10

Periodontology 2000, Vol.
29, 2002, 207222 Copyright C Blackwell Munksgaard 2002

Printed in Denmark. All rights reserved
PERIODONTOLOGY 2000
ISSN 0906-6713
Risk factors for periodontitis in
children and young persons
Jnsir M. AIunNnnn & Tnorns E. Rnrs
Periodontitis are destructive forms of periodontal
diseases that are characterized by inammation of
the periodontal tissue, leading to an apical migration
of the epithelial attachment and loss of periodontal
soft and hard tissues (93). Periodontitis in children
and young subjects encompass four groups of dis-
eases which are clinically distinguishable and are
also believed to have distinct etiopathogenesis and
risk factors.
O Periodontitis as a manifestation of systemic dis-
eases is a classication recommended in the 1999
International Workshop sponsored by the Ameri-
can Academy of Periodontology (24) and includes
a group of diseases in which there has been sig-
nicant evidence showing the occurrence of peri-
odontitis as a manifestation of certain systemic
diseases. This group includes periodontal tissue
loss associated with certain hematological dis-
orders such as acquired neutropenia and leukemi-
as, and various genetic disorders (50).
O Necrotizing periodontal diseases comprises the
second group (51). These diseases are character-
ized by gingival necrosis presenting as punched-
out papillae, accompanied by gingival bleeding
and pain, and in severe cases, necrosis of peri-
odontal ligament and alveolar bone. Necrotizing
periodontal diseases are believed to be associated
with a diminished host resistance to bacterial in-
fection of periodontal tissues. This group includes
necrotizing ulcerative gingivitis and necrotizing
ulcerative periodontitis. However, it is still unclear
whether these are two distinct diseases (51).
O Aggressive periodontitis in young persons are
characterized by a pronounced loss of periodontal
attachment and alveolar bone, and a high rate of
disease progression (3, 38, 68). The recent interna-
tional workshop proposed the new term of aggres-
207
sive periodontitis as a substitute to earlier classi-
cations including that of early onset peri-
odontitis, juvenile periodontitis, and rapidly
progressive periodontitis (24, 49). Localized ag-
gressive periodontitis has a distinctive radio-
graphic bone loss pattern depicted as vertical or
arc-shaped bone defects usually occurring at the
rst molars and one or more incisors, and a mir-
ror image appearance of these defects on teeth on
both sides of the dental arch (21, 66).
O Chronic periodontitis is a new classication rec-
ommended in the 1999 workshop (48) to replace
earlier classications. Other studies have used
various other terms to denote this classication,
such as early periodontitis, incipient peri-
odontitis, incipient periodontal lesions (3, 45, 67),
incidental attachment loss (99), and incidental
periodontitis (10). Le & Brown (99) and Albandar
et al. (10) were among the rst investigators to re-
gard this as a separate disease entity affecting
young persons characterized as a nonaggressive
disease involving a single or few teeth, and a slow
disease progression (4). Other features of this dis-
ease is the lack of the typical radiographic features
of aggressive periodontitis, such as vertical or arc-
shaped bone defects and the mirror image ap-
pearance of bone defects.
Periodontitis as a manifestation of systemic diseases
and necrotizing periodontal diseases occur more
often in children than in adults, though both are un-
common (128, 138). Chronic periodontitis in
children and adolescents is more prevalent than the
other three forms of periodontitis, although it is clin-
ically similar to the chronic periodontitis seen in
adults. Early onset aggressive periodontitis is less
prevalent than chronic periodontitis, and its preva-
Albandar & Rams
lence has been shown to vary signicantly between
various demographic groups (21).
Etiologic and risk factors of
chronic and aggressive
periodontitis
Age
Using data from the 19861987 national survey of
oral health of United States children, Albandar et al.
(11) showed that the prevalence rate of early onset
aggressive periodontitis is twice as high in adoles-
cents aged 1617years than in children aged 1315
years. Also, Le & Brown (99) found that age was a
signicant risk indicator for aggressive periodontitis.
They estimated that 15 years old children were 2.3
times more likely to have generalized early onset
periodontitis, and 1617 years old children were
about 3.3 times more likely to have localized early
onset periodontitis compared to 14 years old
children. On the other hand, they found only a weak
association between the occurrence of chronic (inci-
dental) periodontitis and age.
In a population survey in Chilean secondary
school students, Lopez et al. (106) found a signicant
correlation between age and presence of clinical
attachment loss of 3mm. They estimated that sub-
jects aged 1517years and 1821years, respectively,
were 1.6 and 3 times more likely to have attachment
loss than children 1214years old. Albandar et al.
(18) studied the periodontal status of a group of
Ugandan students and found that the percentage of
subjects having clinical attachment loss of 4mm
was 27% in 1216years olds and 29% among 1719
years olds, and this increased to 35% in subjects 20
25years old. This pattern of positive correlation be-
tween the prevalence of periodontitis and age ap-
pears to be similar for aggressive and chronic peri-
odontitis, and also similar to the pattern of corre-
lation between chronic periodontitis and age
observed in adults (14, 17, 20).
Race-ethnicity
There is strong evidence showing that certain race-
ethnicity groups are associated with a signicantly
higher risk of developing early onset periodontitis,
both the aggressive and chronic forms. Albandar et
al. (11) surveyed 14,000 American adolescents and
found a very high prevalence of aggressive and
chronic periodontitis in blacks, and a moderately
208
high prevalence in Hispanics compared to white
adolescents and young adults of similar age. Simi-
larly, Le & Brown (38) showed a signicant increase
in risk for periodontitis in blacks, and estimated that
1417 years old blacks were 1516 times more likely
to have localized or generalized aggressive peri-
odontitis, and 5.5 times more likely to develop
chronic periodontitis than whites. Hispanics, on the
other hand, were 4 times more likely to have local-
ized aggressive periodontitis, and 1.6 times more
likely to have chronic periodontitis than non-His-
panic adolescents.
Other surveys also have shown a signicantly
higher prevalence of aggressive periodontitis in
blacks than in whites. Bial & Mellonig (32) examined
49000 American male naval recruits and found that
about 3/4 of subjects with aggressive periodontitis
were blacks. Melvin et al. (113) examined about 5000
male and female recruits and found a signicantly
higher prevalence of aggressive periodontitis in
blacks than whites. Perry & Newman (133) measured
the probing depth and attachment loss in 1215
years old schoolchildren in a Los Angeles inner city
school and found that 14.7% of blacks and 9.6% of
Hispanics had periodontitis, which are very high
rates compared to the national average for whites
which is around 1.11.3 (11, 99).
Aass et al. (1) examined a large group representa-
tive of 14-years old schoolchildren in Oslo, Norway
and found a signicantly higher prevalence of radio-
graphic bone loss in children of Asian or other ethnic
background than in Norwegians. In a large survey in
the U.K., Saxby (140) showed that there are statisti-
cally signicant differences in the prevalence of ag-
gressive periodontitis between the various ethnic
groups, with Afro-Caribbeans having a relatively
high prevalence (0.8%) compared to Asians (0.2%)
and Caucasians (0.02%).
Schenkein et al. (144) studied the neutrophil
chemotaxis response to N-formyl-methyl-leucyl-
phenyl-alanine (fMLP) antigens in aggressive peri-
odontitis patients and in periodontally healthy
young persons, and compared these responses in
whites and blacks. They found similar responses in
healthy persons of the same race group, and a sig-
nicantly higher response in whites than in blacks.
These ndings, and the recent data showing signi-
cant differences between races in the prevalence of
certain periodontitis-associated genotypes (24), sug-
gest that the increased risk of periodontal disease in
blacks may be partly due to a biological predis-
position.
However, environmental and other differences be-
Risk factors for periodontitis in children and young persons
tween ethnic-racial groups also exist. Albandar et al.
(9) showed signicant differences in the levels of lo-
cal factors between black, Hispanic, and white ado-
lescents, which were also consistent with differences
in the levels of periodontitis in these subjects. Com-
parison of the types of bacteria that are found in the
saliva and periodontal sites of different groups of
persons tend to suggest that the different race-ethnic
groups may harbor different types of bacteria. Ume-
da et al. (166) estimated that African-Americans had
an increased risk of harboring Porphyromonas gingi-
valis in saliva (odds ratio (OR) 3), Asian-Americans
had an increased risk for harboring Actinobacillus
actinomycetemcomitans in periodontal pockets (OR
6.6), and P. gingivalis in periodontal pockets and in
saliva (OR 5.7 and 5.4), and Hispanics had an in-
creased risk of harboring A. actinomycetemcomitans
in periodontal pockets (OR 12.3) and P. gingivalis in
periodontal pockets and in saliva (OR 6.1 and 8.7).
Recent data also suggest that certain ethnic groups
may harbor highly virulent strains of certain bacteria
which are thought to be associated with aggressive
periodontitis. It has been shown, for instance, that a
highly leukotoxic strain of A. actinomycetemcomitans
may be isolated from subjects of African descent
more often than others (56, 79), and also from ag-
gressive periodontitis patients of African origin who
were living in geographically widespread areas (78).
Gender
A large body of evidence exists showing that, in
adults, males are at higher risk of developing chronic
periodontitis than females (14, 17, 20). However, the
data on the prevalence of periodontitis in adoles-
cents and children are less consistent, and there is a
lack of agreement on whether gender is a risk factor
for the occurrence of periodontitis in this age group.
In a classic review article from the early 1970s,
Baer (29) characterized aggressive (juvenile) peri-
odontitis as a destructive disease commencing dur-
ing the circumpubertal period and affecting females
more frequently than males. Benjamin & Baer (31)
described several cases of this disease, and based on
this and other clinical studies, Baer (29) estimated
that the female/male ratio was about 3: 1, suggesting
that females are 3 times more likely to develop the
disease than males. Hrmand & Frandsen (85) exam-
ined a large group comprising 156 aggressive peri-
odontitis patients ranging in age from 12 to 32years
and concluded that the disease affects females more
often than males with a ratio of 2.5: 1. Other studies
showing a higher prevalence of aggressive peri-
209
odontitis in females than males reported the follow-
ing range of ratios: 1.9: 1 among 1723years old Sau-
di schoolchildren (123), 3.5: 1 among 14years old
Iraqi schoolchildren (5), and 7: 1 among 1519years
old Chilean schoolchildren (102).
