J Clin Periodoniol 199S: 22: 628-636 Copyright © Munks-gaard 1995

Printed in Denmark . Atl rights reserved

Clinical periDdontolDgy
ISSN O.W.1-6<J7{i

Factors associated with different A.D.Haffaiee\ S.Drbart\ R.LKent

Jr.2 and S. S. Socransky^
Departments o f ' Periodontology and

responses to periodontal therapy

^Bioslatistics, Forsylh Dental Center, Boston,
MA, USA

Haffajee AD, Dibart S, Kent Jr. RL, Socransky SS: Factors associated with
different responses to periodontal therapy. J Clin Periodontol 1995; 22: 628-636.
© Munksgaard, 1995,

Ahstract, In a study of the efficacy of modified Widman flap surgery and scaling
and root planing accompanied by 1 of 4 systemic adjunctive agents. Augmentin,
tetracycline, ibuprofen or placebo, it was observed that subjects differed in their
response to therapy. The difference was oniy partially accounted for by the
adjunctive agent employed. The purpose ofthe present investigation was to exam-
ine clinical and microbiological features in subjects who showed different levels of
attachment change post-therapy, 40 subjects were subset into 3 groups based on
mean attachment level change post-therapy, 10 poor response subjects showed
mean attachment loss; 19 moderate response subjects showed mean attachment
gain between 0,02-0,5 mm and 11 good response subjects showed a mean gain
of attachment >0,5 mm. Clinical parameters were measured at 6 sites per tooth
both pre- and post-therapy. Microbiological samples were taken from the mesial
aspect of each tooth and evaluated individually for their content of 14 subgingival
taxa using a colony lift method and DNA probes, % of sites colonized by each
species was computed for each subject both pre- and post-therapy. Significant
differences were observed among treatment response groups for mean probing
pocket depth, attachment level and % of sites with plaque pre-therapy. The poor
response subjects had the lowest mean probing pocket depth and attachment
level, but the highest plaque levels. Post-therapy, the poor response group ex-
hibited the greatest degree of gingival inflammation as assessed by gingival
redness and bleeding on probing. Subjeets in the good response group showed
decreases in the % of sites colonized for 9 of 14 test species, whiie subjects in
the poor response group showed an increase in % of sites colonized for 12 species.
The differences in change in % of sites colonized among groups were significant
for B. forsythus and P. gingivcdis. The majority of attachment loss in poor
response subjects occurred at sites with pre-therapy probing pocket depths <4
mm. Subjeets with moderate or good treatment responses had fewer shallow or
moderate sites showing attachment loss and a large proportion of sites in all
probing pocket depth categories showing attachment gain. Sites that lost attach-
ment >:2 mm post-therapy showed a significant increase in cotints of P. interme-
dia, B. forsythus and A. actinomyectemcotnitans b, while sites that gained
attachment showed a deerease in these species. The data indicated that subjects
who showed a good treatment response exhibited a deerease in the level of gingi-
val inflammation and a marked reduction in the % of sites colonized by suspected
periodontal pathogens. In subjects showing a poor treatment response, the leve!
of gingival inflammation was not deereased and levels of periodontal pathogens Key words: periodontal disease; treatment
increased. response; subgingivai plaque
Accepted for pubiication 31 August 1994

In a companion paper (Haffajee et al.
1995), it was shown that subjects with
monitored periodontal disease pro-
gression responded differently to ther-
apy consisting of modified Widman fiap
surgery ahd scahng and root planing
accompanied by one of the following
systemically administered agents, Aug-
mentin, tetracycline, ibuprofen or pla-
eebo. Subjeets receiving either of the
systemicaily administered antibiotics
showed a better clinical response than
subjeets receiving either ibuprofen or
plaeebo. However, some subjects in
each of the four treatment groups re-
sponded poorly to therapy and showed
an overall loss of mean attachment 10
months post therapy. Thus, the purpose

