RISK FACTORS FOR

PERIODONTAL

DISEASES
 Introduction
In assessing risk for disease,
periodontitis can be thought to be
more like some of our common
medical conditions: certain people
are at higher risk than others, and
efforts at prevention and
intervention involve a combination of
personal behaviors and professional
practices.
 Risk assessment efforts applied to
periodontitis have only recently received
attention, primarily because of the prior
paradigm regarding the etiology and
progression of the disease involved a
ubiquitous condition, gingivitis inevitably
leading to periodontitis.
Under this paradigm, the prevalence of the
condition was extremely high and little error
in prediction resulted when everyone was
categorized as having the disease.
 As our concepts of periodontal diseases
evolved, we realized that the prevalence
and incidence rates for periodontitis
were much lower than were estimated
previously and that some people were
more likely to be affected with the
condition than others.
It is no longer appropriate to consider
all people to be at the same level of risk
for periodontitis.
Thus, the identification of risk factors
serves two important purposes.
Risk factors should be able to be used
to more accurately identify who is at
risk for the condition and
They can provide clues to appropriate
avenues of intervention.
 THE RISK ASSESSMENT PROCESS
In an attempt to clarify the process of
identifying high-risk individuals, a research
group at the University of North Carolina has
delineated a 4-step process.
Identification of risk factors.
Development of a risk assessment model or
models.
Assessment.
Targeting.
Beck JD, Kohout F, Hunt RJ 1988.
 Identification of risk factors

The first step, is to determine if the

disease is distributed randomly or
whether there are identifiable factors
that are associated with the disease.
Clues to these factors usually come
from clinical impressions, animal and in
vitro laboratory experiments, and from
prevalence surveys of populations.
 When a disease is found to have
multiple risk factors (as is the case for
periodontitis), testing the ability of one
risk factor at a time to identify
individuals at risk gives an incomplete
picture and the development of a risk
assessment model becomes necessary.
 Development of a risk assessment
model or models.
Entails putting together the relevant risk
factors into a multivariate model that
identifies the combination of factors that will
most efficiently distinguish between those
who are at high or low risk of developing the
disease.
This model is then verified using data sets
from other populations before being tested
on new populations to determine its utility
and efficiency.
 Assessment

The third step involves screening

population groups for the factors
included in the risk assessment model
and using the model to predict each
individual's risk of developing disease.
 Targeting

The fourth step, targeting, involves the

application of some health
promotion/disease prevention regimen
or treatment procedure to the
individuals at increased risk with
evaluation of the effectiveness of the
intervention.
 Terminologies

Risk is defined as the probability of an

individual's developing a given disease
or experiencing a health status change
over a specified period.
Numerically, risk is expressed as a
dimensionless value between zero and
one, and requires a time referent.
 Terminologies
Risk factor - implies that there are certain
factors associated with an increased or
decreased probability of an individual
developing a disease or experiencing a
health status change.
A risk factor is thought to be causal for a disease. As
such, it should satisfy two criteria:

1) it is biologically plausible as a causal agent for

disease.

2) it has been shown to precede the development of

disease in prospective clinical studies.

