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Background: The aims of this study were to investigate the anti-inflammatory effect and the effect on
bone regeneration of hyaluronan in surgical and non-surgical groups.
Methods: In each of 15 individuals, 2 teeth with defects of similar character and magnitude in the upper
or lower jaw were chosen. There were at least 2 teeth between the test and the control sites. In the surgical group, a bioabsorbable membrane was used for both test and control sites, and hyaluronan was placed
in the intrabony pocket of the test site. In the non-surgical group, the periodontal pockets were scaled and
hyaluronan was administered 3 times with an interval of 1 week in the test pockets. Alveolar bone height
and bone healing patterns were analyzed using digital intraoral radiographs. Measurements of bone height
were performed in the original digital black-and-white radiographs to obtain quantitative data on bone gain
or loss. Bone healing patterns were studied with color-coded radiographs, using specially designed software
in a personal computer with subsequent combinations of radiographs. Gingival crevicular fluid immunoglobulin (Ig)G, C3, and prostaglandin E2 (PGE2) responses; periodontal probing depth; bleeding on probing; and
the presence of plaque were studied to evaluate the anti-inflammatory effect. Data were obtained at baseline before treatment, and at 2 weeks, and 1, 3, 6, and 12 months after treatment.
Results: For the surgical treatments, bone height was increased in the test group treated with hyaluronan (mean value 2.2%, corresponding to an average increase of approximately 0.5 mm) and reduced in
the control group (mean value 1.8%, corresponding to an average decrease of approximately 0.4 mm)
(P <0.05) after 12 months. For the non-surgical treatments, bone height was reduced by a mean value of
1.1% (corresponding to an average decrease of approximately 0.25 mm) in the test group treated with
hyaluronan and 3.3% (corresponding to an average decrease of approximately 0.75 mm) in the control
group after 12 months (N.S.). According to the digital color-coded radiographs, the test sites in the surgical and non-surgical groups showed apposition of bone minerals. Immune responses showed no differences
during the 12 months studied for the surgical and non-surgical sites. Mean periodontal probing depths were
reduced between 2.5 mm and 4.1 mm in the surgical and non-surgical groups.
Conclusions: The observed difference in bone height between test and control sites in the surgical group
after 12 months was less than 1 mm, which was only detectable on radiographs. No statistical difference
was found on radiographs in the non-surgical group, where a decrease in bone height was found for both
groups after scaling. Probing depth reduction after the surgical treatment, as well as after scaling and root
planing, was as expected. Hyaluronan in contact with bone and soft tissues had no influence on the immune
system in this study. Further studies are needed to determine the extent to which hyaluronan can lead to
clinically significant healing of periodontal lesions. J Periodontol 2001;72:1192-1200.
KEY WORDS
Follow-up studies; hyaluronan/therapeutic use; immune response; periodontitis/drug therapy;
radiography, dental, digital; wound healing.
* Division of Clinical Immunology, Department of Microbiology, Pathology and Immunology, Karolinska Institutet, Huddinge University Hospital, Stockholm,
Sweden.
Department of Periodontology, Institute of Odontology, Karolinska Institutet.
Department of Oral Radiology, Institute of Odontology, Karolinska Institutet.
Division of Clinical Chemistry, Department of Medical Sciences, University Hospital, Uppsala, Sweden.
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Table 2.
12
Surgical treatment (n = 6)
Test sites
1.1%
Control sites
0.1%
3.2%
0.1%
1.6%
0.1%
2.2%
1.8%*
Non-surgical treatment (n = 9)
Test sites
0.9%
Control sites
0.5%
0.3%
1.1%
1.7%
2.9%
1.1%
3.3%
* P <0.05, comparison between test and control sites after 12 months; all
other differences were not significant.
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Figure 2.
Non-parametric plots of the individual development of all cases. On the y-axis, the subjectively evaluated change in successive pairs of radiographs is
plotted.The values indicate the sum of the scores according to Table 1. A) Test sites of the surgical group, initial bone loss occurs followed by gain. B)
Control sites of the surgical group, bone loss predominates. C) Test sites of the non-surgical group, bone gain predominates. D) Control sites of the nonsurgical group; the range covers both bone gain and loss. No trend can be detected.
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Table 3.
Table 5.
Month
Group
Baseline
Month
12
Group
Surgical treatment (n = 6)
Test sites
7.8 1.1
Control sites
7.3 0.9
3.7 0.9
4.3 1.2
3.8 0.7
4.3 1.4
Non-surgical treatment (n = 9)
Test sites
6.4 1.3
Control sites
6.8 1.5
3.9 1.2
4.2 1.4
3.9 1.4
3.7 1.5
Table 4.
Baseline
0.5
12
Surgical treatment (n = 6)
Test sites
0
Control sites
1
1
3
1
2
3
3
4
3
5
4
Non-surgical treatment (n = 9)
Test sites
3
Control sites
4
5
4
7
6
3
4
7
6
5
6
Baseline
0.5
12
Surgical treatment (n = 6)
Test sites
5
Control sites
6
4
5
5
5
5
5
5
5
6
6
Non-surgical treatment (n = 9)
Test sites
5
Control sites
5
8
8
6
6
8
8
7
6
8
8
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Test sites
33.6 68.4 16.4 13.8 18.4 25.7 29.5 67.3 25.8 31.8 29.9 27.6
verified in this study in relaControl sites 53.2 78.3 30.6 39.0 69.6 63.7 22.7 38.1 12.1 6.2 19.1 11.6
tion to the IgG, C3 and PGE2
responses.
* N = 4.
N = 7.
Immunoglobulin G levels
N = 6.
in GCF from individuals with
periodontitis were comparaTable 8.
ble to those in earlier reports.23 Prostaglandin
Mean ( SD) Gingival Crevicular Fluid Levels of PGE2
E2 was in the same concentration range as
in pg/l at Baseline and at 0.5, 1, 3, 6, and 12 Months in a study concerning elevated PGE2 levels
in GCF from individuals with Downs synin Surgically Treated Group
drome.24 During the study period, there was
no difference in the acute-phase protein C3
Month
Sites
levels in surgical and non-surgical test or
(n = 6)
Baseline
0.5
1
3
6
12
control groups. This may be due to the fact
that after 2 weeks or more, the inflammatory
Test
4.6 2.5 9.6 3.5* 12.0 14.9 9.1 6.9 2.0 2.5 5.7 6.0*
response in the samples had receded.
Control 8.1 8.0 6.3 5.2
6.6 4.9 4.6 2.2 5.3 6.3 5.1 3.0*
In all groups, the microflora (Prevotella
species,
P. gingivalis, or A. actinomycetem* N = 4.
comitans) showed a stable microecology.
facultative anaerobic microorganisms (A. actinoBone height measurements in original black-andmycetemcomitans) which are often found in cases of
white digital radiographs of the surgical patients
refractory periodontitis.22
demonstrated a decrease at the control examination
Regeneration of the periodontal supporting tissue is
performed 1 month after surgery. Color-coded radipossible under certain conditions through GTR proceographs showed a decrease in mineral contents condures, where the natural ability to regenerate is
firming this finding. No quantitative decrease could be
mechanically guided by a membrane.12,13 The memregistered at control sites. A decrease in mineral conbrane is placed so that the possibility of periodontal ligtents 1 month after periodontal flap surgery has been
Table 6.
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Table 9.
Baseline
2
1
4
0.5
12
1
1
3
1
1
3
1
1
4
2
1
3
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13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
1200
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