of the present investigation was to
identify sotne of the chnical and micro-
biological factors which were associated
with differences in treatment response
in this group of subjects.
Material and Methods
Subject population
The subject population and clinical
monitoring are the same as described
by Haffajee et al. (1995). 98 subjects
ranging in age from 14-71 years with
prior evidence of periodontitis were se-
iected for study, AU subjects had at least
20 teeth and at least 4 pockets >4 mm
and 4 sites with attachment loss > 3
mm. Subjects who had received anti-
biotics or any form of periodontal ther-
apy in the previous 3 months were ex-
cluded from the study, as well as sub-
jects with any systemic condition which
might have affected the progression or
treatment of periodontitis. No subject
with localized juvenile periodontitis or
rapidly progressive periodontitis was in-
cluded in the sttidy.
Ciinical monitoring
Subjects were clinically monitored every
2 months, for a maximum of 6 months,
for plaque accumulation, overt gingi-
vitis, bleeding on probing, suppuration,
probing pocket depth and probing
attachment leve! at 6 sites per tooth
(mesiobuccal, buccal, distobuccal. dis-
toiinguai, lingua! and mesiolingual) at
all teeth excluding third molars. Prob-
ing pocket depth and attachment level
measurements were made to the nearest
mm using a North Carolina peri-
odontal probe. The tip of this probe is
i 5 mm in length marked at 1 mm inter-
vals with distinguishing marks at 5 mm
intervals. The attachment level meas-
urements were repeated at each visit by
the same examiner and the means of the
pairs of measurements taken at con-
secutive 2-fnonth intervals used to de-
termine disease progression. Changes in
attachment levei were evaluated using
the tolerance method (Haffajee et al.
1983), leading effectively to a decision
rule of >2.5 mm al a site to define a
subject exhibiting "disease activity". 40
of 98 subjects exhibited attachment loss
of >2.5 mm at I or more sites during
one of the 2 months periods and were
randomly assigned to one of 4 treat-
ment groups.
Differences in treatment response 629
a colony lift method and DNA probes.
Calibration of examiners After the removal of stipragingival
One examiner was responsible for tak- plaque, subgingival plaque samples
ing all chnical measurements at all visits were taken with sterile Gracey curettes
for a given subject in order to minimize from the mesial aspect of each tooth in
variability due to inter-examiner differ- each subject at each monitoring visit,
ences. The 2 examiners involved in the both pre- and post-therapy The
chnical assessments of the subjects in samples were p!aced in separate tubes
the study have been performing clinical of pre-reduced anaerobicaiiy steri!ized
measurements outlined above for over 5 Ringer's solution. anaerobica!!y dis-
years. However, at approximately 3 persed, diiuted and p!ated on Tryp-
month intervals cahbration studies were ticase soy b!ood agar (Dzink et a!.
performed on patients with different 1988). After 7 days of anaerobic in-
levels of periodontal destruction. In ad- cubation. t!ie colonies were hfted to Ny-
dition, since replicate attachment level tran iilters (Sch!eicher & SchuelL
and probing pocket depth measure- Keene, NH), Iysed with SDS and
ments were made at each visit (by one NaOH, and contaminating macromol-
examiner), the examiner was provided ecules removed using proteinase K and
with an estimate of his/her reproducibil- chloroform (Gunaratnam et al. 1992}.
ity at each subject visit. After pre-hydridization, the filters were
hybridized with digoxigenin-labeled
The same ciinician performed al! whole chromosomal DNA probes in
measurements ai ail visits for a given 50% formamide at 42X overnight;
subject. The clinician making the clin- washed at high stringency (68°C) and
ical measurements did not perform the the bound probe sought using antibody
therapy on that subject and did not to digoxigenin-conjugated to alkaline
know the nature of the adjunctive phosphatase (Boehringer Mannheim,
agents employed, i.e., was "blinded" to Indianapolis, IN). Purple colored colo-
the nature of the treatment procedures nies were revealed using nitro bltie tetra-
employed. Similarly the subject did not zo!ium - 5 - bromo -4 - chloro - 3 - indolyl-
know the nature of the systemicaily ad- phosphate (NBT-BCIP) (Boehringer
ministered agent he or she was taking. Mannheim, Indianapohs, IN) as the
substrate. Positive and negative contro!
filters for each probe were included in
Treatment
every run. The taxa examined included
Treatment consisted of modified Wid- the suspected periodontal pathogens;
man flap surgery at active sites and at Porphyromonas gingivalis. Prevotella in-
sites with probing pocket depths >4 termedia, Prevotetla nigrescens, Bucler-
mm and subgingival sca!ing and root oides forsythus, Aciitiohacillus actuto-
pianing at a!! other sites. The 4 quad- mycetemconiitans serotypes a and b.
rants in each subject were treated at ap- Campytohacter rectus, Fusohacterium
proximately !0 day intervals so that nudeatum ss viticcntii, Peptostreptoe-
treatment was coihpleted in 30 days. oceiis micros and Streptococcus inter-
Subjects also received one of the follow- medius, as wel! as the suspected benefi-
ing systemically administered agents, eia! species Capnocyiophaga ochracea,
Augmentin (3x250 mg amoxicilhn with Streptocoecus oralis. Streptococcus san-
125 mg clavuianic acid/day), tetracy- guis and Veilionella parvuta. Microbio-
chne (3x250 mg/day), ibuprofen iogicai data were avai!ab!e from 29 sub-
(3X400 mg/day) or a placebo (3x250 jects both pre- and post-therapy. Thus,
mg sucrose/day) for the 30 days of ac- ana!yses of the mierobio!ogiea! data
tive treatment. Subjects were also asked and ana!yses examining the reiationship
to rinse twice daily with 0.12% chlor- between clinical and microbiological
hexidine during the treatment phase. In findings used data from these 29 sub-
addition, subjects received subgingival jects on!y A total number of 711 plaque
scahng and root planing every 3 months samples were evaluated at the visit im-
for one year and were re-evaluated clin- mediateiy prior to therapy and at 10
ica!!y 6 to 8 weeks and at approximateiy months post therapy.
!0 (±4) months after completion of the
surgica! and chemotherapeutic phase.
Statistical analyses
Microbiological assessment Subjects were divided into 3 groups
based on their mean attachment change
Total counts and counts of selected sub-
gingival species were determined using from pre-therapy to iO months post
 630 Haffajee et al.