A recent survey of 1221years old Chilean students
found that females were at a higher risk for having
chronic periodontitis (attachment loss of 3mm)
than males (106). However, the estimated risk (odds
ratio) in males was 0.74, which is much less than
the risk reported by Lopez et al. (102) for aggressive
periodontitis in another sample of Chilean students
that were somewhat older.
However, results of other studies did not agree
with the studies cited above (75). Using national data
for approximately 11,000 children, 1417-years-old,
collected in a 19861987 national survey of the oral
health of U.S. children, Le & Brown (99) reported
that males had a higher risk of having periodontitis
than females, irrespective of disease classication.
They also concluded that there was only a weak as-
sociation between sex and the occurrence of peri-
odontitis in their study group. Albandar et al. (11)
used data from more than 14,000 subjects aged 13
19years examined in the same U.S. national survey
and found that periodontitis was only slightly more
prevalent in males than in females. A recent survey
among Ugandan students aged 1225years found
that periodontitis was more prevalent in males, and
the reported female to male ratio was 1: 1.5 (18).
A large survey in 16years old Swiss children found
a similar occurrence frequency of aggressive peri-
odontitis in both sexes (95). Melvin et al. (113) found
a similar overall prevalence of aggressive peri-
odontitis among 1726 years old males and females
American recruits, and a signicantly higher preva-
lence in males than in females (ratio 2: 1) when only
black recruits were studied.
More than two decades ago, Hrmand & Frandsen
(85) have shown that the female to male ratio of the
prevalence of aggressive periodontitis may vary de-
pending on the age of the subjects studied. Thus, the
ratio was 5.3: 1 in subjects aged 1218years, and 2.4
: 1 in subjects aged 1925years, and this ratio de-
creased to about 1.5: 1 in subjects 2632years old.
They concluded that the higher prevalence of dis-
ease in females in the youngest age group might be
related to the earlier eruption of rst molars and in-
cisors in females. This pattern of a higher rate of in-
volvement in females than males in the youngest age
cohorts seems consistent with the above literature
review, and this supports the conclusion that the
earlier onset of adolescence and eruption of perma-
Albandar & Rams
nent teeth in females may contribute to the higher
prevalence of aggressive and chronic periodontitis in
females than males during the circumpubertal age.
This suggests that the effect of gender as a risk
factor for periodontitis in young people is dependent
on the type of periodontitis investigated. Hence,
gender may be a signicant risk factor for chronic
periodontitis with males signicantly more predis-
posed than females, and this seems similar to the
gender predisposition for the adult manifestation of
chronic periodontitis. However, the effect of gender
as a risk factor for aggressive periodontitis and the
exact mode of inheritance of the disease remain un-
clear. The available evidence suggests that young fe-
males in the circumpubertal age may be more pre-
disposed than males, and this effect decreases with
increasing age.
Oral hygiene and local factors
Investigators have observed that adolescents with
aggressive periodontitis, and particularly those with
the initial stages of the disease, show a normal gin-
giva displaying a proper color and physiologic con-
tour. Other clinical features of the disease include a
rate and severity of periodontal tissue loss that are
not commensurate with the amount of local etiolog-
ical factors, such as supragingival and subgingival
calculus in these subjects (29, 31). Subsequent to
these clinical observations, many investigators ac-
knowledged these observations and, in addition,
used these features as classication criteria in their
studies (66, 109). Consequently, studies often have
excluded cases showing severe and rapid peri-
odontal tissue loss if they also exhibited local factors
pertaining to increased plaque accumulation (95,
102, 124, 140, 141, 170).
However, more recent studies have shown that the
level of oral hygiene and presence of local factors
may not be valid diagnostic features of aggressive
periodontitis. In a large population study among
more than 14,000 Americans aged 1320years, Al-
bandar et al. (9) assessed the oral hygiene and gingi-
val status of aggressive and chronic (incidental) peri-
odontitis subjects, and compared these with similar
parameters in subjects without periodontitis who
were matched to the cases on various demographic
variables. The results showed that oral hygiene, as
determined by the amount of supragingival calculus,
was not signicantly different between these three
groups. On the other hand, subjects with aggressive
periodontitis had signicantly more gingival in-
ammation and subgingival calculus than subjects
210
with chronic periodontitis. In addition, subjects who
had aggressive or chronic periodontitis had more of
these two conditions than their matched controls.
Furthermore, gingival inammation and calculus
were associated with the progression of clinical
attachment loss in young subjects (13) and may be
regarded as signicant risk factors for periodontitis.
A very large survey among U.S. male recruits
showed that a high percentage (46%) of aggressive
periodontitis cases had radiographic evidence of
dental calculus (32). A clinical study among 1215-
year-old schoolchildren in a Los Angeles inner city
school with a high level of calculus and poor oral
hygiene showed a high level (12.7%) of periodontitis
(133). Similarly, Albandar (5) examined a group of
Iraqi children with aggressive periodontitis and com-
pared their oral hygiene status with that of a
matched control group and found that both groups
had a high and similar extent of sites with visible
dental plaque, and a tendency towards a higher per-
centage of sites with calculus than the controls.
Schenkein et al. (146) studied 766 young adults
comprising aggressive periodontitis patients and
members of their families, and found a signicant
correlation between the plaque index scores and
measures of attachment loss. In a population study
of Chilean students, Lopez et al. (106) found that
persons who brushed once a day or less often, re-
spectively, were 1.3 and 2 times more likely to have
attachment loss than those brushing 2 or more times
a day. The study concluded that infrequent tooth
brushing is associated with a higher prevalence of
periodontitis.
The importance of dental plaque as the primary
etiological factor in the development of gingival in-
ammation and chronic periodontitis was estab-
lished a few decades ago (96, 98). Axelsson & co-
workers (2527) have shown that adequate levels of
oral hygiene maintained professionally can be effec-
tive in preventing the development of periodontal
diseases in children as well as in adults.
A controlled clinical trial by Albandar et al. (6) as-
sessed the effect of a comprehensive oral hygiene
training program on the incidence of plaque and
gingivitis in a group of Brazilian schoolchildren, and
established that the program had a good efcacy in
controlling plaque accumulation and in preventing
gingival inammation in adolescents. However,
there were some important differences in the ef-
cacy of the program between the subjects, with less
favorable results achieved in males, and in children
who had higher levels of plaque and gingivitis prior
to the beginning of the program. This suggests that
children with behavioral risk factors may be less re-
ceptive to oral hygiene training programs, and that
other additional preventive measures should be tried
in these subjects. Notably also, in the same study
population, the comprehensive oral hygiene training
program, which continued over a 3-year period did
not, by itself, prevent the development of alveolar
bone loss or slow down the rate of tissue loss due to
periodontitis. Based on this nding, Albandar et al.
(8) inferred that secondary prevention of peri-
odontitis in children is of prime importance and
may be achieved through early detection of high risk
subjects.
Among other important local risk factors, Alband-
ar et al. (7) have shown that presence of active caries
lesions and dental restoration on approximal tooth
surfaces may predispose to a signicant loss of
attachment, even if these restorations may seem
nondefective.
Provision of dental care
Albandar (3) compared the prevalence of radio-
graphic bone loss among adolescents with or with-
out community dental programs. The study subjects
comprised 4 groups of 1314 years old children from
Iraq, Norway, and Denmark. The Iraqi group con-
sisted of all 7th graders (N516) in two secondary
schools located in a middle socioeconomic area of
Baghdad. The Norwegian group consisted of all 13
14 years old schoolchildren (N241) in the province
of Konsvinger in the South-east of Norway. The
Danish group consisted of all 7th graders (aged 13
14years, N 561) from eight provincial towns in
Denmark, and included children with or without
school dental care programs. The study subjects
were then divided into two groups. The rst group
included 555 children from Norway and Denmark
who were receiving systematic dental care in the
Norwegian or Danish national dental health pro-
grams which consisted of routine check up visits and
a preventive and treatment procedures. The second
group included 743 Iraqi and Danish children who
were not receiving a community-based systematic
dental care. This study showed signicant differ-
ences between the two groups, with the group not
receiving community dental care showing a signi-
cantly higher prevalence of alveolar bone loss, ir-
respective of their ethnic background.
In addition, infrequent dental attendance pattern
has been found to be associated with a higher fre-
quency of periodontitis. Lopez et al. (106) assessed
periodontal status and dental attendance pattern
211
among Chilean schoolchildren and found that per-
sons who had visited a dentist 612months ago,
more than 1years ago, or had never seen a dentist
before, respectively, were 1.2, 1.7, and 2.1 times more
likely to have chronic periodontitis (attachment loss
of 3mm) than persons who had visited a dentist
6months ago. It has also been estimated that U.S.
children with no dental insurance are 3 times more
likely to have unmet dental needs than children who
have either public or private insurance programs
(125, 171).
Socioeconomic level
It is well recognized that the socioeconomic level is
a good marker of various risk factors for peri-
odontitis such as oral hygiene, provision of dental
care, behaviors, and ethnicity, and therefore this fac-
tor may be a good indicator of the level of peri-
odontitis in a given population. Several studies have
reported a strong association between a low socio-
economic level and a high risk of periodontal dis-
eases.
Drury et al. (63) used data from the U.S. NHANES
III national survey and assessed the socioeconomic
level of individuals on a composite scale comprising
the individuals education and family economic
level, and found a signicantly higher prevalence of
gingival bleeding and loss of attachment of 4mm
in groups with lower socioeconomic levels. Aass et
al. (1) examined a group of 14 years old Norwegian
schoolchildren and found a signicantly higher
prevalence of radiographic bone loss in children in
the low rather than the high socioeconomic groups.
A similar nding was reported in Chilean students
for whom the group with a low socioeconomic level
was associated with a higher prevalence of clinical
attachment loss of 3mm (106). A study in a group
of schoolchildren drawn from schools in Ontario,
Canada found a higher prevalence of gingival in-
ammation and calculus, poorer oral hygiene, and a
signicantly higher periodontal treatment needs in-
cluding subgingival scaling and prophylaxis in immi-
grants with a lower socioeconomic level than in the
better-off Canadian-born children (97).
Smoking
The effect of smoking in the development of chronic
periodontitis is well documented and there is strong
evidence demonstrating that tobacco smoking habit
is a very important risk factor contributing to a
higher prevalence and severity of periodontitis in
Albandar & Rams
adults (15, 20, 163, 164). However, there are only a
few studies that have investigated the effect of smok-
ing on the occurrence of periodontitis in young age
cohorts.
