Efficacy of Enamel Matrix Derivative

With Freeze-Dried Bone Allograft

or Demineralized Freeze-Dried Bone
Allograft in Intrabony Defects: A
Randomized Trial
Shigeki Ogihara* and Dennis P. Tarnow

Background: Promising clinical outcomes have been reported with the combination of enamel matrix
derivative (EMD) and allograft materials. Direct comparison between EMD with a freeze-dried bone allo-
graft (FDBA) and a demineralized FDBA (DFDBA) was evaluated in one case series study. To date, no
randomized controlled trial has been reported. Therefore, a well-controlled randomized clinical trial was
conducted to determine the relative efcacy of EMD/FDBA versus EMD/DFDBA when managing intrab-
ony defects.
Methods: A randomized parallel trial was conducted in a private practice from April 2004 to October
2011. Sixty-nine patients were randomly assigned to one of three groups: EMD/FDBA (EF) intervention
group (n = 23), EMD/DFDBA (ED) intervention group (n = 23), and EMD alone without graft material (E)
as a negative control group (n = 23). All of the grafting material had minocycline added. Each patient had
an intrabony defect. The primary outcomes were the absolute change in probing depth (PD) reduction
and clinical attachment level (CAL) gain from baseline to 1- and 3-year follow-up. Intrabony defects
were surgically treated with EMD/FDBA, EMD/DFDBA, or EMD alone.
Results: Sixty-seven patients (EF, n = 21: ED, n = 23; E, n = 23) were analyzed. All groups demon-
strated signicant improvement in PD reduction and CAL gain from baseline. The changes for PD were
as follows (mm, 95% condence interval [CI]): at 1 year: EF (4.4 mm, 4.0 to 4.7), ED (3.7 mm, 3.4 to
4.0), and E (control) (3.3 mm, 3.0 to 3.6); at 3 years: EF (4.4 mm, 4.1 to 4.8), ED (3.7 mm, 3.4 to
4.0), and E (3.1 mm, 2.8 to 3.4). The changes for CAL were as follows (mm, 95% CI): at 1 year: EF
(4.1 mm, 3.8 to 4.5), ED (3.5 mm, 3.0 to 4.0), and E (3.0 mm, 2.5 to 3.6); at 3 years: EF (4.2 mm,
3.7 to 4.7), ED (3.6 mm, 3.1 to 4.1), and E (3.0 mm, 2.5 to 3.5). The intervention groups (EF and
ED) showed better treatment outcomes than the control group at 1 and 3 years. Statistically, the two
bone-graft groups were not signicantly different from each other at 1 and 3 years.
Conclusions: Both EMD/FDBA and EMD/DFDBA interventions resulted in greater soft tissue improve-
ment at 1 and 3 years of follow-up compared to EMD alone. Both graft materials worked well in managing
deep intrabony defects when combined with EMD. J Periodontol 2014;85:1351-1360.
KEY WORDS
Allografts; bone and bones; clinical trials, randomized; enamel matrix protein; regeneration; tissues.
doi: 10.1902/jop.2014.130520
* Private practice, Tokyo, Japan.
Department of Periodontology, Columbia University College of Dental Medicine, New York, NY.
J Periodontol October 2014
1351
A
llografts, especially freeze-dried bone allograft
(FDBA) and demineralized FDBA (DFDBA),
are most commonly used to correct osseous
periodontal defects. Astudy demonstrated signicant
superior gains in osseous ll (OF) with DFDBA
compared to open ap debridement (OFD) alone.
1
DFDBA supports the formation of a new attachment
apparatus: new bone, cementum, and periodontal
ligament, when placed in intrabony defects.
2,3
A
systematic review of this material also indicated that
DFDBA is inconsistent with its osteoinductivity due
to donor age and processing.
4
This same meta-
analysis failed to support the use of FDBA in the
treatment of intrabony defects because of insufcient
data that would meet inclusion criteria.
4
Thus, the
use of these allografts as monotherapies may be
limited in their use.
Recent attention has focused on the potential for
biologic mediators to improve wound healing and
enhance the clinical benets of bone replacement
grafts.
5
This idea originated in the work of Bowers
and Reddi.