Mean —; r data (Fig. 1) suggested that these values

0.34
SD
•Q represented clinically distinct groupings
0.65
"Gain" in that 10 subjects showed mean attach-
ment loss post-therapy, and 11 subjects
1.45 O
showed a mean gain of attachment
Mean AL o >0.5 mm post-therapy. An average gain
change o in attachment of >0,5 mm represented
(mm) 0 a good response to therapy, considering
0° this value was an average computed at
0.70 - o
oo 168 sites, many of which did not have
0000000°°°°
periodontal attachment loss or deep
oo pockets and thus could tiot show any
improvement after therapy,
—0.05 -
Chnical and microbiological par-
ameters were averaged over sites within
Loss a subject and then averaged across sub-
jects in each of the three treatment re-
-0.80 -
sponse groups. Differences among
Subject groups were sought using the Kruskal-
Fig. I, Plot of ihe mean attachment level change 10 months post-therapy in 40 stibjects who Waihs test. Clinical daia were available
received scaling, root planing and modified Widman flap surgery together with one of systcm- from 6 sites per tooth for up to 28 teeth
icaliy administered Augmentin, tetraeycline, ibuprofen or placebo. Subjects are arranged from in each subject, while microbiological
left to right in ascending order of attachment level change. Each circle represents the mean data were availabie for up to 28 sites in
attachment level change for up to 168 sites for eaeh subject. The unshaded area depicts the each subject. Microbiological data were
11 subjects whose mean attachment level change post-therapy was >0,5 mm. The darkest expressed for each subject as % of sites
shaded area depicts the 10 subjects who showed a mean loss of attachment post-therapy. The colonized by each of the test species al
remaining 19 subjects showed attachment level gain ranging from 0.02 mm to 0.5 mm. levels >I0'', Regression analyses related
mean change in attachment level post-
therapy in a subject to the change in
percent of sites colonized by each ofthe
lest species.
2.0-
The change in the counts of the test
species at sites exhibiting loss ^ 2 mm,
gain > 2 mm or changes between these
"GAIN" values (no change) in attachment level
were computed by averaging the species
counts for each site category within a
subject and then averaging across sub-
0.5- jects.
ATTACHMENT
LEVEL CHANGE
In order to compare the number of
(MM) 0.0 pathogens present in subjects in each
treatment response group, the mean
-0.2 number of pathogens at a site for a sub-
ject was computed. The number of in-
stances that any one of the 8 pathogens
LOSS (listed above) was detected was totalled
-1.0
for a subjecl and divided by the number
PLACEBO TETRACYCLINE of sites sampled (up to 28). The mean
iBUPROFEN AUGMENTIN values for each subject were then aver-
Fig. 2, Plot ofthe mean attachment level change 10 months post-therapy in subjects grouped aged across subjects within each treat-
according to their adjunetive systemic agent. Each circle represents the mean attachment leve! ment response group both pre- and
change for up to 168 sites for each subject. The mean and standard error of the mean are post-therapy.
indicated for eaeh treatment group. The shading is as described for Fig, j .

therapy, A poor treatment response
group consisted of 10 subjects who
showed mean attachment level loss
post-therapy. A second group of 19 sub-
jects showed mean attachment level
gain between 0.02-0,5 mm post-therapy
and were designated as a moderate
treatment response group. The good
treatment response group consisted of
11 subjects each of whom showed mean
attachment level gain of >0.5 mm post
therapy.
The initial grouping of the subjects
was based on the upper and lower quar-
tile values for mean attachment level
change post-therapy. Inspection of the
Results
Differences in clinical parameters among
subjects in the 3 treatment response
groups
Subjects differed in the mean attach-
ment levei change from pre- to post-
therapy. Fig. 1 presents these data with
subjects plotted from the worst to the
best treatment response. 10 of 40 sub-
 Differences in treatment response 631

Tahh J Mean (+SD) clinical characlcristics of subjects who showed poor, moderate or good responses to one of 4 periodontal therapies
Pre-therapy Post-therapy Change

poor moderate good poor moderate good poor moderate good

N subjeeis 10 19 10 19 10 19 11
age (years) 48±9 47±12
no, missing teeth 3-3±2,8 2.2±2.3 3,1±2,1
% males 70 47 64
mean pocket depth (mm) 3,5±0-4 3,7±0,5 4,2±0,6 3,3±0.5 3,^±0,6 2,9±0,4 0,2+0.5 0,5+0.3 1.3 ±0.4
mean attachment level (mm) 3,l±0.7 3,7±1,1 4-4±l.3 3,5±0,8 3,4±1,1 3,2±l,3 -0,4+0,2 0,3+0,1 l,2±0,6

% sites with:
plaque K5±20 73±21 58±26 79±29 67±25 62±37 6 + 36 6=27 -4±26
gingiva! redness 73±22 66±26 65±35 79: 60 ±28 45 ±31 -6+37 6+30 20 ±27
bleeding on probing 47±38 31 ±29 32±26 50: 24 ±30 25 ±38 - 3 ±23 7±15 7±32
suppuration l,2±2,5 2,7±5,2 4,3±5,3 0,l±0,2 0.6±l,4 0,8±1.4 1,1 ±2,3 2.1 ±4,8 3.4±5.5
poeket depth <4 mm 63±12 58±16 44±12 67±17 7O£16 80±i3 -4±11 -36±I5
pocket depth 4-6 mm 34+14 29±I6 26±Ii 18±11 0+9 8±11 26 ±20
29±11 44±13
pocket depth >6 mm 8±4 8±7 12±10 4±3 4±6 2±3 4±6 5+5 10±10
attachment level <4 mm 66±18 55±25 42±25 57±21 62 ±25 64±27 9±5 -6=7 -22±19
attachment level 4-6 mm 27±)6 33±19 40±20 34±17 29±I8 28±18 -7±3 3±7 12±22
attachment level >6 mm 7±5 12±11 18±16 9±5 9±IO 8±12 -2-5 3±2 9±6