Population studies suggest that the effect of smok-
ing on the prevalence of periodontitis in young
populations is similar to the effect reported for adult
populations (77, 107, 122). A recent study in 1221
years old Chilean students estimated that the risk for
chronic periodontitis in smokers and nonsmokers
was similar (OR1)(106). However, in the latter
study, it was noted that the study sample had
smoked on average 5.4 cigarettes per day for 3years,
which is a relatively low exposure to cigarette smok-
ing compared to other populations reported in the
literature, and this may be the reason for the re-
ported lack of association between smoking and
attachment loss.
Among the potential mechanisms of action of
smoking in the pathogenesis of chronic peri-
odontitis, several studies have disclosed effects on
the local vasculature and the host immune systems.
It has been demonstrated that there are differences
in the oxygen saturation of hemoglobin in the gin-
giva of smokers and nonsmokers, suggesting that
smokers have functional impairments in the gingival
microcirculation (73). Furthermore, it has been
shown that smoking has signicant adverse effects
on the immune system, which include the modi-
cation of the humoral and cellular immune systems,
and cytokine and adhesion molecule network (34,
35, 92).
It is unclear, however, whether smoking also con-
tributes to the pathogenesis of early onset aggressive
periodontitis. Schenkein and coworkers (146) in a
series of studies in a large group of patients in Vir-
ginia investigated the effects of smoking on aggres-
sive periodontitis, and whether differences existed in
the prevalence of smoking between various disease
classications. They found that 20% of the localized
aggressive periodontitis subjects, and 43% of the
generalized aggressive periodontitis subjects were
smokers, as compared to 16% of periodontally
healthy subjects. Based on these ndings, they con-
cluded that smoking had a signicant effect, and had
contributed to a greater attachment loss and a
higher number of tooth loss in subjects with general-
ized aggressive disease. However, it should be noted
that age may also have played a signicant role in
these results as subjects in the generalized aggressive
periodontitis group were on average about 67years
older than those in the localized aggressive peri-
odontitis group.
212
Analysis of the Virginia data also showed that
smoking had signicant effects on serum immuno-
globulin levels, and that these effects were both race
and serum IgG subclass antibody specic (136).
Hence, IgG2 and IgG4 antibody levels were reduced
in blacks with generalized aggressive disease who
were smokers, whereas the levels of these immuno-
globulins were not reduced in blacks who were
healthy or with localized disease and who also were
smokers. Further analysis of the same data demon-
strated that smoking was also associated with a sig-
nicant reduction in serum IgG2 anti-A. actinomyce-
temcomitans antibodies in black smokers with gen-
eralized aggressive periodontitis but not in smokers
with localized periodontitis. These results were con-
sistent with clinical ndings in the same study group
showing that generalized aggressive periodontitis
patients who were smokers had more extensive peri-
odontal destruction than their nonsmoking counter-
parts.
More recently, Mooney et al. (119) tested the hy-
pothesis that smokers with generalized aggressive
periodontitis have reduced antibody levels and avid-
ity to ve periodontal pathogens, and found that
antibody titers were not different between these two
groups in untreated subjects. However, in subjects
who have been periodontally treated and who were
in maintenance phase, the antibody titers to A. acti-
nomycetemcomitans, Prevotella intermedia and Tre-
ponema denticola were signicantly lower in
smokers than in nonsmokers. Also the avidity of
antibody to P. gingivalis was signicantly lower in
smokers than in nonsmokers. They concluded that
smoking might cause some interruption of immune
maturation following periodontal treatment. The
ndings of this latter study and that of Quinn et al.
(136) also suggest that the depression of antibody
level by smoking may be more pertinent to blacks
than other races.
Microbiological factors
A large number of bacteria exist as a part of the nor-
mal ecology of the oral cavity, and these consist of
diverse types of microorganisms that differ greatly
in their virulence potential (71, 121), and there is a
continuous insult by some of these microorganisms
to initiate an inammatory reaction in the peri-
odontal tissues. Early studies of the role of micro-
organisms in the pathogenesis of chronic peri-
odontitis concluded that the amount of bacteria and
bacterial products that accumulate locally in the
periodontal tissue is of prime importance in the
pathogenesis of gingivitis as well as periodontitis
and the resulting attachment loss (159).
However, signicant evidence has also emerged
suggesting that only a subgroup of microorganisms
might be responsible for the initiation of the tissue
destruction in chronic periodontitis (100, 151). Other
data also suggested that certain bacterial species
characterized as gram-negative anaerobes and fa-
cultative microorganisms may play an important
role in the pathogenesis of the more aggressive
forms of periodontitis (149). Slots & Rams (152)
found that certain bacterial species, including A.
actinomycetemcomitans, P. gingivalis, Capnocyto-
phaga species, Eikenella corrodens, P. intermedia,
Campylobacter rectus were often cultivated from the
subgingival plaque samples of early onset aggressive
periodontitis patients. Also, Moore & Moore (121)
isolated these as well as other species from aggres-
sive periodontitis patients.
Results of several studies suggest that A. actino-
mycetemcomitans is a major etiological factor in the
pathogenesis of aggressive periodontitis (150, 153,
175). This bacterium has often been identied in
young persons showing severe attachment loss and/
or rapid disease progression (149, 151, 154). Aass et
al. (1) detected this bacterium in about 50% of sites
showing radiographic bone loss in young persons
monitored over 8years.
A. actinomycetemcomitans is a nonmotile, gram-
negative, capnophilic, round-ended rod which pos-
sesses several virulence factors (64), some of which
have the ability to induce an intense immune re-
sponse and/or impair the hosts immune defense,
and these factors may explain its potential pathoge-
nicity. One of the virulence mechanisms of A. actino-
mycetemcomitans is the potential production of
harmful metabolites such as a leukotoxin that
specically kills leukocytes, thus allowing the bac-
terium to evade part of the host defenses. This toxin
is encoded by a gene operon that, in certain strains,
has a 530-bp deletion in the promotor region of the
bacterium DNA, resulting in a signicantly en-
hanced leukotoxin production by the organism. In
addition, A. actinomycetemcomitans has been shown
to be capable of invading human gingival epithelial
cells in vitro (33, 114).
These specic genetic variants of A. actinomyce-
temcomitans with the characteristic deletion pattern
have been shown to signicantly correlate with ag-
gressive forms of periodontal diseases (61), and to
be prevalent in aggressive periodontitis patients
from certain geographic areas, particularly among
subjects of African descent (78, 79). The presence of
213
this strain has also been associated with an in-
creased risk for the initiation and progression of lo-
calized aggressive periodontitis (39, 60). Contreras et
al. (56) investigated the occurrence of these specic
A. actinomycetemcomitans strains in individuals of
various ethnic backgrounds including blacks, His-
panics, Asians and Caucasians, and concluded that
occurrence of the organism containing the sequence
deletion is mainly a characteristic of individuals of
African descent and occurred both in individuals
having severe periodontitis and in adolescents with
no evidence of periodontitis.
In contrast to studies suggesting an important role
for A. actinomycetemcomitans in aggressive peri-
odontitis, there are also reports of low or no detec-
tion of this microorganism in patients. Albandar et
al. (12) used DNA probes to detect A. actinomycetem-
comitans and found a low prevalence of this micro-
organism in the periodontal pockets of aggressive
and chronic (incidental) periodontitis patients. How-
ever, the generalized aggressive periodontitis sub-
jects in the same study group had elevated serum
IgG and IgA antibody levels to this microorganism
(16). Also, Tinoco et al. (161) showed that not all juv-
enile periodontitis patients show detectable levels of
A. actinomycetemcomitans in the mouth. Han et al.
(72) used a selective medium to identify A. actino-
mycetemcomitans and did not detect the bacterium
in any of the diseased sites in 15 aggressive peri-
odontitis patients in China.
Results of several studies suggest that P. gingivalis
and perhaps other bacterial species also may be im-
portant in the pathogenesis of periodontitis in
children. Studies have shown that P. gingivalis is
present in high numbers in patients with aggressive
periodontitis (46, 104, 105, 120). In a case-control
study, Albandar et al. (12) examined the micro-
biology of a large group of adolescents and young
adults selected through a national survey in the
U.S.A., and reported that subjects with generalized
aggressive periodontitis had a 16-fold increase in P.
gingivalis, 5-fold increase in T. denticola, and 2.5-
fold increase in P. intermedia compared to matched
controls. Furthermore, they found that subjects with
rapid disease progression during a period of 6years
had a 5-times more P. gingivalis, 3-times more T.
denticola, and 2-times more P. intermedia compared
to subjects that did not have progressive disease dur-
ing the same period. Based on these ndings, Alban-
dar and coworkers (12) concluded that P. gingivalis
and T. denticola, and possibly also P. intermedia may
play a signicant role in the generalized and rapidly
progressive forms of aggressive periodontitis.
Albandar & Rams
The higher recovery of these bacterial species (12,
46, 104, 105, 120), the association with periodontal
attachment loss and with a high rate of disease pro-
gression (12), the high level of systemic and local
antibodies produced by the host against these bac-
teria (16, 91, 145), and their potent virulence factors
(61, 64, 84), are all evidence indicating that these
bacterial species play a role in the etiopathogenesis
of aggressive periodontitis and possibly also chronic
periodontitis.
Host immune factors
There is strong evidence that certain aggressive
forms of periodontitis, particularly periodontitis
commencing at the prepubertal age, are predisposed
to a higher risk of tissue loss by specic defects in
the host immune systems. Studies in young children
with generalized prepubertal periodontitis have
demonstrated that neutrophils from these patients
have abnormally low levels of binding by antibodies,
which suggests functional abnormalities in these
cells (130). There is also data showing that defects in
the systemic immune response may play a role in
the pathogenesis of other aggressive forms of peri-
odontitis in young subjects. Various functional ab-
normalities in neutrophils and monocytes from lo-
calized juvenile periodontitis patients have been re-
ported (162), such as increased adherence (2),
abnormal signal transduction (57, 148) and de-
pressed chemotaxis and other related functions (167,
168). Page et al. (129) assessed the prevalence of de-
fective neutrophils and monocytes in aggressive
periodontitis patients and detected defective neutro-
phils in 85% and defective monocytes in 74% of
these patients. However, it has also been shown that
these defects are not exclusive, in that some aggres-
sive periodontitis patients do not have neutrophil
chemotactic defects (89).
It is believed that the humoral host immune re-
sponse also plays an important role in the patho-
genesis of various destructive forms of periodontal
diseases. A frequent nding in patients with peri-
odontitis is the increased levels of antibodies to
putative periodontal bacteria (16, 91, 145). However,
the relationship between antibody level and peri-
odontal disease is complex, and may be inuenced
by many factors such as race, smoking, and im-
munoglobulin allotypes (19, 69, 158).