Smoking is an example of a risk factor for

periodontal disease, since there are a number of
biologically plausible explanations for it as a causative
agent for periodontal disease, and prospective clinical
studies have shown that smokers are more likely to
develop periodontitis than nonsmokers.
 Risk factor is more appropriately
reserved for those factors that have
been verified to be associated with
disease through longitudinal studies.
A risk factor that can be used to predict
the future course of the disease, such
as an increased probability of disease is
known as risk marker.
 Risk indicator is a factor that is biologically
plausible as a causative agent for disease but
has only been shown to be associated with
disease in cross-sectional studies.
Some risk indicators may be proven to be risk
factors if prospective studies are able to confirm
that they precede the development of disease.
 Relative risk is the probability of developing
disease if one is exposed to a given factor
compared with the probability of developing
the disease.
It is the ratio of risk of disease in the exposed
group to the risk of disease in the nonexposed
group.
Background characteristics- a risk marker or
predictor that may be strongly predictive of
disease but at present is not changeable.
 Odds ratio is defined as the odds of having
disease if one is exposed to a risk factor
compared with the odds of having the
disease if one is not exposed to the same
factor.
RR is a measure of association that is only
obtained from longitudinal studies while OR is
the measure of association that is obtained
from cross sectional studies.
While both relative risk and odds ratios are
used to quantify risk, relative risk is generally
more intuitively meaningful for clinicians.
 Study Designs Needed For Risk
Assessment
Formalized criteria were set up to assess
whether evidence from observational
studies supported a causal interpretation.
These criteria, discussed by Lilienfeld, are
as follows:
 Strength of the association
Specificity of the association
Degree of exposure
Consistency of association
Temporal consistency/ correct time
sequence
Biological plausibility
 Strength of the association - A valid
study is one that is free from error. The
stronger the association, the less likely
the association is entirely due to error
that might distort the results.
 Specificity of the association - If a given
factor is related to other diseases, its
association with the disease is less likely to be
interpreted as causal.
While a specific association may be more
likely to be causal, lack of specificity cannot
justify rejecting causality, because many
diseases have multiple causes, a single factor
may produce a number of different diseases,
and a single factor may be a vehicle for other
factors.
Furthermore, there is no reason to assume
that the relationships between one factor and
each of a variety of diseases have similar
explanations.
 Degree of exposure (dose-response effect) -
If a factor is of causal importance, then the
risk of developing the disease should be
related to the degree of exposure to the
factor.
Consistency of association - A factor is more
likely to be causal if all studies dealing with
the relationship produce similar results. This
is especially true if the studies involve
different populations, methods, or time
periods.
 Temporal consistency - The potential
factor must precede the occurrence of
the disease.
The inability of cross sectional studies
to determine whether the factor
occurred before the onset of disease is
a major problem in determining
causality and thus whether it is a true
risk factor.
 Biological plausibility - The association
must make sense in light of current
knowledge.
However, the less we know about a
disease, the less likely we are to reject the
association as causal, because it does not
meet this criterion.
Beck et al 1994, Offenbacher 1996 have added
one more criteria -
Support from experimental evidence-
experimental reproduction of the disease
should occur frequently in animals exposed to
risk factor.
RCT which test the effect of intervention to
prevent disease occurrence are also strong
evidence of a causal relationship.
 The majority of evidence for the identification
of possible risk factors for periodontal
diseases comes from observational (non-
experimental) case-control and cross
sectional epidemiologic studies, bolstered by
evidence from in vitro and in vivo laboratory
experiments.
These case-control (case history) and cross-
sectional (survey) studies have either
backward (retrospective) or nondirectional
designs resulting in our inability to show that
the presumed factor actually was present
prior to the development of the disease or
condition.
 Since these types of studies do not have a
forward (prospective) design that
identifies the presence of a potential risk
factor prior to the development of the
disease, they permit the delineation of
associations between factors and disease,
but in no way speak to the temporal
sequence of events.
 To complicate matters, periodontal
disease is considered to have multiple
risk factors.
Thus, we should neither expect a risk
factor to have a perfect relationship
with the disease of interest, nor should
we expect intervention aimed only at
one risk factor to reduce the risk to
zero.
 Putative risk factors- factors that are
confirmed by means of longitudinal
studies and meet the criteria described
by Lilienfeld above are properly called,
putative risk factors but it is recognized
that putative risk factors often are
referred to as risk factors.
How Should High Risk Be Defined?
Periodontal diseases have a number of characteristics
that must be considered in developing risk models.
First, periodontitis appears to be an infectious
disease that has many characteristics of a chronic
disease; i.e., most forms progress slowly and some
aspects are not reversible, even though the infectious
agent is removed.
The disease exhibits a pattern of multiple attack,
often affecting 1 or more sites around 1 or more
teeth. This phenomenon of multiple attack results in
the measures of the disease being very sensitive to
tooth loss and creates a problem of repeated, non-
independent measures.
 Finally, the way in which the disease progresses
is not clear, creating problems in measurement
of active disease and in defining a "case."
Clinical attachment loss over time is generally
accepted as an indicator of periodontal disease
progression and is the measure predominantly
used in longitudinal epidemiologic studies.
How Should High Risk Be Defined?

1) The medical model of "presence or

absence" of the disease;
2) Define high risk as people in the
highest percent (5, 10, 15%, etc.) of
sites with attachment loss;
3) Determine a clinically significant cut-
point; or
4) Use some combination of these
definitions.
 Should Risk Models or Prediction
Models Be Developed?

