8

Risk assessment in clinical
practice
Mauricio Ronderos & Mark I. Ryder
All persons are not equally susceptible to periodontal
diseases and do not respond equally to periodontal
therapy. In a classic longitudinal study of a population
with no access to dental care and poor oral hygiene,
Loe et al. (121) observedenormous variabilitybetween
individuals in their rates of periodontal disease pro-
gression. Inthis fairly homogeneous population, some
persons developed disease at very rapid rates, while
others had little or no progression. Similar variability
inthe response to periodontal treatment has beenwell
documented. Hirschfeld & Wasserman (88) followed
600 patients from a private periodontal practice for an
average of 22 years and divided them according to the
number of teeth lost during maintenance therapy. In
all, 83% of the patients were classied as being ``well
maintained'' (lost 3 teeth during the follow-up
period), 12.6% ``downhill'' (lost 49 teeth), and 4.2%,
despite receiving frequent periodontal therapy, were
consideredto have an``extreme downhill'' response to
therapy (lost 10 teeth). Comparable results were
reported by similar long-term studies (68, 134). These
studies reported on what teeth in the mouth were
more likely to be lost and the impact of furcation
involvement on the long-termoutcome of periodontal
therapy. However, little was known at the time regard-
ing the risk factors that may affect the overall patient
response to therapy. Such information would help
the clinician to establish more accurate prognoses.
The purpose of this paper is to review the available
literatureregardingfactors that maybeassociatedwith
the overall response of patients toperiodontal therapy.
Behavioral risk factors
Tobacco use and smoking
It is now well established from a large body of epi-
demiologic evidence that cigarette smoking is the
major preventable risk factor in the incidence and
progression of periodontal disease (24, 75). Cigarette
smoking is related to periodontal disease in a dose-
related manner (69, 76, 77, 132), and appears to exert
its most deleterious effects on areas in direct contact
with smoke, such as the lingual aspect of maxillary
teeth (84, 228). In addition, the few studies that have
examined the relationship of cigar and pipe smoking
have demonstrateda similar deleterious effect of these
tobaccoproducts onthe patternof periodontal disease
(3, 110). This deleterious relationship between smok-
ing and periodontal disease is seen in smokers
regardless of their overall levels of plaque accumula-
tion. However, the specic microbial ora in smokers
may shift to a more pathogenic prole (83, 229).
There are conicting reports regarding the effects
of smoke on the qualitative and quantitative makeup
of periodontal pathogens (29, 47, 177, 215). Recent
reports have shown that the rate of recovery of such
harmful pathogens from relatively shallower pockets
is greater in smokers (54, 82). These ndings suggest
that tobacco smoking itself may promote the devel-
opment of local environments that favor growth of
such pathogenic species. In addition, substances in
smoke such as cotinine may also promote the patho-
genic activities of periodontal ora (200). Tobacco
products may also exert a deleterious effect on the
periodontium by impairing the normal defenses of
the host response (36, 149, 179) and/or by stimulating
the destructive effects of the host response (79, 173).
Amidst this growing knowledge of the critical role
of tobacco use in periodontal disease, it is no surprise
to the clinician that the smoking patient would not
respond as well to a variety of periodontal therapies if
the patient continued the smoking habit. This gen-
eral clinical opinion is supported by a growing body
of literature that demonstrates the poorer response
of smokers to a variety of periodontal procedures (6,
176). These procedures include scaling and root
planing, ap surgery, a variety of regenerative and
mucogingival procedures, and implants. From these
120
Periodontology 2000, Vol. 34, 2004, 120135 Copyright
#
Blackwell Munksgaard 2004
Printed in Denmark. All rights reserved
PERIODONTOLOGY 2000
treatment studies, it is evident that tobacco use will
adversely affect long-term prognosis in the presence
or absence of periodontal treatment.
In recent years, there have been several lines of
published evidence that dramatically point to the
benets of smoking cessation in periodontal treat-
ment and prognosis. The rst line of evidence comes
from a series of epidemiologic studies that compare
theperiodontal destructionincurrent smokers, former
smokers, and non-smokers (never smoked). The
results from these studies indicate the level of period-
ontal destruction in former smokers lies somewhere
betweenthe level of periodontal destructionof current
smokers and non-smokers (25, 26, 80). These results
imply that the progressive damage seen in smokers
can be retarded or halted with smoking cessation.
The second line of evidence of the benets of smok-
ing cessation to periodontal treatment outcomes
comes from longitudinal studies of the periodontal
treatment response to surgery between current smo-
kers, former smokers, and non-smokers. These stu-
dies demonstrate that while the clinical response to
ap surgery is poorer in smokers when compared to
non-smokers, the clinical response of former smo-
kers is similar to non-smokers as long as the former
smokers do not resume their smoking habit (77, 102,
201). These types of studies demonstrate that smok-
ing cessation can markedly improve the prognosis
and outcomes of periodontal treatment.
Compliance
The most important determinant of treatment out-
comes in clinical periodontics is patient compliance.
Regardless of the type of initial periodontal therapy
rendered, patients with poor oral hygiene who fail to
comply with the recommended recall schedules are
more likely to have less favorable results (21, 163,
194). Lack of compliance with smoking cessation
programs may also have a deleterious effect on the
outcome of periodontal therapy.
Despite the efforts of clinicians to modify patient
behaviors, many patients have poor plaque control.
Plaque has a central role in the initiation of gingival
inammation (120) and calculus formation (232), and
poor plaque control has been shown to have a dele-
terious effect on the success of periodontal treatment,
including regenerative procedures (127, 163). Among
patients with poor oral hygiene, the compliance with
maintenance care may be even more important at
predicting long-term stability and preventing future
disease. Some data suggest that, despite poor oral
hygiene, long-term stability of the periodontal con-
dition can be achieved in most patients if they are
compliant withashort-interval maintenanceprogram.
Ramfjord et al. (182) reported that plaque scores were
not a major determinant of post-treatment probing
depths or clinical attachment levels in patients receiv-
ing periodontal maintenance therapy every 3 months
for 8 years. Other longitudinal studies of populations
receiving maintenance therapy also suggest that pla-
que scores are a poor predictor of periodontal disease
progression(84, 101). However, it is likely that patients
who do not comply with their oral hygiene regimens
are also inconsistent in their compliance with the
recommended recall schedules.
Periodontal maintenance therapy prevents or
minimizes the recurrence and progression of period-
ontal disease, reduces the incidence of caries and
tooth loss, and may prevent the progression and limit
the morbidity of other conditions found within the
oral cavity (5, 13, 14, 28). Patients who comply with
the recommended periodontal maintenance therapy
intervals experience less attachment loss and lose
fewer teeth than patients who are erratic in their
compliance or those who do not receive mainte-
nance care (21, 22, 49, 98, 162, 235, 239). Becker et al.
(20) reported that patients with periodontal disease
who refused periodontal therapy lost an average of
0.36 teeth per year (not including teeth determined
to be hopeless during initial examination). Among
patients who received initial therapy but did not
receive maintenance care the corresponding annual
rate of tooth loss was 0.22, and among those who
received initial and maintenance therapy the annual
rate of tooth loss was 0.11 (21, 22).
Patients who comply with periodontal treatment
and maintenance therapy are generally able to retain
teeth with initially questionable to hopeless prognosis
for a long time (40, 88, 134, 135). For instance, Chace
&Low (40) retrospectively studied data from166 fairly
compliant patients who were seen for periodontal
maintenance therapy every 3 months for 40 years.
Only 12% of the teeth initially classied as having a
questionable prognosis (i.e. teeth with PD 6 mm,
mobility, poor crown-to-root ratio, class II or III fur-
cation involvements) were extracted during the fol-
low-up period. The average survival rate for the teeth
extracted was 8.8 years. These data suggest that when
patients comply with a recommended program of
periodontal maintenance care, they have an excellent
chance of retaining most of their teeth. Unfortuna-
tely, while the rates of compliance vary from one
dental practice to another, patient compliance is
generally poor (63, 158, 161, 217). Wilson et al. (238,
240) reported that 2034% of patients who receive
Risk assessment in clinical practice
121
periodontal therapydonot comebackfor maintenance
care, 4849% are erratic in their compliance, and only
1632% are fully compliant with the recommended
maintenance schedules. Unfortunately, little is known
regarding how to predict patient compliance. Smo-
kers tend to be less compliant than non-smokers in
keeping their periodontal maintenance schedule
(98, 139). Younger patients have also been reported
to be less compliant (158, 160, 165); however, others
have reported better compliance among younger
individuals (41) or no association between age and
compliance (49, 139). Gender (41, 49, 139, 159) and
baseline periodontal status (63, 107, 139) have been
found to be unrelated to patient compliance.
Periodontal maintenance therapy intervals ranging
from weeks to years have been documented to be
appropriate for given groups of subjects (119, 162,
194). In general, shorter recall intervals lead to better
clinical outcomes. Some studies suggest that 2-week
recall intervals yield better clinical results than 3- or
6-month intervals (162, 235). However, there is large
patient variability in the required recall intervals, and
the use of very narrow intervals is neither feasible in
clinical practice nor required for most patients (119).
It is recommended that patients without a history
of periodontal disease should receive periodontal
maintenance therapy every 6 months, while patients
with a history of periodontitis should receive period-
ontal maintenance therapy every 3 months (5). How-
ever, these guidelines should be considered a starting
point. The clinician should tailor the procedures and
intervals of periodontal maintenance therapy based
on the susceptibility and risk factors for future dis-
ease of each individual patient.
Important clinical predictors of disease activity are
bleeding on probing and, to a lesser extent, residual
probingdepth(10, 43, 72, 115). Langet al. (115) reported
that in patients previously treated for severe period-
ontitis, 30% of the sites that bled on probing on four
consecutive recall visits lost attachment. The corres-
ponding percentages for sites bleeding on three,
two, one, or none of the four recall appointments
were 14%, 6%, 3%, and 1.5%, respectively. Long-term
stability of periodontal patients is also determined by
the quality of maintenance care (1315).
Systemic risk factors
Diabetes and glycemic control
There is an extensive body of literature that points to
an emerging ``two-way relationship'' between dia-
betes/poor glycemic control and periodontal diseases.
Specically, the severity of the diabetic condition,
whether insulin-dependent diabetes mellitus or non-
insulin-dependent diabetes mellitus is related to the
incidenceandseverityof periodontal disease(213, 218,
224). Conversely, there is evidence that the severity of
periodontal disease may affect the level of glycemic
control in diabetic patients (74, 145, 214, 218). It has
been proposed that this effect may be due in part to
the role of the chronic bacterial load and chronic
inammation that is characteristic of periodontal
diseases. Products of the bacterial load and products
of the inammatory response could enter the sys-
temic circulation, leading to an increase in the resis-
tance to insulin. This would result in an elevated
blood glucose, which in turn could react with hema-
togenous proteins such as hemoglobin to form glyco-
sylated hemoglobin. Further glycation and oxidation
of proteins and lipids would then lead to formation of
advanced glycation end products that could promote
sequelae of diabetes such as local destructive inam-
matory responses and tissue damage (114).
