1041

Current View of Risk Factors for

Periodontal Diseases*
Robert J. Gerico
Periodontal diseases are infections,
and
many
forms of the disease are associated
with
specific pathogenic
bacteria which colonize
the
subgingival
area. At least two of
these
microorganisms, Porphyromonas gingivalis
and Actinobacillus
actinomycetem-
comitans,
also invade the
periodontal
tissue and are virulent
organisms.
Initiation and
progression
of
periodontal
infections are
clearly
modified
by
local and
systemic
con-
ditions called risk factors. The local factors include
pre-existing
disease as
evidenced
by deep probing depths
and
plaque
retention areas associated with defective restorations.
Systemic
risk factors
recently
have been identified
by large epidemiologie
studies
using
multifactorial statistical
analyses
to correct for
confounding
or associated co-risk
factors.
Risk factors which we know
today
as
important
include diabetes
mellitus,
especially
in
individuals in whom metabolic control is
poor,
and
cigarette smoking.
These two risk
factors
markedly
affect the initiation and
progression
of
Periodontitis,
and
attempts
to
manage
these factors are now an
important component
of
prevention
and treatment of
adult
Periodontitis.
Systemic
conditions associated with reduced
neutrophil
numbers or
function are also
important
risk factors in
children, juveniles,
and
young
adults. Diseases
in which
neutrophil
dysfunction
occurs include the
lazy leukocyte syndrome
associated
with localized
juvenile
Periodontitis,
cyclic neutropenia,
and
congenital
neutropenia.
Recent studies also
point
to
several
potentially
important
periodontal
risk indicators.
These include stress and
coping
behaviors,
and
osteopenia
associated with
estrogen
deficiency.
There are also
background
determinants
associated with
periodontal
disease
including gender (with
males
having
more disease), age (with more disease seen in the
elderly),
and
hereditary
factors. The
study
of risk
in
periodontal
disease is a
rapidly
emerging
field and much is
yet
to be learned.
However,
there are at least
two
significant
risk
factors-smoking
and diabetes-which demand attention in current
management
of
periodontal
disease. J Periodontol
1996;67:1041-1049.
Key
Words: Periodontal
diseases/microbiology; Periodontitis microbiology;
risk fac-
tors/diabetes,
smoking, osteopenia, stress;
Actinobacillus
actinomycetemcomitans;
Bacteroides
forsythus;
Fusobacterium
nucleatum; Porphyromonas
gingivalis;
Prevo-
tella
intermedia;
Wolinella recta.
Changes
in our
knowledge
of the
etiology
of
periodontal
disease,
and the
recognition
of the
potential importance
of
susceptibility
factors as
they
affect initiation and
pro-
gression
of
periodontal
disease,
have led
to
intense
study
of
specific
risk factors for
periodontal
diseases.
It was
previously
believed that the
population
was
universally
susceptible
to
periodontal
disease.
Epidemiologie
studies,
such as the
survey
conducted
by
the National Center for
Health Statistics and those of the National Institute
of
Dental
Research, along
with additional studies from
*Departments
of Oral
Biology, Periodontology,
and
Microbiology
and
Periodontal Disease Research
Center,
School of Dental Medicine and
School of Medicine and Biomedicai
Sciences,
State
University
of New
York, Buffalo,
NY.
abroad,
have
changed
the view of universal
susceptibility,
since
they report
that 5% to 20% of the
population
suffer
from severe forms
of destructive
Periodontitis.1-3
While a
significant proportion
of the
population
is
susceptible
to
Periodontitis,
it
appears
that there is a
larger
segment
of
the
population
that is
not
susceptible
to
the severe
forms
of
Periodontitis.
This observation leads
to
the
proposal
that there are
susceptibility
factors or risk factors that
modulate
susceptibility
or resistance
to destructive
Per-
iodontitis.
Concepts
concerning
the
etiology
of
periodontal
dis-
ease have
also
changed markedly
in the last three decades.
Several
specific
bacteria,
including
Porphyromonas gin-
givalis,
Actinobacillus
actinomycetemcomitans,
Prevotel-
1042 RISK FACTORS FOR PERIODONTAL
DISEASES
J Periodontol
October
1996
(Supplement)
Table 1.
Hierarchy
of Evidence for Risk
Factors*
Study Design
Hypothesis Hypothesis Interpretation
and
Generating Testing
Health
Policy Implication
1. Anecdote
Case
report
Case series
2. Case-control
3. Cross-sectional
4.
Longitudinal (cohort)
5. Intervention
a)
RCT of treatment effects
in
high-
vs. low-risk
groups
b)
RCT in which risk factor
is modified
X
X
X
X
X
X
X
Suggests
a
relationship
Evidence for risk indicator
Evidence for risk
indicator
Evidence for risk
factor
Evidence for risk factor modulation
Strongest
evidence for
specific
in-
teraction to
apply
to
population
*Based on Ibrahim.8 RCT
=
randomized controlled trial.
la
intermedia,
Bacteroides
forsythus,
and
perhaps
others
such as Wolinella recta,
Fusobacterium
nucleatum,
and
spirochetes,
are associated with severe forms of
peri-
odontal
disease.4 In
addition,
a
group
of
pathogens
not
normally
found in the oral
cavity
has been
associated
with
periodontal
disease,
including
Enterobacteracea,
Pseu-
domonadacea,
and Acinetobacter.5 Periodontal disease is
likely
an
infection,
with severe forms of the disease as-
sociated with
specific
bacteria that have
colonized the
subgingival
area in
spite
of the host's
protective
mecha-
nisms.