Differences among treatmem response groups significant al ;?<0,05

jects showed an overall meat] loss of
attachment 10 months post therapy,
while 11 subjects showed a mean "gain''
of attachment >0.5 mm. Fig, 2 presents
Ihe mean attachment level change 10
months post therapy in each of the 4
ti-eatment groups. While subjects in the
groups receiving antibiotics showed a
greater increase in mean attachment
level post-therapy, there were subjects in
each group showing mean loss of
attachment after therapy.
Table 1 presents the clinical charac-
teristics immediately prior to and 10
months post-therapy, as well as the
change in these parameters in the sub-
jects grouped according to mean
attachment level change post therapy.
The tirne from pre-therapy to post-ther-
apy did not differ among groups. The
majority of parameters examined were
not different pre-therapy among
groups. However, the subjects in the
good treatment response group on aver-
age had significantly deeper pockets
and more attachment loss before treat-
ment than subjects in the other two
groups, while the poor response sub-
jects had on average significantly more
sites haboring plaque, 10 months post-
therapy, the good response subjects had
significantly shallower pockets and less
gingivai redness than subjects in the
other two groups, while both rnoderate
and good response subjects had signifi-
cantly less bleeding on probing. As ex-
pected, the good response subjects
showed significantly more reduction in
mean probing poeket depth and greater
improvement in mean attachment level, ject in the 3 treatment response groups
whieh is also refiected in the change in (Fig, 3), Although there is a clear as-
the proportion of sites with different sociation between pre-treatment mean
probing poeket depths and attachment attachment level and a subject's change
level. In addition, these subjects showed in attachment level in response to treat-
a substantial deerease in the pereent of ment, subjects with iow mean attach-
sites with gingival redness. ment levels pre-therapy could be ob-
The daia of Table 1 indicated that the served in each treatment group indi-
poor treatment response subjects had cating that tiie efficacy of therapy was
on average less mean attachment loss not solely dependent on the pre-treat-
pre-therapy than subjects in the other ment attachment level.
groups. This suggested that individuals
with a low pre-therapy attachment level
were likely to show attachment loss as Differences in microbiological parameters
among subjects in the three treatment
a resuit of the therapies employed. In
response groups
order to examine this further, changes
in mean attachment ievei from pre- to Figs. 4, 5 present the mean % of sites
post-therapy were plotted for each sub- colonized by eaeh of the test speeies pre-
° Mean pre-therapy attachment level
" Mean post-therapy attachment level
MEAN AL
(mm)
Poor Moderate Good
TREATMENT RESPONSE
Fig. 3. Plot of the mean pre- and post therapy attachment levels for each subject m the 3 treat-
ment response groups. The me!iii±SEM are presented for each group both pre- and post-
therapy.
 632 Haffajee et al.

PRE-THERAPY crease in 9 of the 14 test species. The de-

60 creases for these species was more
% SITES o Good treatment response marked than the decreases shown by
Good subjects exhibiting a moderate or poor
COLONIZED 0 Moderate treatment response
treatment response. In contrast, subjects
• Poor treatment response
45 H showing a poor clinical response to treat-
ment on average showed an increase in
the percent of sites colonized by 12 of the
Good
test species. The biggest mean change for
30- any species was the mean increase of F.
nuctealum ss vincentii in the poor re-
sponse subjects. One of the more striking
features of the Fig. is the marked de-
15- crease of B. forsythus, P. ititermedia. P.
nigreseens, A. aetinomycetemcomitans
serotype a and P. micros in the good re-
sponse group coupled with the clear in-
crease in the % of sites colonized by these
species in the poor response subjects.
Pg Pi Pn Bf Fn Cr Aab Aaa Pm Si Vp Ss So Co
Some of these changes are presented in
Fig. 4. Bacterial profiles of ihe mean % of sites cobnized for 14 subgingival species in subjects more detail in Fig, 7 where the relation-
in the three treatment response groups pre-therapy. Each circle represents the mean % of sites ship between mean attachment level
coionized by a given species in the indicated treatment response group.
change post-therapy and the change in
percent of sites colonized for P. gingi-
valis, P. intermedia, P. nigrescens and B.
POST-THERAPY forsythus is presented. There was a sig-
60 nificant correlation between a subject's
mean change of attachment and his or
% SITES o Good treatment response
her increase or decrease in the percent of
COLONIZED ® Moderate treatment response sites colonized by P. intermedia and B.
45-1 • Poor treatment response forsythus.

Since the strongest assoeiation be-

Poor
30-
15-
Good
0
Pg Pi Pn Bf
Fig. 5. Bacterial profiles of the mean % of siies colonized for 14 subgingival species in subjects
in the three treatment response groups post-therapy. Each circle represents the mean % of
sites colonized by a given species in the indicated treatment response group.
and post-therapy in the three treatment
response groups. There were no signifi-
cant differences among treatment re-
sponse groups for any species either pre-
or post-therapy. However, the subjects
who showed a good treatment response
had the highest level of the tested species
pre-therapy and the iowest level of the
tested species post-therapy. The mean
number of suspected pathogens at a site
pre- and post-therapy for poor response
subjects was 1.8+0.24 and 2,5+0.4. In
contrast the mean ntimber of suspected
pathogens per site in good response sub-
Poor
Fn Cr Aab Aaa Pm Si Vp Ss So Co
jects was 2.4+0,5 pre-therapy and
L8±0.4 post-therapy. There was htlle
differenee in moderate response subjects
with pre- and post-therapy values of
L8±0,2and].6±0.3,
There were significant differences
among treatment response groups for
some of the speeies in the amount of
change in percent of sites colonized. Fig,
6 presents the change in % of sites colon-
ized for the 14 species identified using
DNA probes in the three treatment re-
sponse groups. Subjects exhibiting the
best treatment response exhibited a de-
tween attachment change and change in
percent of sites colonized was seen for B.
forsythu.s, it was of interest to examine
this relationship in the 3 treatment re-
sponse groups (Fig, 8), Four of 8 poor
responding subjects showed an increase
in the proportion of sites colonized by B.
forsythus, 3 of 13 moderate response
subjects and oniy i of 7 good response
subjects.
Other factors were evaluated that
might have impacted on treatment re-
sponse. For example, 3 of 10 poor re-
sponse subjects, 2 of !9 moderate re-
sponse subjects and 1 of 11 good re-
sponse subjects were current smokers.
These limited data were not statistically
significantly different, but there was a
suggestion that smokers might respond
less well to therapy. There was also no
significant difference among treatment
response groups in terms of age or
gender.
Differences between sites showing a poor
and good treatment response
Attachment level change at sites with
pre-therapy probing pocket depths <4,
4—6 and >6 mm in the three treatment
response groups were examined (Fig.
 Differences in treatment response 633

