A comparative study utilizing open flap debridement with and without enamel matrix derivative in the treatment of periodontal intrabony defects: a 12-month re-entry study.

Abstract

Previous studies have demonstrated that enamel matrix derivative (EMD) has the ability to improve clinical parameters when used to treat intraosseous defects. The purpose of the present study was to compare at 12 months postsurgery sites treated with open flap debridement (OFD) alone to those treated with OFD and EMD.
Twenty-three subjects with at least 2 intrabony defects were chosen. Fifty-three defects received EMD in conjunction with OFD. Thirty-one defects in these same 23 subjects were treated with OFD alone. Stents were fabricated to serve as fixed reference points. Re-entries were performed at least 1 year after initial surgery. Soft tissue measurements were recorded prior to initial surgery and prior to re-entry for gingival (GI) and plaque (PI) indices, probing depth (PD), gingival margin position, and clinical attachment level (CAL). Hard tissue measurements were recorded during the initial and re-entry surgery for level of crestal bone and depth of defect. Statistical analysis was conducted using the method of generalized estimating equations to determine changes in GI, PI, PD, CAL, fill of the osseous defect, and crestal resorption. Percent of defect fill was also calculated.
In all categories, treatment with EMD (test) was superior to treatment without EMD (control). Average PI and GI were not significantly different either initially or prior to re-entry. The average PD reduction was 2.7 mm greater with EMD than controls. The average CAL gains were 1.5 mm greater, and the average fill of osseous defect 2.4 mm greater with EMD than controls. The average percent of defect fill after adjusting for crestal bone loss was more than 3 times greater for EMD versus control-treated sites (74% defect fill with EMD versus 23% defect fill for control sites).
This study indicates that treatment of periodontal intraosseous defects with EMD is clinically superior to treatment without EMD (open flap debridement) in every parameter evaluated. Re-entry data demonstrate that percent fill of osseous defects treated with EMD compares favorably with the treatment results utilizing bone grafts or membrane barriers, according to published literature.

Full text

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j Periodontol • January 2001
51
A Comparative Study Utilizing Open Flap
Debridement With and Without Enamel
Matrix Derivative in the Treatment of
Periodontal Intrabony Defects: A
12-Month Re-Entry Study
Stuart J. Froum,* Mea A. Weinberg/ Edwin Rosenberg,* and Dennis Tarnow*
Background: Previous studies have demonstrated that enamel matrix
derivative (EMD) has the ability to improve clinical parameters when used
to treat intraosseous defects. The purpose of the present study was to
compare at 12 months postsurgery sites treated with open flap debride-
ment (OFD) alone to those treated with OFD and EMD.
Methods: Twenty-three subjects with at least 2 intrabony defects were
chosen. Fifty-three defects received EMD in conjunction with OFD. Thirty-
one defects in these same 23 subjects were treated with OFD alone. Stents
were fabricated to serve as fixed reference points, Re-entries were per-
formed at least 1 year after initial surgery. Soft tissue measurements were
recorded prior to initial surgery and prior to re-entry for gingiva! (GI) and
plaque (PI) indices, probing depth (PD), gingival margin position, and clin-
ical attachment level (CAL). Hard tissue measurements were recorded
during the initial and re-entry surgery for level of crestal bone and depth
of defect. Statistical analysis was conducted using the method of gener-
alized estimating equations to determine changes in Gl, PI, PD, CAL, fill
of the osseous defect, and crestal resorption. Percent of defect fill was also
calculated.
Results: In all categories, treatment with EMD (test) was superior to
treatment without EMD (control). Average PI and Gl were not significantly
different either initially or prior to re-entry. The average PD reduction was
2.7 mm greater with EMD than controls. The average CAL gains were 1.5
mm greater, and the average fill of osseous defect 2.4 mm greater with EMD
than controls. The average percent of defect fill after adjusting for crestal
bone loss was more than 3 times greater for EMD versus control-treated
sites (74% defect fill with EMD versus 23% defect fill for control sites).