Furthermore, some of the
pathology appears
to re-
sult from
host-mediated
responses triggered
by
bacterial
infection.
However,
the
susceptibility
of
individuals
ap-
pears
to
vary
greatly depending upon
which risk factors
are
operative.
Risk
factors can be
thought
to
affect
not
only
both
protective
and destructive host
responses,
but
also the
pathogenic
flora.
In this
paper,
risk
factors for
periodontal
disease
will
be assessed
with
emphasis
on risk
factors for adult
Per-
iodontitis.
Recent studies have
generated
interest in the
association
between
periodontal
infections and other
sys-
temic conditions and
diseases, including
oral infections
that act as foci for disease or
injury
at other
sites
includ-
ing
the
lungs,
and
periodontal
disease as
it
may
affect
diabetic
control,
adverse
pregnancy outcomes,
heart dis-
ease,
and stroke. These will be addressed in detail
by
other
papers
in this
supplement.
SPECIAL CONSIDERATIONS IN THE
ASSESSMENT OF RISK FACTORS FOR
PERIODONTAL DISEASES
Definitions
A risk factor
for
periodontal
disease is a
characteristic,
aspect
of
behavior,
or an environmental
exposure
which
is associated with destructive
Periodontitis.
The associa-
tion
may
or
may
not be causal.6 Some risk factors are
modifiable,
while others cannot be
modified or cannot
easily
be
modified. Those factors that cannot be modified
are'
often called
"determinants,"
or
background
factors.
"Risk factor" often
implies
a modifiable condition. The
term "risk
indicator" is used to describe a
possible
factor
associated
with a
disease,
which is
identified from case-
control or cross-sectional studies. True
risk factors are
those associations with disease that are confirmed in lon-
gitudinal
studies.7 The term "risk marker"
usually
refers
to a risk factor which is
predictive,
i.e.,
associated with
an increased
probability
of disease in the
future.
Study
Design
There are several
study designs
that are useful in the as-
sessment of risk factors for diseases
including Periodon-
titis,
and
which can be considered to constitute evidence
of
increasing strength
(Table 1).
Studies
which are weak-
est,
but
provide
the basis for
generating hypotheses,
in-
clude
anecdotes,
case
histories,
and case series
reports.
The next
strongest
line of evidence
concerning
the asso-
ciation
between a
potential
risk
factor or risk indicator
and disease
is
provided
by
case-control studies. Case-con-
trol
studies can often
identify
risk
indicators,
but are not
often
able to assess the role of
important confounding
factors.
Cross-sectional
population-based
studies are often
more
powerful
than case-control studies
because
they
de-
scribe
large populations
and
allow a more
rigorous
as-
sessment
of
confounders or co-risk
factors
by
multivariate
statistical
analysis.
Cross-sectional studies then are im-
portant
since
they
can lead to identification of risk indi-
cators
which are reasonable or
plausible
correlates of dis-
ease.
Longitudinal
studies are
generally
useful in
providing
strong
evidence that a risk indicator or
putative
risk factor
is indeed a true risk factor. Risk indicators
may be,
but
are not
always,
confirmed as risk factors
in
longitudinal
studies.
Longitudinal periodontal
studies, although they
provide strong evidence,
are often difficult since adult
Periodontitis
is most often a
slowly progressing
disease,
and the definition of a
new
case is
by
no means clear.
Longitudinal
studies are often
necessary, however,
to re-
solve
important questions regarding
which risk indicators
identified
in
cross-sectional, case-control, or case
history
Volume 67
Number 10 GENCO 1043
studies are indeed associated as true risk factors. Fur-
thermore, longitudinal
studies offer the
possibility
for es-
tablishing
the
temporal sequence
of the risk factor as it
relates
to onset or
progression
of the
disease.
Analysis
of risk is
ultimately
directed to
improving
the
health of the
population,
and the final evidence for the
efficacy
of elimination or
suppression
of a risk factor in
modulating
or
reducing
the disease or condition is found
from intervention studies. The
strongest experimental
de-
sign
for an intervention
study
is
the randomized con-
trolled trial in which modification
of the risk factor is
randomly assigned
to a test
group
as
compared
to a con-
trol
group
which receives an
appropriate placebo
inter-
vention. Identification of the mechanism
of action of risk
factors
allows one to
understand the mode of action of
the risk
factor and
possibly
to
design
effective risk inter-
vention studies which address the mechanism of action.8
In a
typical early, randomly
controlled
trial,
the effects
of
treatment are
compared
in a
high-risk
and a low-risk
group
to determine if
outcomes differ. If
they do,
then
other
placebo-controlled
randomized trials are carried out
in which the risk factor is
modified,
and the effects on
disease
initiation, progression,
or
response
to treatment
are measured. These intervention trials
provide strong
ev-
idence that the risk factor is
clinically important
in the
disease,
and hence should be eliminated or reduced in
prevention
or treatment
of the
disease.