For the dental practitioner, an important area of
clinical research centers on improving glycemic con-
trol (as measured by the levels of glycosylated hemo-
globin) through periodontal therapy. Studies using
combinations of debridement, local irrigation, and/
or systemic antibiotics on both NIDDM and IDDM
patients have shown small, but in some cases signi-
cant, reductions in glycosylated hemoglobin after
periodontal treatment (74, 145, 214, 218). Due to the
potential confounding effects of systemic antibiotics
such as tetracycline in not only reducing periodontal
pathogens but also inhibiting tissue destructive
metalloproteinases (such as collagenase), studies on
larger diabetic populations need to be conducted
in the future. Nevertheless, from these early interven-
tion studies, it appears that reducing pathogens and
inammation in periodontal disease may have bene-
cial systemic effects on the diabetic patient.
The effect of diabetes and poor glycemic control
on periodontal treatment outcomes is also unclear at
this time. One study demonstrated that the clinical
outcomes from nonsurgical therapy were similar
between diabetic and non-diabetic patients (220).
However, similar comparisons of clinical outcomes
between diabetic and non-diabetic patients after sur-
gical therapy have yet to be published. Since poor
glycemic control can adversely affect wound healing
and can lead to a more pathogenic bacterial plaque,
the dental practitioner may wish to consult with the
patient's physician to optimize the glycemic control
prior to periodontal therapy.
122
Ronderos & Ryder
HIV infection
The consequences of HIV infection continue to be a
worldwide health concern. While new infection rates
have declined among some high-risk groups, they
continue to rise in other populations throughout
the world (174). The advent of new therapies such
as highly active retroviral therapy (HAART) appears
to be extending both the lifespan and the quality of
life for those HIV-infected patients who have access
to these therapies (44, 174, 187). With the advent of
HAART therapies, the incidence of some oral mani-
festations of HIV infection such as oral candidosis,
hairy leukoplakia, and necrotizing forms of period-
ontal disease appear to have declined in recent years
(39, 52, 137). However, as patients become resistant
to these therapies, these oral manifestations may
begin to rise again in HIV-infected populations.
It is important to keep in mind that HIV-infected
patients may present with common forms of period-
ontal disease such as chronic periodontitis. Epide-
miologic studies have shown a higher prevalence of
bone loss and attachment loss in HIV-infected
patients accompanied by a greater degree of gingival
recession and shallower probing depths compared to
control populations (18, 125, 138, 154, 243). However,
the effects of HIV infection on the long-term prog-
nosis of the dentition in chronic periodontitis remain
unresolved. On the one hand, a more rapid progres-
sion of bone loss and attachment loss in a HIV-
infected periodontal patient may imply a poorer
prognosis for the dentition when compared to the
HIV-negative patient. Several studies have shown
that HIV-positive patients can tolerate dental proce-
dures such as scaling and root planing and tooth
extraction (53, 67, 124, 175, 188). However, the types
of dental procedures (particularly periodontal surgi-
cal procedures) that can be performed may become
more limited during severe immunosuppression at
later stages of the HIV infection (195). These limited
treatment options may adversely affect long-term
prognosis. On the other hand, in the HIV-infected
periodontal patient the pattern of relatively shallower
probing depths accompanied by gingival recession
may make these areas easier to maintain with home
care to control plaque accumulation. Thus long-term
studies are needed to determine how HIV infection
affects long-term periodontal prognosis.
Osteoporosis
It has been hypothesized that osteoporotic persons
are at increased risk for developing periodontitis (73).
The role of osteoporosis in the etiology of periodontal
disease is not fully understood. While some reports
suggest the lack of a signicant association between
these two conditions (56, 126, 236), most observa-
tional studies support the possible role of low skeletal
bone mineral density as a risk indicator for period-
ontitis (94, 146, 221, 230, 231). In a cross-sectional
evaluation of a large sample of U.S. adults, Ronderos
et al. (191) found that, after adjusting for confoun-
ders, females with high calculus scores and low
femoral bone mineral density had signicantly more
clinical attachment loss and recession than females
with normal bone density and similar calculus scores
(P < 0.0001). Meanwhile, no associations were
observed among women with low or intermediate
levels of calculus. The clear interaction between cal-
culus and bone mineral density suggests that in the
presence of local irritants (i.e. calculus), osteoporosis
and, to a lesser extent, osteopenia increase the risk
for periodontal attachment loss. Based on these
results one could speculate that the increased risk
for periodontitis present among osteoporotic and
osteopenic persons may be prevented or attenuated
by frequent calculus removal.
Since estrogen depletion is an important risk factor
for the development of osteoporosis (for review, see
Lindsay (118)), it is important to consider the role of
estrogen as a possible underlying cause for the asso-
ciation between periodontitis and low skeletal bone
mineral density (100). In postmenopausal women,
estrogen supplementation prevents loss of skeletal
(38) and alveolar bone mineral density (97, 172),
and may also be protective against gingival inam-
mation (157, 185) and clinical attachment loss (185,
191). The effect of steroid hormones as metabolic
mediators of the expression of cytokines may be a
plausible explanation for the protective effect of
estrogen supplementation against bone loss, infec-
tious diseases, and periodontitis (99, 166, 167, 216).
Adequate calcium intake also prevents osteoporosis
and may prevent periodontitis (109, 156). It is possi-
ble that hormone replacement therapy, calcium and
vitamin D supplementation, and other medications
used to prevent low bone density have positive effects
on the outcomes of periodontal therapy. Some studies
suggest that alendronate, an effective medication for
the treatment and prevention of osteoporosis, may
have a positive effect on the outcome of periodontal
treatment (27, 184, 189, 241, 242).
In light of the current information, patients with a
diagnosis of osteoporosis or osteopenia should be
advised about their possible increased risk for devel-
oping periodontitis and the importance of frequent
123
periodontal maintenance visits. Patients at high risk
for osteoporosis or osteopenia should be encouraged
to be evaluated by their physicians. It is possible that
medications used for the treatment and prevention
of osteoporosis may also prevent alveolar bone loss,
and enhance the results of regenerative procedures
and periodontal therapy.
Familial and genetic risk factors
In the past it was believed that periodontitis was
strictly caused by environmental factors. It is now
widely accepted that only a portion of the variability
of disease in the population can be attributed to
environmental exposures, while the remaining varia-
tion is attributed to differences in host susceptibility.
Differences in host susceptibility are ultimately
determined by genetic variations. Research indicates
that genetic variations inuence the risk for aggres-
sive and chronic periodontitis.
Aggressive periodontitis tends to cluster within
families (23, 33, 130, 199), and a single/major locus
autosomal dominant gene is involved in the etiology
of the disease (130). Some human leukocyte antigen
(HLA) and interleukin (IL)-1b polymorphisms have
been found to be associated with an increased risk
for aggressive periodontitis (51, 103105, 219). How-
ever, such associations have not been conrmed by
more specic linkage studies (198, 234). No specic
genetic tests have been proven to predict the devel-
opment of aggressive periodontitis or the outcome of
periodontal treatment among affected individuals.
However, based on the strong evidence of familial
aggregation and a dominant mode of disease trans-
mission, clinicians should encourage siblings and
close relatives of patients with aggressive periodon-
titis to receive a periodontal evaluation. Preventive
periodontal therapy and close monitoring is espe-
cially important among young relatives of patients
diagnosed with aggressive periodontitis.
Familial aggregation studies also support the idea
that chronic periodontitis tends to cluster within
families (19, 42, 183, 227). This supports the use of
family history of periodontitis as a risk factor for the
development of future periodontal disease. While
some studies indicate that most of the similarities
within families should be attributed to shared envir-
onmental exposures and behaviors (19, 42, 183),
others also support the role of inheritance as a reason
for familial clustering. Michalowicz et al. (140143)
in two large independent samples of adult twins
found that the similarities in the periodontal condi-
tion within pairs of monozygous (i.e. identical) twins
were greater than the similarities found within pairs
of dizygous (i.e. fraternal) twins. This nding sup-
ports the notion of disease heritability. Both studies
concluded that approximately 50% of the population
variance of periodontitis in adults could be attribu-
ted to genetic differences. Since there is evidence
demonstrating a correlation of the periodontal con-
dition among family members (e.g. siblingsibling,
parentoffspring), closer monitoring may be indi-
cated for persons with a familial history of period-
ontitis. It is possible that patients with a strong family
history of periodontitis are more susceptible than the
average patient and therefore more likely to develop
recurrent or refractory cases of periodontitis.
Various candidate genes including tumor necrosis
factor (TNF)-a polymorphisms, HLA antigens, and
FcgR genotypes have been evaluated for their associa-
tion with chronic periodontitis, but the results have
beenequivocal (45, 62, 71, 106). Byfar, themost studied
candidate genetic region has been the one contain-
ing the IL-1 gene cluster. Studies of this region have
led to the development of the Periodontal Suscepti-
bility Test (PST), the only genetic susceptibility test
for severe chronic periodontitis that is commercially
available. The PST test evaluates the simultaneous
occurrence of allele 2 at the IL-1A 4845 and IL-1B
3954 loci. A patient with allele 2 at both of these loci
is considered to be ``genotype-positive'' and there-
fore more susceptible to developing chronic period-
ontitis. The rationale for this association is that
persons with this combination of alleles tend to pro-
duce more IL-1 in response to a bacterial challenge,
and therefore will be predisposed to have more
inammation and more tissue destruction (58,
108). The development of the PST test was initially
based on the ndings of Kornman et al. (108) who
reported that the composite IL-1 genotype was more
frequently found among a group of 18 non-smoking
patients with periodontitis as compared to controls.
Among this small sample of Northern Europeans, the
odds of being genotype-positive were 6.8 times
higher among subjects with severe periodontitis as
compared to controls with mild or no disease. This
association became non-signicant when smokers
were included in the analysis. Furthermore, neither
of the two alleles was independently associated with
disease. These ndings have not been consistently
supported by subsequent research. While some stu-
dies support an association between the IL-1 com-
posite genotype and periodontitis (133), others have
reported no association (131) or inconsistencies in
the specic alleles found to be associated with period-
ontitis. Gore et al. (70) found allele 2 of IL-1B 3954,
124
Ronderos & Ryder
but not the composite IL-1 genotype, to be more
prevalent in patients with severe chronic periodonti-
tis. Similar lack of consistency is observed in studies of
aggressive periodontitis. Most studies indicate that
allele 1 of IL-1B 3954 is the predominant genotype
among aggressive periodontitis patients (51, 170,
233) while others have reported no associations
(89). The lack of consistent results leads to doubts
regarding the applicability of the PST in clinical
practice.
When evaluating the validity of the IL-1 composite
genotype test as a risk assessment tool for the clinical
practice, one should consider its accuracy in predict-
ing the development of periodontal disease. Being
genotype-positive is neither necessary nor sufcient
for the development of periodontitis. A large propor-
tion of patients with periodontitis test negative for the
composite genotype. For example, wide variations in
the percentages of genotype-negative periodontitis-
positive patients have been reported: 33% (108), 55%
(169), 62% (37, 136), 67% (55), and 80% (203). In
addition, an important proportion of patients with
healthy periodontium or mild disease have been
reported to be genotype-positive: 23% (108), 35%
(223), and 42% (169). Furthermore, there appears
to be signicant racial variability in the prevalence
of the composite IL-1 genotype, which raises ques-
tions regarding the applicability of the test to patients
of different ethnic backgrounds. The reported preva-
lence of genotype-positive persons has been 2343%
among Caucasian and Hispanic groups (12, 34, 50, 70,
108, 116, 133, 136), 815% among African-Americans
(233), and only 2.3% among Chinese (11).
