Periodontology 2000, Vol.

32, 2003, 1123

Printed in Denmark. All rights reserved

Copyright # Blackwell Munksgaard 2003

PERIODONTOLOGY 2000
ISSN 0906-6713

Understanding the etiology of

periodontitis: an overview of
periodontal risk factors
Martha E. Nunn

Periodontitis is a multi-factorial disease with microbial dental plaque as the initiator of periodontal disease (50). However, the manifestation and progression
of periodontitis is inuenced by a wide variety of
determinants and factors, including subject characteristics, social and behavioral factors, systemic factors, genetic factors, tooth-level factors, microbial
composition of dental plaque, and other emerging risk
factors. With the large array of factors that inuence
the development and progression of periodontitis,
understanding what the relationships of these various
factors and determinants are to the initiation and
progression of periodontal disease can be daunting.
The purpose of this paper is to explain some basic
concepts related to understanding periodontal risk
factors and the strength of the association of those
risk factors to the initiation and progression of periodontal disease and to present a brief overview of risk
factors for chronic periodontitis. Terminology, study
design, outcome measures, and measures of association are presented as basic concepts necessary for
understanding periodontal risk factors. The overview
of risk factors is then systematically divided into subject determinants, social and behavioral factors, systemic factors, genetic factors, tooth-level factors,
microbial factors, and emerging risk factors.

Terminology
In most epidemiological studies, the researcher seeks
to establish some sort of causal relationship between
a characteristic, behavior, or exposure and the manifestation of a particular disease. Three types of causation are generally identied: 1) a sufcient cause,
2) a necessary cause, and 3) a risk factor. A sufcient

cause refers to any condition, characteristic, or exposure in the presence of which, the disease will always
occur. This is the strongest type of causal relationship and is relatively rare. Examples of this include
genetic anomalies or conditions. A necessary cause is
any condition, characteristic, or exposure that must
be present for a disease to manifest itself. It differs
from a sufcient cause because its presence does not
necessarily result in manifestation of the disease. A
good example of this is the organism Mycobacterium
tuberculosis, which is a prerequisite for a person to
develop tuberculosis. However, many people can
carry this organism in their bodies without any
symptoms of disease whatsoever. A risk factor is
any characteristic, behavior, or exposure with an
association to a particular disease. The relationship
is not necessarily causal in nature (16). Risk indicator
is a term used to describe a potential risk factor
identied to be associated with disease from casecontrol or cross-sectional studies. Risk factor is more
appropriately reserved for those factors that have
been veried to be associated with disease through
longitudinal studies. A risk factor that can be used to
predict the future course of disease, such as an
increased probability of disease, is known as a risk
marker. Some risk factors can be modied to reduce
one's risk of initiation or progression of disease, such
as smoking cessation or improved oral hygiene to
reduce the risk of periodontal destruction, while
other factors cannot be modied, such as genetic
factors. A risk factor that cannot be modied is often
referred to as a determinant (30).
The terminology associated with risk indicators is
indicative of the level of evidence for its association
to periodontal disease. The distinctions among these
terms are not always clear from the literature, nor is it

11

Nunn

clear how the clinician makes use of such information. Whatever terms are used to designate factors
associated with the initiation and progression of periodontal disease, it is the hierarchy of study design
and the relevance of the outcome measure that govern the strength of the evidence for each risk indicator and its use in clinical decision-making.
In addition to the concept of risk indicators, there
are also terms that refer to the proportion of disease
noted in a particular population. Prevalence is dened
as the number of cases of a disease or condition per
population at risk at a particular point in time. Crosssectional studies are used to assess the prevalence of
a particular disease at some point in time for a specied population. Another measure of disease frequency is incidence. Incidence is dened as the
number of new cases of a disease or condition over
a specied period of time. Longitudinal studies are
used to assess the incidence of a particular disease for
a specied population over a given time period (16).

Study design
The strength of evidence of an association of a risk
factor to any particular disease is based in large part
on the study design utilized. The hierarchy of study
design forms a basis for the relative strength of evidence for any risk factor. The weakest evidence for an
association between a particular factor and the disease under investigation is the case report or case
history. Although such information may form the
basis for future hypotheses and further study, information gained from a case report without further
verication should be given the least weight when
formulating a treatment plan for a patient. The next
type of study in the hierarchy of design is the case
series. This type of study provides only slightly stronger evidence for an association between a risk factor
and a disease than a case report. How much value
one should place upon a case series is related to the
way in which the cases were ascertained and the
number of cases involved. For instance, information
obtained from a series of 10 cases that were handpicked by the investigator out of a much larger available group is far less reliable than a series of 100
cases chosen at random or constituting a convenience sample. Even in the latter example of a large
case series, the strength of the evidence for an association between a risk factor to a particular disease is
considered quite weak.
The next strongest evidence is provided by casecontrol studies. These studies may be retrospective