Measurement of
Periodontitis
Periodontitis is defined as the loss of both the attachment
of the
periodontal ligament
and
bony
support
of the tooth
and most often occurs with inflammation of the
gingival
tissues.9 Features of
Periodontitis
are measured
by
as-
sessing
risk with various
gingival scoring
methods which
measure
gingival
inflammation, usually bleeding; probing
depth;
clinical attachment level
(CAL);
and
radiographie
evidence of loss of alveolar
housing. Probing depths
have
been used in the
past
as a measure of
periodontal disease;
however,
they
are
highly
variable since
they depend
to
a
great
extent on
gingival
inflammation.
Clinical attachment
loss is measured from a fixed
point
on the tooth
(e.g.,
cementoenamel
junction,
or the
margin
of a
restoration)
to
the
depth
of the
periodontal pocket.
Relative attach-
ment
levels are measured from an
arbitrary
but fixed
point
on
a
stent or instrument and are considered
highly repro-
ducible measures and better indications of destructive
Per-
iodontitis than
probing depths.10
Measurement of alveolar
crestal bone loss is also considered an
important defining
feature of
Periodontitis
and is correlated with clinical at-
tachment loss and carried out as an
independent
measure.
Measurement of both CAL and
radiographie
measure-
ment of alveolar
housing
loss is difficult
but informative
in
large-scale
epidemiologie
studies.
However,
for
prac-
tical
reasons,
clinical attachment loss is often used as the
single
measure of destructive
periodontal
disease
(depen-
dent
variable)
in
epidemiologie
studies where risk is as-
sessed. It is clear that
assessment
of
radiographie
alveolar
bone
height
can
give important insights
into risk factors
for
Periodontitis
since
measurement of alveolar bone loss
may
be
more sensitive than CAL in
assessing
risk factors
which affect bone metabolism and bone
rsorption
as oc-
curs in
periodontal
disease. In
fact,
this has been observed
by
Grossi and coworkers.1112
Analysis
of CAL or loss of alveolar bone as a contin-
uous outcome variable is sometimes useful to establish
case definitions. Establishment of a case definition
for
Periodontitis
is
by necessity
arbitrary.
Various
cut-off
points
for CAL have been
suggested; however,
none is
universally
agreed upon.
For
example,
Machtet et al.
sug-
gested
that
on
the basis of error of the
method
(approxi-
mately
2
mm),
the cut-off should be
greater
than 2
mm.13
They
also
argued
that since
histologie
measure-
ments of normal
periodontium
showed that the
apical
ex-
tent of the
junctional epithelium
was at
most
4 mm from
the cementoenamel
junction,
this limit should be consid-
ered in the definition of
Periodontitis.
Therefore, they
se-
lected 6 mm of attachment loss as a level
associated
with
Periodontitis.
Since a
single
area
may
not reflect infec-
tious
Periodontitis
but
may
result from
non-infectious
pro-
cesses such
as
trauma, they argued
that two sites of 6 mm
of clinical attachment
loss,
and one
pocket depth
of 5
mm,
would define a case of
Periodontitis
which is
termed,
"established
Periodontitis."
This
definition,
like all defi-
nitions of a
case,
is somewhat
arbitrary;
however,
it will
likely
result in few
false-positives
for
definition of dis-
ease,
and is of
use
in risk assessment studies.
Another
approach
is to use an extent and
severity
in-
dex.14 Extent refers to the number of teeth in the mouth
with attachment loss of
predetermined
value above a
threshold,
and
severity
is the mean attachment
loss
for
those teeth
exhibiting
the threshold level of attachment
loss.
Perhaps
a case definition which is based
upon
the
extent and
severity
seen in
any particular
study
is a useful
way
to define a case and to dichotomize or further cate-
gorize
members of a
population
with
respect
to
periodon-
tal disease. What is
important,
of
course,
is that there are
a sufficient number of cases and controls so that risk fac-
tors can be assessed in these
populations.
Other estimates
of
periodontal disease,
such as tooth loss or
mobility
mea-
surements,
have not met with reasonable
success,
possibly
because
mobility
is difficult
to measure
objectively,
and
tooth loss is often related to factors other than
periodontal
disease,
such as caries and extractions for
prosthetic
needs.
Lack of
a clear-cut definition of a case of
Periodontitis
also has hindered
longitudinal
studies which
attempted
to
define
incidence or occurrence of new
cases,
and often
progression
of disease is used. The rate of
periodontal
attachment loss
by using repeated
measures and estab-
lishing step-wise
thresholds based
upon
factors which
1044 RISK FACTORS FOR
PERIODONTAL DISEASES
J Periodontol
October 1996
(Supplement)
contribute to error
including pocket depth,
tooth
type,
and
tooth location for each individual
patient
and examiner
has
been used to assess risk factors.14
Analysis
of Data
Correlation or univariate
analysis
is often seen in older
studies of
risk,
especially
in case-control or small cross-
sectional studies.