Strictly speaking, both risk models and

prediction models for periodontitis are
used to predict people who are likely to
experience attachment loss.
The distinction between the two types
of models is based on the purpose of
the models which determines the types
of variables used in the prediction
process.
 There are essentially three types of
variables that are used in the development
of multivariate models
Risk factors
Background characteristics
Risk predictors
 The first type are risk factors; i.e.,
characteristics that are thought to be
etiologic for the disease of interest. Risk
factors may be divided into two types:
*those that can be modified (levels of
putative pathogens) and
*those that are immutable to change
(genetic factors).
 The second type are background
characteristics; i.e., characteristics that
are not thought to be etiologic, but are
immutable to change, which may be
confounders or effect modifiers for the
risk factors.
 The third type are risk predictors. Risk
predictors usually are either biologic markers
that are indicative of disease or disease
progression, but currently are thought not to
be etiologic or are alternative historical
measures of the disease being studied, such
as number of missing teeth or past evidence
of periodontal disease.
 The construction of a multivariate model must
be based on the intended use of the model;
i.e., prediction of people at high risk and
delineation of risk factors, or simply
prediction of people at high risk.
If the purpose is prediction and delineation of
risk factors in order to develop the most
effective prevention or treatment
interventions, then "risk model" should be
developed.
This risk model should contain only risk
factors and appropriate potential background
characteristics, such as age, ethnicity, or
gender that are immutable to change, but
may interact with the risk factors.
 The Piedmont 65 + Dental Study

The Piedmont 65 + Study of the Elderly is a

longitudinal investigation of a random sample of over
4,000 community-dwelling people over the age of 65
in 5 contiguous North Carolina counties under the
direction of investigators from the Duke University
Center on Aging.
One of the primary purposes of the study was to
describe the functioning and health status of older
blacks, for whom little is known. Thus, the sample
was stratified on race to assure equal numbers of
blacks and whites.
 Interview- use of dental services; barriers to
care; pain and discomfort; perception of
mouth dryness, mouth health, and mouth
appearance; family history of edentulism; a
dental impact profile; preventive dental
behaviors; fluoride history; perceived denture
problems; and a multidimensional locus of
control.
Oral examination,
Microbiological and salivary assays- BANA
Test and immunofluorescent assays for
Actinobacillus actinomycetemcomitans,
Prevotella intermedia, and Porphyromonas
gingivalis.
 Definitions of high risk
Since almost everyone had some evidence of
periodontal destruction at baseline, it was
decided that the high-risk group would be those
people with more serious disease.
Serious disease was defined as having 4 or more
sites with loss of attachment of 5 + mm with 1
or more of those sites having a pocket depth of 4
+ mm.
This definition was based on a combination of
the distribution of the condition in the population
and periodontists' judgments as to what
constituted serious disease in this age group.
 Findings from the Piedmont baseline
examination are cross-sectional and are
compared with longitudinal findings from the
same study to determine how frequently risk
indicators are confirmed as risk predictors or
risk factors.
Eg.; The baseline analysis shows that people
who use tobacco have more than 6 times the
odds of being in the serious periodontal
disease (SLA) group and tobacco was
confirmed as a risk factor, but with a lower
odds ratio.
 Findings from the Piedmont 65 +
Dental Study

Risk indicators developed from cross-sectional

studies are quite often not confirmed as risk
factors and the models developed from
longitudinal data implicate putative risk
factors that were not evident in the
prevalence data.
This indicates that we should be reluctant to
accept characteristics associated with
periodontitis in cross-sectional studies as risk
factors.
 The risk models indicated that oral risk
factors were important in explaining disease
progression, but that other categories of risk
factors also played an important explanatory
role and did increase the predictive ability of
the models.
The models did not perform well in
distinguishing between those people who
would have attachment loss during both 18-
month periods and those who had it only one
of the two periods.
 However, the models were able to
predict who would experience
attachment loss at some time during
the 3-year period with a high degree of
accuracy.
Unfortunately, the models had only
moderate success at predicting who
would not experience attachment loss.
 Including risk predictors in the models did
improve the ability of the model for whites to
predict attachment loss, but the risk predictor
did mask the presence of an important risk
factor.
The Piedmont 65 + Dental Study did not
include any measures of host defense
mechanisms. It is highly likely that including
host defense measures along with reducing
the measurement error for attachment loss
can result in improved models.
 Risk factors in periodontics
Genetics
Clinical risk factors
Bacterial risk markers
Neutrophil defects
Diabetes
Oral hygiene and compliance
Tobacco
 Utilization of dental services
Psychosocial stress
Allergy
HIV infection
Osteoporosis
Anemia
 Age
Medicine
Nutrition
Oral hygiene status
Socioeconomic status and
Educational level
Periodontal disease severity at baseline.
Genetic and Heritable Risk Factors in
Periodontal Disease