30.0 n 9}, The data indicate that the mean loss

Poor response group(N = 9)
that occurred \n the poor response
Moderate response group (N = 13)
group was primarily due to losses at
Good response group (N = 7) sites in the <4 and 4-6 mm categories.
INCREASE
17.5 - The moderate response group showed
losses at sites in the <4 mm category
and to a lesser extent at 4-6 mm sites.
These losses were offset by gains pri-
marily at sites with probing pocket
5.0 -
depths > 3 mm pre-therapy. The good
CHANGE IN
% SITES
response subjects showed a small pro-
COLONIZED portion of sites that lost >2 lmn, but a
large proportion of sites with attach-
Co
-7.5 -
Cr ment gain in all probing pockei depth
categories. When sites were subset on
DECREASE the basis of pre-therapy attachment
Bf"
level, instead of probing pocket depth,
-20.0 J in the three treatment response groups,
Fig. 6. Bar plot of the change in mean % of siles colonized by 14 subgingival taxa at peri- a similar distribution of attachment
odontal siLcs in subjects in the three treatment response groups. The groups are distinguished level change was observed.
by the shading of the bars. Bars above ihc horizontal axis represent an increase in % of sites 38 microbiologicaliy-sampled sites in
eolonized post-therapy while bars below the axis represent a decrease in % of sites colonized. 15 subjects showed attachment loss >2
The species evaluated were: Pg=P, gingivalis. Bf~B. forsythus, Vp^V. parvula, Pi=P. inter-
mm 10 months post-therapy, while 104
media, Pn = P. nigreseens, Aaa=A. aetinomycetemcomitans serotype a, Pm=P. micros, Ss=S.
sanguis. Si=S. intermedius, Fn=F. nueleatum, Aab = A. aetinomyeetcmcomitans serotype b.
sites in 23 subjects showed attachment
So=S. oralis, Cr=C- rectus, Co=C. ochraeea. Differences among groups were evaluated using gain s 2 mm. The mean counts for each
the Kruskal-Wallis test (* /i<0,05, ** /)<0,01). species al sites that showed loss, gain or
no change were computed in each sub-
ject and then averaged across subjects.
The resuhing bacteriai profiles (Fig. 10)
indicated that sites that lost attachment
P. intermedia tended to show an increase in counts of
P. gingivaiis
r = -0.35 r =-0.37 most ofthe species tested, while sites that
Q [ r(s) = -0.42 oj r{s)=-0.27 gained attachment tended to show a de-
MEAN AL o
1 - crease in most species. Change in mi-
CHANGE
crobial counts differed significantly at
{mm)
sites that showed attachment gain or loss
0- >2 mm or change less than this value (no
o "-^
change) for P. intermedia. A. actino-
O 1
-1 - mycetemcomitans serotype b and B. for-
sythus. In each instance the species in-
creased at sites which lost attachment
2 1 and decreased at sites that showed a de-
crease in probeable attachment level
P. nigreseens B. forsythus post-therapy.
r=-0.36 j r =-0.49
r(s) =-0.37 o r(s) =-0.51
'Gain" ! o
O 1 Discussion
O 1
*•*.. 1
The resuits of numerous studies evalu-
ating different therapeutic modalities
and the efficacy of therapy obtained in
periodontal practice indicate that not
Loss all subjects respond equally well to peri-
odontal therapy. For example, although
i the results o^ the study by Haffajee et
-50 -25 0 -50 -25 25 50 ai. (1995) suggested that the adjunctive
Decrease use of antibiotics improved the clinical
CHANGE fN % SITES COLONIZED outcome of therapy, some subjects in
Fig. 7, Scatter plots of the change in % of sites eoionized by 4 subgingivai species versus the each of the treatment groups showed
mean attachment level change in the subject post-therapy, Eaeh eirele represents the mean attachment loss post-therapy. Thus, the
vaiues of attachment level change and change in % of sites colonized by the indicated species critical question is what is different
for each subjeet. The horizontal and vertical dashed lines represent no change. The solid about patients who respond well or
diagonal lines represent the regression lines fit to the data. The Pearson product moment poorly to periodontal therapy?
correlation coeffieients (r) and the Spearman rank eorrelation coefficients (r{s)] are presented
for eaeh plot. A number of factors which affect the
 634 Haffajee et al.