It has been shown that P. gingivalis elicit potent
IgG2 antibody responses in patients with generalized
aggressive periodontitis (42). Albandar et al. (16) as-
sessed the serum antibody levels to major peri-
214
odontal pathogens in a large group of early onset
periodontitis subjects and a matched control group
and found that subjects with generalized aggressive
periodontitis had signicant elevations in both IgG
and IgA antibody titers to P. gingivalis and A. actino-
mycetemcomitans compared to healthy controls.
However, the IgG antibody titers to P. intermedia, C.
rectus, E. corrodens, and F. nucleatum were not sig-
nicantly higher in the early onset periodontitis
group than in the controls. Also, other studies have
shown elevated serum and salivary antibody titers to
A. actinomycetemcomitans in aggressive peri-
odontitis patients compared to controls (65, 108,
127). It has been demonstrated that subjects with ag-
gressive periodontitis who are infected with A. acti-
nomycetemcomitans are capable of producing op-
sonic IgG antibodies which may facilitate neutro-
phil-mediated host defense against this organism
(30).
There is also data suggesting that in some cases
the host may not mount an adequate immune re-
sponse to the periodontal pathogen Bacteroides for-
sythus, and that this could be a mechanism of action
by which this organism may cause attachment loss
(41). However, the data about the role of B. forsythus
in aggressive periodontitis are still incomplete, and
more studies are needed to better understand its role
in periodontal tissue loss.
Genetic factors
A study in twins estimated that 38% to 82% of the
population variance in clinical measures of peri-
odontal diseases might be attributable to genetic
factors (115). More recently, Michalowicz & co-
workers (117) studied 117 pairs of adult twins and
found that, after adjusting for use of dental care and
smoking, the risk for chronic periodontitis is ap-
proximately 50% heritable. They also concluded that
clinical periodontal status was more similar in
monozygotic than in dizygotic twins. Although this
suggests a signicant role for genetic factors in
chronic periodontitis, other data suggest that genetic
factors may play a greater role in the pathogenesis
of periodontal tissue loss in the aggressive forms of
periodontitis (116).
It has long been recognized that severe loss of
periodontal tissue often accompanies certain genetic
disorders such as the PapillonLefe`vre syndrome (47,
76, 176), Downs syndrome (44, 118), congenital neu-
tropenia (88, 135, 169), leukocyte adhesion de-
ciency (126, 173), ChediakHigashi syndrome (58),
and other heritable syndromes (172). Also, a heredi-
tary deciency in membraneglycoproteins involved
in granulocyte adherence has been shown to cause
impaired chemotaxis, reduced phagocytosis, peri-
odontal inammation and tissue loss (162).
An interfamilial pattern of increased susceptibility
to prepubertal forms of periodontal diseases has
been established (28, 143, 156). It has also been illus-
trated that generalized prepupertal periodontitis is
associated with leukocyte adhesion deciency (172)
and other leukocyte abnormalities (22) that cause
abnormal local recruitment of neutrophils and
monocytes and inadequate host immune response.
Autosomal recessive (103) as well as autosomal
dominant (147) modes of inheritance for prepuber-
tal periodontitis have been reported.
A variety of study designs have been used to study
the effect of genetic risk factors in the pathogenesis
of aggressive forms of periodontitis. The disease has
also been shown to have a familial pattern and
proven modes of inheritance (31, 37, 40, 87, 112).
Few early studies had suggested that aggressive (juv-
enile) periodontitis might be inherited as X-linked
dominant disease (112, 156). However, more recent
studies have revealed that it is more likely that this
disease is inherited as an autosomal recessive (36,
101, 142) or autosomal dominant disease (82, 110,
147). It is possible that the inconsistencies are attri-
buted to different methods of diagnosis and classi-
cation of the disease.
Recently, there has been a considerable effort to
investigate the molecular basis of the genetic predis-
position to chronic and aggressive forms of peri-
odontitis, and several gene polymorphisms have
been, or are, under investigation to clarify their role
in the increased susceptibility for these diseases.
Kornman et al. (94) presented data showing that cer-
tain interleukin-1 (IL-1) gene polymorphisms were
associated with increased risk for chronic peri-
odontitis in nonsmoker Caucasian adults. However,
other subsequent studies have shown that other IL-
1 polymorphisms may be of importance in the
pathogenesis of aggressive periodontitis. A study in
70 cases and 70 controls demonstrated that individ-
uals with positive IL-1 genotype were 2.2 times more
likely to have aggressive periodontitis, and 2.6 times
more likely to have localized aggressive periodontitis
compared to IL-1 genotype-negative persons (131).
Furthermore, the study found that smokers who
were also IL-1 genotype-positive were 4.9 times
more likely to have aggressive periodontitis com-
pared to smokers who were genotype-negative.
Diehl et al. (59) used linkage disequilibrium analy-
sis to demonstrate that persons who carried the IL-
215
1 alleles had a high risk for having early onset peri-
odontitis, irrespective of their race (African-Ameri-
can or Caucasian-American) or smoking status. Not
surprisingly, this study also illustrated that the con-
tribution of the IL-1 genetic variation as a risk factor
for early onset periodontitis is not exclusive. On the
other hand, Walker et al. (174) investigated the
prevalence of certain IL-1 gene polymorphisms that
have been shown to be associated with aggressive
periodontitis in other studies, and found that all lo-
calized juvenile periodontitis patients and about
99% of the controls in a group of African-Americans
had these polymorphisms. Based on this nding,
they concluded that this allele occurs frequently
among African-Americans, and therefore it may not
provide predictive information about risk predis-
position for periodontitis.
Hennig et al. (80) investigated the association be-
tween vitamin D receptor gene polymorphism and
the occurrence of early-onset aggressive peri-
odontitis in 69 patients and 72 controls, and found a
statistically signicant association between a higher
prevalence of the less frequent allele (t) in subjects
with the localized form of the disease only (52.5%)
compared to the control group (31.9%). However, the
genotype distribution and the allele frequencies
were not signicantly different between the whole
early onset periodontitis group (the localized and
generalized forms) and the controls. This may sug-
gest that vitamin D receptor polymorphism may play
a role in alveolar bone loss in subjects with localized
aggressive periodontitis only.
The frequency of N-formyl-methyl-leucyl-phenyl-
alanine (fMLP) receptor gene polymorphism has
been compared in various periodontitis classi-
cations, and it was found that a very high percentage
of a group of localized aggressive periodontitis pa-
tients had single-strand conformation polymorphism
patterns compared to age and sex matched controls
(70). Furthermore, DNA sequencing of the amplied
fragments showed that the localized aggressive peri-
odontitis patients consistently had two single nucle-
otide base changes that were not present in the con-
trol subjects. Based on these ndings, Gwinn and co-
investigators (70) concluded that these fMLP receptor
gene polymorphism patterns may cause amino acid
variationand a change inthe structure of the fMLP re-
ceptor in these cells, and that this may affect G-pro-
tein activation and ligand binding, which could lead
to a decreased chemotaxis of neutrophils and an in-
creased predisposition to periodontitis.
Other studies of the role of interleukin-10 gene
polymorphism did not identify a signicant associ-
Albandar & Rams
ation between this and the occurrence of aggressive
periodontitis (81, 90).
Viruses
It has previously been proposed that bacteriophages
in A. actinomycetemcomitans and possibly also in
other periodontal bacteria may enhance the virulence
of these microorganisms, and thus may contribute to
the pathogenesis of aggressive and prepubertal peri-
odontitis and possibly also other forms of destructive
periodontal diseases (134). However, there have been
little data to support this, and so far, ndings from at
least one study (139) have challenged the validity of
this hypothesis. Sandmeier et al. (139) isolated A. acti-
nomycetemcomitans from 68 aggressive and chronic
periodontitis patients, and investigated the presence
of temperate bacteriophage in bacterial isolates, and
correlated this with periodontal status and the
amount of periodontal tissue destruction in these pa-
tients. Using data for the whole study group (aggres-
sive and chronic periodontitis), they found a similar
periodontal status in subjects with phage-carrying or
phage-free A. actinomycetemcomitans. In addition,
whenonly chronic periodontitis subjects wereinvesti-
gated, the pocket depth and attachment loss were sig-
nicantly lower in subjects with phage-carrying than
in phage-free A. actinomycetemcomitans. Based on
these ndings, it was concluded that the presence of
bacteriophages was not correlated with the compo-
sition of the subgingival microora or with the
amount of periodontal tissue loss. Furthermore, it was
inferred that temperate bacteriophages are common,
and it is unlikely that these are associated with a sig-
nicant increase inthe virulence of A. actinomycetem-
comitans.
Slots & Contreras (155) recently put forward a hy-
pothesis that active human cytomegalovirus infec-
tion, and possibly also infections with other herpesvi-
ruses, may be a possible etiological factor involved in
the initiation and progression of aggressive (localized
juvenile) periodontitis and other types of periodontal
diseases including chronic periodontitis and necrot-
izing periodontal diseases. Cytomegalovirus, which is
one of the herpes viruses, is common in many people
and is usually acquired as a primary infection during
childhood. Herpesvirus infections are characterized
by a mild or asymptomatic primary phase followed by
an asymptomatic latent phase interrupted sporadi-
cally by periods of reactivation.
Herpesvirus reactivation often occurs subsequent
to a suppression of the host immune system. Inci-
dents have been reported of cytomegalovirus reacti-
216
vation leading to a severe infection presenting as an
acute periodontal inammation and tissue loss (62).
Studies investigating the presence of human cyto-
megalovirus, Epstein-Barr virus, herpes simplex vi-
rus and human papillomavirus show that there is a
higher prevalence of one or more of these viruses in
periodontitis lesions than in gingivitis (132). Cyto-
megalovirus is also detected more frequently in deep
than in shallow periodontal pockets (52, 160). In ad-
dition, study of the subgingival human cytomegalo-
virus mRNA transcription has detected major capsid
protein transcript in deep, but not shallow, peri-
odontal pockets of adult and aggressive periodontitis
patients, which suggests that active cytomegalovirus
replication can occur in periodontal defects (54). It
has also been suggested that the human periodon-
tium might constitute a site of infection or reservoir
for human herpesviruses (111).