The weakness of such an
analysis
re-
sides in the
inability
of
single
correlation
analysis
to
de-
velop comprehensive
models of
the
disease,
since
only
one,
or at most a few,
potential
risk factors can be ana-
lyzed
at one time.
Hence, they
often account for
only
a
small amount of the variance in disease outcome.
Also,
univariate
analysis
does
not
allow
adjustments
for con-
founding
variables.
Powerful,
modern statistical
analyses
using
multiple
regression
models,
linear discriminate
analysis,
and multivariate
logistic regression
have
provid-
ed the
necessary
tools to assess the role of risk factors in
periodontal diseases,
since these
analyses
can account
for
confounding
and co-risk factors.'5
STUDIES OF BACKGROUND FACTORS OR
DETERMINANTS FOR PERIODONTAL
DISEASES
Aging
Studies of
periodontal
disease
prevalence,
or extent
and
severity
from
epidemiologie
studies
show more
periodon-
tal disease in older
age groups
as
compared
to
younger
groups.1'"'12'16-18
Also,
studies
have shown that there is
greater plaque development
and more severe
gingivitis
in
elderly persons
as
compared
to
younger persons, sug-
gesting age-related
effects.18
The
question
of
why
peri-
odontal disease is more severe
in
elderly
people
is still
open.
Most studies
suggest, however,
that
periodontal
dis-
ease is more severe in
elderly people
because of cumu-
lative tissue
destruction over a lifetime rather than an
age-
related,
intrinsic
deficiency
or abnormality
which affects
periodontal susceptibility.
For
example,
an
analysis
of
ep-
idemiologie
data from the National Health and Nutrition
Examination
Survey
I in the United States
concluded that
when oral
hygiene
status was considered, age
was much
less
of a factor in
determining periodontal
disease.'8 More
recent studies
suggest
that at
least in the
moderately
el-
derly (up
to
age 70)
the
rate of
periodontal
destruction is
the same
throughout
adulthood.1920
Therefore,
it
appears
that
age, per se,
is not an intrinsic risk
factor,
at least until
age
70 or 75.
It is still unknown whether deterioration of host
pro-
tective mechanisms or accelerated host destructive
mech-
anisms or
susceptibility
to
periodontal
infection are al-
tered in the
very elderly (those beyond age 75).
There
may
indeed be an increased risk of
periodontal
disease
associated with advanced
age,
per
se.
Race
Studies
by
Beck and coworkers
showed that
approxi-
mately
three more times blacks
had advanced
periodontal
destruction as
compared
to
whites of
the same
age
cohort
(65 years
and
above).21
In an
analysis
of risk indicators
for blacks and
whites,
there were
more indicators related
to socioeconomic status
for blacks than for whites.
They
also
found, however,
that
P. intermedia was a risk indi-
cator for blacks but not for whites.
Hence,
their
analysis
and the
analysis
of other studies
addressing
the issue of
race found that when blacks
and whites
belonged
to the
same socioeconomic
group,
differences in
periodontal
disease often
disappeared."'12'22
Gender
Periodontal disease is often
reported
in
population
studies
to
be more
prevalent
or severe in males than in females
at
comparable ages.
This was seen in
several stud-
ies.1"12'23 Males
usually
exhibit
poorer
oral
hygiene
than
females.24
However,
when
correcting
for oral
hygiene,
so-
cioeconomic
status,
and
age,
male
gender
is associated
with more severe
periodontal
disease
when either attach-
ment loss or bone
height
is used as the
dependent
vari-
able."12 The reasons for these
gender
differences are not
clear,
and their elucidation
may
reveal
important
destruc-
tive or
protective
mechanisms. There are
gingival
inflam-
matory
conditions found in females which are related
to
hormonal
conditions,
such as
pregnancy
gingivitis.
In a
recent
study,
women
aged
50 to 64
who were
receiving
estrogen replacement
therapy
had
less
gingival
bleeding
than women of the same
age
who did not receive
estrogen
replacement therapy.
These differences
persisted
even af-
ter
adjusting
for other
possible
confounding
factors such
as
higher
education levels
and
lower
plaque
accumula-
tion.25 Further
assessment of
the
possible protective
role
of female hormones in destructive
periodontal
disease
may help
understand the small but
definite increase in
periodontal
disease seen in males.
Socioeconomic Status
The
relationship
of
periodontal
disease to socioeconomic
status can be viewed
globally,
where wide variations in
socioeconomic
status
among
different
populations
are
compared.
