-to-high DAS28 and TNF-α in both
scores, n = 30 groups at 3 months
RA patients with low
DAS28 scores, n = 30
Both groups received
OHI + SRP
Okada et al. RA Control: n = 29, no Randomized Greater ↓ in DAS28-
(2013) periodontal treatment − 8 weeks CRP and serum IgG
RA Experimental: n = 26, to P. gingivalis and
OHI + supragingival citrulline in the
scaling periodontal treatment
group than in the
control group; No
change in swollen or
tender joint count,
global well-being,
CRP, RF, or anti-CCP
antibody
 Periodontitis and systemic
diseases: a record of discussions
of working group 4 of the Joint
EFP/AAP Workshop on
Periodontitis and Systemic
Diseases
• “Reports of an epidemiological association
with periodontal disease,including the
NHANES data set and case-control studies,
are inconsistent.
• Animal studies provide biological plausibility.
(Kinloch et al. 2011).
• In human rheumatoid arthritis, antibodies
against citrullinated proteins and peptides are
often detected in the blood reflecting the
enzymic conversion of arginine residues to
citrulline in certain proteins.
• Biological plausibility for an association with
periodontitis is also reflected in the
detection of citrullinated proteins in inflamed
gingiva, which may be associated with
elevated auto-antibodies to self-antigens
(Nesse et al 2012)
Periodontitis and Chronic Renal
Disease
Oral manifestations of CKD
 Effect of Periodontitis on CKD

• 1. Systemic inflammation due to periodontitis can

affect the kidneys
• 2. Bacteria from plaque can invade the endothelium
of kidney forming atheromatous lesions, thus
decreasing blood flow to the organ
• 3. CRP Levels ↑ and levels of albumin in blood↓

• Arsalan Wahid, Saima Chaudhry, Afifa Ehsan, Sidra Butt, Ayyaz Ali Khan
Bidirectional Relationship between Chronic Kidney Disease & Periodontal Disease
.Pak J Med Sci. 2013 Jan-Mar; 29(1): 211–215
 Clinical Trials regarding Effect of periodontal therapy in CKD
patients
Researcher Participants Periodontal Outcome Results
treatment measures

D'AiutoF, et 65 SCRP Serum

al.(London) inflammatory Reduction after
markers CRP, treatment
IL-6
SCRP
Mattila K, et al. CRP decreased
35 CRP, fibrinogen
(Finland) Fibrinogen no effect

MercanogluF, SCRP
Improvement after
et al. 54 Endothelial
periodontal treatment
(Turkey) dysfunction
SCRP CRP and ESR
Kadiroglu AK,
decreased and Hb
et al. 41
CRP, ESR, Hb increased after
(Turkey)
periodontal treatment
 Clinical Trials regarding Effect of periodontal therapy in CKD
patients
Researcher Participants Periodontal Outcome Results
treatment measures

SCRP
Artese HP, et
Significant improvement
al. 40 GFR
after therapy
(Brazil)

Radafshar G, SCRP
Significant decrease
et al. 35 CRP
after therapy
(Iran)

SCRP CRP decreased, IL-6

Vilela EM, et al. CRP, IL-6, decreased,
56
(Brazil) Prohepcidin Prohepcidin levels
decreased
Arsalan Wahid, Saima Chaudhry, Afifa Ehsan, Sidra Butt, Ayyaz Ali Khan
Bidirectional Relationship between Chronic Kidney Disease & Periodontal Disease .
Pak J Med Sci. 2013 Jan-Mar; 29(1): 211–215
 Periodontitis and systemic
diseases: a record of discussions
of working group 4 of the Joint
EFP/AAP Workshop on
Periodontitis and Systemic
Diseases
• “The association between chronic kidney
disease (CKD) and periodontitis in several
studies is statistically significant and
consistent. Although hypertension and
diabetes are the primary aetiological factors,
periodontitis is hypothesized to modify both
these aetiological factors and consequently
the presentation of
CKD.”
Periodontitis and Stress
Periodontitis and Obesity
 Periodontitis and systemic
diseases: a record of discussions
of working group 4 of the Joint
EFP/AAP Workshop on
Periodontitis and Systemic
Diseases
• “Many clinical studies of obesity and
periodontal disease have been reported
including a number of systematic reviews.
There are a few prospective studies indicating
an association with periodontitis. More
specifically, the literature suggests
that obesity might adversely affect
periodontitis, but there is little evidence
from clinical data or for biological plausibility
that periodontitis may affect obesity.”
 Periodontitis and Cancer

Sahingur SE and Yeudall WA (2015) Chemokine function in periodontal disease and oral
cavity cancer. Front. Immunol. 6:214
Author Study Design Oral health Study Results
Criteria Population

Bundgaard et al Case Control Missing teeth 161Patients and Sinificantly

(1995) 400Controls increased risk
of developing
oral SCCA for
patients with
fewer than 15
teeth
Rezende et al Case Control CPITN and 50 Patients and 76% of subjects
(2008) DMFT 50 Controls in cancer group
(Cuba) showed greater
than 10mm
pockets
compared to
control group.