6
Enamel matrix derivatives (EMDs) have
been shown to promote wound healing and new
periodontal tissue formation.
7
Systematic reviews
suggested that the use of EMD for periodontal os-
seous defects yields signicantly higher soft tissue
improvements compared to OFD alone.
8-10
How-
ever, the application of EMD was less effective in
non-supporting defects.
11
Therefore, the addition of
a bone graft such as DFDBA to EMD enhanced the
outcomes for repairing these intrabony defects. In an
experimental animal study, Boyan et al. reported that
the combination of DFDBA and EMD resulted in
enhanced bone formation compared to DFDBA
alone.
12
EMD as a osteopromotor increased the
osteoinductive potential of active DFDBA.
12
A
comparative study examined the clinical outcomes of
EMD/DFDBA compared to EMD alone in the treat-
ment of intrabony defects.
13
EMD/DFDBA yielded
statistically signicant improvement in OF.
13
A
systematic review suggested that the additional use
of a graft (autogenous bone, DFDBA) seemed to
enhance the clinical outcome of EMD.
14
In contrast, there were studies to investigate
whether the addition of EMDto a bone graft enhanced
the outcomes seen for regenerating these intrabony
defects. Hoidal et al.
15
evaluated the effectiveness
of EMD/DFDBA compared to DFDBA alone in the
treatment of intraosseous defects at 6 months
post-surgery. They found that the addition of EMD
to DFDBA provided no statistically signicant im-
provement in the soft and hard tissue compared to
DFDBA alone.
15
A recent randomized, controlled
clinical trial compared EMD/DFDBA to DFDBA
alone in the treatment of intrabony defects at
12 months post-surgery.
16
Statistically signicant
differences were found between EMD/DFDBA and
DFDBA alone in PD (probing depth) reduction
(5.0 versus 4.0 mm), CAL gain (4.0 versus 3.3 mm),
and OF (4.0 versus 3.5 mm).
16
Moreover, a study
comparing FDBA to DFDBA failed to show superi-
ority of either material by similar OF at 6 months.
17
In contrast, a case series reported a trend toward
better efcacy in attachment level gains when com-
bining FDBA/EMD versus DFDBA/EMD for intrabony
defects, suggesting that the scaffold may matter.
18
These studies raise the question of whether FDBA
could have a greater potential therapeutic role as
a scaffolding agent with EMD than DFDBA. However,
to date, there has been no randomized, controlled
clinical trial to answer this question. Therefore, a well-
controlled randomized clinical trial to determine the
efcacy of EMD/FDBA versus EMD/DFDBA for in-
trabony defects is conducted.
MATERIALS AND METHODS
The study protocol was approved by the institutional
review board of the Tokyo Adachi Dental Society,
Tokyo, Japan, and conducted in accordance with
the Helsinki Declaration of 1975, as revised in 2000.
The trial was registered at the Japan Medical Asso-
ciation Center for Clinical Trials, which is a member
of the World Health Organization international
clinical trials registry (#JMA-IIA00077). All pa-
tients were informed of the nature of the study
and procedures involved, as well as potential
risks and benets associated with this therapy,
which were explained prior to obtaining written
informed consent to participate in this voluntary
clinical trial.
A randomized, parallel clinical trial was conducted
in a private periodontal practice (SO) in Tokyo from
April 2004 to October 2011. Consecutive patients
with chronic periodontitis (CP) requiring periodontal
treatment were recruited from this private practice
to participate in a parallel study. Complete medical
and dental histories were obtained along with com-
prehensive clinical and radiographic examinations.
The exclusion criteria included: 1) systematic dis-
eases inuencing periodontal surgery; 2) systematic
medications affecting periodontal status; 3) preg-
nancy or lactation; 4) smoking; and 5) sensitivity to
minocycline and tetracycline. To be eligible, patients
with CAL 6 mm, associated with radiographic bone
loss, had to have completed the initial phase of
therapy. This included full-mouth scaling and root
planing, occlusal adjustment where indicated, and
oral hygiene instructions 2 months before enroll-
ment. Each patient contributed no more than one
intrabony defect. Following the completion of base-
line measurements, 69 participants were randomly
assigned by a computer-generated list of random
EMD/FDBA Versus EMD/Demineralized FDBA Volume 85 Number 10
1352
numbers into one of three treatment groups:
EMD/FDBA (EF) group (n = 23; six males and 17
females, mean age [years] SD = 53 11); EMD/
DFDBA (ED) group (n = 23; four males and 19 fe-
males, mean age SD = 56 9); and EMD alone
without graft material (E) as a negative control group
(n = 23; four males and 19 females, mean age SD =
54 4). Participants were seen from baseline to 3
years of follow-up for outcome measurements. Fig-
ure 1 shows the recruitment, inclusion, assignment,
and subsequent follow-up of the study patients.