12

or prospective in nature. A case-control study is an

outcome-based study. Subjects are classied with
respect to disease status. The investigator takes a
sample of individuals who have the disease in question (cases) and a sample of individuals who are also
at risk for the disease but are disease-free (controls).
Subject characteristics and/or the subjects' prior
exposure history to potential risk factors are then
investigated as a function of disease status. Comparisons are then made of the relative distributions of
these characteristics or history of exposures among
cases and controls. A subject characteristic or history
of exposure would then be considered to be a risk
indicator if a signicantly greater proportion of cases
possessed that characteristic or had a history of that
exposure in question compared to healthy controls.
The major disadvantages to this type of study include
the inability to completely control for confounding
and the lack of control over the exposures under
investigation. Confounding is the confusion of two
supposedly causal factors so that part or all of the
purported effect of one of these factors is actually
due to the other (16). In addition to these disadvantages, the vast majority of case-control studies are
retrospective in nature with the inherent biases associated with a retrospective study:
 hypothesis is formulated after events have occurred.
 incomplete and/or poor record keeping, especially when incomplete records comprise missing
data that are not missing totally at random.
The next strongest form of evidence is the result of
a population-based cross-sectional study. These studies generally are more powerful than case-control
studies because they involve large populations with
data collected on a multitude of variables so that a
more rigorous assessment of potential risk factors is
possible, with the ability to more completely adjust
for confounding as well as assessing possible effect
modication. Effect modication occurs when a third
variable affects the direction of the association or the
strength of the association between a risk factor and
the disease under investigation (16). Another advantage to a large population-based cross-sectional
study is that data are often collected to study a wide
variety of phenomena so that the bias of formulating
an hypothesis after events have occurred is minimized.
The strongest form of evidence provided by an
epidemiologic study comes from a cohort study,
which is longitudinal in nature. A cohort study is
an exposure-based study design. In this type of study,
subjects are classied with respect to exposure and

Understanding the etiology of periodontitis: an overview of periodontal risk factors

followed longitudinally. The rate of occurrence of the

disease under investigation is studied as a function of
the exposure. The bias of formulating a hypothesis
after events have occurred is eliminated, and poor
record keeping can generally be minimized with
cohort studies. However, subjects may be lost to
follow-up in a longitudinal study, and if the level of
attrition becomes too high, the inference drawn from
the study is seriously compromised.
At the pinnacle of the hierarchy of study design is
the randomized controlled clinical trial. In the case of
risk factors, such a trial is referred to as an intervention trial. In a randomized controlled clinical trial,
subjects are randomized to either a treatment group
or a control group. In the context of an intervention
trial, the hypothesized risk factor is eliminated from
the treatment group while the control group is followed without any intervention to eliminate the
hypothesized risk factor. This type of study offers
the strongest evidence of a potential causal relationship between a risk factor and the disease under
investigation.

Outcome measures
The relevance of the outcome measure is also a factor
in assessing the strength of evidence for an association between a risk factor and disease. With respect
to periodontal disease, the goal of prevention and
treatment is to maintain teeth in a state of comfort
and function. Hence, the most accurate measure of
the inuence of a risk factor in the progression of
periodontal disease is tooth loss as a direct or indirect result of periodontal disease. Unfortunately, the
number of subjects and the time involved to accurately assess the relationship of potential risk factors
to actual tooth loss from periodontal disease makes it
extremely difcult, if not impossible, to dene all risk
factors for periodontal disease in terms of tooth loss.
In addition, in large longitudinal studies where tooth
loss is known, such as the VA Dental Longitudinal
Study, the actual reason for tooth loss is often not
known. Because of this problem, other clinical measures are often used to assess the periodontal status
of a tooth at any given point in time.
Two outcome measures that are often used in
place of tooth loss from periodontal disease are
alveolar bone level and clinical attachment level.
Both of these measures are strongly associated with
tooth loss from periodontal disease. Both alveolar
bone level and clinical attachment level are quantitative measures, although these outcome measures