36 deed, the average proportion of sites

0
Increase with plaque in all three treatment groups
0; was high both pre- and post-therapy.
This suggests that supragingival plaque
21- " 0
Change in % levels may have had little bearing on the
sites colonized G therapeutic outcome in these subjects.
by However, it is also likely that daily fluc-
B. forsythus o
6- O tuations in plaque levels occurred mak-
0 ing this a somewhat less reliable par-
o ameter. In addition, the method of as-
o sessment could not distinguish day old
o T
Q plaque from plaque that has been pres-
O
OT ent for weeks. In contrast the proportion
Decrease of sites showing gingival redness or
OX bleeding on probing pre-therapy was
O
-24 R similar among groups. However, treat-
ment decreased the level of infiammation
Poor Moderate Good
and bleeding especially in the good re-
Fig. 8. Point of the change in % of sites colonized by B. forsythm in subjects in the 3 treatment sponse subjects while these parameters
response groups. Each circle represents the change in Vi, of sites colonized by B. forsythus for
worsened post-therapy in the poor re-
each subject. The mean and SEM are indicated for each group. The horizontal line represents
no change. sponse subjects. This suggests that re-
ducing inflammation may be an import-
Moderate response
ant component in the successful treat-
% sites P"'"" response Good response
ment of periodontal diseases.

The level of periodontal destruction in

<4 4-6 >6
Pre-treatment pocket depth
Change < 2 mm
Loss > 2 mm
Fig. 9. Stacked bar chart of the % of sites that showed attachment level change of >2 mm
post therapy at sites with different pre-therapy probing pocket depths in the subjects in the
three treatment response groups. The numbers over the bars represent the number of sites in
each pre-treatment probing pocket depth category.
hosi as a whole have been suggested
that might impact on periodontal thera-
peutic outcotne. These include the
medical status of the patient, certain
habits such as smoking and unknown
host susceptibility factors to name a
few. The importance of the medical sta-
tus of the subjects in affecting the re-
sponse to therapy could not be evalu-
ated in the present investigation, since
subjects were excluded who had known
medicai conditions. However, the pres-
ent investigation suggested that the age
or gender of the subject was not as-
sociated with therapeutic outcome.
Further, cigarette smoking, was not as-
sociated with a poor treatment re-
784
CI7
Gain > 2 mm
sponse, although only 6 of the subjects
in the study were current smokers.
A number of local factors have also
been suggested that may impact on peri-
odontal therapy. For example, some
studies have suggested that lack of an ap-
propriate ievei of orai hygiene post-ther-
apy may reduce the success of therapy
(Lindhe & Nyman 1975, Rosling et al.
1976). The poor response subjects in the
current study had significantly more
plaque than the subjects in the other two
groups pre-therapy. Treatment had little
long-term effect on the plaque levels in
any of the groups and the difference
among groups was still evident post-
therapy, aithough not significant. In-
a subject prior to therapy could affect
therapeutic outcome. On the one hand,
a subject with extensive attachment loss
might be expected to be more difficult to
treat simply because there is more dis-
ease to treat. Alternatively, it might be
suggested that a subject with more dis-
ease would show the best treatment re-
sponse, because there is more potential
for attachment gain. In general, the lat-
ter hypothesis was supported in this
. study, since before therapy the good re-
sponse subjects on average had the most
mean attachment ioss while the poor re-
sponse subjects exhibited the least mean
attachment loss. When interpreting such
data one must bear in mind "'ceiiing ef-
fects". Good response subjects in this
study gained on average 0.5 to 2.1 mm of
attachment post-therapy (average 1.2
mm). Such gains would be unlikely in
subjects whose pre-therapy mean attach-
ment level was <2.5 mm. This is particu-
larly true given the recognition that shal-
iow sites tend to lose attachment post-
therapy, while deeper sites are more
likely to exhibit marked attachment level
gain. Nonetheless, despite these recog-
nitions, subjects with relatively little
attachment loss pre-therapy were found
in each of the treatment response
groups.
Mechanical therapy often results in
the loss of attachment at shallow sites
(Knowles et al. 1979, Pihlstrom et ai.
1981, Lindhe et al. 1982). Examination
of the treatment response at sites with
different initial probing pocket depths in