Periodontal diseases are a heterogenous

group of diseases that affect more than
hundreds of millions around the world.
While microbial and other environmental
factors are believed to initiate and modulate
periodontal disease progression, there now
exists strong supporting evidence that genes
play a role in the predisposition to and
progression of periodontal diseases.
 Results suggest that <20% of variability
in periodontal disease expression can be
explained by specific microbes alone.
A major part of the shift in thinking
therefore involves the recognition that
bacteria are necessary for initiation and
progression, but other factors such as
genetics, smoking strongly influence
severity of disease.
 However, it seems clear that most forms of
periodontitis with postpubertal onset are not
inherited as Mendelian diseases, that is, they are
probably not caused by major genes.
Rather, many polymorphic genes with relatively
small but significant associations with disease
risk may interact to contribute to overall risk.
 Terminologies
Gene-a hereditary unit that occupies a
specific position (locus) within a chromosome.
Allele one of the several alternate forms of
a given gene differing in DNA sequence.
Polymorphism a region on the genome that
varies between individual members of a
population present in a significant no. of
individuals.
When a specific allele occurs in at least
1% of the population, it is said to be a
genetic polymorphism.
 Genes which are involved in complex
multifactorial diseases are called
modifying disease genes. (Hart 1996)
Genes which in the presence of
abberant allelic form are responsible for
disease expression according to
Mendels law major disease genes.
To date, in relation to periodontitis only
one major disease gene, identified and
localized on chromosome 11
responsible for severe form of
prepubertal periodontitis (Hart et al
2000)
 Cytokine gene polymorphism
There are several arguments as to why genes
encoding for IL-1 and TNF- are good
candidates for genetic studies in relation to
periodontitis.
IL-1 and TNF- play important roles in
pathogenesis of periodontitis. Both are potent
immunologic mediators with proinflammatory
properties.
IL-1 and TNF-- increase bone resorption and
regulate fibroblast cell proliferation both from
gingival and PDL origin.
 Levels of these cytokines are increased in
periodontal tissues.
Genetically determined interindividual
differences have been observed for IL-1 and
TNF- production by peripheral blood PMNs.
It is conceivable that these differences in
production and secretion play a role as
susceptibility or severity factor.
These alleles have been suggested as a
potential genetic marker for diseases eg; IL-1
polymorphism Sjogren syndrome.
TNF- polymorphism chronic inflammatory
disease processes.
 Interleukin 1
polymorphism
It is a powerful and potent bone-resorbing
cytokine and the gene for the same is located on
chromosome 2. It exists in two forms IL-1 and
IL-1; Both IL-1 and IL-1 have the above
effect. It stimulates the production and release
of PGE2 thereby stimulating bone resorption.
Direct action of IL-1 on osteoclast is also known
to occur through an 80 kDa receptor.
 In 1997, Kornman et al. found an association
between polymorphisms in the genes encoding for
IL-1 (-889) and IL-1 (+3953) and an increased
severity of periodontitis. This initial study has since
spawned numerous publications and has been the
most influential in creating interest in gene
polymorphisms and periodontal disease.
Functionally, the specific periodontitis-associated IL-
1 genotype consists of a variant in the IL-1B gene
that is associated with high levels of IL-1
production (Pociot et al., 1992, 1993).
Kornman et al. (1997) found that 86.0% of the
severe periodontitis patients were accounted for by
either smoking status or by the IL-1 genotype.
 The combined carriage of R-allele of IL-1 (-
889) and IL-1(+3953) is designated the IL-1
composite genotype (Kornman et al 1997).
IL-1 composite genotype increased the risk of
tooth loss by 2.7times and when combined
with heavy smoking the risk was 7.7 times.
McGuire and Nunn(1999)
Patients with IL-1 composite genotype often
harbor putative periodontal pathogens.
Socransky et al 2000.
 Laine et al 2001 reported increased
frequency of R-alleles for IL-1 ,IL-1
and IL-1RA genes in nonsmoking
patients in whom P.g and A.a could not
be detected.
All these studies suggest that IL-1
polymorphism play a role in the
absence of other putative risk factors.
Smoking and IL-1 gene cluster