are often reclassied into categorical variables for

evaluating the relationship of a potential risk factor
to these outcomes. Alveolar bone levels can also be
quantied in terms of percentage of alveolar bone
loss based on the ratio of the distance from the height
of the alveolar crest to the cemento-enamel junction
to the length of the root. The percentage alveolar
bone loss determined from these measurements
can then be reclassied into categories of periodontal destruction (mild, moderate, severe). Percentage
bone loss is also often dichotomized into ``signicant
bone loss'', for bone loss above a specied percentage of alveolar bone loss, and ``not signicant bone
loss'', where bone loss falls below this percentage of
alveolar bone loss. Clinical attachment level can
similarly be reclassied categories of periodontal
destruction, or dichotomized into teeth with ``signicant attachment loss'' and teeth with ``no signicant
attachment loss.
In addition to the measures of alveolar bone level
and clinical attachment level described above,
changes in these measures can also be used as outcome measures when a longitudinal study is conducted. In the case of alveolar bone loss, digitized
subtraction radiography (35) is often employed. With
respect to clinical attachment level in a longitudinal
study, clinical attachment loss over the period of the
study can be found by taking the difference in clinical
attachment levels from the initial measurement to
the nal measurement. In longitudinal studies, these
outcome measures can also be reclassied into categories. Both clinical attachment loss and alveolar bone
loss are subject to measurement error. In addition,
alveolar bone loss is not always possible to assess for
each tooth because malposed, overlapping teeth,
cervical caries, and extensive dental restorations
can either obscure the crest of alveolar bone or make
it difcult to locate the cemento-enamel junction.
Other outcome measures gathered on a tooth level
that are used to assess periodontal disease status
include periodontal probing depth, gingival recession, gingival inammation index, bleeding index,
and furcation involvement. Periodontal probing
depth and gingival recession are quantitative measures. Gingival inammation index, bleeding index,
and furcation involvement are ordinal measures.
Since periodontal probing depth and gingival recession are the component measures that constitute
clinical attachment level, these are the next best
tooth-level clinical measures of periodontal disease
destruction. Since gingival inammation index
and bleeding index are both indicators of inammation but are less strongly associated with actual

13

Nunn

periodontal breakdown, these two indices are less

compelling measures of periodontal destruction.
Furcation involvement clearly reects loss of clinical
attachment and alveolar bone loss, but this outcome
measure is limited to molar teeth, so that a risk factor
identied with an increased risk of furcation involvement is limited to inferences of molar teeth.
Tooth-level clinical outcome measures can also be
summarized for each subject to obtain other outcome measures for assessing periodontal destruction. For instance, tooth-level alveolar bone loss
can be summarized as the percent of teeth (or sites)
with ``signicant alveolar bone loss'' as dened by
some dichotomized measure of alveolar bone loss.
Similarly, tooth-level clinical attachment loss can be
summarized as the percent of teeth (or sites) with
clinical attachment loss exceeding a certain value,
such as the percent of teeth with clinical attachment
loss greater than 4 mm. The percentage of teeth with
signicant alveolar bone loss can also be used to
classify each subject's level of periodontal disease
(i.e. mild, moderate, severe). Similarly, percentage
of teeth with signicant clinical attachment loss
can also be used to categorize subjects into different
levels of periodontal destruction (i.e. mild, moderate,
severe). When subjects are classied into those with
periodontitis and those without periodontitis, varying denitions may be employed to dene the subject's status, but all denitions of periodontitis will
include
 a minimum number of teeth with signicant periodontal destruction as measured by alveolar
bone loss or clinical attachment loss,
 a percentage of teeth with signicant periodontal
destruction or
 some combination of missing teeth and number
of remaining teeth with signicant periodontal
breakdown.
In general, the strongest outcome measure of periodontal disease is that measure that most closely
reects the eventual negative outcome of tooth loss
from periodontal disease and that can be assessed
objectively with the least measurement error.

Measures of association
The strongest association for identifying a parameter
as a risk factor for disease is relative risk. Relative risk
is generally dened as the ratio of the risk of disease
in the ``exposed'' group to the risk of disease in the
``unexposed'' group (16). Relative risk is a measure of
association that is only obtained from a longitudinal

14

study. In the context of periodontitis, the strongest

association for identifying a parameter as a periodontal risk factor is the relative risk of tooth loss. Time
until tooth loss (or time until last observation, if tooth
is not lost) is the outcome measure used to estimate
relative risk. Because relative risk is a ratio, a relative
risk of ``1'' means that the presence of the factor
under investigation (exposed) is no more likely to
result in tooth loss from periodontal disease than
when the factor is not present (not exposed). When
the relative risk is less than 1, this means that the
exposure actually reduces the likelihood of tooth loss
from periodontal disease. For instance, a relative risk
of 0.8 for an exposure would mean that a tooth with
that exposure was only 80% as likely to be lost
because of periodontal disease compared to a tooth
without the exposure. When the relative risk is
greater than 1, an exposed tooth is more likely to
be lost from periodontal disease compared to an
unexposed tooth. In other words, for a relative risk
of 2.2, an exposed tooth is 2.2 times as likely to be lost
because of periodontal disease compared to an unexposed tooth. The estimate for relative risk alone does
not completely explain any potential association of a
particular exposure to tooth loss. The 95% condence interval for the relative risk provides the statistical evidence for an increased or decreased risk for
tooth loss as a result of exposure to a particular
factor. If the 95% condence interval for the relative
risk for any factor contains ``1'', there is a lack of
statistical evidence that exposure to the factor under
investigation will either increase or decrease the likelihood of tooth loss from periodontal disease. When
the value of ``1'' is not within the 95% condence
interval for the relative risk for a factor, this is equivalent to rejecting the null hypothesis and concluding
that the factor under investigation will either
increase the likelihood of tooth loss from periodontal
disease (when the estimated relative risk is greater
than 1) or decrease the likelihood of tooth loss from
periodontal disease (when the estimated relative risk
is less than 1). For a factor with a statistically signicant relative risk, the greater the value of the relative
risk, the greater is the negative impact by the risk
factor on the periodontium as measured by tooth
loss.
A measure of association obtained from case-control studies is the odds ratio. The odds ratio is the
ratio of the odds of exposure in the diseased group to
the odds of exposure in the non-diseased group (16).
Because information about exposure is gathered
after the disease status has been ascertained, the
odds ratio is the only way to quantify the relative