Contreras et al. (55) investigated the presence of
herpesviruses in subgingival sites in 140 subjects ex-
hibiting either periodontitis or gingivitis, and studied
the relationshipbetweenthese andperiodontal status
and subgingival colonization of potential peri-
odontopathic bacteria. Their ndings showed that
Epstein-Barr virus type 1 was positively correlated
withsevere periodontitis (OR5.1) andP. gingivalis (OR
3.4), and with coinfections of P. gingivalis and P. inter-
media (OR 4), P. gingivalis and B. forsythus (OR 3.8),
P. gingivalis and T. denticola (OR 4.2), P. gingivalis, B.
forsythus, and T. denticola (OR 4.1), and P. gingivalis,
P. nigrescens, and T. denticola (OR 3.3). Furthermore,
human cytomegalovirus was positively associated
with severe periodontitis (OR 4.7), and with coinfec-
tions of P. gingivalis and P. nigrescens (OR3.2), P. gingi-
valis, B. forsythus, and P. nigrescens (OR 3.2), and P.
gingivalis, P. nigrescens, and T. denticola (OR 2.6). The
authors concluded that subgingival EBV-1, cytomeg-
alovirus, and coinfections by both viruses are associ-
ated with the subgingival presence of these peri-
odontal pathogens and periodontitis. They also
speculated that herpesviruses may exert peri-
odontopathic potential by decreasing the host re-
sistance against subgingival colonization and multi-
plication of periodontal pathogens. Other ndings
have been reported suggesting a similar role for these
viruses in the pathogenesis of other destructive peri-
odontal diseases including Trisomy 21 periodontitis
(74) and aggressive (localized juvenile) periodontitis
(160).
A key element in this hypothesis is the notion that
herpesviruses are immunosuppressive and that this
may facilitate and promote the establishment and
growth of subgingival periodontal pathogens (155).
However, as discussed earlier in this chapter, sup-
pression of the host immune response due to other
systemic factors is also animportant risk factor for ag-
gressive andchronic periodontitis. Nonetheless, more
studies are required to better understand the possible
role of active human herpesviruses infection as a po-
tential etiological factor in the initiation and pro-
gression of various forms of destructive periodontal
diseases.
Etiological and risk factors of
necrotizing periodontal diseases
Although it is generally recognized that necrotizing
periodontal diseases are infectious diseases, their
etiology is not fully understood, and antigenic chal-
lenge by virulent microorganisms, together with host
immunosuppression, have been associated with the
onset and progression of these diseases (128, 138).
Microbiological and histological studies have shown
the presence of spirochaetes, gram-positive cocci, b-
hemolytic streptococci, Borrelia species, P. gingivalis,
P. intermedia and Candida albicans in diseased sites
(152). In addition, Contreras et al. (53) have shown a
higher presence of human cytomegalovirus, Epstein-
Barr virus and herpes simplex virus in a population of
malnourished Nigerian children aged 314years with
NUG, when compared to a control group with non-
acuteNUG, suggestingapotential rolefor theseorgan-
isms inthe progressionof the disease. Rams et al. (137)
showed that the predominant microora in HIV-
associated periodontitis was similar to that of pro-
gressing periodontitis lesions in systemically healthy
adults, but with higher proportions of yeasts and en-
teric rods.
Systemic diseases such as measles, impaired en-
docrine balance and acquired immunodeciency
syndrome (AIDS), in combination with malnutrition,
can render the host susceptible to the onset of these
diseases. Other factors including poor oral hygiene,
preexisting gingivitis, psychological stress, alcohol
use and smoking have also been reported to predis-
pose an individual to necrotizing periodontal dis-
eases (83). In a survey of Nigerian dental patients,
Taiwo (157) found a strong association between the
occurrence and severity of necrotizing periodontal
diseases and social class.
Conclusions
Four groups of destructive periodontal diseases,
each with distinctive clinical features, occur in
217
children and young people. Periodontitis, when oc-
curring as a manifestation of certain systemic dis-
eases, usually commence before puberty and may
affect the deciduous and the permanent teeth. These
diseases have a clear genetic etiology, although local
factors are responsible for the initiation of the peri-
odontal inammation.
Necrotizing periodontal diseases are associated
with a diminished host resistance to bacterial infec-
tion of periodontal tissues, and this immunosup-
pression may occur due to various environmental
factors such as malnutrition, psychological and
physical stress, poor oral hygiene, alcohol use and
smoking. Necrotizing periodontal diseases are more
common in the poor populations of underdeveloped
countries.
Aggressive periodontitis includes a group of dis-
eases characterized by severe and rapid loss of peri-
odontal tissues that commences at or after the cir-
cumpubertal age. These diseases are caused by
multiple factors, and there is a signicant genetic
predisposition. Local factors also appear to play a
signicant role in the etiopathogenesis of these dis-
eases. These include certain bacterial species, par-
ticularly A. actinomycetemcomitans and P. gingivalis,
and specic genotypes of A. actinomycetemcomitans.
In addition, other bacterial species including T.
denticola, and possibly B. forsythus may also play an
important role. Furthermore, immune defects, poor
oral hygiene, local plaque-retaining factors and
smoking play signicant roles and have been shown
to increase the risk of disease occurrence and pro-
gression. Aggressive periodontitis is more frequent in
older age groups, and in certain race-ethnic groups,
particularly those of African or Hispanic ethnicity.
Chronic periodontitis in young people is much
more prevalent than the other three groups of dis-
eases (21). This is a nonaggressive disease featured
by a more localized and less severe periodontal
tissue loss, and is believed to be similar to chronic
adult periodontitis. Local factors and environmental
risk factors appear to play a major role in the initia-
tion and progression of this disease, with a smaller
role for genetic predisposition. Poor oral hygiene, lo-
cal plaque-retaining factors, and smoking are im-
portant etiological factors.
Recent data show that cigarette smoking in adoles-
cents is increasing. Studies have reported that daily
smoking among high school seniors in the U.S. has
increased from 17% in 1992 to 22% in 1996 (86), and
that high school students who reported smoking in
the preceding month increased from 27.5% in 1991
to 36% in 1997 (43, 165). Given the strong evidence
Albandar & Rams
for smoking as a risk factor in the etiopathogenesis
of various forms of periodontal diseases (20, 92, 164),
the increase in smoking frequency among adoles-
cents is alarming.
There are signicant differences in the prevalence
of periodontitis between demographic subgroups of
young populations. The disparities appear to occur
largely between the poor and the rich, but also be-
tween the various ethnic groups, and by geographic
regions (21). The low level of periodontitis among
young populations in developed countries, particu-
larly in Northern and other West European coun-
tries, may be attributable to the provision of free,
community-based dental health systems. Typically,
these programs provide a means for improving den-
tal health through well-designed disease prevention
and control, and the employment of a systematic ap-
proach of risk identication. Applying this model for
other high-risk groups may be an effective way to
resolve the disparity in the level of disease between
different groups.
References
1. Aass AM, Albandar JM, Aasenden R, Tollefsen T, Gjermo P.
Variation in prevalence of radiographic alveolar bone loss
in subgroups of 14-year-old schoolchildren in Oslo. J Clin
Periodontol 1988: 15: 130133.
2. Agarwal S, Suzuki JB, Piesco NP, Aichelmann-Reidy MB.
Neutrophil function in juvenile periodontitis: induction of
adherence. Oral Microbiol Immunol 1994: 9: 262271.
3. Albandar JM. Prevalence of incipient radiographic peri-
odontal lesions in relation to ethnic background and den-
tal care provisions in young adults. J Clin Periodontol 1989:
16: 625629.
4. Albandar JM, Buischi YA, Barbosa MF. Destructive forms of
periodontal disease in adolescents. A 3-year longitudinal
study. J Periodontol 1991: 62: 370376.
5. Albandar JM. Juvenile periodontitis pattern of pro-
gression and relationship to clinical periodontal par-
ameters. Community Dent Oral Epidemiol 1993: 21: 185
189.
6. Albandar JM, Buischi YAP, Mayer MPA, Axelsson P. Long-
term effect of two preventive programs on the incidence
of plaque and gingivitis in adolescents. J Periodontol 1994:
65: 605610.
7. Albandar JM, Buischi YAP, Axelsson P. Caries lesions and
dental restorations as predisposing factors in the pro-
gression of periodontal diseases in adolescents. J Peri-
odontol 1995: 66: 249254.
8. Albandar JM, Buischi YAP, Oliveira LB, Axelsson P. Lack of
effect of oral hygiene training on periodontal disease pro-
gression during 3 years in adolescents. J Periodontol 1995:
66: 255260.
9. Albandar JM, Brown LJ, Brunelle JA, Le H. Gingival state
and dental calculus in early-onset periodontitis. J Peri-
odontol 1996: 67: 953959.
10. Albandar JM, Brown LJ, Genco RJ, Le H. Clinical classi-
218
cation of early-onset periodontitis in adolescents and
young adults. J Periodontol 1997: 68: 545555.
11. Albandar JM, Brown LJ, Le H. Clinical features of early-
onset periodontitis. J Am Dent Assoc 1997: 128: 13931399.
12. Albandar JM, Brown LJ, Le H. Putative periodontal
pathogens in subgingival plaque of young adults with and
without early-onset periodontitis. J Periodontol 1997: 68:
973981.
13. Albandar JM, Kingman A, Brown LJ, Le H. Gingival in-
ammation and subgingival calculus as determinants of
disease progression in early-onset periodontitis. J Clin
Periodontol 1998: 25: 231237.
14. Albandar JM, Brunelle JA, Kingman A. Destructive peri-
odontal disease in adults 30 years of age and older in the
United States, 19881994. J Periodontol 1999: 70: 1329.
15. 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.
16. Albandar JM, DeNardin AM, Adesanya MR, Diehl SR, Winn
M. Associations between serum antibody levels to peri-
odontal pathogens and early-onset periodontitis. J Peri-
odontol 2001: 72: 14631469.
17. Albandar JM. Periodontal diseases in North America. Peri-
odontol 2000 2002: 29: 3169
18. Albandar JM, Muranga MB, Rams TE. Prevalence of ag-
gressive periodontitis in school attendees in Uganda. J
Clin Periodontol 2002: 29: in press.