Conclusions: This study indicates that treatment of periodontal
intraosseous defects with EMD is clinically superior to treatment without
EMD (open flap debridement) in every parameter evaluated. Re-entry data
demonstrate that percent fill of osseous defects treated with EMD compares
favorably with the treatment results utilizing bone grafts or membrane bar-
riers, according to published literature. J Periodonlol 2001;72:25-34.
KEY WORDS
Periodontal regeneration; intrabony defects; clinical trials; comparison
studies; follow-up studies; proteins, enamel matrix; surgical flaps.
* Division of Surgical Sciences, Department of Implant Dentistry, Mew York University, College of Dentistry,
New York, NY.
+ Division of Surgical Sciences.
* Department of Implant Dentistry, Mew York University, College of Dentistry.
T
preventing disease recurrence,
and regenerating lost perio-
dontium. The latter, which is
defined as reconstruction of a
functionally oriented perio-
dontal ligament inserting in
new alveolar bone and cemen-
tum, can only be determined
by histologic examination of
the healed tissues following
surgery. Human evidence of
periodontal regeneration has
been presented in several lit-
erature reviews.1 6
However, since this evi-
dence requires human block
section and is therefore lim-
ited, clinicians rely on param-
eters such as probing depth
(PD) reduction, clinical attach-
ment level (CAL) gain, and
radiographic and re-entry evi-
dence of fill of the osseous
defect (OF) to clinically eval-
uate a treatment modality.
Several thorough literature
reviews have documented
success using various graft
and barrier materials in achiev-
ing statistically superior clini-
cal results compared to open
flap debridement.1'7 A recent
he goals of periodontal
therapy include arrest-
ing the disease process,
25

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Treatment of Intrabony Defects With Enamel Matrix Derivative
Volume 72 • Number I
meta-analysis demonstrated clinically improved PD
reduction, CAL gain, and OF following treatment of
intrabony defects with membranes compared to grafts,
and with both materials compared to open flap debride-
ment.8
In 1997 enamel matrix dervative^ was introduced
into the periodontal literature and has demonstrated
the potential to mediate periodontal regeneration in
both human and animal model systems.911
This material is composed primarily of amelogenin
and related proteins that are derived from porcine tooth
buds. The detection of enamel matrix proteins between
the peripheral dentin and the developing cementum
provides the basic concept for use of an EMD mate-
rial in regenerative therapy.12
The use of EMD has been shown to result in signif-
icant clinical improvement in PD reduction, CAL gain,
and bone fill in several recent clinical studies.13'15
A multicenter study involving 33 subjects with 34
paired test and control sites compared the long-term
effect of EMD treatment as an adjunct to modified Wid
man flap surgery to the same surgical procedure with
a placebo. Clinical attachment measurements and radi-
ographic assessments were performed at baseline and
8, 16, and 36 months postsurgery. No re-entry sur-
geries were done. Results showed significantly greater
gains in attachment at all measurement periods in the
EMD-treated sites compared to the controls. Clinical
attachment gain in test and control sites at 8 months
was 2.1 mm and 1.5 mm, respectively; at 16 months,
2.3 mm and 1.7 mm, respectively; and at 36 months,
2.2 mm and 1.7 mm. respectively. There was a sta-
tistically significant radiographic bone gain of 2.6 mm
at 36 months at test sites, compared to no evidence
of bone gain at control sites.13
A recent clinical study in 108 patients included 145
angular interproximal bone defects with a >3 mm intra-
bony component that were treated with EMD and re-
examined 12 months following surgery. Results
reported mean CAL gain of 4.6 mm and a PD reduc-
tion of 5.2 mm. Eighty-seven percent of treated sites
exhibited a CAL gain >2 mm. Moreover, radiographic
assessment revealed an average decrease in depth of
bone defect of 2.9 mm. However, no control treatment
was performed in this study.14
A recent randomized controlled clinical trial com-
pared 4 treatment groups of 10 subjects each. Three
different barriers (2 bioabsorbable and 1 non-
absorbable) were evaluated in 3 groups of 10 patients
with intrabony defects. The fourth group received EMD.