Understanding the etiology of periodontitis: an overview of periodontal risk factors

likelihood of disease based on exposure. This odds

ratio is mathematically equivalent to the ratio of the
odds of disease in the exposed group to the odds of
disease in the unexposed group. We make use of this
mathematical equivalence in interpreting an odds
ratio obtained from a case-control study. By making
use of this mathematical equivalence, the interpretation of the odds ratio is similar to that explained
above for relative risk. An odds ratio of ``1'' indicates
that the odds of disease in the exposed group is equal
to the odds of disease in the unexposed group. An
odds ratio greater than 1 implies that the odds of
disease in the exposed group is greater than the odds
of disease in the unexposed group. For instance, if
cases are dened as subjects with periodontitis and
controls are dened as subjects without periodontitis, then an odds ratio of 3 for a particular exposure
would mean that the odds of periodontitis among
exposed subjects was three times that of the odds
of periodontitis among unexposed subjects. In other
words, an exposed subject is three times as likely to
have periodontitis compared to an unexposed subject. Similarly, if the odds ratio is less than 1, an
exposure reduces the subject's likelihood of periodontitis compared to unexposed subjects. As in relative risks, the 95% condence interval explains
whether the difference in likelihood of disease
between the exposed group and the unexposed
group has statistical support. If the value of ``1'' is
in the 95% condence interval, then the exposure has
no effect on the likelihood of experiencing disease.
When disease prevalence is relatively rare (<5%) , the
odds ratio can be used to approximate relative risk.
Hence, the interpretation that is often presented for
odds ratios obtained from a case-control study may
be identical to the interpretation for relative risks.
With the advent of methods for analyzing correlated
outcomes, such as the method of generalized estimating equations, the concept of the odds ratio can
be extended to explaining the relationship of a risk
factor to the periodontal status of a tooth.
For continuous outcome measures, such as the
percentage of teeth with signicant clinical attachment loss, correlation can be used to describe the
association. A correlation of zero implies no association between the risk factor and the outcome measure used to describe periodontal disease. A
correlation greater than zero would mean that an
exposure is associated with an increased level of
periodontal disease as measured by percentage of
teeth with signicant periodontal destruction. A correlation less than zero implies that an exposure is
associated with decreased evidence of periodontal

destruction. Further quantication of the relationship between a risk factor and a continuous outcome
measure can be obtained from linear regression
modeling. An increase of one unit of exposure in a
linear model would have the effect of changing the
outcome measure by the value of the coefcient for
the risk factor under investigation. For instance, a
coefcient of 2 for age in years to describe the percent of teeth with signicant periodontal destruction
would mean that for each additional year of age, the
percent of teeth with signicant periodontal destruction will increase by 2%. A statistically signicant
association between a risk factor and a continuous
outcome measure in a regression model will be
reected by a 95% condence interval for the corresponding coefcient that does not include zero.

Subject determinants
Aging is commonly associated with periodontal disease, although this relationship is thought to be more
related to the cumulative periodontal breakdown
over time than to an age-related, intrinsic deciency
that contributes to susceptibility to periodontal disease (30). Epidemiological studies have shown more
periodontal disease, both in terms of attachment loss
as well as bone loss, among older age groups compared to younger age groups (36, 37, 104). In addition, research has shown that certain physiological
changes in the periodontium occur with age (48,
113), although these changes alone are not responsible for periodontal breakdown. In fact, in a study of
the rst National Health and Nutrition Examination
Survey, the effect of aging on periodontal destruction
appears to be negligible compared to the role of
plaque as represented by oral hygiene practices (1).
These results appear to also hold for the old elderly
(85 years old) as well. In a 5-year follow-up of
elderly patients in Finland, very little change in the
periodontal status was noted, with the authors concluding that periodontal disease in the elderly who
are relatively healthy is not caused by the aging process alone (3).
The role of race as a risk factor for periodontal
disease is a more complicated issue. For instance,
in a study of older community-dwelling blacks and
whites (65 years of age and above) , blacks were three
times more likely to exhibit advanced periodontal
destruction compared to whites in the same age
cohort. In addition, Prevotella intermedia was found
to be a risk factor for blacks but not for whites (8).
However, in this study, blacks had more indicators