PD and clinical attachment
level (CAL) of the treated sites
were measured by one examiner
(SO) with a calibrated peri-
odontal probe

at baseline and
1- and 3-year follow-up. The PD
was the greatest distance from the
gingival margin to the base of the
pocket, whereas CAL was the
corresponding distance from the
cemento-enamel junction (CEJ),
crown, or restoration margin to
the base of the pocket. The pri-
mary outcome measures were
the absolute change in mean
PD reduction and CAL gain from
baseline to 1 and 3 years. The
secondary outcome measure
was absolute change in mean
open probing attachment level
(OPAL) gain from baseline to
6-month re-entry to evaluate ad-
ditional effects of the interventions,
i.e., the hard tissue improve-
ment. OPAL was the greatest
distance from CEJ, crown, or
restoration margin to the base of
defect.
Procedure
Immediately before surgery, all
patients rinsed with a 0.12%
chlorhexidine solution for 30 sec-
onds. After topical and local an-
esthesia, sulcular incisions were
made before a full-thickness ap
was reected. The intrabony de-
fects were completely debrided
and root planed with hand in-
struments and a piezo-electric
ultrasonic generator,

then cate-
gorized according to their mor-
phology (Table 1). The same
examiner (SO) measured OPAL.
Minocycline solution (10 mg/mL),
which has anticollagenase activity and antibacterial
effects,
19
was used as a root-conditioning agent for
3 minutes. The surgical site was well isolated and
thoroughly irrigated with sterile water before EMD
i
was
applied. A composite graft consisting of FDBA
(250 to 1,000 mm) or DFDBA (250 to 710 mm)

obtained from the same tissue bank was mixed

with minocycline solution (10 mg/mL) (0.5 mL
Figure 1.
Flowchart of the recruitment, inclusion, assignment, and subsequent follow-up of the study
patients.
Williams probe, Hu-Friedy, Chicago, IL.
Piezotome, Satelec Acteon, Merignac Cedex, France.
i Emdogain, Institute Straumann, Basel, Switzerland.
Oragraft, LifeNet Health, Virginia Beach, VA.
J Periodontol October 2014 Ogihara, Tarnow
1353
FDBA/DFDBA containing 0.1 mL minocycline so-
lution) and EMD (0.5 mL FDBA/DFDBA containing
0.3 mL of EMD) and placed into the intrabony
defect until a slight overll was achieved. Flaps were
reapproximated and sutured to achieve tension-free
primary closure. Horizontal mattress and single in-
terrupted sutures using a 5-0 monolament suture
#
were placed to ensure ap adaptation and closure.
The remaining EMD was gently applied onto the ap
margins to enhance soft tissue wound healing.
Patients were instructed to avoid brushing and
ossing at the surgical site until the sutures were re-
moved 7 days after surgery. Minocycline for 4 days,
100 mg per day, was prescribed. Patients were seen
weekly for postoperative treatment, including plaque
debridement, the topical use of an oral rinse with 0.12%
chlorhexidine solution, and reinforcement of oral hy-
giene before the restorative program was completed.
The patients were seen weekly for the rst month
and every month for up to 6 months. At 6 months
after the initial surgery, a re-entry procedure was
performed and OPAL was measured. The patients
were then seen at least every 6 months for up to 3
years (Figs. 2 and 3).
Radiographic Measurements
Periapical radiographs (baseline and 1 and 3 years)
were taken with parallel technique using lm
holders.** Radiographic bone gain, which was the
corresponding distance from CEJ to the bottom of
the bony defect, was chosen as radiographic out-
come variable related to OPAL. The differences
among baseline and 1- and 3-year radiographic bone
gain were measured by one examiner (SO) with
a calibrated periodontal probe.