Increase
Loss > 1.5
Counts
Gain > 1.5
-3*
Decrease
Pg Pi Pn Fn Cr Aab Bf
Fig, JO. Mean bacterial coonts at sites which lost or gained attachmein or did not change post-
therapy. The sites used in the analyses were confined to those at which microbioiogical samples
were taken both pre- and post-lhcrapy. Counts at sites that lost >2 mm or gained s 2 mm or
changed less than these values were averaged within a subjecl and averaged across subjects. Each
circle represents the mean count for a species for one of the three treatment response groups.
The * indicate species that differed significantly ai;!<0,05 using the Kruskal-Wallis test.
all subjects in the three response groups
supported this notion. However, the pro-
portion of shallow and moderate sites
that lost attachment was highest in poor
response subjects. Thus, loss at shallow
sites in large part accounted for the
mean loss of attachment in this group of
subjects. Conversely, moderate and good
response subjects had relatively few sites
showing attachment loss in any probing
pocket depth category. The difference
between moderate and good response
subjects appeared to be due lo greater
attachment gain at all probing pocket
depth categories in the good treatment
response group. In contrast, a poor
treatment response was due to an in-
ability to control disease progression at
shallow sites coupled with the failure to
achieve attachment gain at deep siles.
Since periodontal diseases are infec-
tions caused by a select group of subgin-
gival species, the most important factor
in determining the success of peri-
odontal therapy would be the nature of
the subject's microbiota and the effect
that treatment has on the subgingival
microbial complex. The results of the
present study support the notion that a
decrease in the level of periodontal
pathogens is accompanied by a good
clinical response to therapy; a finding in
accord with numerous other studies (for
review, see Haffajee & Socransky
(1994)). Pre-therapy the good response
subjects had more sites colonized by the
majority of periodontal pathogens
Vp Pm Si Ss So Co Aaa
evaluated than subjects in the other re-
sponse groups. After therapy the pro-
portion of infected sites was decreased,
the most dramatic decreases occurring in
the percent of sites colonized by B. for-
svlhus or P. gingivalis. In contrast, the
poor response subjects exhibited the
greatest prevalence of all the suspected
pathogens evaluated post-therapy and
in most instances, except for P, gingi-
valis, this reflected an increase in the per-
cent of sites colonized.
The actual change in percent of sites
colonized pre- and post-therapy was
presented in Fig, 6 and for some species
this change was impressive. However,
from a therapeutic standpoint, it is
worth examining the percent reduction
in the number of sites colonized for the
different species tested. For example, B.
forsvthus was found on average at 30%
(or about 9 sites per subject) in the good
response subjects pre-therapy and at
15% (or about 4 sites) post-therapy.
This change ot \5% translates to a 5O%o
reduction in the number of sites colon-
ized after treatment. A similar compu-
tation in the poor response subjects in-
dicates that there was an increase of
27% in the number of sites colonized by
B. forsythus. Thus, it appears that suc-
cessful periodonta] therapy is ac-
companied by a decrease in the preva-
lence of certain periodontal pathogens.
Failure to decrease the pathogenic load
is consistent with a less favorable treat-
ment response.
Differences in irealment response 635
The present investigation involved a
post-hoc analysis of therapeutic out-
comes for subjects randomized to treat-
ment with different adjunctive agents in
an effort to identify clinical and es-
pecially microbial factors associated
with poor, moderate and good re-
sponses to treatment regardless of mo-
dality. Despite limitations due to
sample size (affecting statistical power),
and the issue of multiple comparisons,
several suggestive findings emerged.
Successfully treated subjects were char-
acterized by reduced inflammation and
bleeding and by generally reduced levels
of periodontai species, particularly pre-
sumptive pathogens. Subjects with poor
treatment responses exhibited disease
progression, primarily at shallow sites,
few sites gaining attachment and in-
creased levels of most species monitored
after treatment. The fact that 10 of 11
subjects with good responses and only
3 of 10 subjects with poor responses re-
ceived antimicrobial therapy serves to
underscore the association between re-
duced pathogen levels and successful
treatment outcomes. Thus, some of the
variability observed in treatment re-
sponses may be due to our inability to
select and administer therapies that are
appropriate for the control of the sub-
gingival microbiota in patients with dif-
ferent infections.
Acknowledgments
This work was supported in part by re-
search grant DE-04881 from the Na-
tional Institute of Dental Research,
USA.
Zusammenfassung
Fakloren. die mi! uiUerschiedlichen Reaktio-
nen iiuf eine Parodunialhehandlung verbunden
sind
in einer Studie uber die Wirksamkeit der mo-
difizierten Widman-Lappenoperation und
von Scaling und Wurzelgiiittung in Verbin-
dung mit einem der vier Adjuvantien, Aug-
menian, Tetracyclin, Ibuprofen und Plazebo
wurde beobachtet. daB die Personen sich in
ihrer Reaktion auf die Therapie unterschei-
den, Der Unterschied konnie nur teilweise
durch das eine gesetzte Medikament erklart
werden. Der Zweck der voriiegenden Studie
was es, die klinischeii und mikrobiologischen
Merkmale von Personen zu untersuchen. die
nach der Therapie unterschiedliche AusinaBc
von Attachmentveranderungen zeigten, Auf
der Grundlage der mittieren Attachmentver-
anderung nach der Therapie wurden 40 Per-
sonen in 3 Gruppen aufgeteilt. iO Personen
mit schlechter Reaklion zeigten einen mittle-
 636 Haffajee et al.
rcn Auachmentverlust; 19 Personen mit einer
maBigen Reaktion zeigten einen mittleren At-
tachmentgewinn von 0,02-0,5 mm und 11
Personen mit einer guten Reaktion zeigten ei-
