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J Periodontol • June 2009

A Surgical Reentry Study on the


Influence of Platelet-Rich Plasma in
Enhancing the Regenerative Effects of
Bovine Porous Bone Mineral and Guided
Tissue Regeneration in the Treatment of
Intrabony Defects in Humans
Paulo M. Camargo,* Vojislav Lekovic,*† Michael Weinlaender,‡ Tihana Divnic-Resnik,†
Marija Pavlovic,† and E. Barrie Kenney*

Background: The purpose of this study was to evaluate the ad-


ditional benefits provided by the incorporation of platelet-rich
plasma (PRP) into a regenerative protocol consisting of bovine
porous bone mineral (BPBM) and guided tissue regeneration
(GTR) in the treatment of intrabony defects in humans.
Methods: Twenty-three paired intrabony defects were surgi-
cally treated using a split-mouth design. Defects were treated

P
eriodontal regeneration involves
with BPBM/GTR/PRP (experimental group) or with BPBM/GTR the formation of alveolar bone,
(control group). The clinical parameters evaluated included cementum, and a new func-
changes in probing depth, clinical attachment level, and defect tional periodontal ligament.1 For peri-
fill as revealed by reentry surgeries at 6 months. odontal regeneration to occur, a
Results: Preoperative probing depths, attachment levels, and number of biologic events, including
transoperative bone measurements were similar for the two cell migration, adherence, multiplica-
groups. Post-surgical measurements taken at 6 months revealed tion, and differentiation, need to oc-
that both treatment modalities resulted in a significant decrease cur in a well-orchestrated sequence.
in probing depth, gain in clinical attachment, and bone fill of Therefore, therapeutic modalities that
the defects compared to baseline. Postoperative differences ob- aim at facilitating periodontal tissue
served between the two groups were 0.72 – 0.36 mm at buccal cells to behave in a way that is
sites and 0.90 – 0.32 mm at lingual sites for probing depth, conducive to regenerate the peri-
0.82 – 0.41 mm at buccal sites and 0.78 – 0.38 at lingual sites odontium have potential application
for gain in clinical attachment, and 0.85 – 0.36 mm at buccal in patient care.
sites and 0.94 – 0.42 mm at lingual sites for defect fill, all favoring Polypeptide growth factors (PGFs)
the experimental sites. However, none of the differences were sta- are biologic mediators that have the
tistically significant. ability to regulate cell multiplication,
Conclusion: Within the limitations related to using a small sam- migration, and differentiation. There-
ple size, PRP did not significantly augment the effects of BPBM fore, PGFs have potential applications
and GTR in promoting the clinical resolution of intrabony defects. in periodontal regeneration. Several
J Periodontol 2009;80:915-923. PGFs have been identified in human
periodontal tissues by immunohisto-
KEY WORDS
chemistry and in situ hybridization.2
Guided tissue regeneration; periodontal regeneration; Moreover, these PGFs were shown to
platelet-rich plasma. promote cell growth and differentia-
tion in vitro and periodontal regenera-
tion in animals.3-12 Human studies on
* Division of Associated Clinical Specialties, Section of Periodontics, University of California,
Los Angeles School of Dentistry, Los Angeles, CA. the effects of PGFs on periodontal
† Faculty of Stomatology, Department of Periodontics, University of Belgrade, Belgrade,
Republic of Serbia.
‡ Private practice, Vienna, Austria.
doi: 10.1902/jop.2009.080600

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Xenograft and GTR With or Without PRP in Intrabony Defects Volume 80 • Number 6