Meisel et al., (2002) in a Caucasian study

evaluated the extent of attachment loss
defined associated with the composite
genotype of IL-1/1 in smokers. They found
no differences in genotype negative subjects
irrespective of their smoking status. They had
nearly identical attachment loss as genotype
positive non-smokers. Hence, they concluded
that smoking + combined genotype positive
for IL-1/ IL-1RN, showed enhanced risk of
attachment loss.
 Tumor Necrosis Factor (TNF-)
gene polymorphisms
The TNF- cytokine is crucial to both the
immune and inflammatory responses.
The gene is located on chromosome 6 within
the MHC gene cluster.
The genetic polymorphisms are mainly G to A
transitions.
Craandijk et al., (2002) also found no
significant associations between a different
series of four TNF- gene polymorphisms and
periodontitis patients.
 Shapira et al., (2001) studied L-EOP
affected and healthy subjects within the
families for polymorphism at -308
position of the TNF- promoter region. In
affected children 81% were G/G
genotype and 19% with A/G genotype; in
healthy 74% were G/G genotype, while
26% had A/G genotype. They concluded
that there was no link between L-EOP
and of the TNF- (-308) promoter
polymorphism.
 One microsatellite at the TNF locus on
chromosome 6, TNF was analyzed in 77 GAgP
patients by Kinane et al., (1999). Due to the
highly polymorphic nature of the microsatellite
loci, a statistical comparison with ethnically
matched healthy controls (TNF- n = 91) was
conducted. No significant differences were
observed between cases and controls for
carriage of these TNF- microsatellite
polymorphisms.

Based on literature to date, it is concluded that

there is no indication that any reported gene
variation are related to susceptibility or severity
of periodontitis.
 Other gene polymorphisms
Interleukin-4 (IL-4) is a potent down regulator of
macrophage function. A higher occurrence of IL-
4 gene polymorphism has been demonstrated in
a group of aggressive periodontitis patients than
controls.
Michel J, Gonzales JR, Wunderlich D, Diete A,
Herrmann JM, Meyle J. J Clin Periodontol 2001.
Interleukin-10 gene polymorphism

Studies assessing the interleukin-10 gene

polymorphism failed to identify a significant
association between this genotype and
chronic periodontitis or aggressive
periodontitis.
RECEPTOR POLYMORPHISMS
Fc Receptors are the membrane glycoproteins which
have affinity for the Fc portion of the antibody
molecule. They allow passive acquisition of antibody
by many cell types like B and T lymphocytes, PMNs,
Mast cells, Eosinophils, Macrophages and NK cells.

Loos et al., (2003) studied Northern European

Caucasian with AgP, Chronic Periodontitis for the
presence of FcRIIa (R131 or H131), FcRIIIa (V158
or F158) and FcRIIIb (NA1 or NA2) genotypes.
 They reported that FcRIIa-H/H131
genotype may be a putative
susceptibility and severity factor, and
FcRIIIa-V158 allele a putative
susceptibility factor for periodontitis in
Northern European Caucasians.
On the other hand, Fc gamma RIIIa
gene polymorphism was associated with
a significantly higher risk (OR=45) for
severe bone loss and chronic
periodontitis in Japanese and Caucasian
subjects.
 A study in a group of elderly Japanese
found that human neutrophils IgG Fc
receptor IIIb gene polymorphism was
prevalent in subjects with little attachment
loss and high tooth retention, and
concluded that this genotype was
associated with resistance to periodontitis.
FMLP Receptor polymorphisms

Decreased chemotaxis of neutrophils may be

caused by a number of abnormalities
including a reduced fMLP receptor density
and other defects in neutrophil cells .
Gwinn et al. reported a strong association
between fMLP receptor single nucleotide
polymorphism and localized aggressive
periodontitis.
They noted that 29 out of 30 localized
aggressive periodontitis patients had single-
strand conformation polymorphism patterns.
 Vitamin D Receptor (VDR) gene
polymorphisms
It has been suggested that genetic
polymorphisms in the vitamin D receptor
gene are associated with bone
homeostasis and increased risk for
systemic bone loss, such as osteoporosis.
Furthermore, it has been hypothesized
that vitamin D receptor polymorphism may
play a role in alveolar bone loss and in the
development of periodontal diseases.
 Hennig et al. studied this gene
polymorphism in aggressive periodontitis
patients and controls and found a
significant association between the
genotype distribution and the occurrence
of localized aggressive periodontitis.
They attributed this association to a higher
prevalence of the less frequent allele (t) in
the localized aggressive periodontitis
group (52.5%) than in the control group
(31.9%).
Conclusion of status of genetics as a
risk factor
Genetic polymorphisms probably exist in many if
not most of the inflammatory and immune
mediators, however it is likely that
Not all polymorphisms impart differential
susceptibility to destructive aspects of the
disease.
A number of genes will be identified as important
in this regard.
Knowledge of these may permit determination of
individual risk for many individuals.
TOBACCO AS A RISK FACTOR
 The concept that smoking tobacco may
be prejudicial to periodontal health is
not new, an association between acute
necrotizing ulcerative gingivitis and
smoking having been observed in the
late 1940s (Pindborg, 1947).
 STRENGTH OF ASSOCIATION