The clinical applicability of a genetic test is also
dependent on the accuracy of the test at predicting
treatment outcomes. The available information indi-
cates that the PST test may not be a predictor of the
response to scaling and root planing (55), the outcome
of root coverageprocedures (35), theshort-termresults
of regenerative procedures (50), or dental implant fail-
ure (190, 209, 237). However, there is debate regarding
the effectiveness of the test at predicting long-term
stability during maintenance therapy. DeSanctis &
Zucchelli (50) reported no differences between geno-
type-positive and negative patients in their response
during the rst year after guided tissue regeneration
procedures. Nevertheless, from the second to the fth
postoperative years, genotype-positive patients lost
45% of the attachment gained during the rst year,
whereas genotype-negative patients with similar oral
hygiene only lost 19%. A 14-year cohort study of
patients initially diagnosed with moderate to severe
periodontitis suggested that teeth fromIL-1 genotype-
positive patients were 2.7 times more likely to be lost
during maintenance care compared to genotype-
negative patients (136). Genotype-positive patients
lost 27 of 386 teeth (7%), whereas genotype-negative
individuals lost 16 of 657 teeth (2.4%). The authors
concluded that knowledge of the patient's IL-1 gen-
otype was important in identifying patients with high
risk for tooth loss, which would be of value in devel-
oping a treatment plan. These results should be eval-
uated with caution because teeth and not persons
were used as the unit of analysis, making the statis-
tical interpretation of the results unreliable. The
results from this study also indicated that individual
tooth prognosis determined at baseline, smoking his-
tory, tooth mobility and crown-to-root ratio were
stronger independent predictors of tooth loss than
the genotypic information. An independent effect of
the genotype status, after statistical adjustment for
oral hygiene and pockets, on the percentage of sites
withbleeding onprobing during maintenance therapy
has alsobeennoted(116). By contrast, Cattabriga et al.
(37) reported no differences in bone levels or tooth
loss between genotype-positive and genotype-nega-
tive patients with moderate to severe periodontitis
who were followed during 10 years of maintenance
therapy. Genotype-positive patients lost 3.9% of their
teeth during the 10-year follow-up, indicating that
maintenance therapy at 3-month intervals is effec-
tive in attaining long-term stability among genotype-
positive patients with periodontitis.
Based on the lack of consistent results from asso-
ciation studies, the need for more specic genetic
linkage studies, the limited information on positive
and negative predictive values, and the limited gen-
eralizability of the test, the introduction of the com-
posite IL-1 genotype test as a risk assessment tool for
periodontitis susceptibility may be premature. It is
possible that the test may have some applicability
among non-smoking Caucasians. It has been sug-
gested that genotype-positive patients may need
more aggressive therapy and more frequent mainte-
nance visits than genotype-negative patients. At the
present time there is no strong evidence to support
the modication of maintenance schedules or treat-
ment regimens based on the results from this test.
The profession is only beginning to understand the
role of specic genes in the pathogenesis of period-
ontal diseases. In the future, genetic testing may
prove useful for identifying people at increased risk
for periodontitis, and for predicting treatment out-
comes. Information regarding individual susceptibil-
ity and patient-specic understanding of the
physiopathology of the disease may become a very
125
important way to tailor treatment plans and to max-
imize the effectiveness of preventive strategies.
Psychological factors
For the past 50 years, psychological factors in gen-
eral, and stress in particular, have been postulated as
risk factors for the incidence and progression of per-
iodontal diseases (144). One classical hypothesis for
the role of stress in periodontal diseases was that it
caused parafunctional habits such as bruxism and
clenching that led directly to loss of the periodontal
attachment apparatus in the absence of other factors
and/or acted as a cofactor in the progression of per-
iodontal diseases (202). While this possible relation-
ship has not received much attention in the literature
of the past 10 years, previous investigations have
failed to demonstrate a clear relationship between
stress-derived parafunctional habits and periodontal
diseases (59, 93). However, in the past several years,
there has been an emerging interest in the role of
other psychological factors and periodontal diseases
(4, 9, 57, 65, 150). These recent epidemiologic studies
point to a possible relationship and/or association
between psychological states such as emotional
stress and depression and periodontal diseases.
Perhaps the most intriguing of these recent studies
centers on the relationship of stress itself, as well as
coping strategies to stress, to the incidence and
severity of periodontal diseases. Several studies have
examined relatively large populations for a possible
connection. The general trend in these studies is that
while either self-reported or diagnosed stress per se
was not directly related to periodontal disease, an
inability to develop a successful coping strategy for
stress was indeed correlated to the incidence and
severity of periodontal diseases (64, 65). For example,
more successful coping strategies would include
rational problem-solving approaches, while less suc-
cessful coping strategies would include emotional
responses such as passive aggression. Several the-
ories have been proposed for the higher incidence
of periodontal diseases in patients with high stress
and inadequate coping strategies (30). It has been
shown that such high stress/low coping patients
have elevated systemic levels of cortisol (64). Ele-
vated levels of cortisol can suppress several host
response mechanisms such as T-helper cell function,
antibody production and activity, and neutrophil
function (64). A suppressed host response to period-
ontal infections could make a patient with stress and
inadequate coping strategies more susceptible to
periodontal breakdown (65). In addition, subjects
with stress and inadequate coping strategies as well
as subjects with clinical depression may also have
less oral health motivation, poorer home care levels,
and more plaque accumulation (9, 48, 65, 150). This
increased intraoral bacterial load could also make
such a patient more susceptible to periodontal
breakdown.
As this area is further explored, the implications for
the practitioner in managing patients with stress and
depression may become more signicant. As with
smoking, psychological factors such as stress and
depression may adversely affect treatment outcomes
(57). However, studies that examine treatment out-
comes in patients with stress and inadequate coping
strategies have yet to be published. Despite this
paucity of literature on the relationship or associa-
tion of stress to prognosis and treatment outcomes,
the dental practitioner may nevertheless decide to
refer patients with potentially important psychologi-
cal problems to the appropriate professional for
assistance and counseling. Reducing psychological
depression and improving coping strategies for
stressful life events may improve periodontal prog-
nosis and treatment outcomes.
Aging
With increasing age, loss of clinical attachment and
alveolar bone support become more prevalent,
extensive, and severe (2). However, aging per se is
not likely to be a predisposing factor for periodontal
disease. Loss of both periodontal attachment and
alveolar bone are not fully reversible with treatment,
and represent the cumulative amount of tissue des-
truction. The strong association between age and
periodontal destruction reported in cross-sectional
studies is mostly due to the effect of age as surrogate
for the length of exposure to etiologic factors. Long-
itudinal studies conducted in untreated populations
and groups with regular access to dental care indi-
cate that young and older adults loose periodontal
support at very similar rates (31, 87, 96, 153, 168).
Age-related differences in soft tissue wound heal-
ing have been well documented in the medical lit-
erature (66). The slower healing observed in the
elderly may be due to decreased or delayed inam-
matory and proliferative responses. Animal studies
indicate that macrophage and broblast functions,
capillary growth, collagen synthesis, and degrada-
tion (i.e. remodeling) can be affected by aging (66).
Studies in humans also indicate that epithelization
rates (60, 91), strength of wounds during early heal-
ing phases (197), and inammatory response of
126
Ronderos & Ryder
elderly patients are reduced. However, the clinical
impact of these differences in soft tissue wound heal-
ing appears to be small (222). It is not clear whether
these differences in healing are due to aging or to
concomitant conditions (e.g. vascular diseases, dia-
betes, osteoporosis, nutritional deciencies) that
occur more frequently in older populations (225).
Limited information also suggests that increased
age may be associated with slower bone healing after
fractures (17), dental extractions (7, 8), placement of
intraosseous implants (207, 208), and bone grafting.
It is possible that the success of bone grafts may be
associated with the age of the person receiving the
graft and also, in the case of allografts, with age of the
donor. Animal studies indicate that human-derived
demineralized freeze-dried bone allograft from older
donors is less likely to have strong bone-inducing
activity (164, 203) and the amount of bone formation
induced by bone morphogenetic protein tends to
decrease as the recipient's age increases (92, 152).
Furthermore, in rats the number of viable osteopro-
genitor cells in bone marrow decreases with increas-
ing age (95, 178). However, the validity of animal
models of aging is questionable and, to our knowl-
edge, such ndings have not been corroborated in
humans.
The experimental gingivitis model has been used
to assess whether the onset of gingivitis, and the
healing of inamed gingiva after periodontal instru-
mentation, is affected by aging. After discontinuation
of oral hygiene measures, younger subjects tend to
develop clinical signs of gingivitis faster than older
persons (226). However, age does not appear to have
a signicant effect on the resolution of gingivitis after
mechanical debridement and reinstitution of oral
hygiene (90, 226). Furthermore, the patient's age
has not been found to inuence the clinical response
to periodontal surgery or maintenance therapy (1, 15,
117). By contrast, age differences in healing response
after surgical extraction of third molars have been
well documented. Teenagers and young adults (i.e.
<25 years) are less likely to have residual periodontal
defects on the distal aspect of the second molar after
extraction of impacted third molars than older per-
sons (111113).
Although aging does not appear to affect the out-
come of periodontal therapy, age is a very important
factor that should always be considered when asses-
sing patient susceptibility. The prognosis of a 25-
year-old patient with generalized moderate chronic
periodontitis is less favorable than the prognosis of a
55-year-old patient with similar environmental risk
factors and the same severity and extent of period-
ontal destruction. Although the prevalence and
severity of attachment loss increases with age, per-
sons with more aggressive types of periodontitis are
generally young. The particular diagnosis of a patient
should also be considered. Not every type of period-
ontitis has the same prognosis. Patients with loca-
lized aggressive periodontitis tend to respond more
favorably to therapy than patients with generalized
aggressive periodontitis. Gunsolley et al. (78) studied
the clinical response of 40 patients with localized and
48 patients with generalized aggressive periodontitis
for 4 years after initial diagnosis. Despite treatment,
the patients with the generalized disease continued
losing attachment, while the patients with localized
disease responded favorably to periodontal therapy.
Systemic diseases that affect the treatment out-
come or increase the risk of complications are fre-
quently found in older individuals. Medications,
reduced salivary ow, depression, physical and men-
tal impairments, and reduced access to health care
are some factors that may have a deleterious effect
on the oral health status of the elderly. Vital informa-
tion can generally be obtained from the medical his-
tory; but such information is not always accurate. For
instance, approximately 40% of the cases of diabetes
mellitus in the United States are undiagnosed (210).
Given the deleterious effect of poorly controlled dia-
betes on the progression of periodontal disease and
the outcome of periodontal treatment, clinicians
should consider medical evaluations for patients
whose destruction or response to treatment is worse
than expected after considering other factors.
Microbiological risk factors
Modications of the host response by such factors as
stress, metabolic conditions, tobacco, and systemic
health may have major adverse effects on treatment
outcomes and prognosis. However, the clinician
must also consider the role of microorganisms as
the primary etiologic agents for periodontal diseases.