regeneration in vivo are limited. Of all known PGFs, reported by de Obarrio et al.28 and showed that the
platelet-derived growth factor (PDGF) was shown to positive outcome observed could not be attributed
exert a favorable effect on periodontal regeneration to the flap surgical procedure alone. The design of
as measured by gain in clinical attachment and radio- those studies did not allow for the identification of
graphic defect fill in humans.13,14 which component(s) of the triple therapy contributed
The combination of graft materials with guided tis- to the positive results obtained.
sue regeneration (GTR) is a proven modality of ther- Döri et al.30,31 examined the role played by PRP in
apy for the treatment of intrabony defects15-18 and augmenting the effects of BPBM/GTR. They reported
Class 2 furcation invasions.19,20 Results from the that PRP did not provide an additional benefit to that of
above-mentioned studies showed that the outcomes the BPBM/GTR combination, either when a collagen
achieved with the combination of the two agents are membrane30 or an expanded polytetrafluoroethylene
at least as effective as, and in some cases superior (ePTFE) membrane was used as a barrier.31 In yet an-
to, those achieved with bone grafts alone. Bovine po- other study, Döri et al.32 showed that PRP did not en-
rous bone mineral (BPBM) is a graft material prepared hance the regenerative capabilities of beta tricalcium
by protein extraction of bovine bone that results in a phosphate used in combination with ePTFE mem-
trabecular structure of hydroxyapatite similar to hu- branes in the treatment of intrabony defects. The pri-
man cancellous bone, and it has the ability to enhance mary outcomes of the three studies listed above were
bone formation.21 Therefore, it has been widely used gain in clinical attachment and probing depth resolu-
in periodontal regenerative procedures alone or in tion. No reentry of the treated areas was conducted;
combination with GTR. In a controlled clinical trial, therefore, it is still unknown if PRP exerts an additional
Camargo et al.22 examined the effects of BPBM and positive effect on the formation of hard tissue in de-
a collagen membrane of porcine origin for GTR on fects treated with a bone graft and GTR.
the treatment of intrabony defects and showed a mean The purpose of this study was to compare the clin-
clinical attachment gain >3 mm and mean defect fill ical effectiveness of two regenerative techniques in
>3.5 mm; both values were significantly better than treating intrabony defects in humans: a combination
those observed in controls treated with open flap de- of PRP/BPBM/GTR versus a combination of BPBM/
bridement. Camelo et al.23 reported on two cases of GTR. Specifically, this study was designed to examine
intrabony defects treated with BPBM and GTR; they the role played by PRP in augmenting the effects of
demonstrated that clinical attachment levels can be BPBM/GTR in promoting probing depth reduction,
improved and histologic regeneration of the attach- clinical attachment gain, and intrabony defect fill.
ment apparatus can be achieved using this combined
technique. MATERIALS AND METHODS
The PGFs PDGF and transforming growth factor- Patients
beta (TGF-b) are abundant in the alpha granules of The study was conducted at the School of Dentistry,
platelets.24 Therefore, the use of platelet-rich plasma University of Belgrade, from May 15, 1999 to March
(PRP) is a convenient approach to obtain autologous 20, 2000. Twenty-three systemically healthy patients
PDGF and TGF-b. The technique to obtain such a (14 females and nine males; age range: 34 to 67 years;
platelet preparation was reported elsewhere;25-27 it mean age: 47 – 10 years; 11 smokers and 12 non-
basically involves the sequestration and concentra- smokers) with matched pairs of interproximal defects
tion of platelets in plasma with the subsequent appli- were recruited for the study. Inclusion criteria consisted
cation of that preparation to the wound-healing site. It of patients having two similar interproximal defects with
was shown that the application of PRP to the wound- probing depths ‡6 mm after initial therapy. Radio-
healing site can increase the local concentration of graphic evidence of intrabony defects had to exist.
platelets substantially because PRP contains ;338% Upon surgical exposure, defects needed to have a min-
more platelets than peripheral blood.26 imum depth of 3 mm (as measured from the most cor-
In a case report series,28 de Obarrio et al. incorpo- onal point of the bony walls surrounding the defect to
rated PRP into a bone allograft/GTR combination the deepest point in the defect) and present with two
technique as periodontal therapy for intrabony de- or three bony walls as a final criterion for patients to
fects in humans. This initial investigation showed a be included in the study. The exclusion criteria were
significant gain in clinical attachment and defect fill systemic illnesses, compromised immune system,
in the treated defects as revealed by 2-year reentry pregnant and/or lactating women, and patients taking
surgeries. Camargo et al.29 subsequently compared any drug known to cause gingival enlargement. Pa-
the effectiveness of BPBM/PRP/GTR to that of an open tients allergic or sensitive to any of the medications to
flap debridement procedure in the treatment of intra- be used in the study were not included. Teeth non-re-
bony defects. The results of that study confirmed the sponsive to cold or endodontically treated were also ex-
effectiveness of the triple therapy as anecdotally cluded from the study. The two defects to be treated