Statistical Analyses
The allocation schedule was created as the source of
a computer-generated list of random numbers and
was concealed from investigators by SO alone. Pa-
tients were enrolled and assigned to groups. To de-
tect mean differences of clinical parameters with a
two-sided 5% signicance level and a power of 97%,
a sample size of 20 patients per group was necessary,
given an anticipated dropout rate of 10%. To recruit
this number of patients, a 1-year inclusion period was
anticipated. Therefore, the sample size (21, 23, 23)
for this study was adequate. Data were analyzed
using an intention-to-treat and per-protocol principle.
In all endpoints, 95% condence intervals (CIs) for
within-group changes and between-group differences
are reported. Analysis of covariance indicated a sta-
tistically signicant difference between the groups
Table 1.
Baseline Demographic and Clinical Characteristics of 69 Patients Undergoing EMD/FDBA
(EF), EMD/DFDBA (ED), and EMD (E; negative control)
Characteristic EF (n = 23) ED (n = 23) E (n = 23)
Age (years), mean (SD) 53 (11) 56 (9) 54 (4)
Females, n (%) 17 (74) 19 (83) 19 (83)
Males, n (%) 6 (26) 4 (17) 4 (17)
Defect morphology, n (%)
1-wall 0 (0) 0 (0) 0 (0)
2-wall 7 (30) 8 (35) 8 (35)
3-wall 12 (52) 12 (52) 13 (57)
Combination 4 (18) 3 (13) 2 (8)
Tooth, n (%)
Incisor 1 (4) 0 1 (4)
Canine 1 (4) 0 1 (4)
Premolar 1 (4) 2 (9) 1 (4)
Molar 20 (88) 21 (91) 20 (88)
Location, n (%)
Maxilla 10 (43) 11 (48) 12 (52)
Mandible 13 (57) 12 (52) 11 (48)
PD (mm), mean (SD) 6.57 (0.95) 6.43 (0.72) 6.56 (0.59)
CAL (mm), mean (SD) 7.30 (0.70) 7.26 (0.96) 7.13 (0.87)
# Ethicon, Johnson & Johnson, Somerville, NJ.
** Dentsply-Rinn, Chicago, IL.
EMD/FDBA Versus EMD/Demineralized FDBA Volume 85 Number 10
1354
in PD, CAL, and OPAL. Further analysis with Tukey
multiple comparison procedure was conducted.
Wilcoxon signed-ranked tests were used to determine
the differences in within-group changes in PD, CAL,
OPAL, plaque index (PI), bleeding on probing (BOP),
and radiographic bone gain; a was set at 0.05, and all
tests were two-tailed. To interpret negative study
results (P 0.05), post hoc power analysis using the
mean difference and the standard deviation was
conducted. Statistical

and spreadsheet software

were used in the analysis.

RESULTS
Clinical and Demographic Results
From April 2004 to October 2008, 69 patients with
a diagnosis of CP were recruited from a periodontal
private practice. The EF group (n = 23), ED group
(n = 23), and E (control) group (n = 23) had similar
demographic and baseline characteristics (Table 1).
Figure 1 shows the recruitment, inclusion, assignment,
and subsequent follow-up of the study patients.
Outcomes at 6 months, 1 year, and 3 years were
missing for 2 male patients due to move (n = 1 at 5
months) and lack of motivation (n = 1 at 6 months).
Primary Outcome Parameter
All groups demonstrated signicant improvement
in PD reduction and CAL gain from baseline. The
changes for PD were as follows (mm, 95% CI): at 1
year: EF (4.4 mm, 4.0 to 4.7), ED (3.7 mm, 3.4 to
4.0), and E (control) (3.3 mm, 3.0 to 3.6); at 3 years:
EF (4.4 mm, 4.1 to 4.8), ED(3.7 mm, 3.4 to 4.0), and
E (3.1 mm, 2.8 to 3.4). The changes for CAL were as
Figure 2.