19. Albandar JM, DeNardin AM, Adesanya MR, Winn M, Diehl
SR. Associations of serum concentrations of IgG, IgA, IgM
and interleukin-1b with early-onset periodontitis classi-
cation and race. J Clin Periodontol 2002: 29: 421426
20. Albandar JM. Global risk factors and risk indicators for
periodontal diseases. Periodontol 2000 2002: 29: 177206
21. Albandar JM, Tinoco EMB. Global epidemiology of peri-
odontal diseases in children and young persons. Peri-
odontol 2000 2002: 29: 153176
22. Altman LC, Page RC, Vandesteen GE, Dixon LI, Bradford
C. Abnormalities of leukocyte chemotaxis in patients with
various forms of periodontitis. J Periodontal Res 1985: 20:
553563.
23. Armitage GC. Development of a classication system for
periodontal diseases and conditions. Ann Periodontol
1999: 4: 16.
24. Armitage GC, Wu Y, Wang HY, Sorrell J, di Giovine FS, Duff
GW. Low prevalence of a periodontitis-associated interleu-
kin-1 composite genotype in individuals of Chinese heri-
tage. J Periodontol 2000: 71: 164171.
25. Axelsson P, Lindhe J. The effect of a preventive programme
on dental plaque, gingivitis and caries in schoolchildren.
Results after one and two years. J Clin Periodontol 1974:
1: 126138.
26. Axelsson P, Lindhe J. Effect of controlled oral hygiene pro-
cedures on caries and periodontal disease in adults. J Clin
Periodontol 1978: 5: 133151.
27. Axelsson P, Lindhe J, Nystrm B. On the prevention of
caries and periodontal disease. Results of a 15-year longi-
tudinal study in adults. J Clin Periodontol 1991: 18: 182
189.
28. Baab DA, Page RC, Morton T. Studies of a family mani-
festing premature exfoliation of deciduous teeth. J Peri-
odontol 1985: 56: 403409.
29. Baer PN. The case of periodontosis as a clinical entity. J
Periodontol 1971: 42: 516519.
30. Baker PJ, Wilson ME. Opsonic IgG antibody against
Actinobacillus actinomycetemcomitans in localized juven-
ile periodontitis. Oral Microbiol Immunol 1989: 4: 98105.
31. Benjamin SD, Baer PN. Familial patterns of advanced al-
veolar bone loss in adolescents (periodontosis). Peri-
odontics 1967: 5: 8288.
32. Bial JJ, Mellonig JT. Radiographic evaluation of juvenile
periodontitis (periodontosis). J Periodontol 1987: 58: 321
326.
33. Blix IJ, Hars R, Preys HR, Helgeland K. Entrance of Actino-
bacillus actinomycetemcomitans into Hep-2 cells in vitro.
J Periodontol 1992: 63: 723728.
34. Bostrm L, Linder LE, Bergstrm J. Clinical expression of
TNF-a in smoking-associated periodontal disease. J Clin
Periodontol 1998: 25: 767773.
35. Bostrm L, Linder LE, Bergstrm J. Smoking and crevic-
ular uid levels of IL-6 and TNF-a in periodontal disease.
J Clin Periodontol 1999: 26: 352357.
36. Boughman JA, Beaty TH, Yang P, Goodman SB, Wooten
RK, Suzuki JB. Problems of genetic model testing in early
onset periodontitis. J Periodontol 1988: 59: 332337.
37. Boughman JA, Astemborski JA, Suzuki JB. Phenotypic as-
sessment of early onset periodontitis in sibships. J Clin
Periodontol 1992: 19: 233239.
38. Brown LJ, Albandar JM, Brunelle JA, Le H. Early-onset
periodontitis: progression of attachment loss during 6
years. J Periodontol 1996: 67: 968975.
39. Bueno LC, Mayer MP, DiRienzo JM. Relationship between
conversion of localized juvenile periodontitis-susceptible
children from health to disease and Actinobacillus actino-
mycetemcomitans leukotoxin promoter structure. J Peri-
odontol 1998: 69: 9981007.
40. Butler JH. A familial pattern of juvenile periodontitis (peri-
odontosis). J Periodontol 1969: 40: 115118.
41. Califano JV, Gunsolley JC, Schenkein HA, Tew JG. A com-
parison of IgG antibody reactive with Bacteroides forsythus
and Porphyromonas gingivalis in adult and early-onset
periodontitis. J Periodontol 1997: 68: 734738.
42. Califano JV, Schifferle RE, Gunsolley JC, Best AM, Schenk-
ein HA, Tew JG. Antibody reactive with Porphyromonas
gingivalis serotypes K16 in adult and generalized early-
onset periodontitis. J Periodontol 1999: 70: 730735.
43. Centers for Disease Control and Prevention. Tobacco use
among high school students United States, 1997. MMWR
Morb Mortal Wkly Rep 1998: 47: 229233.
44. Cichon P, Crawford L, Grimm WD. Early-onset peri-
odontitis associated with Downs syndrome: clinical inter-
ventional study. Ann Periodontol 1998: 3: 370380.
45. Clerehugh V, Lennon MA. A two-year longitudinal study
of early periodontitis in 14- to 16-year-old schoolchildren.
Community Dent Health 1986: 3: 135141.
46. Clerehugh V, Seymour GJ, Bird PS, Cullinan M, Drucker
DB, Worthington HV. The detection of Actinobacillus acti-
nomycetemcomitans, Porphyromonas gingivalis and Pre-
votella intermedia using an ELISA in an adolescent popu-
lation with early periodontitis. J Clin Periodontol 1997: 24:
5764.
47. Coccia CT, McDonald RE, Mitchell DF. PapillonLefevre
syndrome: precocious periodontosis with palmar-plantar
hyperkeratosis. J Periodontol 1966: 37: 408414.
48. Consensus report: Chronic periodontitis. Ann Periodontol
1999: 4: 38.
49. Consensus report: Aggressive periodontitis. Ann Peri-
odontol 1999: 4: 53.
219
50. Consensus report: Periodontitis as a manifestation of sys-
temic diseases. Ann Periodontol 1999: 4: 64.
51. Consensus report: Necrotizing periodontal diseases. Ann
Periodontol 1999: 4: 78.
52. Contreras A, Slots J. Mammalian viruses in human peri-
odontitis. Oral Microbiol Immunol 1996: 11: 381386.
53. Contreras A, Falkler WA Jr, Enwonwu CO, Idigbe EO, Sav-
age KO, Afolabi MB, Onwujekwe D, Rams TE, Slots J. Hu-
man Herpesviridae in acute necrotizing ulcerative gingi-
vitis in children in Nigeria. Oral Microbiol Immunol 1997:
12: 259265.
54. Contreras A, Slots J. Active cytomegalovirus infection in
human periodontitis. Oral Microbiol Immunol 1998: 13:
225230.
55. Contreras A, Umeda M, Chen C, Bakker I, Morrison JL,
Slots J. Relationship between herpes viruses and adult
periodontitis and periodontopathic bacteria. J Periodontol
1999: 70: 478484.
56. Contreras A, Rusitanonta T, Chen C, Wagner WG, Mich-
alowicz BS, Slots J. Frequency of 530-bp deletion in
Actinobacillus actinomycetemcomitans leukotoxin pro-
moter region. Oral Microbiol Immunol 2000: 15: 338340.
57. Daniel MA, McDonald G, Offenbacher S, Van Dyke TE. De-
fective chemotaxis and calcium response in localized juv-
enile periodontitis neutrophils. J Periodontol 1993: 64:
617621.
58. Delcourt-Debruyne EM, Boutigny HR, Hildebrand HF.
Features of severe periodontal disease in a teenager with
ChediakHigashi syndrome. J Periodontol 2000: 71: 816
824.
59. Diehl SR, Wang Y, Brooks CN, Burmeister JA, Califano JV,
Wang S, Schenkein HA. Linkage disequilibrium of in-
terleukin-1 genetic polymorphisms with early-onset peri-
odontitis. J Periodontol 1999: 70: 418430.
60. DiRienzo JM, Slots J. Genetic approach to the study of epi-
demiology and pathogenesis of Actinobacillus actinomyce-
temcomitans in localized juvenile periodontitis. Arch Oral
Biol 1990: 35 (Suppl.): 79S84S.
61. DiRienzo JM, Slots J, Sixou M, Sol MA, Harmon R, McKay
TL. Specic genetic variants of Actinobacillus actinomyce-
temcomitans correlate with disease and health in a re-
gional population of families with localized juvenile peri-
odontitis. Infect Immun 1994: 62: 30583065.
62. Dodd CL, Winkler JR, Heinic GS, Daniels TE, Yee K,
Greenspan D. Cytomegalovirus infection presenting as
acute periodontal infection in a patient infected with the
human immunodeciency virus. J Clin Periodontol 1993:
20: 282285.
63. Drury TF, Garcia I, Adesanya M. Socioeconomic disparities
in adult oral health in the United States. Ann N Y Acad Sci
1999: 896: 322324.
64. Fives-Taylor PM, Meyer DH, Mintz KP, Brissette C. Viru-
lence factors of Actinobacillus actinomycetemcomitans.
Periodontol 2000 1999: 20: 136167.
65. Genco RJ, Zambon JJ, Murray PA. Serum and gingival uid
antibodies as adjuncts in the diagnosis of Actinobacillus
actinomycetemcomitans-associated periodontal disease. J
66. Genco RJ, Christersson LA, Zambon JJ. Juvenile peri-
odontitis. Int Dent J 1986: 36: 168176.
67. Gjermo P, Bellini HT, Santos VP, Martins JG, Ferracyoli JR.
Prevalence of bone loss in a group of Brazilian teenagers
assessed on bite-wing radiographs. J Clin Periodontol
1984: 11: 104113.
Albandar & Rams
68. Gunsolley JC, Califano JV, Koertge TE, Burmeister JA,
Cooper LC, Schenkein HA. Longitudinal assessment of
early onset periodontitis. J Periodontol 1995: 66:
321328.
69. Gunsolley JC, Pandey JP, Quinn SM, Tew J, Schenkein HA.
The effect of race, smoking and immunoglobulin allotypes
on IgG subclass concentrations. J Periodontal Res 1997: 32:
381387.
70. Gwinn MR, Sharma A, De Nardin E. Single nucleotide poly-
morphism of the N-formyl peptide receptor in localized
juvenile periodontitis. J Periodontol 1999: 70: 11941201.
71. Haffajee AD, Socransky SS. Microbial etiological agents of
destructive periodontal diseases. Periodontol 2000 1994: 5:
78111.
72. Han NM, Xiao XR, Zhang LS, Ri XQ, Zhang JZ, Tong YH,
Yang MR, Xiao ZR. Bacteriological study of juvenile peri-
odontitis in China. J Periodontal Res 1991: 26: 409414.