The stronger an association between a given

factor and a disease, the more likely this factor
will implicated as a risk factor.
Numerous cross-sectional studies on the effect
of smoking on periodontal health have been
reported, with odds ratios generally in the order
of 2 to 6.
 One of the largest studies of risk factors for
periodontal disease was that undertaken in
Erie County, New York State.
Involving 1361 subjects aged 25 to 74 years,
this study showed that those who smoked
were at greater risk for experiencing severe
bone loss than those who did not smoke, with
odds ratios ranging from 3.25 to 7.28 for light
and heavy smokers, respectively
Grossi et al., 1995.
 A more recent study of 540 Swedish adults
20-70 years of age has revealed that the
three variables- smoking, greater age, and
higher mean plaque levels were potential risk
factors for severe periodontitis (Norderyd and
Hugoson, 1998).
In 1991, a radiographic study of alveolar
bone loss in Swedish dental hygienists
demonstrated that the distance between the
cemento-enamel junction and the interdental
septum was significantly greater in smokers
than in nonsmokers and increased with
increasing smoking exposure.
This study, in adults with good oral hygiene,
suggested that smoking-related bone loss
was not simply correlated with plaque levels
(Bergstrom et al., 1991).
 Longitudinal study

In a ten-year longitudinal radiographic study

of alveolar bone loss which began in 1970, it
was shown that in those subjects who had at
least 2(0 teeth at the start of the study,
smoking was a significant predictor of future
bone loss
Bolin, 1986
In a five-year study of attachment loss in 800
community- dwelling adults, smokers were
found to be at an increased risk for
attachment loss
Beck et al., 1997.
 A further longitudinal study, in which a wide
range of clinical microbiological, and
immunological indicators was correlated with
disease progression, reported that over the
one-year period of the investigation, smokers
exhibited both greater attachment loss and
bone loss when compared with their non-
smoking counterparts.
Smokers were shown to be at significantly
greater risk for further attachment loss when
compared with non-smokers, the odds ratio
being quoted as 5.4
Machtei et al. 1997
 CONSISTENCY OF OBSERVATIONS
While many of the initial studies on the
relationship between smoking and periodontal
disease reached conflicting and contradictory
conclusions, in retrospect, such findings can be
explained by the failure to account sufficiently
for the multifactorial nature of periodontal
disease.
The ambiguity that clouded the early studies on
the role of smoking in periodontal disease has
been by an array of studies with well-defined
clinical criteria and more sophisticated data
analysis
Mandel 1994
 DOSE-RESPONSE

In determining attributable risk, it is of

value to examine the relationship between
the degree of exposure to an alleged risk
factor and disease prevalence.
The ability to demonstrate a dose-
response strengthens the evidence of risk
factor status.
 Grossi et al. (1994) examined the relationship
between smoking and attachment loss and
demonstrated a dose dependent response, the
odds for more severe attachment loss in smokers,
compared with non-smokers, ranging from 2.05
for light smokers to 4.75 in heavy smokers.
These findings support those of Alpagot and
colleagues 1996, who reported that probing depth
was significantly correlated with 'pack years' (i.e.,
packs of cigarettes smoked per day multiplied by
the number of years the subject has smoked)
 A Spanish survey involving 889 patients
reported that gingival recession, pocket
depth, and probing attachment level were
significantly related to smoking status, and
that attachment levels were proportionate to
the quantity of cigarettes smoked. Smoking
one cigarette per day, up to ten, and up to
20, increased probing attachment level by
0.5%, 5%, and 10%, respectively.
Martinez-Canut et al, 1995
 In one of the few studies which, to date,
have measured cotinine, the severity of
periodontal destruction, measured either as
clinical attachment level or crestal bone
height, was shown to be statistically positively
correlated with serum cotinine levels
(Gonzalez et al., 1996).
Cotinine is the principle metabolite of nicotine
and as such provides a valuable quantitative
measure of smoking status. Patients' cotinine
levels have recently been shown to correlate
directly with outcomes of progressive
periodontal breakdown
(Machtei et al., 1997).
Smoking and periodontitis in young
adults