EMD/DFDBA in the treatment of an intrabony defect. A) Baseline radiograph. B) Extent of the intrabony defect demonstrated by the insertion of
a periodontal probe. C) EMD/DFDBA compacted into the intrabony defect. D) Re-entr y 6 months after initial surger y conrmed complete lling
of the intrabony defect. E) Radiograph at 1-year follow-up.
Figure 3.
EMD/FDBA in the treatment of an intrabony defect. A) Baseline radiograph. B) Extent of the intrabony defect demonstrated by the insertion of
a periodontal probe. C) EMD/FDBA compacted into the intrabony defect. D) Re-entry 6 months after initial surgery conrmed complete lling of the
intrabony defect. E) Radiograph at 1-year follow-up.
XLSTAT-Pro, Addinsoft USA, New York, NY.
Microsoft Ofce 2010, Microsoft, Tokyo, Japan.
J Periodontol October 2014 Ogihara, Tarnow
1355
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EMD/FDBA Versus EMD/Demineralized FDBA Volume 85 Number 10
1356
follows (mm, 95% CI): at 1 year: EF (4.1 mm, 3.8 to
4.5), ED(3.5mm, 3.0to4.0), andE(3.0mm, 2.5to3.6);
at 3 years: EF (4.2 mm, 3.7 to 4.7), ED(3.6 mm, 3.1 to
4.1), and E (3.0 mm, 2.5 to 3.5) (Table 2). Between 1
and 3 years, all groups had no statistically signicant
differences in PD reduction and CAL gain (Table 2).
The intervention groups showed better treatment
outcomes than the control group at 1 and 3 years.
There were statistically signicant differences as well as
clinical differences in PD reduction and CAL gain be-
tween the EF and the control group at 1 and 3 years.
The differences for PD at 1 year were 1.1 mm (0.7 to
1.6); at 3 years, 1.3 mm (0.9 to 1.8). The differences
for CAL at 1 year were 1.1 mm (0.8 to 1.4); at 3 years:
1.2 mm(0.8 to 1.6). In contrast, there were statistically
signicant differences only in PD reduction and CAL
gain between the ED and the control group at 1 and 3
years. The differences for PD were; at 1 year, 0.4 mm
(0.01 to 0.9), and at 3 years, 0.7 mm (0.3 to 1.1). The
differences for CAL were; at 1 year, 0.5 mm(0.1 to 0.8)
and at 3 years, 0.6 mm (0.2 to 1.0) (Table 3; see
supplementary Tables 1 and 2 in online Journal of
Periodontology). There were no statistically signicant
differences in PD reduction and CAL gain between EF
and the ED at 1 and 3 years. The differences for PD
were: at 1 year, 0.7 mm (0.2 to 1.1 mm); at 3 years,
0.7 mm (0.2 to 1.2 mm). The differences for CAL
were: at 1 year, 0.6 mm (0.1 to 1.1 mm); at 3 years,
0.6 mm (0.1 to 1.1 mm). (Table 3; see supplementary
Table 3 in online Journal of Periodontology).
Secondary Outcome Parameter
All groups demonstrated signicant improvement
in OPAL gain from baseline. The changes for OPAL at
6 months reentry were EF (4.1 mm[3.2 to 5.1 mm]), ED
(4.2 mm [3.3 to 5.7 mm]) and E (control) (3.3 mm
[2.8 to 3.7 mm]). (Table 2). There were statistically
signicant differences as well as clinical differences
in OPAL gain between the two intervention groups
and the control group at 6-month re-entry. The
differences for OPAL were for EF/control: 0.9 mm
(0.01 to 1.7); for ED/control: 0.9 mm (0.01 to 1.8)
(Table 3; see supplementary Tables 1 and 2 in
online Journal of Periodontology). There was no
statistically signicant difference in OPAL gain be-
tween ED and EF at 6-month re-entry (Table 3; see
supplementary Table 3 in online Journal of Peri-
odontology).
There were no adverse outcomes, such as allergic
reactions to either EMD or the graft materials or root
resorption, to report fromany of the treatment groups.
Radiographic Outcome Parameter
All groups demonstrated signicant improvement in
radiographic bone gain frombaseline. Between 1 and 3
years, all groups had no statistically signicant differ-
ences (Table 2). There were statistically signicant
differences as well as clinical differences in radiographic
bone gain among both intervention groups and the con-
trol group at 1 and 3 years (Table 3; see supplemen-
tary Tables 1 and 2 in online Journal of Periodontology).