Controls were treated with the EMD vehicle (propyl-
ene glycol alginate) only following open flap debride-
ment. Re-examination 12 months after surgery showed
a significantly greater PD reduction (4.4 mm versus 3.5
mm) and CAL gain (2.9 mm versus 1.8 mm) in the
barrier and EMD-treated sites compared to the control.
Moreover, the EMD treatment appeared to be equally
effective in terms of PD reduction and CAL gain as
the barrier treatment.15
Another controlled clinical trial compared the treat-
ment of intrabony defects with EMD to that with guided
tissue regeneration (GTR) utilizing a bioabsorbable
membrane. Sixteen patients with contralateral intra-
bony defects in the same jaw were treated and sites
evaluated prior to surgery and 8 months later. Sites
treated with EMD demonstrated a PD reduction of 3.8
mm and a CAL gain of 3.1 mm. Sites treated with GTR
demonstrated a PD reduction of 4.0 and a CAL gain
of 3.0 mm. The authors noted membrane exposure in
7 out of 16 cases within the first 3 postsurgical weeks.
The authors concluded that "no statistically significant
differences in any of the investigated parameters were
observed between the EMD and GTR groups."15
In a human histological study, 14 teeth in 14 patients
scheduled for extraction and associated with advanced
intrabony defects were randomly treated with EMD or
bioabsorbable membrane. Six-month histological
analysis revealed 2.6 mm of new attachment (new
cementum with inserting collagen fibers) and a mean
0.9 mm gain of new bone in the EMD-treated sites. In
the GTR group, mean new attachment gain was 2.4
mm and mean gain of new bone was 2.1 mm. The
authors noted that the new cementum was predomi-
nantly cellular in both treatment groups. The authors
concluded that treatment with EMD or with a bioab-
sorbable membrane enhanced the formation of a new
connective tissue attachment in humans.17
To date there has been no report in the literature of
a controlled clinical trial with re-entry data utilizing
EMD. The purpose of the current investigation was to
clinically compare the 1 -year results of the treatment
of intraosseous defects with either open flap debride-
ment (OFD) alone or in conjunction with the use of
EMD.
MATERIALS AND METHODS
Twenty-three patients were selected from those requir-
ing periodontal treatment who presented to the New
York University College of Dentistry. Each patient had
at least 2 angular osseous defects as detected on radi-
ographs and had completed full-mouth scaling and
root planing, occlusal adjustment where indicated, and
home care instructions at least 2 months prior to
screening for participation in the present study. All
patients had undergone initial head and neck oral can-
cer examination. No patients required antibiotic pre-
medication or had any systemic disease which con-
traindicated periodontal surgery. Each patient was told
the nature of the study and signed an informed con-
sent prior to any treatment. Both the study and the
ij Emdogain, Biora, Chicago, IL.

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Periodoncol • January 2001 Froum. Weinberg. Rosenberg, Tarnow
% Defect Fill =
consent were approved by the University
Committee on Activities Involving Human
Subjects. Prior to surgery, defects were
assigned by a coin flip to receive either
enamet matrix derivative (EMD) following
open flap debridement or debridement alone.
All defects in the treated quadrant received
the same treatment during surgery.
If three quadrants contained study defects,
a blind draw determined the control defect
and all defects in the remaining 2 quadrants
were treated by OFD with EMD. If 4 quad-
rants contained treatment defects, a blind
draw again determined the 2 EMD-treated
quadrants and the 2 control-treated quadrants.
Measurements
Prior to surgery, a customized acrylic stent
was fabricated for each patient and stored
on the study cast to minimize distortion. The
stent was grooved in an occlusal apical direc-
tion with a tapered bur so that the silver point
was returned to the same position for each
successive measurement. Measurements for
gingival recession PD. and CAL were recorded from
a fixed reference point (stent) to the nearest 0.01 mm
using a digital Boley gauge, silver point, and locking
pliers.18 All measurements were recorded by a single
investigator. The investigator performing the mea-
surements did not perform the surgical treatment.