Garrote et al Case Control Missing teeth 200 Patients Significantly

(2001) and controls increased risk
(Cuba) of oral cancer
for patients
missing16 or
Author Study Design Oral health Study Results
Criteria Population

Tezal et al (2005) Cohort Clinical 131 oral Significantly

attachment tumours and increased risk
loss(CAL) 323 oral of oral tumour
precancerous and
lesions. (United precancerous
States) lesion
with>1.5mm
CAL
Tezal et al (2009) Case Control Alveolar bone 266 Patients Significantly
loss and 207 increased risk
Controls of oral cavity
SCC with
periodontitis.
Wen et al (2014) Cohort Medical records 96,375 gingivitis Significantly
from insurance and 51,791 increased risk
claims periodontitis of oral cancer
cases.(Taiwan) with the history
of periodontitis
Sahingur SE and Yeudall WA (2015) Chemokine function in periodontal disease and oral
cavity cancer. Front. Immunol. 6:214
 Periodontitis and systemic
diseases: a record of discussions
of working group 4 of the Joint
EFP/AAP Workshop on
Periodontitis and Systemic
Diseases
• “Prospective and case-control studies suggest
an association between periodontitis and oral
and oro-pharyngeal
cancer. Whereas some oral microbes can alter
cells and tissues consistent with features of
malignant changes, additional biological
plausibility, clinical and robust epidemiological
data are needed to strengthen such
associations.”
 SYSTEMIC DISEASES ASSOCIATED WITH
PERIODONTAL DISEASE
• Alzheimers disease • Intellectual function
• Aneamia • Leukemia
• Atheroschlerosis • Low birth weight
• Auto-immune disease • Lung cancer
• Cancer • Lupus
• Chronic obstructive pulmonary disease • Metabolic syndrome
• Colon cancer • Miscarriage
• Crohns disease • Mouth cancer
• Death • Multiple sclerosis
• Dementia • Obesity
• Diabetes • Obstructive sleep apnea
• Dry mouth • Osteoporosis
• Endometriosis • Pneumonia
• Erectile dysfunction • Polycystic ovaries
• Fatigue • Pre-eclampsia
• Fever • Premature birth
• Fibromyalgia • Psoriasis
• Gastro-oesophageal reflux disease • Renal disease
• Hypertension • Rheumatoid arthritis
• Infertility • Stroke
• Inflammatory bowel disease • Stomach ulcers

Mark Bartold Editor, Australian Dental Journal ,2012

CONCLUSION
 Slot’s Criteria for Causal link between
Periodontitis & Systemic Diseases
• 1.The prevalence and incidence of the systemic disease
in question should be significantly higher in periodontitis
patients than in periodontally healthy ones (retrospective
research);
• 2. The onset of the systemic disease should follow the
onset of periodontitis (prospective research);
• 3. The removal or reduction of periodontitis should
decrease the incidence of the medical disease
(intervention research);

Casual or causal relationship between periodontal infection and non-oral disease? Slots,
Jorgen. Journal of Dental Research; Houston77.10 (Oct 1998): 1764-5.
• 4. The microorganism(s) of the systemic disease should
be the same species, biotype, serotype, and genotype as
the oral microorganism(s) (research on specific etiologic
agents);
• 5. Appropriate experimental animals with periodontitis or
with inoculated microorganism should develop more
systemic disease than periodontally healthy animals
(animal research);
• 6. The postulated association between periodontal
disease and systemic disease should be biologically
feasible (research on pathogenic mechanisms).

Casual or causal relationship between periodontal infection and non-oral disease?

Slots, Jorgen. Journal of Dental Research; Houston77.10 (Oct 1998): 1764-5.
• Thus these and other criteria have to be
fulfilled for a link between Periodontitis and
other systemic diseases.
• As of now the evidence is weak, many
longitudinal interventional studies have to be
conducted and substantial evidence gathered,
to uphold earlier research about periodontal
medicine.
 Questions
• 1.Discuss the inter-relationship of Diabetes and
Periodontal Disease. (March 2007)
• 2.Describe in detail the significance of periodontal
diseases in the etiology of preterm low birth
weight.(Sept 2007)
• 3.Periodontal Medicine (November 2007)
• 4. Discuss the effect of Periodontal disease on
systemic health. (March 2008)
• 5. Discuss the role of stress in periodontal
disease.(March 2009)
• 6.Discuss the influence of diabetes mellitus on
the periodontium. (March 2009)
• 7.Periodontal disease and diabetes-
Discuss.(March 2010)
• 8. Periodontal disease and preterm labour.
Discuss(Sept 2010)
• 9.Elaborate on periodontitis as a risk factor for
adverse pregnancy outcomes. (October 2012)
• 10. Periodontitis as a risk factor for
cardiovascular diseases. (October 2014)