15

Nunn

related to socioeconomic status than whites. When

limited to subjects in the same socioeconomic status,
differences in periodontal status between blacks and
whites often disappeared (36, 37). Racial differences
in the distribution of certain genetic risk factors may
also contribute to differences in the prevalence and
severity of periodontal disease among difference
races. For instance, the prevalence of polymorphisms
of the composite interleukin (IL) -1a/IL-1b genotype
among Chinese is signicantly lower than among
Europeans (6).
Associations between gender and periodontal disease have been mixed. In one study after adjustment
for oral hygiene, socioeconomic status, and age,
males were found to have signicantly more clinical
attachment loss and bone loss (36, 37). Based on
studies of postmenopausal women, estrogen may
be part of the reason for gender differences noted
in periodontal disease. In a study comparing a group
of postmenopausal women receiving estrogen supplements to postmenopausal women without estrogen supplementation, women receiving estrogen
exhibited signicantly less gingival bleeding compared to women not on estrogen-replacement therapy (85). Another study suggested that estrogen
supplementation may be associated with reduced
gingival inammation and a reduced frequency of
clinical attachment loss in osteopenic/osteoporotic
women in early menopause (93).

Social and behavioral factors

Cigarette smoking has long been recognized as a risk
factor for periodontal disease. One of the earliest
studies to show a relationship between smoking
and periodontal health was conducted on Swedish
army conscripts where smokers were shown to be at
an increased risk of gingivitis, although no differences were noted in bone loss or periodontal pocketing (89). In another study, the alveolar bone height
of smokers was shown to be signicantly reduced
compared to non-smokers (10). In addition, a casecontrol study showed that smokers were 2.7 times as
likely to have moderate to advanced periodontal disease compared to non-smokers (38). Signicant
associations between cigarette smoking and both
clinical attachment loss and alveolar bone loss were
shown in a study of clinical risk indicators (36, 37). In
addition, cigarette smoking signicantly increases
the risk of tooth loss from periodontal disease (70).
The relationship of cigarette smoking to tooth loss
from periodontal disease also appears to be dose-

16

related, with heavy cigarette smokers exhibiting a

signicantly greater risk of tooth loss from periodontal disease compared to non-smokers and lessthan-heavy smokers (71). Cigar and pipe smoking
have also been shown to be signicantly related to
both tooth loss and alveolar bone loss (4, 49, 55).
Overall, smoking is probably the single most signicant modiable risk factor for periodontal disease.
Socioeconomic status has been proposed as a risk
factor for periodontal disease. On a global level, an
early study suggested that nutritional deciencies in
developing countries could contribute to more
advanced periodontal disease (95). However, a study
comparing the periodontal condition of young men
in India with clinical symptoms of malnutrition to
the periodontal condition of well-nourished men
showed no difference in the periodontal condition
of the malnourished group compared to the wellnourished group (91). Other similar studies failed
to demonstrate an association between periodontal
disease and nutrition (6, 94, 116).
Related to nutrition, research has been conducted
into possible associations of dietary calcium and
dietary Vitamin C to periodontal disease. In a study
of the Third National Health and Nutrition Examination Survey (NHANES III) , low calcium intake was
found to be associated with a signicant increased
risk of periodontal disease among young males,
young females, and older males (82). A randomized
trial of supplemental calcium and Vitamin D was
conducted to determine if these supplements would
slow bone loss from various skeletal sites among
subjects 65 years of age and older. Based on this trial,
supplemental calcium and Vitamin D, originally
aimed to reduce osteoporosis, was shown to also
signicantly reduce tooth loss (56). The relationship
of Vitamin C intake and periodontal disease was
explored in the Third National Health and Nutrition
Examination Survey (NHANES III). A weak, but statistically signicant association was found between
Vitamin C intake and periodontal disease, with that
association being a dose-response relationship. Low
Vitamin C intake among former and current smokers
showed an even higher increased risk of periodontal
disease (83).
Psychological factors have also been proposed as a
risk factor for periodontal disease. In one study,
stress related to nancial strain was found to be signicantly associated with greater loss of clinical
attachment and greater bone loss (31). In a casecontrol study to investigate the relationship of periodontitis to social factors, a signicant association
was found between elevated scores of social strain

Understanding the etiology of periodontitis: an overview of periodontal risk factors

and periodontitis (80). Another case-control study

showed that the negative impact of life events, number of negative life events, and being unemployed
were all signicantly associated with periodontitis
(21).
Excessive alcohol consumption has been associated with an increased risk of clinical attachment
loss as well as an increased risk of gingival bleeding.
However, no association between alcohol consumption and alveolar bone loss has been found (110).