Moreover, since the measurements were performed
prior to the coin flip that determined treatment, the
measurement evaluator was blinded to the treatment
performed. This was also true of the measurements
recorded at re-entry surgery. Local site scores were
recorded for: 1) plaque index (PI);59 2) gingival index
(Gl);20 3) gingival recession (Rec); 4) probing depth
(PD); 5) clinical attachment level (CAL); and 6) mobil-
ity.21 Prior to surgery (baseline), measurements were
made from the stent to the gingival margin (GM), stent
to the base of the pocket (BP), and stent to the
cemento-enamel junction (CEJ). During surgery, mea-
surements were made from the stent to the alveolar
crest (AC), stent to the base of the osseous defect (BD),
and stent to CEJ. The latter was used to check for seat-
ing of the stent. Approximately 12 months following ini-
tial surgery, prior to, and during re-entry surgery, the
above measurements were repeated (Table 1).
Recordings were also made for plaque index (PI)
and gingival index (Gl) prior to initial surgery and re-
entry. Patients who smoked more than one-half pack
per day were classified as "smokers," and this was
documented.
Fifty-three defects in 23 patients received EMD in
conjunction with OFD surgery. Six of these defects
were treated in 3 smokers. Thirty-one defects in the
Table I.
Measurement Parameter Calculations
Parameter
Initial probing depth (IPD)
Initial osseous depth
Gingival recession
2-month probing depth
Probing depth reduction
Gam in clinical attachment leveS
Alveolar crest resorption
1 2-month osseous depth
Defect fill
Measurement
Stent to BP minus stent to GM
Stent to BD minus stent to AC
Re-entry stent to GM minus baseline stent to GM
Re-entry stent to BP minus ne-entry stent to GM
IPD mmus 12-month PD
Baseline stent to BP minus re-entry stent to BP
Re-entry stent to AC minus baseline stent to AC
Re-entry stent to BD minus ne-entry stent to AC
Baseline stent to BD minus re-entry stent to BD
Defect fill
100
initial osseous depth
. . Initial osseous depth - 12 month osseous depth x !00
i Defect Resolution =
_ , _
v-
Initiat osseous depth
t-
same 23 patients were treated with OFD alone. Three
of these defects were treated in the 3 smokers.
Surgical Procedures and Postsurglcal Care
Following measurement recording and administration
of local anesthesia, all sites were treated via reflec-
tion of a full thickness mucoperiostea! flap attempt-
ing to retain all soft tissue. The exposed roots and
osseous defects were debrided with hand and ultra-
sonic instruments. The flap debridement-only (OFD)
sites then had the flaps repositioned and sutured using
4-0 silk sutures. The EMD sites were dried with non-
woven gauze. Citric acid (pH = 1) was then applied
with cotton pledgets to the exposed root for 15 sec-
onds. Care was taken to avoid the spread of the liq-
uid to adjacent sites The arej was then irrigated with
sterile saline or water for 60 seconds. In all cases
suturing, using the same 4-0 silk sutures, was begun
prior to EMD application to allow more rapid closure
of the site once the EMD was applied. The needle
and suture were passed through the buccal flap and
the flap reflected with an elevator. The root and defect
were again dried and EMD applied to both the root
and the defect. The EMD was prepared by mixing the
30 mg powder with the propylene glycol alginate vehi-
cle using a 3 cc syringe^ with an 18-gauge, 2-inch
needle.* Preparation of this mix was made at least 15
minutes prior to application, Using the supplied 19-
I! Ethicon Inc., Sommerville, NJ.
1| Monoject Luer Lock syringe, Sherwood Medical. St. Louis, MO.
# Luer Lock hypodermic needle. Air-Tite Products Co.. Inc.. Virginia Beach.
VA.