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J Periodontol • June 2009 Camargo, Lekovic, Weinlaender, Divnic-Resnik, Pavlovic, Kenney

could not be present in the same interproximal space. 48 hours were similar to the nearest whole millimeter
Patients were informed as to the character and purpose at ‡90% level.
of the study and were required to sign informed consent.
Presurgical Clinical Measurements
The University Institutional Review Board approved the
Occlusal stents for positioning measuring probes
study design and consent form.
were fabricated with cold-cured acrylic resin on a cast
Presurgical Therapy model obtained from an alginate impression. The oc-
Therapy consisted of oral hygiene instructions, which clusal stents were made to cover the occlusal surface
was repeated until patients achieved a modified of the tooth being treated and the occlusal surfaces of
O’Leary plaque score33 £25%. Scaling and root plan- at least one tooth in the mesial and distal directions.
ing of the quadrant(s) involving the teeth to be treated Stents were also extended apically on the buccal
were performed with hand curets§ under local anes- and lingual surfaces to cover the coronal third of the
thesia. Occlusal adjustment was performed if trauma teeth involved. Grooves were placed so that measure-
from occlusion was diagnosed. Trauma from occlu- ments made post-surgery were at the same position
sion was evaluated by examining the presence of and angulation as those made prior to surgery. All
fremitus in centric occlusion or in working or balanc- steps described above were developed to obtain an
ing excursions. occlusal stent that was stable when in position and
Six to 8 weeks after phase I therapy, a periodontal easily removed by the therapist.
reevaluation was performed to confirm the suitability Prior to surgery, the plaque index37 and gingival
of the sites for this periodontal surgical study, and a sulcus bleeding index38 were measured. With the
preoperative periapical radiograph was taken that acrylic stent in position, the periodontal probe was in-
provided baseline data. The study used a split-mouth serted at the angle necessary to reach the deepest
design, and two interproximal sites were randomly portion of the interproximal pocket. Angulation varied
(toss of a coin) assigned to the control and experimen- between 10 and 20. A pencil mark was made where
tal groups. the probe made contact with the acrylic stent, and a
The experimental therapy consisted of surgical ex- groove was made on the pencil-marked area with a
posure of the defects and treatment with BPBM, GTR, cylindric low-speed burr. Using the groove as a guide,
and PRP (experimental group) and BPBM and GTR the periodontal probe was reinserted into the pocket,
(control group). and probing depth (using the gingival margin as refer-
ence) and relative attachment level (using the most
PRP Preparation
apical end of the stent as reference) were recorded.
PRP was prepared using the Curasan method.34-36
Measurements were performed with a Marquis peri-
Ten milliliters of blood was drawn from each patient
odontal probe¶ and recorded to the nearest millimeter.
by venipuncture of the antecubital vein. Blood was
The same measurements were repeated on the buccal
collected into glass tubes,i which contained 10% triso-
and lingual surfaces of each interproximal defect.
dium citrate solution as an anticoagulant. The blood-
containing glass tubes were centrifuged at 5,600 Surgical Procedures and
revolutions per minute for 6 minutes, which resulted Intrasurgical Measurements
in the separation of three basic fractions: platelet-poor Surgical procedures were performed after local infil-
plasma (PPP) at the top of the preparation, PRP in the tration of 2% lidocaine containing epinephrine at a
middle, and the red blood cell (RBC) fraction at the concentration of 1:100,000. Buccal and lingual sulc-
bottom. Two milliliters of the top layer corresponding ular incisions were performed, and mucoperiosteal
to PPP was aspirated with a Pasteur pipette and dis- flaps were elevated. Care was exercised to preserve
carded. The PRP was collected in conjunction with as much interproximal soft tissue as possible. Com-
the top 1 to 2 mm of the RBC fraction because the lat- plete debridement of the defects as well as scaling
ter is also rich in newly synthesized platelets. This and root planing were achieved with an ultrasonic de-
preparation typically yields a platelet concentration vice# and hand curets. Measurements of the osseous
that is 1.7 to 3.5 times greater than in blood. defects were made using the grooves previously used
to record probing depth and attachment levels. The
Calibration of Surgeons and Examiner distance between the most apical end of the stent
All surgeries were performed by two periodontists. and the point at which the groove-adapted probe
An examiner other than the surgeons performed all made contact with the bottom of the defect was re-
clinical measurements without knowledge of the corded at buccal and lingual sites. Other grooves,
treatment groups. Intraexaminer calibration was
achieved by examining three patients twice, 48 hours § Hu-Friedy, Chicago, IL.
i Vacutainer, Becton Dickinson, Franklin Lakes, NJ.
apart, prior to beginning the study. Calibration was ¶ Hu-Friedy.
accepted if measurements at baseline and at # Cavitron, Dentsply, York, PA.