Systemic factors
One of the strongest systemic risk factors for periodontal disease is diabetes mellitus. There is strong
evidence of a direct relationship between diabetes
mellitus and periodontitis (51, 92). In addition, diabetes mellitus has been shown to be positively associated with clinical attachment loss (30). However,
there are also studies that do not support this association of diabetes mellitus with periodontal disease
(102). Insulin and non-insulin dependent diabetics
appear to be at equal risk for periodontal disease. The
severity and extent of periodontitis in the diabetic
patient appears to be related to control of the diabetes (109). In addition to the risk progression of
periodontal disease posed by poorly controlled diabetes, it has also been suggested that effective periodontal therapy can have a positive effect on the
control of diabetes (111). In a longitudinal study of
non-insulin dependent diabetics, severe periodontal
disease at baseline was found to be a signicant risk
factor for poor glycemic control (107). Similarly, poor
glycemic control in non-insulin dependent diabetics
has been shown to be associated with signicantly
greater alveolar bone loss over time compared to
well-controlled non-insulin-dependent diabetics
(108). A substantial body of evidence has begun to
emerge suggesting a bidirectional relationship
between both types of diabetes and periodontal disease (106).
Certain systemic conditions require the use of
drugs that may pose a risk for periodontitis from
plaque accumulation as a result of gingival overgrowth. Calcium channel blockers have been associated with gingival overgrowth, although the risk for
gingival overgrowth varies according to the specic
drug. Gingival overgrowth is signicantly more prevalent among patients taking nifedipine compared to
patients taking either amlodipine or diltiazem,
although the overall prevalence among all patients
taking calcium channel blockers is still fairly low. The

extent and severity of the gingival overgrowth also

appears to be related to local plaque control as well
as genetic factors. Although calcium channel blockers have been associated with gingival overgrowth,
no association with periodontal disease has yet been
found (27). Gingival enlargement among patients
taking the anti-epileptic drug phenytoin is welldocumented. The greatest risk factor for phenytoininduced gingival overgrowth is plaque (67). The
immunosuppressant drug cyclosporine is a risk factor for gingival overgrowth which resembles phenytoin-induced gingival enlargement. Steroid therapy
has been linked to osteoporosis. However, studies of
the relationship of steroid therapy to alveolar bone
loss are conicting. In one study of long-term prednisone therapy, no signicant loss of alveolar bone
was noted (18). In another study, hydrocortisone
induced periodontal breakdown in a rat model (60).
Evidence has been mounting for an association
between osteoporosis and periodontal disease (54,
115). In addition, evidence has begun to emerge that
calcium supplements, Vitamin D supplements,
estrogen-replacement therapy, and other drugs used
to treat osteoporosis may also be benecial for reducing alveolar bone loss and tooth loss (54).
Oral lesions manifested in HIV-infected patients
that have previously been noted include:
 linear gingival erythema,
 necrotizing ulcerative gingivitis (NUG),
 severe localized periodontitis, and
 severe necrotizing stomatitis which affects both
the gingival and bone (97, 118120).
Associations between periodontal disease and
other systemic diseases have also been reported,
although it is not clear what the role of these relationships play. For instance, several studies have shown
an association between cardiovascular disease and
periodontal disease (9). However, a recent study that
made use of the First National Health and Nutrition
Examination Survey Epidemiologic Follow-up Study
failed to show a signicant association between cardiovascular disease and periodontal disease (42). An
association between rheumatoid arthritis and periodontitis has also been reported (75). Exactly what
these associations reect is still unknown. With the
discovery of emerging risk factors, inammatory
responses, and genetic regulators of these responses,
it is quite possible that these associations actually
reect common underlying risk factors rather than
any sort of causal relationship. In a recent study, a
relationship between upper body obesity, a risk factor for other systemic diseases including type 2 diabetes and cardiovascular disease, and periodontal

17

Nunn

disease has been shown in a group of 643 healthy,

dentulous Japanese adults enrolled in the study (96).
This nding reinforces the need to develop a better
understanding of the true relationships of these various systemic conditions and the manifestation of
periodontal disease.