73. Hanioka T, Tanaka M, Ojima M, Takaya K, Matsumori Y,
Shizukuishi S. Oxygen sufciency in the gingiva of
smokers and non-smokers with periodontal disease. J
Periodontol 2000: 71: 18461851.
74. Hanookai D, Nowzari H, Contreras A, Morrison JL, Slots J.
Herpesviruses and periodontopathic bacteria in Trisomy
21 periodontitis. J Periodontol 2000: 71: 376384.
75. Hart TC, Marazita ML, Schenkein HA, Brooks CN, Gunsol-
ley JG, Diehl SR. No female preponderance in juvenile
periodontitis after correction for ascertainment bias. J
Periodontol 1991: 62: 745749.
76. Hart TC, Hart PS, Bowden DW, Michalec MD, Callison SA,
Walker SJ, Zhang Y, Firatli E. Mutations of the cathepsin C
gene are responsible for PapillonLefevre syndrome. J Med
Genet 1999: 36: 881887.
77. Hashim R, Thomson WM, Pack AR. Smoking in adoles-
cence as a predictor of early loss of periodontal attach-
ment. Community Dent Oral Epidemiol 2001: 29: 130135.
78. Haubek D, Poulsen K, Westergaard J, Dahlen G, Kilian M.
Highly toxic clone of Actinobacillus actinomycetemcomit-
ans in geographically widespread cases of juvenile peri-
odontitis in adolescents of African origin. J Clin Microbiol
1996: 34: 15761578.
79. Haubek D, Ennibi OK, Poulsen K, Poulsen S, Benzarti N,
Kilian M. Early-onset periodontitis in Morocco is associ-
ated with the highly leukotoxic clone of Actinobacillus
actinomycetemcomitans. J Dent Res 2001: 80: 15801583.
80. Hennig BJ, Parkhill JM, Chapple IL, Heasman PA, Taylor JJ.
Association of a vitamin D receptor gene polymorphism
with localized early-onset periodontal diseases. J Peri-
odontol 1999: 70: 10321038.
81. Hennig BJ, Parkhill JM, Chapple IL, Heasman PA, Taylor JJ.
Dinucleotide repeat polymorphism in the interleukin-10
gene promoter (IL-10.G) and genetic susceptibility to early-
onset periodontal disease. Genes Immun 2000: 1: 402404.
82. Hodge PJ, Teague PW, Wright AF, Kinane DF. Clinical and
genetic analysis of a large North European Caucasian fam-
ily affected by early-onset periodontitis. J Dent Res 2000:
79: 857863.
83. Holmstrup P, Westegaard J. HIV-associated periodontal
diseases. In: Lang N, Karring T. Proceedings of the First
European Workshop on Periodontology 1994: 439461.
84. Holt SC, Kesavalu L, Walker S, Genco CA. Virulence factors
of Porphyromonas gingivalis. Periodontol 2000 1999: 20:
168238.
85. Hrmand J, Frandsen A. Juvenile periodontitis localiz-
220
ation of bone loss in relation to age, sex and teeth. J Clin
Periodontol 1979: 6: 407416.
86. Johnston LD, Bachman JG, OMalley PM. Monitoring the
future: questionnaire responses from the nations high
school seniors, 1995. Ann Arbor. Michigan: Survey Re-
search Center. Institute for Social Research. University of
Michigan, 1997.
87. Jorgenson RJ, Levin LS, Hutcherson ST, Salinas CF. Peri-
odontosis in sibs. Oral Surg 1975: 39: 396402.
88. Kamma JJ, Lygidakis NA, Nakou M. Subgingival microora
and treatment in prepubertal periodontitis associated
with chronic idiopathic neutropenia. J Clin Periodontol
1998: 25: 759765.
89. Kinane DF, Cullen CF, Johnston FA, Evans CW. Neutrophil
chemotactic behaviour in patients with early-onset forms
of periodontitis (II). Assessment using the under agarose
technique. J Clin Periodontol 1989: 16: 247251.
90. Kinane DF, Hodge P, Eskdale J, Ellis R, Gallagher G. Analy-
sis of genetic polymorphisms at the interleukin-10 and tu-
mor necrosis factor loci in early-onset periodontitis. J Peri-
odontal Res 1999: 34: 379386.
91. Kinane DF, Mooney J, Ebersole JL. Humoral immune re-
sponse to Actinobacillus actinomycetemcomitans and Por-
phyromonas gingivalis in periodontal disease. Periodontol
2000 1999: 20: 289340.
92. Kinane DF, Chestnutt IG. Smoking and periodontal dis-
ease. Crit Rev Oral Biol Med 2000: 11: 356365.
93. Kinane DF, Podmore M, Ebersole J. Etiopathogenesis of
periodontitis in children and adolescents. Periodontol
2000 2001: 26: 5491.
94. Kornman KS, Crane A, Wang HY, di Giovine FS, New-
man MG, Pirk FW, Wilson TG Jr, Higginbottom FL,
Duff GW. The interleukin-1 genotype as a severity fac-
tor in adult periodontal disease. J Clin Periodontol
1997: 24: 7277.
95. Kronauer E, Borsa G, Lang NP. Prevalence of incipient juv-
enile periodontitis at age 16 years in Switzerland. J Clin
Periodontol 1986: 13: 103108.
96. Lindhe J, Hamp SE, Le H. Plaque induced periodontal
disease in beagle dogs. A 4-year clinical, roentgeno-
graphical and histometrical study. J Periodontal Res 1975:
10: 243255.
97. Locker D, Clarke M, Murray H. Oral health status of Can-
adian-born and immigrant adolescents in North York. On-
tario Community Dent Oral Epidemiol 1998: 26: 177181.
98. Le H, Theilade E, Jensen SB. Experimental gingivitis in
man. J Periodontol 1965: 36: 177187.
99. Le H, Brown LJ. Early onset periodontitis in the United
States of America. J Periodontol 1991: 62: 608616.
100. Loesche WJ. The role of spirochetes in periodontal dis-
ease. Adv Dent Res 1988: 2: 275283.
101. Long JC, Nance WE, Waring P, Burmeister JA, Ranney RR.
Early onset periodontitis: a comparison and evaluation of
two proposed modes of inheritance. Genet Epidemiol
1987: 4: 1324.
102. Lopez NJ, Rios V, Pareja MA, Fernandez O. Prevalence of
juvenile periodontitis in Chile. J Clin Periodontol 1991: 18:
529533.
103. Lopez NJ. Clinical, laboratory, and immunological studies
of a family with a high prevalence of generalized prepu-
bertal and juvenile periodontitis. J Periodontol 1992: 63:
457468.
104. Lopez NJ, Mellado JC, Giglio MS, Leighton GX. Occurrence
of certain bacterial species and morphotypes in juvenile
periodontitis in Chile. J Periodontol 1995: 66: 559567.
105. Lopez NJ, Mellado JC, Leighton GX. Occurrence of Actino-
bacillus actinomycetemcomitans, Porphyromonas gingi-
valis and Prevotella intermedia in juvenile periodontitis. J
Clin Periodontol 1996: 23: 101105.
106. Lopez R, Fernandez O, Jara G, Baelum V. Epidemiology of
clinical attachment loss in Chilean adolescents. J Peri-
odontol 2001: 72: 16661672.
107. Machuca G, Rosales I, Lacalle JR, Machuca C, Bullon P.
Effect of cigarette smoking on periodontal status of
healthy young adults. J Periodontol 2000: 71: 7378.
108. Mandell RL, Ebersole JL, Socransky SS. Clinical immunol-
ogic and microbiologic features of active disease sites in
juvenile periodontitis. J Clin Periodontol 1987: 14: 534
540.
109. Manson JD, Lehner T. Clinical features of juvenile peri-
odontitis (periodontosis). J Periodontol 1974: 45: 636640.
110. Marazita ML, Burmeister JA, Gunsolley JC, Koertge TE,
Lake K, Schenkein HA. Evidence for autosomal dominant
inheritance and race-specic heterogeneity in early-onset
111. Mardirossian A, Contreras A, Navazesh M, Nowzari H,
Slots J. Herpesviruses 6, 7 and 8 in HIV- and non-HIV-
associated periodontitis. J Periodontal Res 2000: 35: 278
284.
112. Melnick M, Shields ED, Bixler D. Periodontosis: a pheno-
typic and genetic analysis. Oral Surg 1976: 42: 3241.
113. Melvin WL, Sandifer JB, Gray JL. The prevalence and sex
ratio of juvenile periodontitis in a young racially mixed
population. J Periodontol 1991: 62: 330334.
114. Meyer DH, Sreenivasan PK, Fives-Taylor PM. Evidence for
invasion of a human oral cell line by Actinobacillus actino-
mycetemcomitans. Infect Immun 1991: 59: 27192726.
115. Michalowicz BS, Aeppli D, Virag JG, Klump DG, Hinrichs
JE, Segal NL, Bouchard TJ, Pihlstrom BL. Periodontal nd-
ings in adult twins. J Periodontol 1991: 62: 293299.
116. Michalowicz BS. Genetic and heritable risk factors in peri-
odontal disease. J Periodontol 1994: 65: 479488.
117. 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
118. Modeer T, Barr M, Dahllof G. Periodontal disease in
children with Downs syndrome. Scand J Dent Res 1990:
98: 228234.
119. Mooney J, Hodge PJ, Kinane DF. Humoral immune re-
sponse in early-onset periodontitis: inuence of smoking.
J Periodontal Res 2001: 36: 227232.
120. Moore WE, Holdeman LV, Cato EP, Smibert RM, Burmeis-
ter JA, Palcanis KG, Ranney RR. Comparative bacteriology
of juvenile periodontitis. Infect Immun 1985: 48: 507519.
121. Moore WEC, Moore LVH. The bacteria of periodontal dis-
eases. Periodontol 2000 1994: 5: 6677.
122. Mullally BH, Breen B, Linden GJ. Smoking and patterns of
bone loss in early-onset periodontitis. J Periodontol 1999:
70: 394401.
123. Nassar MM, Afi O, Deprez RD. The prevalence of local-
ized juvenile periodontitis in Saudi subjects. J Periodontol
1994: 65: 698701.
124. Neely AL. Prevalence of juvenile periodontitis in a circum-
pubertal population. J Clin Periodontol 1992: 19: 367372.
125. Newacheck PW, Hughes DC, Hung YY, Wong S, Stoddard
221
JJ. The unmet health needs of Americas children. Pedi-
atrics 2000: 105: 989997.