Such microorganisms may include not only specic
pathogenic bacterial species in adherent bacterial
plaque, but also microorganisms that may invade
the periodontal soft tissues. In addition to bacteria,
colonization by viruses may also affect treatment
outcomes and prognosis (211). In the past century,
the understanding of the role of bacteria per se has
evolved from a ``nonspecic plaque hypothesis'',
where plaque quantity was the major etiologic factor
of periodontal diseases, to a specic plaque hypoth-
esis, where the presence of individual bacterial
127
species or groups of species in elevated numbers
and proportions in the plaque may lead to the onset
and progression of periodontal diseases (122). The
use of rapid identication techniques such as DNA
probe analysis and PCR amplication have enabled
researchers and clinicians to observe the effects of
specic bacteria on treatment outcomes and prog-
nosis. It should, however, be considered that even
with these newer technologies, there remains a pro-
portion of bacteria in plaque that has yet to be fully
characterized. New technologies such as 16S rDNA
analysis have enabled clinical researchers to identify
new species of bacteria that may also play a central
role in the progression of periodontal disease and the
response to treatment (46, 171, 196).
Well over 500 species of bacteria have been detec-
ted in the oral ora and some of them most certainly
play a role in periodontal pathogenesis. In the past
10 years the majority of studies have focused on a
small subset of these microorganisms that are believed
to be etiologically important. These species include
Actinobacillus actinomycetemcomitans, Porphyromo-
nas gingivalis, Tannerella forsythensis (Bacterioides
forsythus), Prevotella intermedia, and Treponema
denticola. Several studies have shown that elevated
numbers of one or more of these bacterial species
either within the patient or within individual sites
correlate with future increases in pocket depth and
clinical attachment loss (75, 86, 128, 129). In addi-
tion, poorer clinical responses to therapy have been
reported in patients who initially harbor elevated
numbers of pathogenic bacteria such as A. actinomy-
cetemcomitans, P. gingivalis, P. intermedia, and
T. forsythensis (61, 87, 147, 155, 212). Other studies
have found that the initial presence of A. actinomy-
cetemcomitans, P. gingivalis, and P. intermedia may
have limited predictive value in treatment outcomes
(32, 204). The successful reduction of these bacterial
species through various combinations of mechanical
debridement, antibiotics and surgery appears to in-
uence the long-term clinical results of therapy (86,
147, 151, 186, 192, 205, 206). The prognostic and
predictive value of microbial testing for all patients
with periodontitis appears to be unresolved (16).
However, microbial testing and subsequent bac-
teria-reduction approaches may have particular
value in treating periodontitis patients who do not
respond to conventional therapy and continue to
show attachment loss (i.e. patients who have refrac-
tory cases of periodontitis) (16, 193).
Several investigators have proposed a treatment
approach based on not only reducing or eliminating
pools of these potentially pathogenic bacteria from
periodontally involved sites, but also from other
potential niches in the oral cavity that may harbor
these species. This treatment approach has been
termed ``total disinfection.'' Larger scale studies are
warranted to determine the particular value of this
approach (181). However, recent studies using this
approach have demonstrated sustained suppres-
sion of bacterial species in initially deeper sites with
sustained improvement in clinical parameters (180).
In the future, therapeutic approaches such as total
disinfection and specic microbial diagnosis coupled
with specic antimicrobial therapy may play a larger
role in improving treatment outcomes and prognosis.
Summary and conclusions
In this review, the potential adverse inuences of a
variety of factors on periodontal prognosis and treat-
ment have been discussed. The factors include poor
compliance, age, genetics, microbiology, smoking,
diabetes, stress, HIV infection, and other factors.
While each of these factors alone may have a detri-
mental effect on prognosis and treatment outcomes,
it should be kept in mind that the presence of any of
these factors alone or in combination does not auto-
matically imply that there will be poorer treatment
outcomes. In other words, the presence of any of
these risk factors alone or in combination cannot
predict treatment outcomes with complete accuracy.
Perhaps the best way to understand the impact of
these factors in periodontal prognosis and treatment
outcomes is to compare periodontal diseases with
cardiovascular diseases. The risk of developing car-
diovascular disease and the prognosis of patients
with cardiovascular disease is related to a variety of
risk factors. Some of these risk factors such as age,
smoking, stress, presence of a specic microbiota,
genetics, diabetes, etc., are similar to the periodontal
disease risk factors discussed in this paper (128). In
cardiovascular diseases, the presence of these risk
factors may have an additive effect on a patient's
overall risk and prognosis. In order to reduce the
likelihood of developing cardiovascular disease and
improving prognosis, patients are encouraged to
reduce and/or eliminate as many of these risk factors
as possible. The dental practitioner should employ
similar risk factor reduction strategies to reduce the
potentially additive adverse effects of risk factors dis-
cussed in this paper. Such strategies may include
smoking cessation programs, stress reduction pro-
grams, microbial testing followed by antimicrobial
treatment, patient motivational programs to improve
128
Ronderos & Ryder
compliance, etc. By identifying and reducing these
risk factors, the dental practitioner may help increase
the likelihood of an improved prognosis and out-
come for periodontal treatment.
References
1. Abbas F, van der Velden U, Hart AAM. Relation between
wound healing after surgery and susceptibility to period-
ontal disease. J Clin Periodontol 1984: 11: 221229.
2. Albandar JM, Brunelle JA, Kingman A. Destructive period-
ontal disease in adults 30 years of age and older in the
United States, 1988-1994. J Periodontol 1999: 70: 1329.
3. Albandar JM, Streckfus CF, Adesanya MR, Winn DM. Cigar,
pipe, and cigarette smoking as risk factors for periodontal
disease and tooth loss. J Periodontol 2000: 71: 18741881.
4. Aleksejuniene J, Holst D, Eriksen HM, Gjermo P. Psycho-
social stress, lifestyle and periodontal health. A hypothe-
sised structural equation model. J Clin Periodontol 2002:
29: 326335.
5. American Academy of Periodontology. Position Paper.
Supportive periodontal therapy (SPT). J Periodontol 1998:
69: 502506.
6. American Academy of Periodontology. Position paper. To-
bacco use and the periodontal patient. J Periodontol 1999:
70: 14191427.
7. Amler MH. The age factor in human extraction wound
healing. J Oral Surg 1977: 35: 193197.
8. Amler MH. Age factor in human alveolar bone repair. J Oral
Implantol 1993: 19: 138142.
9. Anttila SS, Knuuttila ML, Sakki TK. Relationship of depres-
sive symptoms to edentulousness, dental health, and den-
tal health behavior. Acta Odontol Scand 2001: 59: 406412.
10. Armitage GC. Periodontal diseases: diagnosis. Ann Period-
ontol 1996: 1: 37215.
11. Armitage GC, Wu Y, Wang H-Y, Sorrell J, di Giovine FS,
Duff GW. Low prevalence of a periodontitis-associated
interleukin-1 composite genotype in individuals of Chi-
nese heritage. J Periodontol 2000: 71: 164171.
12. Arregui I, Guisasola C, Menendez M, Martin-Villa L, Blan-
co-Moreno J, Tejerina JM, Sicilia A. IL-1 genotype distribu-
tion in a periodontally diseased population in Spain. J Clin
Periodontol 2000: 27 (Suppl. 1): 86 (Abstr. 271).
13. Axelsson P, Lindhe J. Effect of controlled oral hygiene
procedures on caries and periodontal disease in adults.
Results after 6 years. J Clin Periodontol 1981: 8: 239248.
14. Axelsson P, Lindhe J. The significance of maintenance care
in the treatment of periodontal disease. J Clin Periodontol
1981: 8: 281294.
15. Axelsson P, Lindhe J, Nystrom B. On the prevention of
caries and periodontal disease. Results of a 15-year long-
itudinal study. J Clin Periodontol 1991: 18: 182189.
16. Baehni PC, GuggenheimB. Potential of diagnosticmicrobiol-
ogy for treatment and prognosis of dental caries and period-
ontal diseases. Crit Rev Oral Biol Med 1996: 7: 259277.
17. Bak B, Andreassen TT. The effect of aging on fracture
healing in the rat. Calcif Tissue Int 1989: 45: 292297.
18. Barr C, Lopez MR, Rua-Dobles A. Periodontal changes by
HIV serostatus in a cohort of homosexual and bisexual
men. J Clin Periodontol 1992: 19: 794801.
19. Beaty TH, Colyer CR, Chang YC, Liang KY, Graybeal JC,
Muhammad NK, Levin S. Familial aggregation of period-
ontal indices. J Dent Res 1993: 72: 544551.
20. Becker W, Berg L, Becker BE. Untreated periodontal dis-
ease: A longitudinal study. J Periodontol 1979: 50: 234244.
21. Becker W, Becker BE, Berg LE. Periodontal treatment with-
out maintenance. A retrospective study in 44 patients.
J Periodontol 1984: 55: 505509.
22. Becker W, Berg L, Becker BE. The long-term evaluation of
periodontal maintenance in 95 patients. Int J Periodontics
Restorative Dent 1984: 4: 5471.
23. Benjamin SD, Baer PN. Familial patterns of advanced al-
veolar bone loss in adolescence (periodontosis). Period-
ontics 1967: 5: 8288.
24. Bergstrom J, Preber H. Tobacco use as a risk factor.
J Periodontol 1994: 65: 545550.
25. Bergstrom J, Eliasson S, Dock J. A 10-year prospective
study of tobacco smoking and periodontal health. J Period-
ontol 2000: 71: 13381347.
26. Bergstrom J, Eliasson S, Dock J. Exposure to tobacco
smoking and periodontal health. J Clin Periodontol 2000:
27: 6168.
27. Binderman I, Adut M, Yaffe A. Effectiveness of local delivery
of alendronate in reducing alveolar bone loss following per-
iodontal surgery in rats. J Periodontol 2000: 71: 12361240.
28. Bostanci HS, Arpak MN. Long-term evaluation of surgical
periodontal treatment with and without maintenance care.
J Nihon Univ Sch Dent 1991: 33: 152159.
29. Bostrom L, Bergstrom J, Dahlen G, Linder LE. Smoking and
subgingival microflora in periodontal disease. J Clin Peri-
odontol 2001: 28: 212219.
30. Breivik T, Thrane PS, Murison R, Gjermo P. Emotional
stress effects on immunity, gingivitis and periodontitis.
Eur J Oral Sci 1996: 104 (4): 327334.
31. Brown LF, Beck JD, Rozier RG. Incidence of attachment
loss in community-dwelling older adults. J Periodontol
1994: 65: 316323.
32. Buchmann R, Muller RF, Heinecke A, Lange DE. Actinoba-
cillus actinomycetemcomitans in destructive periodontal
disease. Three-year follow-up results. J Periodontol 2000:
71: 444453.
33. Butler JH. A familial pattern of juvenile periodontitis (per-
iodontosis). J Periodontol-Periodontics 1969: 40: 115118.
34. Caffesse RG, De LaRosa MR, De LaRosa GM, Mota LF. Pre-
valence of interleukin 1 periodontal genotype in a Hispanic
dental population. Quintessence Int 2002: 33: 190194.