Genetic factors
In studies of both monozygotic and dizygotic twins
reared together and apart, a signicant genetic component for gingivitis, probing depth, attachment loss,
and plaque was found (76, 77). In a recent study
involving both monozygotic and dizygotic twins, it
has been estimated that genetic inuences account
for as much half of the variance in disease in the
population (78).
Specic genotypes have been identied and linked
to periodontal destruction. Polymorphisms of IL-1,
IL-1b, and IL-1RN genotypes have been identied as
potential risk factors for periodontal destruction. In a
recent study that evaluated these polymorphisms
and smoking, it was found that being positive for
the composite IL-1a/IL-1b polymorphism in smokers
resulted in four times the risk of signicant attachment loss (as measured by the percentage of sites
>4 mm attachment loss) compared to genotypenegative smokers (73). Patients positive for the composite IL-1a/IL-1b polymorphism have also been
shown to have a 2.7 times increased risk of tooth loss
from periodontal disease compared to genotypenegative patients (71). In addition, interactions between a positive IL-1 genotype and age, smoking, and
P. gingivalis have been identied, indicating that the
composite IL-1a/IL-1b polymorphism is a contributory but non-essential risk factor for periodontal disease progression (22).
Polymorphism of the tumor necrosis factor- (TNFa) gene has been suggested as a possible risk factor
for periodontitis. However, studies have failed to link
polymorphism of the TNF-a gene to either earlyonset periodontitis (98) or adult periodontitis (19).
Recently, a study of a group of middle-aged men
enrolled the VA Dental Longitudinal Study demonstrated a signicant association between a polymorphism of the Vitamin D receptor genotype and
alveolar bone loss, clinical attachment loss, and tooth
loss (43). Studies have also identied an association
between polymorphisms of the Vitamin D receptor
genotype and early-onset periodontitis (40, 122).
Functional polymorphisms of immunoglobulin G
(IgG) Fc receptors (Fc g R) have been shown to be

18

associated with recurrence of chronic periodontitis

among Japanese patients (52). In another study of
Caucasians, the extent and severity of alveolar bone
loss was found to be signicantly associated with the
genotype of the receptor Fc g RIIIa. The study also
demonstrated an increased risk of severe bone
destruction among subjects carrying the Fc g RIIIaVV genotype. This study shows that the Fc g RIIIa
genotype coding for the high afnity receptor and the
Fc g RIIIb genotype coding for the low afnity receptor impose additional risks for alveolar bone loss (72).
Polymorphism of the N-acetyltransferase (NAT 2)
has been shown to be signicantly associated with
more severe bone loss (53). In addition, smoking may
exacerbate the effect of NAT2 on the progression of
periodontal disease (74).

Tooth factors
Various aspects of tooth anatomy have been shown
to be associated with clinical manifestations of periodontal disease. For instance, some studies have
shown an association between enamel projections
and furcation involvement among molars (11, 41,
68). Similarly, enamel pearls have been implicated
in molar furcation involvement (20, 32, 99, 114). It
has been hypothesized that the enamel in these locations prevents the attachment of connective tissue,
thus making the area more susceptible to periodontal
breakdown.
Tooth position can also present a risk for periodontal disease. Malalignment, crowding, and migration or tipping of a tooth distal to an edentulous area
have all been implicated in loss of periodontal support (2, 26, 28, 45, 46). In addition, extreme labial or
lingual positioning of a tooth has been correlated
with gingival recession (34, 63). Tooth malposition
poses an even stronger risk among individuals with
suboptimal oral hygiene. Areas with thin or absent
cortical alveolar bone and prominent teeth in the
dental arch are particularly prone to periodontal
breakdown.
Related to tooth position is the issue of occlusion.
A recent cross-sectional study evaluated the relationship of occlusal discrepancies on a tooth level to
periodontal probing depth. Occlusal discrepancies
were found to be an even stronger predictor of periodontal probing depth than smoking (86). In a longitudinal study to investigate occlusal treatment of
these occlusal discrepancies, it was shown that teeth
with treated occlusal discrepancies had signicantly
less of an increase in periodontal probing depth than

Understanding the etiology of periodontitis: an overview of periodontal risk factors

teeth with untreated occlusal discrepancies, indicating that occlusal discrepancies constitute a modiable risk factor for periodontal disease (39).
Root proximity has been hypothesized to be a risk
factor for periodontal disease because bone and connective tissue are reduced in these areas so that
inammation and periodontal destruction may be
enhanced. However, there is no scientic evidence
to support root proximity as a risk factor for initiation
and progression of periodontal disease. A long-term
follow-up of subjects treated orthodontically showed
no association between root proximity and periodontal breakdown (7). In another study of periodontal
patients in maintenance therapy following active
treatment, root proximity was not signicantly associated with either a worsening in clinical condition as
measured by prognosis (69) or an increased risk of
tooth loss from periodontal disease (70).
Open contacts have been shown to be associated
with increased probing depths and loss of clinical
attachment (47). These results were found in a study
of 104 subjects with unilateral open contacts and
contralateral closed contacts.
Root abnormalities have been shown to be associated with periodontal breakdown. In particular,
palato-gingival grooves in maxillary incisors have
been found to be associated with loss of clinical
attachment and bone loss (121). In addition to the
risk posed by palato-gingival grooves among maxillary incisors, proximal root grooves among incisors
and maxillary premolars have also been associated
with attachment loss and bone loss (58). One reason
that these grooves pose such a risk for periodontal
breakdown may be that they impede the removal of
plaque and provide a reservoir for plaque microorganisms in the subgingival area. Cemental tears have
also been associated with attachment loss in an in
vitro study of root surfaces (59). Unsatisfactory root
form has also been linked to the progression of periodontal disease (69) as well as an increased likelihood of tooth loss from periodontal disease (70).
Tooth restorations can also be a risk factor for
periodontal breakdown. This can be the result of
marginal discrepancies of restorations (12, 13, 57,
101) or xed orthodontic appliances (24). Amalgam
overhangs have been linked to signicant alveolar
bone loss (88). Subgingival crown margins as
opposed to supragingival margins have been implicated in increased inammation and greater gingival
recession (81, 87). In addition to the anatomical considerations of restorations, there is also the issue of
tissue response to particular restorative materials.
Allergic reactions to metals used in cast restorations,