Haber et al reported that prevalence of

periodontitis, defined as having CAL 2mm
and PPD 4mm was 3-4 times higher in
young smokers 19-30 years of age
compared to nonsmokers.
The high periodontal cost of smoking has
been calculated as 27 years of disease
progression.
Haffajee, Socransky et al 2001
 Subgingival microflora
Smokers may have a more 'pathogenic'
microbial flora, in that T. forsythus was
harbored subgingivally more in smokers than
in non-smokers
Zambon et al., 1996
There was also a tendency for
Porphyromonas gingivalis counts to be higher
in smokers than in non-smokers, but this
failed to reach significance. The data were
adjusted for attachment loss and age, and
thus the reported T. forsythus increase in
smokers (former and current) is not simply
because they have more severe periodontal
disease.
 A more recent study using molecular analyses
techniques for six putative periodontal pathogens
found that current smokers displayed an increased
risk for harboring Treponema denticola (OR = 4.61)
(Umeda et al., 1998).
Haffajee et al. (1997) have reported significant
clinical improvements, following scaling and root
planing (SRP), in subjects who had never smoked
or who were past smokers, but not in current
smokers. P. gingivalis, T. forsythus, and Treponema
denticola were equally prevalent among current,
past, and "never" smokers before therapy and
decreased significantly post-SRP in all but the
current smokers.
 Clinical improvement post-SRP in all
patients was accompanied by a modest
change in the subgingival microbiota,
primarily reductions in P. gingivalis, T.
forsythus, and T. denticola.
 Proposed mechanism for the
negative periodontal effects of
smoking
Vascular alterations
Altered neutrophil function
Decreased IgG production
Decreased lymphocyte production
Increased prevalence of
periodontopathogens
 Altered fibroblast attachment and
function
Difficulty in eliminating pathogens by
mechanical therapy
Negative local effects on cytokine and
growth production
 Biological effects of smoking
(A) EFFECT OF NICOTINE ON THE PERIODONTAL TISSUES
Nicotine may cause a vasoconstriction in the peripheral
blood vessels (Clarke et al., 1981) and thus may reduce
the clinical signs of gingivitis.
Bergstrom 1991, who compared the compliance of
smokers with that of non-smokers in an oral hygiene
intervention program. The plaque index decreased in
both groups, and, despite the similarity in plaque index,
gingival bleeding was significantly lower in smokers than
in non-smokers. These results suggest that, in smokers,
the clinical expression of gingivitis (i.e., chronic
inflammation) in response to plaque is suppressed.
 Effect on GCF
GCF nicotine concentrations can be upto nearly 300
times that of in plasma(20ng/ml).
A study by Holmes (1990) compared crevicular fluid flow
in smokers and non-smokers with clinically healthy
gingiva and the crevicular fluid flow of smokers in the
areas physically exposed to smoke (maxillary lingual)
and in areas not physically exposed to smoke (maxillary
buccal).
Smokers had significantly less crevicular fluid flow than
non-smokers. Interestingly, the exposed lingual areas of
smokers showed no significant difference from the less
exposed buccal areas.
 This study suggests that the effect of nicotine
may not be local or, if it is local, that it may be
modified by the saliva and its effects dispersed.
The effect of tobacco smoke on clinically
healthy gingiva may be through
vasoconstriction rather than direct physical
irritation.
Kinane and Radvar 1997, investigating the
responses of smokers and non-smokers, with
and without subgingival antimicrobials, to
instrumentation, also reported that gingival
crevicular fluid (GCF) volumes were significantly
lower among smokers than non-smokers.
Effects of nicotine on immune and
inflammatory systems
Smoking may have an adverse effect on
- fibroblast function (Raulin et al.,1988),
-chemotaxis
-phagocytosis by neutrophils (Kenney et al., 1977;
Kraal et al., 1977), and
-immunoglobulin production.
Nicotine increases intercellular adhesion molecule- I
(ICAM-I) and endothelial leukocyte adhesion
molecule-l (ELAM- ) on human umbilical vein cells
(endothelial cells) and appears to increase soluble
ICAM- I in the serum of smokers (Koundouros et
al.,1996.
 These adhesion molecule changes may
affect leukocyte binding to endothelial
cells lining the capillaries and post-
capillary venules and thus, may impede
the recruitment of important host defense
cells to the area of inflammation and
microbial challenge.
 CYTOKINES AND SMOKING