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Xenograft and GTR With or Without PRP in Intrabony Defects Volume 80 • Number 6

one buccal and one lingual, were fabricated as de- for hard tissue measurements were to remove all
scribed earlier to measure the distance between the granules of the graft material that were surrounded
most apical end of the stent and the interproximal al- by soft tissue and that were clearly loose and not in-
veolar crest that formed the superficial border of the corporated into a hard tissue matrix that was judged
defect. to be bone upon clinical inspection. Granules of the
Experimental sites were treated as follows. At the graft material that were visible within the regenerated
time of the surgery, coagulation of PRP was achieved tissues but surrounded by hard tissue that was judged
by its combination with an equal volume of a sterile to be bone upon clinical inspection were left undis-
saline solution containing 10% calcium chloride and turbed. If the tip of the periodontal probe touched
100 U/ml sterile bovine thrombin.** Within a few sec- any of the incorporated graft particles during any of
onds it assumed a sticky gel consistency. Cancellous the measurements, it was regarded as a legitimate
BPBM granules, with a particle size of 0.25 to 1.0 landmark.
mm,†† were mixed with the coagulated PRP prepara-
Statistical Analysis
tion at a proportion of 1:1. Prior to grafting, PRP and
This clinical trial was conducted to test the potential
the coagulating solution were applied to the defect
superiority of the experimental protocol compared
walls and root surfaces. The BPBM/coagulated PRP
to controls.
mixture was tightly packed into the experimental de-
Results were averaged (mean – SE) for probing
fects using amalgam condensers to the level of the
depth, clinical attachment level, defect fill, and alveo-
surrounding bony walls. Care was taken not to overfill
lar crest resorption. The net difference between each
defects. A porcine-derived collagen membrane‡‡ was
pair of measurements (pre- and postoperative) was
adapted over the grafted defect. Membranes were ex-
calculated, followed by computation of the difference
tended over the periphery of the defect in the buccal
between treatment groups. The Student paired t test
and lingual directions and secured in place using
was used to compare the differences between the
5-0 gut sutures anchored to the adjacent teeth.
two groups.
Defects in the control group were treated in the
For the plaque index and the gingival sulcus bleed-
same manner as in the experimental group, but they
ing index, the frequency with which each score oc-
did not receive PRP. In brief, defects were filled with
curred was recorded for the experimental and
BPBM granules over which a collagen membrane
control groups. Intra- and intergroup comparisons
was adapted and sutured.
were conducted using the x2 test.
Flaps in both groups were sutured at the original
P values £0.05 were regarded as statistically
levels using 4-0 silk with a continuous sling technique.
significant.
Periodontal dressing was placed over the area, and
antibiotics (penicillin vk, 500 mg, every 6 hours for RESULTS
14 days) and 0.12% chlorhexidine gluconate rinses
All 23 patients completed the study. Defects in the ex-
(every 12 hours for 14 days) were prescribed. Oral an-
perimental and control groups healed uneventfully.
algesics (ibuprofen, 800 mg, every 8 hours as neces-
No cases of flap dehiscence or infection were de-
sary) were also dispensed.
tected.
Postoperative Care At baseline, no statistically significant differences
Dressing and silk sutures were removed 1 week were detected between experimental and control sites
postoperatively. Patients initiated mechanical oral with respect to probing depth, clinical attachment
hygiene, consisting of brushing and flossing or inter- level, and depth of the intrabony defects.
proximal brushing, at the end of the second postop- An individual description of defect location and an-
erative week. Patients were examined weekly up to atomic characteristics are shown in Table 1. The
1 month after surgery and then at 3 and 6 months. experimental group had 19 2-wall defects and four
Postoperative care included reinforcement of oral 3-wall defects, whereas the control group had 17
hygiene and mechanical plaque removal whenever 2-wall defects and six 3-wall defects.
necessary. The majority of the experimental and control sites
presented with granules of BPBM that could be iden-
Reentry Procedures
tified within the regenerated tissues at reentry surger-
Six months after the initial surgery, all clinical mea-
ies. These granules appeared to be incorporated into
surements were repeated, and surgical reentries were
the newly developed hard tissue and could not be re-
performed. Surgical reentries consisted of buccal and
moved easily with a periodontal curet.
lingual full-thickness flaps to access the interproximal
bone. All measurements described for the first surgi-
** Tissucol, Immuno, Vienna, Austria.
cal procedure were repeated during reentries using †† Bio-Oss, Geistlich, Wolhusen, Switzerland.
the acrylic stent as described earlier. The criteria used ‡‡ Bio-Gide, Geistlich.