such as nickel and palladium, have been reported

(17, 79). However, a study of 16 patients with known
allergies to nickel were treated with crowns or
bridges made of an alloy containing 66% nickel with
porcelain fused to the metal framework and followed
for fteen years without any adverse consequences
reported (103). This latter report does not address
tissue response to cast crowns with alloys containing
nickel without porcelain so that nickel in alloys used
in cast restorations may still pose a risk for some
people with sensitivity to nickel. Acrylics have also
been linked to allergic reactions and may contribute
to gingival inammation (15, 44).
Pulpal involvement may contribute to periodontal
destruction, particularly when there is preexisting
periodontitis. Pulpal necrosis can be associated with
inammatory involvement of the periodontium (29,
90, 100). In addition, when periodontitis is absent, a
sinus tract along the periodontal ligament can be
caused by an endodontic abscess. In some cases,
the defect will persist after endodontic therapy,
necessitating periodontal therapy as well for complete resolution of the problem (14).
Tooth fractures are another factor to consider
among risk factors for periodontal disease. The position and extent of a tooth fracture plays a key role in
assessing the risk potential. Thus far, there has been
no evidence that fractures of the crown of a tooth
pose a risk for the development or progression of
periodontal disease, although the fracture itself
may enhance the accumulation of plaque (100). Root
fractures, however, do present a risk for periodontal
disease, especially vertical root fractures that involve
a substantial portion of the root (33, 62, 105).
External root resorption can also present a risk
when there is some communication with the oral
cavity. This provides access to bacteria which can
then destroy the periodontal attachment and alveolar
bone (5).

Microbial risk factors

Microbial dental plaque has long been recognized as
the initiator of periodontal disease. However, not all
bacteria that make up dental plaque have been
shown to be consistently associated with the progression of periodontal disease. Three specic pathogens
have been repeatedly identied as etiologic agents in
the periodontal destruction associated with chronic
periodontitis: Actinobacillus actinomycetemcomitans, Bacteroides forsythus, and Porphyromonas gingivalis (123). However, evaluation of these three

19

Nunn

pathogens as risk factors for identication of attachment loss over time has resulted in conicting evidence. Three studies indicated that none of these
pathogens were useful in predicting periodontal disease progression (61, 64, 117). In another study,
B. forsythus was predictive of tooth loss among subjects with little or no periodontitis at baseline (66). In
a recent prospective londitudinal study, B. forsythus
was identied as a risk marker for attachment loss in
a population with low prevalence and severity of
chronic periodontitis (112). B. forsythus and P. gingivalis were found to be associated with disease progression in established periodontal patients (65) and were
also found to be associated with alveolar bone loss (36).
Although several studies have evaluated the relationship of A. actinomycetemcomitans to periodontal disease progression, studies have failed to produce
convincing evidence that A. actinomycetemcomitans
can be used to predict future periodontal destruction.

Emerging risk factors

Increasingly, evidence for a relationship of newly
identied risk factors for systemic diseases, such as
emerging risk factors for cardiovascular disease, to
periodontal disease is starting to emerge. C reactive
protein, which has been implicated in cardiovascular
disease, has also been found in elevated levels in
subjects with adult periodontitis compared to
healthy adults (84). In addition to elevated levels of
C reactive protein, other acute phase reactants and
chemokines, including alpha 1-antitrypsin, haptoglobin, brinogen, and IL-8, have been signicantly
increased during gingivitis and/or periodontitis in
non-human primates (25). In addition, serum lipid
levels (cholesterol, triglycerides, HDL, LDL) and lipoproteins (apoA-I) were also elevated during periodontitis (112). Clinical studies have also suggested a
relationship between hyperlipidemia and periodontitis (23).

Conclusions
Numerous studies have shown associations between
a myriad of factors and progression of periodontal
disease. In addition, studies of other factors hypothesized to be related to periodontal disease progression
have failed to provide compelling evidence. Understanding and evaluation of these risk factors and
determinants demands that the evidence for each
association be weighed according to the study

20

design, the outcome measures utilized, and the

strength of the association. With further longitudinal
studies evaluating all reported risk factors for periodontal disease progression, it is hoped that we can
one day use these risk factors to more accurately
predict disease progression as well as long-term outlook for treated teeth.

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