35. Caffesse RG, De La Rosa RM, De La Rosa GM, Weltman R.
Effect of interleukin-1 gene polymorphism in a periodon-
tally healthy Hispanic population treated with mucogingi-
val surgery. J Clin Periodontol 2002: 29: 177181.
36. Califano JV, Schifferle RE, Gunsolley JC, Best AM, Schen-
kein HA, Tew JG. Antibody reactive with Porphyromonas
gingivalis serotypes K1-6 in adult and generalized early-
onset periodontitis. J Periodontol 1999: 70:730735.
37. Cattabriga M, Rotundo R, Muzzi L, Nieri M, Verrocchi G,
Cairo F, Pini Prato G. Retrospective evaluation of the in-
fluence of the interleukin-1 genotype on radiographic
bone levels in treated periodontal patients over 10 years.
J Periodontol 2001: 72: 767773.
38. Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cum-
mings SR. Estrogen replacement therapy and fractures in
older women: study of osteoporotic fractures research
group. Ann Intern Med 1995: 122: 916.
129
39. Ceballos-Salobrena A, Gaitan-Cepeda LA, Ceballos-Garcia
L, Lezama-Del Valle D. Oral lesions in HIV/AIDS patients
undergoing highly active antiretroviral treatment includ-
ing protease inhibitors: a new face of oral AIDS? AIDS
Patient Care STDS 2000: 14: 627635.
40. Chace R, Low SB. Survival characteristics of periodontally-
involved teeth: a 40-year study. J Periodontol 1993: 64:
701705.
41. Checchi L, Pelliccioni GA, Gatto MRA, Kelescian L. Patient
compliance with maintenance therapy in an Italian period-
ontal practice. J Clin Periodontol 1994: 21: 309312.
42. Chung CS, Kau MCW, Chung SSC, Rao DC. A genetic and
epidemiologic study of periodontal disease in Hawaii. II.
Genetic and environmental influence. Am J Hum Genet
1977: 29: 7682.
43. Claffey N, Egelberg J. Clinical indicators of probing attach-
ment loss following initial periodontal treatment in ad-
vanced periodontitis patients. J Clin Periodontol 1995:
22: 690696.
44. Collier AC, Coombs RW, Schoenfeld DA, Bassett RL,
Timpone J, Baruch A, Jones M, Facey K, Whitacre C,
McAuliffe VJ, Friedman HM, Merigan TC, Reichman RC,
Hooper C, Corey L (for the AIDS Clinical Trials Group).
Treatment of human immunodeficiency virus infection
with saquinavir, zidovudine, and zalcitabine. N Engl
J Med 1996: 334: 10111017.
45. Colombo AP, Eftimiadi C, Haffajee AD, Cugini MA, So-
cransky SS. SerumIgG2 level, Gm(23) allotype and FcgRIIa
and FcgRIIIb receptors in refractory periodontal disease.
J Clin Periodontol 1998: 25: 465474.
46. Colombo AP, Haffajee AD, Dewhirst FE, Paster BJ, Smith
CM, Cugini MA, Socransky SS. Clinical and microbiological
features of refractory periodontitis subjects. J Clin Period-
ontol 1998: 25: 169180.
47. Darby IB, Hodge PJ, Riggio MP, Kinane DF. Microbial
comparison of smoker and non-smoker adult and early-
onset periodontitis patients by polymerase chain reaction.
48. Deinzer R, Hilpert D, Bach K, Schawacht M, Herforth A.
Effects of academic stress on oral hygiene a potential link
between stress and plaque-associated disease? J Clin Per-
iodontol 2001: 28: 459464.
49. Demirel K, Efeodlu A. Retrospective evaluation of patient
compliance with supportive periodontal treatment.
J Nihon Univ Sch Dent 1995: 37: 131137.
50. De Sanctis M, Zucchelli G. Interleukin-1 gene polymorph-
isms and long-term stability following guided tissue regen-
eration therapy. J Periodontol 2000: 71: 606613.
51. Diehl SR, Wang YF, Brooks CN, Burmeister JA, Califano JV,
Wang S, Schenkein HA. Linkage disequilibrium of inter-
leukin-1 genetic polymorphisms with early-onset period-
ontitis. J Periodontol 1999: 70: 418430.
52. Dios PD, Ocampo A, Miralles C, Limeres J, Tomas I.
Changing prevalence of human immunodeficiency virus-
associated oral lesions. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 2000: 90: 403404.
53. Dodson TB. HIV status and the risk of post-extraction
complications. J Dent Res 1997: 76: 16441652.
54. Eggert F-M, McLeod MH, Flowerdew G. Effects of smoking
and treatment status on periodontal bacteria: evidence
that smoking influences control of periodontal bacteria
at the mucosal surface of the gingival crevice. J Periodontol
2001: 72: 12101220.
55. Ehmke B, Kress W, Karch H, Grimm T, Klaiber B, Flemmig
TF. Interleukin-1 haplotype and periodontal disease pro-
gression following therapy. J Clin Periodontol 1999: 26:
810813.
56. Elders PJM, Habets LLMH, Netelenbos JC, van der Linden
LWJ, van der Stelt PF. The relation between periodontitis
and systemic bone mass in women between 46 and
55 years of age. J Clin Periodontol 1992: 19: 492496.
57. Elter JR, White BA, Gaynes BN, Bader JD. Relationship of
clinical depression to periodontal treatment outcome.
J Periodontol 2002: 73: 441449.
58. Engebretson SP, Lamster IB, Herrera-Abreu M, Celenti RS,
Timms JM, Chaudhary AGA, di Giovine FS, Kornman KS.
The influence of interleukin gene polymorphisms on ex-
pression of interleukin-1b and tumor necrosis factor-a in
periodontal tissue and gingival crevicular fluid. J Period-
ontol 1999: 70: 567573.
59. Ericsson I, Lindhe J. Lack of effect of trauma from occlu-
sion on the recurrence of experimental periodontitis. J Clin
Periodontol 1977: 4: 115127.
60. Fatah MF, Ward CM. The morbidity of split-skin graft
donor sites in the elderly: the case for mesh-grafting the
donor site. Br J Plast Surg 1984: 37: 184190.
61. Flemmig TF, Milian E, Karch H, Klaiber B. Differential
clinical treatment outcome after systemic metronidazole
and amoxicillin in patients harboring Actinobacillus acti-
nomycetemcomitans and/or Porphyromonas gingivalis.
62. Galbraith GMP, Steed RB, Sanders JJ, Pandey JP. Tumor
necrosis factor alpha production by oral leukocytes: influ-
ence of tumor necrosis factor genotype. J Periodontol 1998:
69: 428433.
63. Galgut PN. Compliance with maintenance therapy after
periodontal treatment. Dent Health (London) 1991: 30
(6): 37.
64. Genco RJ, Ho AW, Kopman J, Grossi SG, Dunford RG,
Tedesco LA. Models to evaluate the role of stress in period-
ontal disease. Ann Periodontol 1998: 3: 288302.
65. Genco RJ, Ho AW, Grossi SG, Dunford RG, Tedesco LA.
Relationship of stress, distress, and inadequate coping
behaviors to periodontal disease. J Periodontol 1999: 70:
711723.
66. Gerstein AD, Phillips TJ, Rogers GS, Gilchrest BA. Wound
healing and aging. Dermatol Clin 1993: 11: 749757.
67. Glick M, Abel SN, Muzyka BC, DeLorenzo M. Dental com-
plications after treating patients with AIDS. J Am Dent
Assoc 1994: 125: 296301.
68. Goldman MJ, Ross IF, Goteiner D. Effect of periodontal
therapy on patients maintained for 15 years or longer. A
retrospective study. J Periodontol 1986: 57: 347353.
69. Gonzalez YM, De Nardin A, Grossi SG, Machtei EE,
Genco RJ, De Nardin E. Serum cotinine levels, smoking,
and periodontal attachment loss. J Dent Res 1996: 75:
796802.
70. Gore EA, Sander JJ, Pandey JP, Palesch Y, Galbraith GM.
lnterleukin-lb
3953
allele 2: association with disease status
in adult periodontitis. J Clin Periodontol 1998: 25: 781785.
71. Goteiner D, Goldman MJ. Human lymphocyte antigen
haplotype and resistance to periodontitis. J Periodontol
1984: 55: 155158.
72. Grbic JT, Lamster IB. Risk indicators for future clinical
attachment loss in adult periodontitis. Tooth and site vari-
ables. J Periodontol 1992: 63: 262269.
130
Ronderos & Ryder
73. Groen JJ, Menczel J, Shapiro S. Chronic destructive period-
ontal disease in patients with presenile osteoporosis.
J Periodontol 1968: 39: 1923.
74. Grossi SG. Treatment of periodontal disease and control
of diabetes: an assessment of the evidence and need for
future research. Ann Periodontol 2001: 6: 138145.
75. Grossi SG, Zambon JJ, Ho AW, Koch G, Dunford RG,
Machtei EE, Norderyd OM, Genco RJ. Assessment of risk
for periodontal disease. I. Risk indicators for attachment
loss. J Periodontol 1994: 65: 260267.
76. Grossi SG, Genco RJ, Machtei EE, Ho AW, Koch G, Dunford
R, Zambon JJ, Hausmann E. Assessment of risk for period-
ontal disease. II. Risk indicators of alveolar bone loss.
77. Grossi SG, Zambon J, Machtei EE, Schifferle R, Andreana S,
Genco RJ, Cummins D, Harrap G. Effects of smoking and
smoking cessation on healing after mechanical
periodontal therapy. J Am Dent Assoc 1997: 128: 599607.
78. Gunsolley JC, CalifanoJV, Koertge TE, Burmeister JA, Cooper
LC, Schenkein HA. Longitudinal assessment of early onset
periodontitis. J Periodontol 1995: 66: 321328.
79. Gustafsson A, A
sman B, Bergstrom K. Cigarette smoking as

an aggravating factor in inflammatory tissue-destructive
diseases. Increase in tumor necrosis factor-a priming of
peripheral neutrophils measured as generation of oxygen
radicals. Int J Clin Lab Res 2000: 30: 187190.
80. Haber J, Kent RL. Cigarette smoking in periodontal prac-
tice. J Periodontol 1992: 63: 100106.
81. Haber J, Wattles J, Crowley M, Mandell R, Joshipura K, Kent
RL. Evidence for cigarette smoking as a major risk factor
for periodontitis. J Periodontol 1993: 64: 1623.
82. Haffajee AD, Socransky SS. Relationship of cigarette smok-
ing to the subgingival microbiota. J Clin Periodontol 2001:
28: 377388.
83. Haffajee AD, Socransky SS. Relationship of cigarette smok-
ing to attachment level profiles. J Clin Periodontol 2001: 28:
283295.
84. Haffajee AD, Socransky SS, Goodson JM. Clinical para-
meters as predictors of destructive periodontal disease
activity. J Clin Periodontol 1983: 10: 257265.
85. Haffajee AD, Socransky SS, Lindhe J, Kent RL, Okamoto H,
Yoneyama T. Clinical risk indicators for periodontal
attachment loss. J Clin Periodontol 1991: 18: 117125.