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J Periodontol • June 2009 Camargo, Lekovic, Weinlaender, Divnic-Resnik, Pavlovic, Kenney

Table 1. Table 1. (continued)


Individual Defect Location and Individual Defect Location and
Anatomic Characteristics Anatomic Characteristics

Tooth Tooth
Number Treatment Defect Bony Walls Number Treatment Defect Bony Walls
Patient and Surface Group Type Present Patient and Surface Group Type Present

1 22 D PRP/BPBM/GTR 3-wall DBL 16 2D BPBM/GTR 2-wall DL

1 27 D BPBM/GTR 2-wall DL 17 19 D PRP/BPBM/GTR 2-wall DL


2 15 M PRP/BPBM/GTR 2-wall ML 17 30 D BPBM/GTR 2-wall DL
2 2M BPBM/GTR 2-wall ML 18 2M PRP/BPBM/GTR 2-wall MB

3 13 D PRP/BPBM/GTR 3-wall DBL 18 15 M BPBM/GTR 2-wall MB


3 4M BPBM/GTR 2-wall ML 19 28 M PRP/BPBM/GTR 2-wall ML
4 20 D PRP/BPBM/GTR 2-wall DL 19 22 D BPBM/GTR 3-wall DBL

4 29 D BPBM/GTR 2-wall DB 20 21 M PRP/BPBM/GTR 2-wall ML


5 14 M PRP/BPBM/GTR 2-wall ML 20 28 M BPBM/GTR 3-wall MBL
5 3M BPBM/GTR 2-wall ML 21 14 M PRP/BPBM/GTR 2-wall MB
6 5D PRP/BPBM/GTR 3-wall DBL 21 3M BPBM/GTR 2-wall ML

6 12 D BPBM/GTR 3-wall DBL 22 27 M PRP/BPBM/GTR 2-wall MB


7 13 D PRP/BPBM/GTR 2-wall DL 22 28 D BPBM/GTR 2-wall DL
7 18 M BPBM/GTR 2-wall ML 23 21 D PRP/BPBM/GTR 2-wall DL

8 3M PRP/BPBM/GTR 2-wall ML 23 28 D BPBM/GTR 2-wall DL


D = distal; B = buccal; L = lingual; M = mesial.
8 2M BPBM/GTR 2-wall ML
9 20 D PRP/BPBM/GTR 2-wall DL
Changes in probing depth are reported in Table 2.
9 29 D BPBM/GTR 2-wall DL The experimental and control groups showed a signif-
10 27 M PRP/BPBM/GTR 3-wall MBL icant probing depth reduction at 6 months. The postop-
erative differences in probing depth between the two
10 22 M BPBM/GTR 3-wall MBL groups were 0.72 – 0.36 mm at buccal sites and
11 20 M PRP/BPBM/GTR 2-wall ML 0.90 – 0.32 mm at lingual sites in favor of the experi-
mental sites, but they were not statistically significant.
11 29 M BPBM/GTR 3-wall MBL Clinical attachment level changes are shown in Ta-
12 21 M PRP/BPBM/GTR 2-wall ML ble 3. Experimental sites presented with greater clin-
ical attachment gain of 0.82 – 0.41 mm at buccal sites
12 29 M BPBM/GTR 3-wall MBL and 0.78 – 0.38 at lingual sites, but these differences
13 31 M PRP/BPBM/GTR 2-wall ML were not statistically significant.
Table 4 reports changes in defect hard tissue fill for
13 18 M BPBM/GTR 2-wall ML the experimental and control groups. Both treatments
14 2M PRP/BPBM/GTR 2-wall MB resulted in significant defect fill with hard tissue. The
postoperative differences observed between the two
14 15 M BPBM/GTR 2-wall MB groups were 0.85 – 0.36 mm at buccal sites and
15 14 M PRP/BPBM/GTR 2-wall ML 0.94 – 0.42 mm at lingual sites, both favoring the ex-
perimental sites, but these differences were not statis-
15 3M BPBM/GTR 2-wall ML tically significant. Resorption of the alveolar crest was
16 15 D PRP/BPBM/GTR 2-wall DL similar for both groups (Table 4).
Plaque measurements and the gingival sulcus
bleeding index were not significantly different