These studies
comparing populations
from de-
veloping
countries with those from
industrialized coun-
tries
suggested
that
periodontal
disease
may
be associated
with nutritional deficiencies seen in
developing
coun-
tries.2226
However,
Ramfjord
et
al. found that the
peri-
odontal condition
of
young
men
in India who exhibited
clinical
symptoms
of
general
malnutrition was not
differ-
ent from the
periodontal
condition
of well-nourished in-
dividuals.27 Similar
findings
were
made in a nutritional
survey
of 700 men in
Alaska,
where it was found that the
periodontal
condition of
individuals with nutritional de-
ficiencies was
not
different from the
periodontal
status of
Volume 67
Number 10 GENCO 1045
controls who were
nutritionally healthy.28
Other studies
comparing
the
periodontal
status
of individuals in devel-
oped
and in
developing
countries of
varying
levels
of
socioeconomic
status
also failed
to
show a
relationship
between
periodontal
disease and nutrition.2629-30 Another
perspective
comes from a
study
of
periodontal
disease in
developed
countries such as the United
States,
where it
is found that
periodontal
disease
is
more
severe in indi-
viduals of lower
socioeconomic status.23-24
However,
in
more recent
studies,
when
periodontal
status was
adjusted
for oral
hygiene
and
smoking,
the association between
lower
socioeconomic status
and more severe
periodontal
disease was
not seen.11-12
Genetics
The
genetic aspects
of localized
juvenile Periodontitis
are
covered in a recent review.31 Hart and coworkers also re-
ported
a detailed
analysis
of the literature which
they pro-
pose
supports
autosomal modes of transmission of local-
ized
juvenile Periodontitis.32 They
also note that
juvenile
Periodontitis
is
likely heterogeneous and, indeed,
some
rare X-linked
forms
may
exist.
Linkage analysis
and iden-
tification of abnormal
genes
in
juvenile Periodontitis
will
ultimately
be needed
to
prove
the
genetic aspects
of this
disease
and
to
explain,
in
part,
the
abnormality
in
neutro-
phil
function which
appears
to
be familial.33
The
genetic aspects
of adult
Periodontitis
also have
been addressed. In
earlier
studies,
adult forms of
peri-
odontal
disease were shown to
be associated with human
leukocyte antigens.
For
example, negative
associations of
Periodontitis
have been
reported
for HLA-A2.34
36
An in-
crease of HLA-A9 also has been
reported
in
patients
with
a severe form
of
adult
periodontal
disease.37-38 It is
not
clear, however,
from the studies
showing
a
positive
as-
sociation with
HLA-A9 whether their
populations
includ-
ed some individuals who had
previously
suffered from
juvenile Periodontitis,
since Reinholdt et al.39
reported
an
increase of
HLA-A9, as well as HLA-28 and
HLA-W15,
in localized
juvenile
Periodontitis patients.
Studies of
adult
Periodontitis patients
who have not
previously
suf-
fered from localized
juvenile
Periodontitis
are needed to
resolve this
question.
Studies on 26
sets
of twins
(aged
12
to
17;
seven
mono-
zygotic
and 19
dizygotic)
found no
evidence for differ-
ences in
gingival recession,
gingival
crevice
depth, gin-
gival bleeding,
calculus, or
plaque40
More
recently,
Mich-
alowicz and coworkers41 studied 110
pairs
of adult twins
which included 63
pairs
of
monozygotic
twins reared
to-
gether,
33
pairs
of same-sex
dizygotic
twins reared
to-
gether,
and 14
pairs
of
monozygotic
twins
reared
apart.
They reported significant genetic
variance in the
popula-
tion for
proportional
alveolar bone
height.
A second re-
port by
the same
group
found a
genetic component
for
gingivitis, probing depth,
attachment
loss,
and
plaque.42
These
studies
suggest
a
genetic component
for
periodon-
tal disease.
However,
the interactions are
complex,
and
confirmatory
studies in
twins, families,
and studies of
ge-
netic
polymorphisms
are
necessary
before
genetic
influ-
ences on
periodontal
disease can be understood.
STUDIES OF RISK FACTORS OR INDICATORS
FOR PERIODONTAL DISEASES
Periodontal Microflora
Recent studies have
pointed
to a few members of the
periodontal
microflora as candidate
pathogens
for initia-
tion and
progression
of
periodontal
disease.
Recently,
im-
munofluorescent
techniques
have
been
developed
for
identification and
semi-quantitation
of these
organisms
in
the
large
numbers of
subgingival samples
taken in
epi-
demiologie
studies.
These
microbial
epidemiologie
stud-
ies have shed
light
on the role of
specific periodontal
organisms
in
periodontal
disease. Carlos and coworkers43
found that the
presence
of P. intermedia
(formerly
called
Bacteroides
intermedius),
along
with
gingival bleeding
and
calculus,
was correlated with attachment loss in a
group
of
Navajo
adolescents
aged
14 to 19. Grossi and
coworkers tested a
panel
of
microorganisms including
A.
actinomycetemcomitans,
B.
forsythus, Campylobacter
rectus,
Capnocytophaga species,
Eubacterium sabur-
reum,
F.
nucleatum,
P.
gingivalis,
and P. intermedia." 2
Of these
organisms, only two,
P.
gingivalis
and B.
for-
sythus,
were associated with increased risk for attachment
loss as a measure of
periodontal
disease after
adjustment
for
age, plaque,
smoking,
and diabetes." The same two
organisms
were also identified as risk indicators for
peri-
odontal alveolar bone loss.12
Interestingly,
in both studies
Capnocytophaga
species
were found in
higher
levels in
subjects
with lower levels of
periodontal
disease, sug-
gesting
that these
species may
be
part
of the normal flora.