86. Haffajee AD, Socransky SS, Dibart S, Kent RL Jr. Response
to periodontal therapy in patients with high or low levels of
P. gingivalis, P. intermedia, P. nigrescens and B. forsythus.
87. Haffajee AD, Cugini MA, Dibart S, Smith C, Kent RL Jr,
Socransky SS. Clinical and microbiological features of
subjects with adult periodontitis who responded poorly
to scaling and root planing. J Clin Periodontol 1997: 24:
767776.
88. Hirschfeld L, Wasserman B. A long-term survey of tooth
loss in 600 treated periodontal patients. J Periodontol 1978:
49: 225237.
89. Hodge PJ, Riggio MP, Kinane DF. Failure to detect an
association with IL-1 genotypes in European Caucasians
with generalised early-onset periodontitis. J Clin Period-
ontol 2001: 28: 430436.
90. Holm-Pedersen P, Agerbk P, Theilade E. Experimental
gingivitis in young and elderly individuals. J Clin Period-
ontol 1975: 2: 1424.
91. Holt DR, Kirk SJ, Regan MC, Hurson M, Lindblad WJ,
Barbul A. Effect of age on wound healing in healthy human
beings. Surgery 1992: 112: 293297.
92. Hosny M, Sharawy M. Osteoinduction in young and old
rats using demineralized bone powder allografts. J Oral
Maxillofac Surg 1985: 43: 925931.
93. Houston F, Hanamura H, Carlsson GE, Haraldson T, Ry-
lander H. Mandibular dysfunction and periodontitis. A
comparative study of patients with periodontal disease
and occlusal parafunctions. Acta Odontol Scand 1987: 45:
239246.
94. Inagaki K, Kurosu Y, Kamiya T, Kondo F, Yoshinari N,
Noguchi T, Krall EA, Garcia RI. Low metacarpal bone den-
sity, tooth loss, and periodontal disease in Japanese wo-
men. J Dent Res 2001: 80: 18181822.
95. Inoue K, Ohgushi H, Yoshikawa T, Okumura M, Sempuku
T, Tamai S, Dohi Y. The effect of aging on bone formation
in porous hydroxyapatite: biochemical and histological
analysis. J Bone Miner Res 1997: 12: 989994.
96. Ismail AI, Morrison EC, Burt BA, Caffesse RG, Kananagh
MT. Natural history of periodontal disease in adults: find-
ings from the Tecumseh Periodontal Disease Study. J Dent
Res 1990: 69: 430435.
97. Jacobs R, Ghyselen J, Koninckx P, van Steenberghe D.
Long-term bone mass evaluation of mandible and lumbar
spine in a group of women receiving hormone replace-
ment therapy. Eur J Oral Sci 1996: 104: 1016.
98. Jansson LE, Hagstrom KE. Relationship between compli-
ance and periodontal treatment outcome in smokers.
J Periodontol 2002: 73: 602607.
99. Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC,
Abrams JS, Boyce B, Broxmeyer H, Manolagas SC. In-
creased osteoclast development after estrogen loss: med-
iation by interleukin-6. Science 1992: 257: 8891.
100. Johnson RB, Gilbert JA, Cooper RC, Dai X, Newton BI,
Tracy RR, West WF, DeMoss TL, Meyers PJ, Streckfus CF.
Alveolar bone loss one year following ovariectomy in
sheep. J Periodontol 1997: 68: 864871.
101. Kaldahl WB, Kalkwarf KL, Patil KD, Molvar MP. Relation-
ship of gingival bleeding, gingival suppuration, and supra-
gingival plaque to attachment loss. J Periodontol 1990: 61:
347351.
102. Kaldahl WB, JohnsonGK, Patil KD, Kalkwarf KL. Levels of
cigarette consumption and response to periodontal ther-
apy. J Periodontol 1996: 67: 675681.
103. Kaslick RS, West TL, Chasens AI, Terasaki PI, Lazzara R,
Weinberg S. Association between HL-A2 antigen and var-
ious periodontal diseases in young adults. J Dent Res 1975:
54: 424.
104. Kaslick RS, West TL, Chasens AI. Association between ABO
blood groups, HL-A antigens and periodontal diseases in
young adults: a follow-up study. J Periodontol 1980: 51:
339342.
105. Katz J, Goultschin J, Benoliel R, Brautbar C. Human
leukocyte antigen (HLA) DR
4
. Positive association with
rapidly progressing periodontitis. J Periodontol 1987: 58:
607610.
106. Kobayashi T, Westerdaal NA, Miyazaki A, van der Pol W-L,
Suzuki T, Yoshie H, van de Winkel JGJ, Hara K. Rele-
vance of immunoglobulin G Fc receptor polymorphism
to recurrence of adult periodontitis in Japanese patients.
Infect Immun 1997: 65: 35563560.
131
107. Konig J, Plagmann H-C, Langenfeld N, Kocher T. Retro-
spective comparison of clinical variables between compli-
ant and non-compliant patients. J Clin Periodontol 2001:
28: 227232.
108. Kornman KS, Crane A, Wang H-Y, di Giovine FS,
Newman MG, Pirk FW, Wilson TGJr, HigginbottomFL, Duff
GW. The interleukin-1 genotype as a severity factor in adult
periodontal disease. J Clin Periodontol 1997: 24: 7277.
109. Krall EA. The periodontal-systemic connection: implica-
tions for treatment of patients with osteoporosis and per-
iodontal disease. Ann Periodontol 2001: 6: 209213.
110. Krall EA, Garvey AJ, Garcia RI. Alveolar bone loss and tooth
loss in male cigar and pipe smokers. J Am Dent Assoc 1999:
130: 5764.
111. Kugelberg CF. Periodontal healing after impacted lower
third molar surgery. J Oral Maxillofac Surg 1990: 19:
341345.
112. Kugelberg CF, Ahlstrom U, Ericson S, Hugoson A. Period-
ontal healing after impacted lower third molar surgery. A
retrospective study. Int J Oral Surg 1985: 14: 2940.
113. Kugelberg CF, Ahlstrom U, Ericson S, Hugoson A, Kvint S.
Periodontal healing after impacted lower third molar sur-
gery in adolescents and adults a prospective study. J Oral
Maxillofac Surg 1991: 20: 1824.
114. Lalla E, Lamster IB, Stern DM, Schmidt AM. Receptor for
advanced glycation end products, inflammation, and ac-
celerated periodontal disease in diabetes: mechanisms and
insights into therapeutic modalities. Ann Periodontol 2001:
6: 113118.
115. Lang NP, Joss A, Orsanic T, Gusberti FA, Siegrist BE. Bleed-
ing on probing. A predictor for the progression of period-
ontal disease? J Clin Periodontol 1986: 13: 590596.
116. Lang NP, Tonetti MS, Suter J, Sorrell J, Duff GW, Kornman
KS. Effect of interleukin-1 gene polymorphisms on gingival
inflammation assessed by bleeding on probing in a period-
ontal maintenance population. J Periodont Res 2000: 35:
102107.
117. Lindhe J, Socransky S, Nyman S, Westfelt E, Haffajee A.
Effect of age on healing following periodontal therapy.
118. Lindsay R. Sex steroids in the pathogenesis and prevention
of osteoporosis. In: Riggs, BL, editor. Osteoporosis: etiology,
diagnosis and management. New York: Raven Press, 1988:
333.
119. Listgarten MA, Sullivan P, George C, Nitkin L, Rosenberg
ES, Chilton NW, Kramer AA. Comparative longitudinal
study of 2 methods of scheduling maintenance visits: 4-
year data. J Clin Periodontol 1989: 16: 105115.
120. Loe H, Theilade E, Jensen SB. Experimental gingivitis in
man. J Periodontol 1965: 36: 155161.
121. Loe H, Anerud A, Boysen H, Morrison E. Natural history of
periodontal disease in man. Rapid, moderate, and no loss
of attachment in Sri Lankan laborers 14 to 46 years of age.
122. Loesche WJ. The antimicrobial treatment of periodontal
disease: changing the treatment paradigm. Crit Rev Oral
Biol Med 1999: 10: 245275.
123. Lowe GDO. The relationship between infection, inflamma-
tion, and cardiovascular disease: an overview. Ann Period-
ontol 2001: 6: 18.
124. Lucartorto FM, Franker CK, Maza J. Postscaling bacteremia
in HIV-associated gingivitis and periodontitis. Oral Surg
Oral Med Oral Pathol 1992: 73: 550554.
125. Lucht E, Heimdahl A, Nord CE. Periodontal disease in HIV-
infected patients in relation to lymphocyte subsets and
specific micro-organisms. J Clin Periodontol 1991: 18:
252256.
126. Lundstrom A, Jendle J, Stenstrom B, Toss G, Ravald N.
Periodontal conditions in 70-year-old women with osteo-
porosis. Swed Dent J 2001: 25: 8996.
127. Machtei EE, Cho MI, Dunford R, Norderyd J, Zambon JJ,
Genco RJ. Clinical, microbiological, and histological fac-
tors which influence the success of regenerative period-
ontal therapy. J Periodontol 1994: 65: 154161.
128. Machtei EE, Dunford R, Hausmann E, Grossi SG, Powell J,
Cummins D, Zambon JJ, Genco RJ. Longitudinal study of
prognostic factors in established periodontitis patients.
129. Machtei EE, Hausmann E, Dunford R, Grossi S, Ho A, Davis
G, Chandler J, Zambon J, Genco RJ. Longitudinal study of
predictive factors for periodontal disease and tooth loss.
130. Marazita ML, Burmeister JA, Gunsolley JC, Koertge TE,
Lake K, Schenkein HA. Evidence for autosomal dominant
inheritance and race-specific heterogeneity in early-onset
131. Mark LL, Haffajee AD, Socransky SS, Kent RL Jr, Guerrero
D, Kornman K, Newman M, Stashenko P. Effect of the
interleukin-1 genotype on monocyte IL-1b expression in
subjects with adult periodontitis. J Periodont Res 2000: 35:
172177.
132. Martinez-Canut P, Lorca A, Magan R. Smoking and period-
ontal disease severity. J Clin Periodontol 1995: 22: 743749.
133. McDevitt MJ, Wang H-Y, Knobelman C, Newman MG, di
Giovine FS, Timms J, Duff GW, Kornman KS. Interleukin-1
genetic association with periodontitis in clinical practice.
J Periodontol 2000: 71: 156163.
134. McFall WT Jr. Tooth loss in 100 treated patients with per-
iodontal disease. A long-term study. J Periodontol 1982: 53:
539549.
135. McGuire MK. Prognosis versus actual outcome: a long-
term survey of 100 treated periodontal patients under
maintenance care. J Periodontol 1991: 62: 5158.
136. McGuire MK, Nunn ME. Prognosis versus actual outcome.
IV. The effectiveness of clinical parameters and IL-1 geno-
type in accurately predicting prognoses and tooth survival.
137. McKaig RG, Thomas JC, Patton LL, Strauss RP, Slade GD,
Beck JD. Prevalence of HIV-associated periodontitis and
chronic periodontitis in a southeastern US study group.
J Public Health Dent 1998: 58: 294300.
138. McKaig RG, Patton LL, Thomas JC, Strauss RP, Slade GD,
Beck JD. Factors associated with periodontitis in an HIV-
infected southeast USA study. Oral Dis 2000: 6: 158165.