Tappia et al 1995; have shown that the

plasma responses of smokers following
lipopolysaccharide stimulation differed from
those of non-smokers, in that smokers had
significantly more tumor necrosis factor alpha
(TNFa-) and Interleukin-6 (IL-6) and also the
acute phase protein 2-macroglobulin.
Kuschner et al. (1996) have reported a dose-
dependent effect of smoking on IL- 1, IL-6,
IL-8, and monocyte chemotactic protein
(MCP)- I levels.
 Macrophages play important roles in both
cell mediated and humoral immunity as
antigen-presenting cells. However,
antigens are presented in the context of
class II major histocompatibility complex
(MHCII) surface molecules.
It has been shown that alveolar
macrophages from smokers exhibit
reduced expression of class II MHC
 Reduced concentration of serum IgG generally
(Ferson et al., 1979; Gulsvik and Fagerhol, 1979.
Smokers have been shown to have reduced
titers of serum IgG to P intermedia and F.
nucleatum (Haber, 1994).
Smoking tends to limit the production of IgG2 in
GEOP patients- Quinn et al. (1996)
Level of IgG2 against A. actinomycetemcomitans
is lower in smokers than in non-smokers among
EOP patients (Tangada et al., 1997).
Smoking and Periodontal Treatment
Outcome in smokers is less favorable than in non-
smokers. Ah et al. (1994) have demonstrated a
poorer response to periodontal treatment in smokers
compared with non-smokers.
Preber and Bergstrom (I990) found that, 12 months
following surgery, smokers had a statistically
significantly reduced probing depth reduction
compared with nonsmokers, despite accounting for
differences in levels of plaque accumulation.
Reduced probing attachment level gain following
GTR.
When using regenerative procedures with allografts,
have also found smoking to be detrimental to
healing.
 HEALING IN SMOKERS

It has been hypothesized that, in smokers,

much of the inflammatory tissue swelling
before treatment may be absent, and thus
this part of the post-therapy tissue change
may not contribute as much to the post-
treatment pocket depth reduction in
smokers compared with non-smokers
(Kinane and Radvar, 1997).
 Fibroblasts are an important cell in the periodontal
healing response, and Raulin et al. (1988) has
reported an impaired function of fibroblasts in
smokers.
Fibroblasts have been shown to bind and internalize
nicotine (Hanes et al., 1991), which may be
detrimental to their function.
Poorly functioning fibroblasts may not produce
collagen fibers as efficiently, and thus gingival tissue
support and adaptation will be impaired or at least
slowed, and poor tissue form will often result in
greater microbial plaque retention around teeth.
 Another crucial cell of the dento-gingival
barrier is the keratinocyte. Johnson et al.
(1996) have shown that human gingival
keratinocytes are induced to produce
significantly increased amounts of IL-1 and
prostaglandin E-2 (PGE2) by tobacco
extracts.
Evidence for Smoking as an Etiologic
Factor in Periodontitis

Criterion Evidence

Strength of Cross-sectional and

association case-control studies
demonstrate a
moderate to strong
association between
smoking and
periodontitis.
 Criterion Evidence

Consistency Multiple studies of

various designs (cross-
sectional, case-control,
and longitudinal) and in
various populations have
demonstrated an
association between
smoking and periodontal
attachment loss.
Criterion Evidence

Specificity Disease progression

slows in patients who
quit smoking as
compared to those
who continue to
smoke.
 Criterion Evidence

Temporality Longitudinal studies

show that smokers do
not respond as well to
periodontal therapy as
non-smokers.
 Criterion Evidence

Biologic gradient There is a dose-

response effect in that
heavy smokers have
increased disease
severity compared to
light smokers.
Criterion Evidence

Biologic The biologic plausibility

plausibility of the explanation of
the relationship
between smoking and
periodontitis is
supported by tobacco's
adverse impact on
microbial and host
response parameters.
Criterion Evidence

Coherence The effects of smoking

on periodontitis are
consistent with our
knowledge of the
natural history of
periodontal disease.
 Analogy Periodontal effects of
smoking are analogous
to other adverse
smoking-related
general health effects.

Experiment Evidence not currently

available.
 Conclusion as to status as a risk
factor
There is overwhelming scientific evidence to
consider tobacco as a behavioral risk factor for
destructive periodontal disease.
Countless analytic epidemiological studies
consistently report the conclusion that cigarette
smokers are more than five times more likely to
develop severe periodontitis than nonsmokers and
that the level of risk for the disease is
proportionate to the number of "pack- years" of
smoking.
Data are currently insufficient to support an
association between the use of smokeless tobacco
and generalized or advanced periodontal disease.