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Xenograft and GTR With or Without PRP in Intrabony Defects Volume 80 • Number 6

Table 2. versely, the data pre-


sented in this study are
Probing Depth (mm; mean – SE) Measured From the Gingival
the first to suggest that
Margin (N = 23 paired defects) PRP does not exert a
positive effect on the
Mean Difference fill of intrabony defects
Site PRP/BPBM/GTR BPBM/GTR P Value Between Groups treated with BPBM/GTR
Initial Buccal 8.19 – 1.56 8.11 – 1.48 >0.05 NS as revealed by reentry
Lingual 8.21 – 1.62 8.23 – 1.52 >0.05 NS surgeries.
In addition to clinical
6 months Buccal 3.31 – 1.38 3.95 – 1.46 >0.05 NS attachment gain and
Lingual 3.49 – 1.46 4.41 – 1.49 >0.05 NS
probing depth reduc-
Mean reduction Buccal 4.88 – 1.08 4.16 – 1.11 >0.05 NS 0.72 – 0.36 tion, defect fill is a
Lingual 4.72 – 1.12 3.82 – 0.98 >0.05 NS 0.90 – 0.32 desirable outcome of
NS = not statistically significant. periodontal regenera-
tive procedures because
Table 3. alveolar bone is an inte-
gral component of the
Changes in Clinical Attachment Levels (mm; mean – SE) Measured periodontium. One of
From the Acrylic Stent (N = 23 paired defects) the reasons why we hy-
pothesized that greater
Mean Difference defect fill would occur
Site PRP/BPBM/GTR BPBM/GTR P Value Between Groups with BPBM/GTR/PRP
than with BPBM/GTR
Mean gain (initial to 6 months) Buccal 4.38 – 1.22 3.56 – 1.21 >0.05 NS 0.82 – 0.41
was because PRP was
Lingual 4.12 – 1.18 3.34 – 1.18 >0.05 NS 0.78 – 0.38 shown to have an ana-
NS = not statistically significant.
bolic effect on bone
healing.26 Because peri-
odontal regeneration in-
Table 4.
cludes the formation of
Defect Fill and Alveolar Crest Resorption (mm; mean – SE) new bone, it was be-
Measured From the Acrylic Stent (N = 23 paired defects) lieved that PRP could
influence the regenera-
Mean Difference tion of the bony compo-
Site PRP/BPBM/GTR BPBM/GTR P Value Between Groups nent of the periodontal
unit. A possible expla-
Mean defect fill Buccal 4.81 – 1.26 3.96 – 0.91 >0.05 NS 0.85 – 0.36 nation for PRP not hav-
(initial to 6 months) Lingual 4.72 – 1.24 3.78 – 0.88 >0.05 NS 0.94 – 0.42
ing an added positive
Mean resorption Buccal 0.69 – 0.66 0.88 – 0.72 >0.05 NS 0.19 – 0.21 effect on bone forma-
(initial to 6 months) Lingual 0.72 – 0.71 0.79 – 0.76 >0.05 NS 0.07 – 0.11 tion in the defects trea-
NS = not statistically significant. ted in this study may lie
in the fact that BPBM is
between the experimental and control groups at base- a very powerful osteoconductive agent in the process
line or at 6 months postoperatively (Table 5). of bone formation and that GTR also has the ability to
enhance osteogenesis in the periodontal regenerative
DISCUSSION process. Therefore, the BPBM/GTR combination may
The results of this clinical study suggest that PRP did have optimized the regenerative potential of the de-
not significantly augment the effects of BPBM com- fects and, therefore, obfuscated any additional posi-
bined with GTR in terms of decreasing probing depth, tive osteogenic effect exerted by PRP. It was reported
promoting clinical attachment gain, and enhancing hard that fill of intrabony defects treated with BPBM/GTR
tissue fill of intrabony defects. These results confirm data can be substantial, leaving little room for further im-
from studies30-32 in which an osseous graft or a hard tis- provement.22
sue substitute graft combined with a non-absorbable or Lekovic et al.39 compared BPBM/GTR/PRP to
bioabsorbable membrane for GTR did not benefit from BPBM/PRP as regenerative treatment modalities for in-
the addition of PRP with regard to promoting probing trabony defects that were similar in severity to the ones
depth resolution or increasing clinical attachment. Con- examined in this study. Data from that study showed