A
study
of oral bacteria as risk indicators for
Periodontitis
in older adults found that the differences in the
prevalence
of
periodontal
disease between blacks and whites is ex-
plained,
in
part, by
different
prevalences
of P.
gingivalis
and P. intermedia.*4 This
study
also found that non-bac-
terial factors such as
having
visited the dentist more than
3
years ago, having
fewer
teeth,
and
using
tobacco were
associated with
periodontal
diseases as evidenced
by
hav-
ing
a loss of
attachment of 7 mm
or
greater.
The
epide-
miologie
data of Beck and coworkers44
suggest
that
spe-
cific
bacteria such as P.
gingivalis
and P. intermedia
play
a role in
periodontal
disease in older adults. The
impor-
tance of
specific
bacteria in
periodontal
destruction is
highlighted by
the
finding
that the
quantity
of total
plaque
accumulation is
only weakly
correlated with destructive
periodontal
disease.11-12,45
SYSTEMIC DISEASES AND CONDITIONS
AND
PERIODONTAL DISEASES
Several recent studies have addressed the
question
of
which
systemic
disorders or diseases
increase the risk for
1046
RISK FACTORS FOR PERIODONTAL
DISEASES
J Periodontol
October 1996
(Supplement)
periodontal
disease. Grossi and coworkers studied a
large
number of
systemic
diseases as risk indicators for
peri-
odontal disease in a
population
of
1,426 subjects aged
25
to
75
residing
in Erie
County,
New York."
'2
It was found
that there were 17
systemic
diseases and conditions re-
ported
in
enough
frequency
in this
population
to
be able
to assess whether or not
they
were risk indicators for
peri-
odontal disease. These
included
allergy, hives, asthma,
hay fever,
high
blood
pressure, arthritis, anemia, cancer,
gall
bladder
disease, mononucleosis, kidney disease, thy-
roid
disease, gout,
venereal
disease,
hepatitis, diabetes,
angina,
and
cataracts.
Of these
diseases,
only
diabetes
mellitus was found
to
be associated with more severe de-
structive
periodontal disease,
when
measuring
attachment
level as a
dependent
variable.
It
is of interest that when
measuring
clinical attachment level or bone
loss, allergies
were found to
be associated with less severe
periodontal
disease, an association which
may
be related to medica-
tions taken
by
individuals with
allergies. Furthermore,
anemia was found to be
associated
with less
periodontal
disease when
using
attachment loss as a
measurement,
and a
history
of
kidney
disease was associated with less
periodontal
disease when
using
bone loss as a
measure-
ment. The
explanation
of these latter
findings
is not
clear;
however,
it does illustrate the
potential
for alveolar bone
measurements and
probing
attachment
measurements to
give
a different
assessment
of risk indicators
or,
in
this
case,
protective
factors. In a
previous
study
of
1,300
hos-
pitalized patients,
no correlations were seen with
various
diseases.46
However,
in a
larger
study
of
4,000
subjects,
of all the diseases
assessed, only patients
with
diabetes
mellitus had a
statistically
significantly higher prevalence
of
periodontal
disease than others47
Population-based
studies
may
not
have a sufficient
number
of individuals afflicted with rare or
uncommon
systemic
diseases
to
derive
any
conclusion about their
relationship
to
periodontal
disease. Case-control studies
or case histories have
provided hypotheses regarding
the
associations of these rare conditions with
periodontal
dis-
ease. For
example,
diseases associated with
neutrophil
de-
fects such as
Chediak-Higashi syndrome,
Down's
syn-
drome,
and
Papillon-LeFvre syndrome
have been shown
from case-control and
case
history
studies
to
be associ-
ated with severe forms of destructive
Periodontitis (see
Genco and Le for
review31). Acquired immunodeficiency
syndrome (AIDS)
also
appears
to
be associated with se-
vere forms of
gingivitis
and
Periodontitis.
The
association
of risk factors in
HIV-seropositive
or AIDS
patients
is an
active
area of
research,
and it
appears
that reduction of
CD4 cell numbers and
smoking
are associated with severe
forms
of
periodontal
disease in these
patients.31
Diabetes Mellitus
A series of
population-based epidemiologie
studies has
elucidated the
relationship
between destructive
periodon-
tal disease and
non-insulin-dependent
diabetes mellitus
(NIDDM).