139. Mendoza AR, Newcomb GM, Nixon KC. Compliance with
supportive periodontal therapy. J Periodontol 1991: 62:
731736.
140. Michalowicz BS. Genetic and heritable risk factors in per-
iodontal disease. J Periodontol 1994: 65: 479488.
141. Michalowicz BS, Aeppli DM, Kuba RK, Bereuter JE, Conry
JP, Segal NL, Bouchard TJ Jr, Pihlstrom BL. A twin study of
genetic variation in proportional radiographic alveolar
bone height. J Dent Res 1991: 70: 14311435.
142. Michalowicz BS, Aeppli D, Virag JG, Klump DG, Hinrichs
JE, Segal NL, Bouchard TJ Jr, Pihlstrom BL. Periodontal
findings in adult twins. J Periodontol 1991: 62: 293299.
132
Ronderos & Ryder
143. Michalowicz BS, Diehl SR, Gunsolley JC, Sparks BS, Brooks
CN, Koertge TE, Califano JV, Burmeister JA, Schenkein HA.
Evidence of a substantial genetic basis for risk of adult
144. Miller SC, Thaller JL, Soberman A. The use of the Minne-
sota Multiphasic Personality Inventory as a diagnostic aid
in periodontal disease a preliminary report. J Periodontol
1956: 27: 4446.
145. Miller LS, Manwell MA, Newbold D, Reding ME, Rasheed
A, Blodgett J, Kornman KS. The relationship between re-
duction in periodontal inflammation and diabetes control:
a report of 9 cases. J Periodontol 1992: 63: 843848.
146. Mohammad AR, Brunsvold M, Bauer R. The strength of
associationbetweensystemic postmenopausal osteoporosis
andperiodontal disease. Int J Prosthodont 1996: 9: 479483.
147. Mombelli A, Gmur R, Gobbi C, Lang NP. Actinobacillus
actinomycetemcomitans in adult periodontitis. II. Charac-
terization of isolated strains and effect of mechanical per-
iodontal treatment. J Periodontol 1994: 65: 827834.
148. Monteiro da Silva AM, Oakley DA, Newman HN, Nohl FS,
Lloyd HM. Psychosocial factors and adult onset rapidly
progressive periodontitis. J Clin Periodontol 1996: 23:
789794.
149. Mooney J, Hodge PJ, Kinane DF. Humoral immune re-
sponse in early-onset periodontitis: influence of smoking.
J Periodont Res 2001: 36: 227232.
150. Moss ME, Beck JD, Kaplan BH, Offenbacher S, Weintraub
JA, Koch GG, Genco RJ, Machtei EE, Tedesco LA. Explora-
tory case-control analysis of psychosocial factors and adult
151. Muller H-P, Heinecke A, Borneff M, Kiencke C, Knopf A,
Pohl S. Eradication of Actinobacillus actinomycetemcomi-
tans from the oral cavity in adult periodontitis. J Periodont
Res 1998: 33: 4958.
152. Nagai N, Qin CL, Nagatsuka H, Inoue M, Ishiwari Y. Age
effects on ectopic bone formation induced by purified
bone morphogenetic protein. Int J Oral Maxillofac Surg
1999: 28: 143150.
153. Ndiaye CF, Critchlow CW, Leggott PJ, Kiviat NB, Ndoye I,
Robertson PB, Georgas KN. Periodontal status of HIV-1 and
HIV-2 seropositive and HIV seronegative female commer-
cial sex workers in Senegal. J Periodontol 1997: 68: 827831.
154. Neely AL, Holford TR, Loe H, A
nerud A
, Boysen H. The
natural history of periodontal disease in man. Risk factors
for progression of attachment loss in individuals receiving
no oral health care. J Periodontol 2001: 72: 10061015.
155. Nieminen A, Siren E, Wolf J, Asikainen S. Prognostic criteria
for the efficiency of non-surgical periodontal therapy
in advanced periodontitis. J Clin Periodontol 1995: 22:
153161.
156. Nishida M, Grossi SG, Dunford RG, Ho AW, Trevisan M,
Genco RJ. Calcium and the risk for periodontal disease.
J Periodontol 2000: 71: 10571066.
157. Norderyd OM, Grossi SG, Machtei EE, Zambon JJ, Haus-
mann E, Dunford RG, Genco RJ. Periodontal status of
women taking estrogen supplementation. J Periodontol
1993: 64: 957962.
158. Novaes AB Jr, Novaes AB. Compliance with supportive
periodontal therapy. Part 1. Risk of non-compliance in
the first 5-year period. J Periodontol 1999: 70: 679682.
159. Novaes AB Jr, Novaes AB. Compliance with supportive
periodontal therapy. Part II: Risk of non-compliance in a
10-year period. Braz Dent J 2001: 12: 4750.
160. Novaes AB, Novaes AB Jr, Moraes N, Campos GM, Grisi
MFM. Compliance with supportive periodontal therapy.
J Periodontol 1996: 67: 213216.
161. Novaes AB Jr, Novaes AB, Bustamanti A, Villavicencio JJ,
Muller E, Pulido J. Supportive periodontal therapy in South
America. A retrospective multi-practice study on compli-
ance. J Periodontol 1999: 70: 301306.
162. Nyman S, Rosling B, Lindhe J. Effect of professional tooth
cleaning on healing after periodontal surgery. J Clin Peri-
odontol 1975: 2: 8086.
163. NymanS, Lindhe J, Rosling B. Periodontal surgery inplaque-
infected dentitions. J Clin Periodontol 1977: 4: 240249.
164. Nyssen-Behets C, Delaere O, Duchesne PY, Dhem A. Aging
effect on inductive capacity of human demineralized bone
matrix. Arch Orthop Trauma Surg 1996: 115: 303306.
165. Ojima M, Hanioka T, Shizukuishi S. Survival analysis for
degree of compliance with supportive periodontal therapy.
166. Pacifici R. Estrogen, cytokines, and pathogenesis of
postmenopausal osteoporosis. J Bone Miner Res 1996: 8:
10431051.
167. Pacifici R, Rifas L, McCraken R, Vered I, McMurtry C, Avioli
LV, Peck WA. Ovarian steroid treatment blocks a postme-
nopausal increase in blood monocyte interleukin 1 release.
Proc Natl Acad Sci USA 1989: 86: 23982402.
168. Papapanou PN, Wennstrom JL, Grondahl K. A 10-year ret-
rospective study of periodontal disease progression. J Clin
Periodontol 1989: 16: 403411.
169. Papapanou PN, Neiderud A-M, Sandros J, Dahlen G. Inter-
leukin-1 gene polymorphism and periodontal status. A
case-control study. J Clin Periodontol 2001: 28: 389396.
170. Parkhill JM, Hennig BJW, Chapple ILC, Heasman PA, Tay-
lor JJ. Association of interleukin-1 gene polymorphisms
with early-onset periodontitis. J Clin Periodontol 2000:
27: 682689.
171. Paster BJ, Boches SK, Galvin JL, Ericson RE, Lau CN,
Levanos VA, Sahasrabudhe A, Dewhirst FE. Bacterial diver-
sity in human subgingival plaque. J Bacteriol 2001: 183:
37703783.
172. Payne JB, Zachs NR, Reinhardt RA, Nummikoski PV, Patil
K. The association between estrogen status and alveolar
bone density changes in postmenopausal women with a
history of periodontitis. J Periodontol 1997: 68: 2431.
173. Persson L, Bergstrom J, Ito H, Gustafsson A. Tobacco
smoking and neutrophil activity in patients with period-
ontal disease. J Periodontol 2001: 72: 9095.
174. Piot P, Bartos M, Ghys PD, Walker N, Schwartlander B. The
global impact of HIV/AIDS. Nature 2001: 410: 968973.
175. Porter SR, Scully C, Luker J. Complications of dental sur-
gery in persons with HIV disease. Oral Surg Oral Med Oral
Pathol 1993: 75: 165167.
176. Preber H, Bergstrom J. Effect of cigarette smoking on per-
iodontal healing following surgical therapy. J Clin Period-
ontol 1990: 17: 324328.
177. Preber H, Bergstrom J, Linder LE. Occurrence of perio-
pathogens in smoker and non-smoker patients. J Clin Per-
iodontol 1992: 19: 667671.
178. Quarto R, Thomas D, Liang CT. Bone progenitor cell def-
icits and the age-associated decline in bone repair capa-
city. Calcif Tissue Int 1995: 56: 123129.
179. Quinn SM, Zhang J-B, Gunsolley JC, Schenkein HA, Tew JG.
The influence of smoking and race on adult periodontitis
and serum IgG2 levels. J Periodontol 1998: 69: 171177.
133
180. Quirynen M, Mongardini C, Pauwels M, Bollen CML, Van
Eldere J, van Steenberghe D. One stage full- versus partial-
mouth disinfection in the treatment of chronic adult or
generalized early-onset periodontitis. II. Long-termimpact
on microbial load. J Periodontol 1999: 70: 646656.
181. Quirynen M, De Soete M, Dierickx K, van Steenberghe D.
The intra-oral translocation of periodontopathogens jeo-
pardises the outcome of periodontal therapy. A review of
the literature. J Clin Periodontol 2001: 28: 499507.
182. Ramfjord SP, Morrison EC, Burgett FG, Nissle RR, Shick
RA, Zann GJ, Knowles JW. Oral hygiene and maintenance
of periodontal support. J Periodontol 1982: 53: 2630.
183. Rao DC, Chung CS, Morton NE. Genetic and environmen-
tal determinants of periodontal disease. Am J Med Genet
1979: 4: 3945.
184. ReddyMS, WeatherfordTW, SmithCA, West BD, Jeffcoat MK,
Jacks TM. Alendronate treatment of naturally-occurring per-
iodontitis in beagle dogs. J Periodontol 1995: 66: 211217.
185. Reinhardt RA, Payne JB, Maze CA, Patil KD, Gallagher SJ,
Mattson JS. Influence of estrogen and osteopenia/osteo-
porosis on clinical periodontitis in postmenopausal wo-
men. J Periodontol 1999: 70: 823828.
186. Renvert S, Dahlen G, Wikstrom M. Treatment of period-
ontal disease based on microbiological diagnosis. Relation
between microbiological and clinical parameters during
5 years. J Periodontol 1996: 67: 562571.
187. Richman DD. HIV chemotherapy. Nature 2001: 410:
9951001.
188. Robinson PG, Cooper H, Hatt J. Healing after dental ex-
tractions in men with HIV infection. Oral Surg Oral Med
Oral Pathol 1992: 74: 426430.
189. Rocha M, Nava LE, Vazquez de la Torre C, Sanchez-Mar n
F, Garay-Sevilla ME, Malacara JM. Clinical and radiolo-
gical improvement of periodontal disease in patients
with type 2 diabetes mellitus treated with alendronate: a
randomized, placebo-controlled trial. J Periodontol 2001:
72: 204209.
190. Rogers MA, Figliomeni L, Baluchova K, Tan AE, Davies G,
Henry PJ, Price P. Do interleukin-1 polymorphisms predict
the development of periodontitis or the success of dental
implants? J Periodont Res 2002: 37: 3741.