There was no statistically signicant difference in
radiographic bone gain between ED and EF at 1 and
3 years (Table 3; see supplementary Table 3 in online
Journal of Periodontology).
The multiple comparisons were made with the
Tukey procedure, and the results of this comparison
are given in Table 3.
Table 3.
Results of Multiple Comparisons of PD, CAL, OPAL, and Radiographic Bone Gain
(CEJ-bony defect)
Primary outcome
EMD/FDBA versus EMD (Control) EMD/DFDBA versus EMD (Control) EMD/FDBA versus EMD/DFDBA
Difference (95% CI) P Difference (95% CI) P Difference (95% CI) P
PD reduction
1 year 1.12 (0.68 to 1.56) <0.0001 0.44 (0.01 to 0.87) 0.048 0.68 (0.22 to 1.14) 0.009
3 years 1.34 (0.89 to 1.79) <0.0001 0.70 (0.30 to 1.10) 0.002 0.69 (0.23 to 1.15) 0.008
CAL gain
1 year 1.10 (0.78 to 1.42) <0.0001 0.48 (0.14 to 0.82) 0.014 0.62 (0.10 to 1.14) 0.017
3 years 1.19 (0.80 to 1.58) <0.0001 0.61 (0.21 to 1.01) 0.006 0.58 (0.08 to 1.08) 0.044
Secondary outcome
OPAL gain at 6 months 0.88 (0.02 to 1.74) 0.043 0.91 (0.01 to 1.83) 0.049 -0.04 (-1.26 to 1.18) 0.096
Radiographic bone gain
CEJ-bony defect
1 year 0.93 (0.05 to 1.81) 0.039 0.96 (0.03 to 1.89) 0.04 -0.03 (-1.28 to 1.22) 0.970
3 years 0.93 (0.01 to 1.85) 0.047 1.0 (0.04 to 1.96) 0.045 -0.07 (-1.37 to 1.23) 0.915
J Periodontol October 2014 Ogihara, Tarnow
1357
DISCUSSION
Overall, the current trial indicated that both graft
materials worked well in the management of deep
intrabony defects when combined with EMD. Both
EMD/FDBA and EMD/DFDBA interventions resulted
in signicantly higher soft tissue improvement at 1-
and 3-year follow-up and signicantly greater hard
tissue improvement at 6-month re-entry compared to
EMD control.
Direct comparisons among interventions are dif-
cult due to differences in multiple factors, including
patient population, measurement techniques, surgical
approach, operator skill with a given material, type
of defect treated, and level of plaque control.
20
The
current trial shows the effect of only one of these
variables, graft material difference. Therefore, the
current trial both contrasts the results of EMD/FDBA-
treated sites compared to the EMD control and
contrasts the results of EMD/DFDBA-treated sites
compared to the EMD control. Further study of the
effectiveness of intervention should be compared to
the standard (current available best treatment) or
placebo treatment.
21
Systematic reviews demon-
strated that use of EMD for periodontal osseous
defects yields signicantly higher soft tissue im-
provements compared to open ap debridement
(OFD) alone.
8-10
Therefore, the choice of compari-
son treatment in the current trial was EMD alone
without graft materials as the negative control, not
OFD. In the current trial, CAL gain and PD reduction
of 3.0 and 3.3 mm, respectively, in the EMD control
sites at 1 year post-surgery were within the ranges of
CAL gain (2.0 to 4.5 mm) and PD reduction (3.0 to
5.1 mm) in EMD sites reported by a review paper.
22
These ndings suggest that it is possible to draw
conclusions on the contributions of these graft ma-
terials to improve the primary and secondary out-
comes compared to the EMD control. Reviewing
baseline data, the groups are very similar (Table 1);
therefore randomization might be an effective design
to implement in conducting the study and also would
prevent selection bias. Other researchers conducting
regenerative therapy using EMD found CAL gain
associated with initial defect depth,
23
number of
walls,
23,24
and width of the defect (radiographic
defect angle).