nen initlleren Attachmentgewinn "von >0,5
mm, Sowohl vor als auch naeh der Therapie
wnrden die klinischen Parameter an 6 Fla-
chen pro Zahn gemessen, Mittels Kolonie-
Lift-Methode und DNA-Sonden wurden die
mikrobiologischen Proben. die von den Me-
siaiflachen jedes Zahnes entnommen wurden,
individuell auf ihren Gehalt von 14 subgingi-
valen Taxa hin beurteilt. Fur jede Person
wurden vor und nach der Therapie von jeder
Spezies die Prozentsatze von Taschen, die ko-
lonisiert wurden, berechnet. Die Personen
mit schlechler Reaktion zeigten die niedrig-
sten mittleren Sondierungstiefen und das
niedrigste klinische Attachmentniveau, aber
die hochsten Plaquewerte, Nach der Therapie
zeigte die Gruppe entspreehend der Beurtei-
lung der Gingivaroiung und Sondierungsblu-
tung das hochste Ausmafi an Gingivaentziin-
dnng. Personen mit der guten Reaktion zeig-
ten cine Reduktion der Prozentsatze von
Taschen, die mit 9 der 14 Testspezies koloni-
siert waren, wahrend Personen aus der Grup-
pe mit der schlechtestcn Reaktion eine Zu-
nahme der Prozenlsatzc von Tasehen, die mit
12 Testspezies kolonisiert waren, zeigten. Die
Unterscbiede der Vcriinderung der Prozent-
satze von kolonisierten Taschen zwischen den
einzelnen Gruppen war fur B. Jorxythus und
P. gingivalis signifikant. Die Mehrheit des
Attachmentverlusts ereignete sich in Taschen.
die vor der Therapie eine Sondierungstiefe
von <4 mm aufwiesen, Personen mit norma-
ler bis guter Reaktion hatten weniger flache
nnd maBigtiefe Taschen, die Attachment ver-
lust zeigten. und ein groBer Teil der Taschen
aus alien Sondierungstiefenkategorien zeigte
Attachmentgewinn, Die Taschen, die nach
der Therapie mehr als 2 mm Attachment ver-
loren, zeigten eine signifikante Zunahme der
Anzahl von P. intermedia. B. forsythus und
A. uctinamycetcmconutans b., wahrend Ta-
schen. die Attachment gewannen, eine Rc-
dnktion dieser Spezies zeigten. Die Daten
zeigten, daB Personen mit guter Reaktion
eine Verminderung der Gingivaentziindung
aufwiesen und in den Taschen eine deutliche
Abnahme der potentiellen Pathogene hatien,
Bei Personen mit schlechter Reaktion nahm
die Gingivaentztindung nieht ab und die pa-
rodontalen Pathogene nahmen zu.
Resume
Facteurs associes avec les differentes reponses
au traitement parodontal
Dans un travail sur J'cfficacite du traitement
par operation a lambeau de Widman modi-
fiee, detartrage ct surfagage radieulaire, ac-
compagne de l'un des 4 adjuvants suivants;
Augmentin, tetracyeline, ibuprofene ou pla-
cebo, administres par voie generale, on a
constate que les sujets repondaient differem-
ment au traitement. Les differences ne pou-
vaient que partieliement etre imputees a I'ad-
juvant employe, Le but de la presente etude
etait d'examiner les caracteristicjues cliniqnes
et raicrobiologiques des sujets qui presen-
taient differents niveaux de changement de
I'attache apres traitement. 40 sujets ont eie
subdivises en 3 groupes bases sur le change-
ment moyen du niveau de I'attache apres trai-
tement, 10 sujets rcpondant mal {groupe
"poor") ont en moyenne presente une perte
d'attache; 19 sujets a reponse moderee (gron-
pe "moderate") presentaient un gain moyen
d'attaehe situe entre 0.02-0,5 mm, et 11
sujets reagissant bien {groupe "good") pre-
sentaient nn gain moyen d'attache >0.5 mm.
L'enregistrement des parametres eliniques a
ete pratique en 6 sites par dent, avant et apres
traitement. Les prelcvements microbiens oni
ete faits du cote mesial de chaque dem ei eva-
lucs indn'iduellement pour deceler 14 taxons
sous-gingivaux, a I'aide d'une methode avec
transfert de colonies (colony lift method) et
sondes ADN, Les proportions de sites colo-
nises par chaque cspece ont ete caiculces
pour chacun des sujets, avant et apres traite-
ment, Des differences significatives concer-
nant les moyennes des profondeurs dc poches
au sondage, des niveaux d'attache et des pro-
portions de sites avec plaque avani le traite-
ment (pre-therapy) ont etc observees parmi
les groupes de reponse au traitement, Les su-
jets du groupe "poor" avaient les plus basses
moyenne de profondeurs de poches et de ni-
veaux d'attache, mais les niveaux de plaque
les plus eleves, Apres traitement {post-thera-
py), on constatait dans ie groupe •"poor"' le
degrc Ie plus fort d'inflammation gingivale, a
en juger par la rougeur de la gencive et le
saignement provoque par sondage, Chez les
sujets du groupe ''good", les proportions de
sites colonises etaient reduites pour 9 des 14
e.speces testees, tandis que, chez les sujets du
groupe "poor", Ies proportions de sites colo-
nises etaicnt augmentees pour 12 des especes,
Les differences entre ies groupes, concernant
les changements de proportions de sites colo-
nises, etaient significatives pour B. forsythus
et P, girtgivaiis. La majorite des pertes d'atta-
che constatees chez les sujets du groupe
"poor" se produisaient dans des sites ou les
profondeurs de poches avant traitement
etaient <4 mm. Les sujets des groupes "mo-
derate" et "good" avaient moins de sites de
profondeur faible ou moderee presentant une
perte d'attache et une forte proportion de si-
tes de toutes les categories de profondeur de
poches presentant un gain d'attache. Les sites
ayant apres traitement une perte d'attache
^ 2 mm presentaient une augmentation signi-
ficative des nombres de P. intermedia. B. for-
sythus et A. actinomycetemcomitans b, tandis
que les sites ayant un gain d'attache presen-
taient une diminution de ces especes, Ces re-
sultats indiquaient que les sujets repondant
bien au traitement presentaient une diminu-
tion du niveau de I'inflamination gingivale et
une reduction marquee des proportions de si-
tes colonises par des microorganismes sus-
pects d'etre pathogenes pour ie parodonte,
Chez les sujets repondant ma! au traitement,
ie niveau d'inflammation gingivale n'etait pas
diminue et les niveaux de pathogenes paro-
dontaux etaient augmentes.
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Address:
A. D. Haffajee
Department of Periodontology
Forsyth Dental Center
140 Fenway
Boston. MA 02115
USA