27

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Treatment of Intrabony Defects With Enamel Matrix Derivative
Volume 72 • Number 1
gauge, 1.5-inch needle^ on the same syringe, EMD
was slowly applied to the deepest part of the exposed
root moving coronally until the defect was filled. The
flaps were repositioned and sutured with interrupted
or horizontal mattress sutures. In cases where flap
coverage was judged to be incomplete, vertical releas-
ing incisions or partial thickness periosteal releasing
incisions were made at the inner portion of the base
of the flap prior to root conditioning. Following sutur-
ing, additional EMD was placed at the tooth flap junc-
tion. Pressure was maintained on flaps in both exper-
imental and control groups with damp gauze for 5 to
10 minutes. A resin dressing** was applied, cover-
ing the tissue and apical one-half of the teeth. Each
patient was prescribed tetracycline HCL 1 g per day
for 2 weeks following surgery. Patients were then
instructed in homecare. Homecare consisted of rins-
ing twice a day with 0.12% chlorhexidine gluconate+t
for 8 weeks. Sutures and dressings were removed 10
to 14 days postsurgery. The patients returned every
2 weeks for 6 weeks, then once a month for the next
10 months. The surgical areas were debrided profes-
sionally with supragingival scaling, and home care
instructions were reinforced. Patients were instructed
not to brush or floss the treated areas for 6 weeks
following suture removal and then return to their nor-
mal regimen of home care. The surgical sites were not
probed until 6 months postsurgery. Approximately 12
months after initial surgery, re-entry surgery was per-
formed (Fig. 1A-D). Prior to surgery, all soft tissue
measurements were repeated and recorded. At the
time of re-entry, local anesthesia was administered
and full thickness flaps were reflected. Defects were
debrided and hard tissue measurements performed
(Fig. 2A-D). Residual defects were treated with sur-
gical elimination and the flaps sutured.
Prior to initial and re-entry surgeries, radiographs
** Coe pak. GC America Inc., Alsip, IL.
t + Peridex. Zila Pharmaceuticals Inc.. Phoenix. AZ.
Figure I.
A. Control open debndement site, mesia/ tooth #6. Presurgical probing depth measured 9.93 mm. B. Exposure of the 2-wali osseous defect
measuring 5,25 mm in depth, C. At re-entry (12 months), probing depth 5.8 mm wtth CAL gain of I.58 mm. D. Remodeling of the osseous defect
with on osseous fill of 1.36 mrr. Thy, represents a defect fill of 26%.
28

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J Periodoncol
Froum, Weinberg, Rosenberg, Tarnow
and photographs were taken. Photographs of initial
and re-entry hard tissue were taken of each surgical
site during the surgical procedure (Fig. 3A through D).
Statistical Methods
The design of the study was a split-mouth design so
that each subject served as his own control. In other
words, there were periodontal defects within each
patient that were treated without EMD and similar peri-
odontal defects within the same patients that were
treated with EMD. Data were collected initially and 12
months after surgery for mobility, probing depth,
osseous depth, and plaque and gingival indices. In
addition, data were collected on the change in PD over
12 months, the change in gingival recession over 12
months, the change in CAL over 12 months, the amount
of crestal resorption over 12 months, the amount of
defect fill over 12 months, and the percent of defect
resolution over 12 months (the net gain in percent of
defect fill after accounting for crestal resorption).
Statistical analysis was conducted using the method
of generalized estimating equations (GEE) assuming
an exchangeable working correlation matrix. This
method of statistical analysis was used in order to
appropriately control for baseline differences among
sites while at the same time taking into account the
lack of independence of sites within each subject. In
addition, some subjects had multiple sites treated with
EMD and/or multiple sites treated without EMD. All
subjects received treatment for at least one periodon-
tal defect with EMD and for at least one defect with-
out EMD.
Descriptive Statistics
The average age of the subjects in the study was
45.5 years (SD = 15.9), ranging from 19 to 71 years.
Summary statistics for initial clinical parameters are
given in Table 2. Using patient averages for control
sites (sites without EMD) and test sites (sites with
EMD), differences in initial PD, osseous depth, PI,
Figure 2.
A. EMD-treoted site on the mesial of tooth #30. Presurgical probing depth measured 9.96 mm. B. Exposure of the osseous defea which measured
6.35 mm. C. At re-entry (12 months), probing depth of 3.90 mm with a CAL gain of 5.46 mm. D. Fi of the osseous defea measured 4.24 mm. This
represents a defect fill of 67%.
29