25
In the current trial, initial defect depth
and width were not measured. However, randomi-
zation provides a powerful tool for controlling con-
founding factors that may be unknown or difcult to
measure. Furthermore, between 1 and 3 years, all
groups had no statistically signicant differences in
PD reduction and CAL gain. The positive results seen
in the current patient population might be attributable
to the level of plaque control and the frequency of
professional maintenance visits. In the current trial,
all patients were seen at least every 6 months for up
to 3 years. As a result, PI and BOP showed no sig-
nicant differences between 1 and 3 years, which
eliminated any bias (Table 2). In light of the factors
above, evidential results are the statistically signi-
cant differences found in all participants among
both interventions and EMD control. Moreover,
clinically signicant differences were found in PD
reduction (1.1 and 1.3 mm) and CAL gain (1.1 and
1.2 mm) at 1 and 3 years, respectively, and OF
(0.9 mm) at 6-month re-entry between EMD/FDBA
and EMD control sites, and in OF (0.9 mm) at 6-
month re-entry between EMD/DFDBA and EMD
control sites.
26-28
Comparison With Other Studies
Clinically, a case series documented that FDBA/EMD
had a better CAL gain than DFDBA/EMDat 6 months
post-surgery for the treatment of intrabony defects.
18
Using the contrasting results of EMD/FDBA-treated
sites compared to the EMD/DFDBA-treated sites
from the study by Rosen and Reynolds,
18
similar
ndings in the current trial were also obtained, i.e.,
that EMD/FDBA had better soft tissue improvements
compared to EMD/DFDBA. One possible explana-
tion for the small differences in the probing of these
cases may be nothing more than the FDBA may be
more resistant to probing due to the residual graft
particles and did nothing more to help actually gain
any true attachment. Besides, Rummelhart et al.
17
reported the response to treatment demonstrating
that when differences occurred, the FDBA implant
site usually exhibited a better response to treatment
by CAL gain, PD reduction, and OF.
17
Importantly, in
the current trial, between both intervention groups
and the control group, there were statistically
signicant differences as well as clinical differences
in OPAL gain and radiographic bone gain at 1 and
3 years (Table 3). Neither surgical hard tissue mea-
surement nor radiographic hard tissue measurement
was inuenced by the probing resistance from FDBA
graft particles.
Strengths and Limitations
One potential limitation is that stents were not used
to facilitate reproducible measurements. Between
the 1- and 3-year follow-up period, in many cases,
provisional restorations were replaced by nal res-
torations, causing problems for the use of stents. A
possible limitation is that all of the grafting material
had minocycline added. It was not used for the
EMD-alone groups and might have an effect on the
treatment outcomes. A recent study suggested that
application of locally delivered minocycline with ap
surgery had statistically signicant PD reduction
and CAL gain compared to ap surgery alone for the
EMD/FDBA Versus EMD/Demineralized FDBA Volume 85 Number 10
1358
treatment of CP at 6 months post-surgery.
29
A pos-
sible limitation is that the graft material used did not
come from a single donor. This could have inuenced
the treatment outcome because variation in age and
sex of the donor may have impacted the grafts in-
ductivity.
30
However, all graft materials in the current
study were obtained from the same tissue bank to
minimize different tissue bank protocols on pro-
cessing of the graft.
31
A possible limitation is that the
surgical operator and examiner is the same person
(SO), since the current trial was conducted in a solo
periodontal practice. Finally, a possible limitation is
that the physical linear measurements using a peri-
odontal probe were used for a morphometric analysis.
Highly accurate and reproducible linear measurements
using cone beam computed tomography are currently
available.
32
CONCLUSIONS
This study provides evidence that both EMD/FDBA
and EMD/DFDBA combination therapies result in
greater soft tissue improvements at 1- and 3-year
follow-up and greater hard tissue improvements at
6-month re-entry compared to EMDalone. Both graft
materials worked well in managing deep intrabony
defects when combined with EMD.
ACKNOWLEDGMENT
The authors report no conicts of interest related to
this study.
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Correspondence: Dr. Shigeki Ogihara, 23-5, Adachi 4
chome, Adachi-ku, Tokyo, 1200015, Japan. E-mail:
oshigeki@spn1.speednet.ne.jp.
Submitted August 19, 2013; accepted for publication
February 24, 2014.
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