Some of these studies were carried out on a
population
with the
highest
reported prevalence
of
NIDDM,
the Pirna Indians from the Gila River Indian
Community
in Arizona.48-50 In one
study
of this
popula-
tion,
an
analysis
was carried out
by using
two
indepen-
dent
measures of
periodontal
disease-attachment loss and
radiographie
bone loss.48 The
3,219
subjects, aged
5 to
over
95,
were evaluated for their diabetic status
by
a
2-hour
glucose
tolerance
test
and for
periodontal
disease
by
assessing
clinical attachment levels and
interproximal
alveolar bone levels.
They
were also evaluated for a
large
number of
general
and oral health abnormalities.
Diabetes
prevalence ranged
from 3% in the 5- to
24-year-old age
group
to 60% to 70% in the
45 and older
age
group.
In
all
groups studied, subjects
with diabetes mellitus had
a
higher prevalence
of
periodontal
disease when
using
ei-
ther measure of
periodontal
disease,
even after
correcting
for
age,
plaque,
and other
possible confounding
factors.
These studies indicate that
diabetes
is a risk
indicator for
periodontal
disease.
A further
study
was carried out on this
population
in
which the correlation of diabetes and
periodontal
disease
was further
analyzed
to determine whether it
could be
accounted for
by age, gender, calculus, plaque, gingival
index, fluorosis,
or
caries,
factors that
might
confound the
relationship
with diabetes mellitus.49
Only
diabetic
status,
age,
and the
presence
of
subgingival
calculus were
sig-
nificantly
associated with increased
prevalence
and se-
verity
of
periodontal
destruction in this
population.
Next,
Nelson and coworkers carried out a
longitudinal study
in
which the incidence of
periodontal
disease was deter-
mined in
a subset of 701 Pirna
Indians, aged
15
to
54,
who
initially
had little or no evidence of
periodontal
dis-
ease.50
The
age-
and
gender-adjusted
incidence of
peri-
odontal disease in NIDDM
subjects
was found to be 78
cases
per 1,000 person years, significantly higher
than the
rate of
29 cases
per 1,000 person years
in
subjects
without
diabetes
(relative
risk
2.6).
This
longitudinal study pro-
vides
convincing
evidence that
non-insulin-dependent
di-
abetes mellitus is a risk factor for
periodontal
disease.
Several recent studies of
large populations, taking
into
consideration the effects of
age
on
periodontal disease,
have
consistently
found that
diabetes mellitus is a risk
factor for
periodontal
disease.48-51
With
respect
to
insulin-dependent
diabetes mellitus
(IDDM),
Cianciola et al.52 found that 11.3%
to 16% of
those
aged
13
to
18 had
Periodontitis,
and after
age
18
more than 25% had
Periodontitis.
This is
compared
to
1.7%
of
the 13- to
18-year-old
non-diabetic
controls who
had
Periodontitis.
Hence,
insulin-dependent
diabetics in
the
teenage years appear
to be more
susceptible
to
de-
structive
Periodontitis.
Glavind et al.53 found that between
the
ages
of 30 to
40,
insulin-dependent
diabetics had an
increase in
periodontal
breakdown as
compared
to
non-
Volume 67
Number 10 GENCO
1047
diabetics.
Furthermore, they
showed that those who had
greater
duration of diabetes and diabetics with retinal
changes
also had
greater
loss of
periodontal
attachment
than the others. There are several studies that failed
to
demonstrate
significant
differences in
periodontal
disease
between diabetics and non-diabetic
subjects.54-56 However,
clinical studies
comparing
diabetics with non-diabetics
must
consider not
only age matching
but also the
age
range
of the
patients
before
making
conclusions. Patients
too
young may
not show differences in the
prevalence
or
severity
of
periodontal
disease between
groups
with and
without
diabetes,
since the onset of
Periodontitis appears
to
be around
puberty.
On the other
hand,
patients
who are
older
may
not have differences in
periodontal
disease be-
cause of tooth extractions.
Smoking
There is a
long
history
of association between tobacco
smoking
and
periodontal
disease.57-59
However,
the
per-
ception
that
greater
levels of
plaque
and calculus in smok-
ers than non-smokers
fully
accounted for the association
left the clinical
community largely
unconvinced of the
importance
of
smoking per
se in
periodontal
disease. In
1983,
Ismail et al.60
analyzed
smoking
and
periodontal
disease and found that after
adjusting
for
potential
con-
founding
variables such as
age,
oral
hygiene, gender,
and
socioeconomic
status, smoking
remained a
major
risk in-
dicator for
periodontal
diseases. In studies
by
Grossi
et
al.,"12
smoking
was shown
to
be a
strong
risk indicator
for
periodontal
disease with an odds ratio of 2.0 to 5.0
when
using
attachment loss as a
measurement,
and odds
ratios of 1.5
to
7.0 when
using
alveolar bone loss as the
measure of
periodontal
disease after
adjusting
for
age,
gender,
socioeconomic
status, plaque,
and calculus. Gros-
si and coworkers found a direct and linear dose
response
between the level of
smoking (pack years)
and destructive
Periodontitis, lending
further
support
to
smoking
as
a risk
factor for
periodontal
disease."12 There
is
mounting
evi-
dence that smokers also have a different
periodontal
mi-
croflora61 and also heal less
satisfactorily
after
periodontal
therapy
than non-smokers.62 It is
likely
that
smoking
is a
major
risk factor for
destructive
periodontal
disease
in
man,
and that modification of this risk factor is
important
in the
treatment
and
prevention
of
periodontal
disease.