191. Ronderos M, Jacobs DR, Himes JH, Pihlstrom BL. Associa-
tions of periodontal disease with femoral bone mineral
density and estrogen replacement therapy: cross-sectional
evaluation of US adults from NHANES III. J Clin Period-
ontol 2000: 27: 778786.
192. Rooney J, Wade WG, Sprague SV, Newcombe RG, Addy M.
Adjunctive effects to non-surgical periodontal therapy of
systemic metronidazole and amoxycillin alone and com-
bined. A placebo controlled study. J Clin Periodontol 2002:
29: 342350.
193. RosenbergES, TorosianJP, HammondBF, Cutler SA. Routine
anaerobic bacterial culture and systemic antibiotic usage in
treatment of adult periodontitis: a 6-year longitudinal study.
Int J Periodontics Restorative Dent 1993: 13: 213243.
194. Rosling B, Nyman S, Lindhe J, Jern B. The healing potential
of the periodontal tissues following different techniques
of periodontal surgery in plaque-free dentitions. A 2-year
clinical study. J Clin Periodontol 1976: 3: 233250.
195. Ryder MI. An update on HIV and periodontal disease.
J Periodontol 2002: 73: 10711078.
196. Sakamoto M, Umeda M, Ishikawa I, Benno Y. Compari-
son of the oral bacterial flora in saliva from a healthy
subject and two periodontitis patients by sequence analy-
sis of 16S rDNA libraries. Microbiol Immunol 2000: 44:
643652.
197. Sandblom PH, Petersen P, Muren A. Determination of the
tensile strength of the healing wound as a clinical test. Acta
Chir Scand 1953: 105: 252257.
198. Saxen L, Koskimies S. Juvenile periodontitis no linkage
with HLA-antigens. J Periodont Res 1984: 19: 441444.
199. Saxen L, Nevanlinna HR. Autosomal recessive inheritance
of juvenile periodontitis: test of a hypothesis. Clin Genet
1984: 25: 332335.
200. Sayers NM, James JA, Drucker DB, Blinkhorn AS. Possible
potentiation of toxins from Prevotella intermedia, Prevo-
tella nigrescens, and Porphyromonas gingivalis by cotinine.
J Periodontol 1999: 70: 12691275.
201. Scabbia A, Cho K-S, Sigurdsson TJ, Kim C-K, Trombelli L.
Cigarette smoking negatively affects healing response fol-
lowing flap debridement surgery. J Periodontol 2001: 72:
4349.
202. Schulger S, Youdelis R, Page RC, Johnson RH. Occlusal
traumatism as an etiologic factor. In: Schulger, S, Youdelis,
R, Page, RC, Johnson, RH, editors. Periodontal diseases, 2
nd
edn. Philadelphia: Lea & Febiger, 1990: 125152.
203. Schwartz Z, Somers A, Mellonig JT, Carnes DL Jr, Dean DD,
Cochran DL, Boyan BD. Ability of commercial deminera-
lized freeze-dried bone allograft to induce new bone for-
mation is dependent on donor age but not gender.
J Periodontol 1998: 69: 470478.
204. Sewon L, Karjalainen S, Soderling E, Hyyppa T, Luukkala-
Wardi E, Makela M, Paunio K, Varrela T. The limited value
of three pathogen species in predicting healing of period-
ontal pockets. Acta Odontol Scand 1999: 57: 267270.
205. Shiloah J, Patters MR, Dean JW, Bland P, Toledo G. The
survival rate of Actinobacillus actinomycetemcomitans,
Porphyromonas gingivalis, and Bacteroides forsythus fol-
lowing 4 randomized treatment modalities. J Periodontol
1997: 68: 720728.
206. Shiloah J, Patters MR, Dean JW, Bland P, Toledo G. The
prevalence of Actinobacillus actinomycetemcomitans, Por-
phyromonas gingivalis, and Bacteroides forsythus in hu-
mans 1 year after 4 randomized treatment modalities.
J Periodontol 1998: 69: 13641372.
207. Shirota T, Ohno K, Suzuki K, Michi K, Tatsuo S, Kohsuke O,
Kanako S, Ken-Ichi M. The effect of aging on the healing of
hydroxylapatite implants. J Oral Maxillofac Surg 1993: 51:
5156.
208. Shirota T, Donath K, Ohno K, Matsui Y, Michi K. Effect of
age and radiation on bone healing adjacent to hydroxya-
patite placed in the tibia of rats. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1995: 79: 285294.
209. Siervo S, Wirz J, Schmidli F, Coraini C, Siervo P. Late im-
plant failures and genetic susceptibility: Links and hints.
J Clin Periodontol 2000: 27 (Suppl. 1): 78 (Abstract 240).
210. Sirmon MD, Kirkpatrick WG. Diabetic nephropathy: new
directions in management. Ren Fail 1991: 13: 5159.
211. Slots J, Contreras A. Herpesviruses: a unifying causative
factor in periodontitis? Oral Microbiol Immunol 2000: 15:
277280.
212. Socransky SS, Haffajee AD. Dental biofilms: difficult ther-
apeutic targets. Periodontol 2000 2002: 28: 1255.
213. Soskolne WA, Klinger A. The relationship between period-
ontal diseases and diabetes: an overview. Ann Periodontol
2001: 6: 9198.
134
Ronderos & Ryder
214. Stewart JE, Wager KA, Friedlander AH, Zadeh HH. The
effect of periodontal treatment on glycemic control in
patients with type 2 diabetes mellitus. J Clin Periodontol
2001: 28: 306310.
215. Stoltenberg JL, Osborn JB, Pihlstrom BL, Herzberg MC,
Aeppli DM, Wolff LF, Fischer GE. Association between
cigarette smoking, bacterial pathogens, and periodontal
status. J Periodontol 1993: 64: 12251230.
216. Styrt B, Sugarman B. Estrogen and infection. Rev Infect Dis
1991: 13: 11391150.
217. Tan AE, Powell RN, Seymour GJ. Patient attendance
compliance in periodontal therapy. Aust Dent J 1992: 37:
467471.
218. Taylor GW. Bidirectional interrelationships between dia-
betes and periodontal diseases: an epidemiologic perspec-
tive. Ann Periodontol 2001: 6: 99112.
219. Terasaki PI, Kaslick RS, West TL, Chasens AI. Low HL-
A2 frequency and periodontitis. Tissue Antigens 1975: 5:
286288.
220. Tervonen T, Knuuttila M, Pohjamo L, Nurkkala H. Immedi-
ate response to non-surgical periodontal treatment in sub-
jects with diabetes mellitus. J Clin Periodontol 1991: 18:
6568.
221. Tezal M, Wactawski-Wende J, Grossi SG, Ho AW, Dunford
R, Genco RJ. The relationship between bone mineral den-
sity and periodontitis in postmenopausal women. J Period-
ontol 2000: 71: 14921498.
222. Thomas DR. Age-related changes in wound healing. Drugs
Aging 2001: 18: 607620.
223. Thomson WM, Edwards SJ, Dobson-Le DP, Tompkins GR,
Poulton R, Knight DA, Braithwaite AW. IL-1 genotype and
adult periodontitis among young New Zealanders. J Dent
Res 2001: 80: 17001703.
224. Tsai C, Hayes C, Taylor GW. Glycemic control of type 2
diabetes and severe periodontal disease in the US adult
population. Community Dent Oral Epidemiol 2002: 30:
182192.
225. Van de Kerkhof PC, Van Bergen B, Spruijt K, Kuiper JP. Age-
related changes in wound healing. Clin Exp Dermatol 1994:
19: 369374.
226. Van der Velden U, Abbas F, Hart AAM. Experimental gin-
givitis in relation to succeptibility to periodontal disease.
(1.) Clinical observations. J Clin Periodontol 1985: 12:
6168.
227. Van der Velden U, Abbas F, Armand S, de Graaff J, Timmer-
man MF, van der Weijden GA, van Winkelhoff AJ, Winkel
EG. The effect of sibling relationship on the periodontal
condition. J Clin Periodontol 1993: 20: 683690.
228. Van der Weijden GA, de Slegte C, Timmerman MF, van der
Velden U. Periodontitis in smokers and non-smokers: in-
tra-oral distribution of pockets. J Clin Periodontol 2001: 28:
955960.
229. Van Winkelhoff AJ, Bosch-Tijhof CJ, Winkel EG, van der
Reijden WA. Smoking affects the subgingival microflora in
230. Von Wowern N, Klausen B, Kollerup G. Osteoporosis: A
risk factor in periodontal disease. J Periodontol 1994: 65:
11341138.
231. Wactawski-Wende J, Grossi SG, Trevisan M, Genco RJ,
Tezal M, Dunford RG, Ho AW, Hausmann E, Hreshchyshyn
MM. The role of osteopenia in oral bone loss and period-
ontal disease. J Periodontol 1996: 67: 10761084.
232. Waerhaug J. Effect of toothbrushing on subgingival plaque
formation. J Periodontol 1981: 52: 3034.
233. Walker SJ, Van Dyke T, Rich S, Kornman KS, Hart TC.
Genetic polymorphisms of the IL-1a and IL-1b genes in
African-American LJP patients and an African-American
control population. J Periodontol 2000: 71: 723728.
234. Wang S, Sun C, Gillanders E, Wang Y-F, Freas-Lutz D,
Zhang Y-J, Burmeister JA, Gunsolley JC, Schenkein HA,
Diehl SR. Evidence for susceptibility genes for early onset
periodontitis. J Dent Res 1997: 76: 151 (Abstract 1098).
235. Westfelt E, Nyman S, Socransky S, Lindhe J. Significance of
frequency of professional tooth cleaning for healing fol-
lowing periodontal surgery. J Clin Periodontol 1983: 10:
148156.
236. Weyant RJ, Pearlstein ME, Churak AP, Forrest K, Famili P,
Cauley JA. The association between osteopenia and peri-
odontal attachment loss in older women. J Periodontol
1999: 70: 982991.
237. Wilson TG Jr, Nunn M. The relationship between interleu-
kin-1 periodontal genotype and implant loss. Initial data.
J Periodontol 1999: 70: 724729.
238. Wilson TG Jr, Glover ME, Baus C, Jacobs T. Compliance
with maintenance therapy in a private periodontal prac-
tice. J Periodontol 1984: 55: 468473.
239. Wilson TG Jr, Glover ME, Malik AK, Schoen JA, Dorsett D.
Tooth loss in maintenance patients in a private period-
ontal practice. J Periodontol 1987: 58: 231235.
240. Wilson TG Jr, Hale S, Temple R. The results of efforts to
improve compliance with supportive periodontal treat-
ment in a private periodontal practice. J Periodontol
1993: 64: 311314.
241. Yaffe A, Iztkovich M, Earon Y, Alt I, Lilov R, Binderman I.
Local delivery of an amino bisphosphonate prevents the
resorptive phase of alveolar bone following mucoperios-
teal flap surgery in rats. J Periodontol 1997: 68: 884889.
242. Yaffe A, Golomb G, Breuer E, Binderman I. The effect of
topical delivery of novel bisacylphosphonates in reducing
alveolar bone loss in the rat model. J Periodontol 2000: 71:
16071612.
243. Yeung SCH, Stewart GJ, Cooper DA, Sindhusake D. Pro-
gression of poriodontal disease in HIV seropositive pa-
tients. J Periodontol 1993: 64: 651657.
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