126. Niederman R, Westernoff T, Lee C, Mark LL, Kawashima
N, Ullman-Culler M, Dewhirst FE, Paster BJ, Wagner DD,
Mayadas T, Hynes RO, Stashenko P. Infection-mediated
early-onset periodontal disease in P/E-selectin-decient
mice. J Clin Periodontol 2001: 28: 569575.
127. Niemienen K, Kari K, Saxen L. Specic antibodies against
Actinobacillus actinomycetemcomitans in serum and sal-
iva of patients with advanced periodontitis. Scand J Dent
Res 1993: 101: 196201.
128. Novak MJ. Necrotizing ulcerative periodontitis. Ann Peri-
odontol 1999: 4: 7477.
129. Page RC, Sims TJ, Geissler F, Altman LC, Baab DA. Defec-
tive neutrophil and monocyte motility in patients with
early onset periodontitis. Infect Immun 1985: 47: 169175.
130. Page RC, Beatty P, Waldrop TC. Molecular basis for the
functional abnormality in neutrophils from patients with
generalized prepubertal periodontitis. J Periodontal Res
1987: 22: 182183.
131. Parkhill JM, Hennig BJ, Chapple IL, Heasman PA, Taylor
JJ. Association of interleukin-1 gene polymorphisms with
early-onset periodontitis. J Clin Periodontol 2000: 27: 682
689.
132. Parra B, Slots J. Detection of human viruses in periodontal
pockets using polymerase chain reaction. Oral Microbiol
Immunol 1996: 11: 289293.
133. Perry DA, Newman MG. Occurrence of periodontitis in an
urban adolescent population. J Periodontol 1990: 61: 185
188.
134. Preus HR, Olsen I, Gjermo P. Bacteriophage infection a
possible mechanism for increased virulence of bacteria
associated with rapidly destructive periodontitis. Acta
Odontol Scand 1987: 45: 4954.
135. Prichard JF, Ferguson DM, Windmiller J, Hurt WC. Prepu-
bertal periodontitis affecting the deciduous and perma-
nent dentition in a patient with cyclic neutropenia. A case
report and discussion. J Periodontol 1984: 55: 114122.
136. Quinn SM, Zhang JB, Gunsolley JC, Schenkein JG, Schenk-
ein HA, Tew JG. Inuence of smoking and race on im-
munoglobulin G subclass concentrations in early-onset
periodontitis patients. Infect Immun 1996: 64: 25002505.
137. Rams TE, Andriolo M, Feik D, Abel SN, McGivern TM, Slots
J. Microbiological study of HIV-related periodontitis. J
138. Rowland RW. Necrotizing ulcerative gingivitis. Ann Peri-
odontol 1999: 4: 6573.
139. Sandmeier H, van Winkelhoff AJ, Bar K, Ankli E, Maeder
M, Meyer J. Temperate bacteriophages are common
among Actinobacillus actinomycetemcomitans isolates
from periodontal pockets. J Periodontal Res 1995: 30: 418
425.
140. Saxby MS. Juvenile periodontitis: an epidemiological study
in the west Midlands of the United Kingdom. J Clin Peri-
odontol 1987: 14: 594598.
141. Saxen L. Prevalence of juvenile periodontitis in Finland. J
142. Saxen L, Nevanlinna HR. Autosomal recessive inheritance
of juvenile periodontitis: test of a hypothesis. Clin Genet
1984: 25: 332335.
143. Sbordone L, Ramaglia L, Bucci E. Generalized juvenile
periodontitis: report of a familial case followed for 5 years.
J Periodontol 1990: 61: 590596.
Albandar & Rams
144. Schenkein HA, Best AM, Gunsolley JC. Inuence of race
and periodontal clinical status on neutrophil chemotactic
responses. J Periodontal Res 1991: 26: 272275.
145. Schenkein HA, Van Dyke TE. Early-onset periodontitis:
systemic aspects of etiology and pathogenesis. Periodontol
2000 1994: 6: 725.
146. Schenkein HA, Gunsolley JC, Koertge TE, Schenkein JG,
Tew JG. Smoking and its effects on early-onset peri-
odontitis. J Am Dent Assoc 1995: 126: 11071113.
147. Shapira L, Schlesinger M, Bimstein E. Possible autosomal-
dominant inheritance of prepubertal periodontitis in an
extended kindred. J Clin Periodontol 1997: 24: 388393.
148. Shibata K, Warbington ML, Gordon BJ, Kurihara H, Van
Dyke TE. Defective calcium inux factor activity in neutro-
phils from patients with localized juvenile periodontitis. J
Periodontol 2000: 71: 797802.
149. Slots J. The predominant cultivable organisms in juvenile
periodontitis. Scand J Dent Res 1976: 84: 110.
150. Slots J. Subgingival microora in periodontal disease. J
151. Slots J. Bacterial specicity in adult periodontitis A sum-
mary of recent work. J Clin Periodontol 1986: 13: 912917.
152. Slots J, Rams TE. Microbiology of periodontal disease. In:
Slots J, Taubman M. Contemporary oral microbiology and
immunology. St Louis, Mosby 1992: 425443.
153. Slots J. Actinobacillus actinomycetemcomitans and Por-
phyromonas gingivalis in periodontal disease: introduc-
tion. Periodontol 2000 1999: 20: 713.
154. Slots J, Ting M. Actinobacillus actinomycetemcomitans and
Porphyromonas gingivalis in human periodontal disease:
occurrence and treatment. Periodontol 2000 1999: 20: 82
121.
155. Slots J, Contreras A. Herpesviruses: a unifying causative
factor in periodontitis? Oral Microbiol Immunol 2000: 15:
277280.
156. Spektor MD, Vandesteen GE, Page RC. Clinical studies of
one family manifesting rapidly progressive, juvenile and
prepubertal periodontitis. J Periodontol 1985: 56: 93101.
157. Taiwo JO. Effect of social class on the prevalence and se-
verity of necrotising ulcerative gingivitis in Nigerian
children. Afr J Med Med Sci 1996: 25: 357360.
158. Tangada SD, Califano JV, Nakashima K, Quinn SM, Zhang
JB, Gunsolley JC, Schenkein HA, Tew JG. The effect of
smoking on serum IgG2 reactive with Actinobacillus acti-
nomycetemcomitans in early-onset periodontitis patients.
J Periodontol 1997: 68: 842850.
159. Theilade E. The non-specic theory in microbial etiology
of inammatory periodontal diseases. J Clin Periodontol
1986: 13: 905911.
160. Ting M, Contreras A, Slots J. Herpesvirus in localized juv-
enile periodontitis. J Periodontal Res 2000: 35: 1725.
161. Tinoco EMB, Beldi MI, Loureiro CA, Lana M, Campedelli
F, Tinoco NMB, Gjermo P, Preus HR. Localized juvenile
periodontitis and Actinobacillus actinomycetemcomitans
in a Brazilian population. Eur J Oral Sci 1997: 105: 914.
162. Tolo K. Periodontal disease mechanisms in immunocom-
promised patients. J Clin Periodontol 1991: 18: 431435.
222
163. Tomar SL, Asma S. Smoking-attributable periodontitis in
the United States: ndings from NHANES III. National
Health and Nutrition Examination Survey. J Periodontol
2000: 71: 743751.
164. Tonetti MS. Cigarette smoking and periodontal diseases:
etiology and management of disease. Ann Periodontol
1998: 3: 88101.
165. US Department of Health and Human Services. Preventing
tobacco use among young people: a report of the Surgeon
General. Atlanta: Centers for Disease Control and Preven-
tion, National Center for Chronic Disease Prevention and
Health Promotion, Ofce on Smoking and Health, 1994.
166. Umeda M, Chen C, Bakker I, Contreras A, Morrison JL,
Slots J. Risk indicators for harboring periodontal patho-
gens. J Periodontol 1998: 69: 11111118.
167. Van Dyke TE, Schweinebraten M, Cianciola LJ, Offenbach-
er S, Genco RJ. Neutrophil chemotaxis in families with lo-
calized juvenile periodontitis. J Periodontal Res 1985: 20:
503514.
168. Van Dyke TE, Zinney W, Winkel K, Tauq A, Offenbacher
S, Arnold RR. Neutrophil function in localized juvenile
periodontitis. Phagocytosis, superoxide production and
specic granule release. J Periodontol 1986: 57: 703708.
169. van Winkelhoff AJ, Schouten-van Meeteren AY, Baart JA,
Vandenbroucke-Grauls CM. Microbiology of destructive
periodontal disease in adolescent patients with congenital
neutropenia. A report of 3 cases. J Clin Periodontol 2000:
27: 793798.
170. Wagaiyu EG, Wagaiyu CK. Prevalence of juvenile peri-
odontitis in national youth service trainees. East Afr Med
J 1992: 69: 3133.
171. Waldman HB. More children are unable to get dental care
than any other single health service. J Dent Child 1998: 65:
204208.
172. Waldrop TC, Anderson DC, Hallmon WW, Schmalstieg FC,
Jacobs RL. Periodontal manifestations of the heritable
mac-1, lfa1, deciency syndrome. Clinical, histopatho-
logical and molecular characteristics. J Periodontol 1987:
58: 400416.
173. Waldrop TC, Hallmon WW, Mealey BL. Observations of
root surfaces from patients with early-onset periodontitis
and leukocyte adhesion deciency. J Clin Periodontol
1995: 22: 168178.
174. Walker SJ, Van Dyke TE, Rich S, Kornman KS, di Giovine
FS, Hart TC. Genetic polymorphisms of the IL-1a and IL-
1a genes in African-American LJP patients and an African-
American control population. J Periodontol 2000: 71: 723
728.
175. Zambon JJ, Umemoto T, De Nardin E, Nakazawa F, Chris-
tersson LA, Genco RJ. Actinobacillus actinomycetemcomit-
ans in the pathogenesis of human periodontal disease.
Adv Dent Res 1988: 2: 269274.
176. Zhang Y, Lundgren T, Renvert S, Tatakis DN, Firatli E, Uyg-
ur C, Hart PS, Gorry MC, Marks JJ, Hart TC. Evidence of
a founder effect for four cathepsin C gene mutations in
PapillonLefevre syndrome patients. J Med Genet 2001: 38:
96101.

10

Загружено:

Сведения о документе

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

10

Загружено:

Авторское право:

Доступные форматы

Periodontology 2000, Vol.

29, 2002, 207222 Copyright C Blackwell Munksgaard 2002

Вам также может понравиться