Other Possible Risk Factors for Periodontal Diseases
There are
preliminary
studies which
suggest
that
stress,
distress,
and
coping
behaviors63 are associated with in-
creased
severity
of destructive
periodontal
disease. This
association has
long
been
suspected
but
was
difficult to
scientifically
assess before
valid, reproducible
measures
of
stress, distress,
and
coping
behaviors were
applied
to
periodontal
risk
assessment
studies. Instruments for as-
sessing
these
psychosocial
variables are now available
which allow this to
be
done,
and the indication is that
stress, distress,
and
coping
behaviors are
important
risk
indicators for
periodontal
disease. In the Erie
County
study
reported
by Moss,63
it was found that financial stress
was related
to more severe
periodontal
disease and that
effective
coping
behaviors
modulated this effect.
Osteopenia/Osteoporosis
Osteopenia
and
osteoporosis
have been
studied
in case-
control and anecdotal studies
(see
Genco and Le31 for
review).
For
example,
in a
study by Danieli,
208 women
aged
60 to 69 were assessed for
smoking habits, peri-
odontal
disease,
and current
osteoporosis
severity
based
upon
the
percentage
of cortical area at the
metacarpal
midshaft.64 In this
study,
52% of the
smokers,
26% of the
non-smokers,
and
only
8% of the
non-osteoporotic
non-
smokers
required
dentures since
reaching
the
age
of 50.
This series of case
reports
suggests
that
osteoporosis
and
smoking
are
important
factors
promoting
tooth loss. In
another
study,
Kribbs
compared osteoporotic patients
with controls and found that the
osteoporotic group
had
a
greater percentage
of
subjects
who were edentulous or
had
greater
tooth loss.65
However,
the reason for tooth loss
is difficult to
determine,
and it is
not
clear whether tooth
loss was
weakly
or
significantly
associated with more se-
vere
Periodontitis.
Evaluation of
osteopenia
and
periodontal
disease af-
fords an
interesting insight
into metabolic bone abnor-
malities and
locally
induced bone
rsorption
caused
by
periodontal
infection. A direct association between skel-
etal and mandibular
osteopenia
and destructive
periodon-
tal disease as measured
by
loss of
interproximal
alveolar
bone in
postmenopausal
women has been
reported by
Wactawski-Wende and coworkers.66
SUMMARY
Extensive evaluation
of risk factors for
periodontal
dis-
ease has led
to
the identification of the
following
as risk
indicators: P.
gingivalis,
B.
forsyihus,
P. intermedia,
gen-
der,
and
age.
Both
type
I
(insulin-dependent)
and
type
II
(non-insulin-dependent)
diabetes mellitus are
important
systemic
diseases which are risk factors for
periodontal
disease.
Smoking
is
perhaps
one of the
most
important
risk factors
for
periodontal
disease, increasing
the risk 2-
to 7-fold
depending
on the level of
smoking.
Future studies will
help
us to
better understand the role
of
osteoporosis,
as well as
stress, distress,
and
coping
as
they
increase the
susceptibility
of individuals to
peri-
odontal disease. These associations and the
strength
of
evidence
supporting
these are summarized in Table 2. A
new
generation
of studies is needed
not
only
to
identify
other
potential
risk factors for
periodontal
diseases,
but
also
to
determine the effective interventions directed
to
modulating important
risk factors and to
assess
their ef-
fects on the initiation and
progression
of
periodontal
dis-
ease,
and their effects on
periodontal therapy.
1048 RISK FACTORS FOR PERIODONTAL DISEASES
J Periodontol
October 1996
(Supplement)
Table 2. The
Strength
of Association of Putative Risk Factors and Destructive Periodontal Disease
Putative
Case Case- Cross-
Report
Control Sectional Longitudinal
Intervention
1.
Specific
bacteria
P.
gingivalis
B.
forsythus
P. intermedia
2. Gender
male
3.
Age
yes
yes
yes
yes
yes
4. Diabetes mellitus
(NIDDM) yes
IDDM
yes
5.
Smoking
NR
6.
Osteoporosis yes
7. Stress, distress,
coping
8. PMN disorders
yes
yes
yes
yes
NR
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
NR
yes
yes
yes
NR
no to 7th decade
yes
NR
yes
NR
NR
yes (case series)
yes
yes
yes
NR
NR
yes (treatment
re-
duces
glycosy-
lated
hemoglo-
bin)
NR
yes (smokers
heal
poorly)
NR
NR
NR
NR
=
not
reported,
or not relevant.
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Send
reprint requests
to: Dr. Robert J.
Genco,
State
University
of New
York at
Buffalo,
School of Dental Medicine,
Department
of Oral Biol-
ogy,
115 Foster
Hall, Buffalo,
NY 14214.