920
J Periodontol • June 2009 Camargo, Lekovic, Weinlaender, Divnic-Resnik, Pavlovic, Kenney

Table 5. cells from the flap.42 If membranes and PRP work by


controlling the dynamics of periodontal defect cell re-
Plaque Index and Gingival Sulcus Bleeding
population, this might explain why PRP failed to aug-
Index (N = 23 paired defects) ment the effects of BPBM and GTR in the present
study. Further supporting this theory are the facts that
BPBM/GTR PRP/BPBM/GTR P Value PRP significantly increased the effects of BPBM com-
Plaque index pared to BPBM used alone in the treatment of intrabony
Initial 0 (70.6%) 0 (72.8%) ‡0.05 NS defects43 and that autologous platelet concentration (a
1 (14.1%) 1 (10.9%) preparation similar to PRP) failed to augment the effect
2 (9.8%) 2 (9.8%) of GTR in regenerating periodontal defects.44,45
3 (5.4%) 3 (6.5%) This clinical trial was conducted to examine the
6 months 0 (71.7%) 0 (76.1%) ‡0.05 NS working hypothesis that adding PRP to BPBM/GTR
1 (13.0%) 1 (7.6%) would result in superior results in the clinical param-
2 (8.7%) 2 (6.5%)
eters evaluated compared to BPBM/GTR without
3 (6.5%) 3 (9.8%)
PRP. The sample size used in this study was relatively
P value ‡0.05 NS ‡0.05 NS
small, but it was within the range of most periodontal
Sulcus bleeding index regenerative studies.46 This sample size was adopted
Initial 0 (30.4%) 0 (30.4%) ‡0.05 NS because it was within the range used in other peri-
1 (23.9%) 1 (22.8%) odontal regenerative studies conducted by the authors’
2 (19.6%) 2 (21.7%) research group in which a statistically significant dif-
3 (17.4%) 3 (16.3%)
ference was reached between various control and ex-
4 (8.7%) 4 (8.7%)
perimental protocols with respect to the parameters
6 months 0 (32.61%) 0 (36.96%) ‡0.05 NS
1 (33.70%) 1 (26.09%) evaluated.47,48 That does not mean that this study
2 (15.22%) 2 (17.39%) had the power to demonstrate superiority or equiva-
3 (13.04%) 3 (14.13%) lency.49 In conducting a post hoc power analysis of
4 (5.43%) 4 (5.43%) the data reported in this study, all differences in the
P value ‡0.05 NS ‡0.05 NS magnitude observed between the control and experi-
NS = not statistically significant. mental groups would have been statistically signifi-
cant if 61 paired defects had been used instead of
23. This post hoc power analysis was based on the pa-
that GTR did not have an additional benefit to BPBM/ rameter that presented with the smallest difference
PRP for any of the parameters evaluated, i.e., decrease between control and experimental sites, i.e., probing
in probing depth, gain in clinical attachment, and de- depth on the buccal aspect (95% power at alpha =
fect fill. Although comparisons between independent 0.05). Therefore, if the current study were conducted
studies should be conducted with care, and definitive with 61 paired defects, all differences between treat-
conclusions cannot be drawn from such comparisons, ment groups would have reached statistical signifi-
when the data sets from the current study and the one cance. Within the subject of statistical significance,
by Lekovic et al.39 are compared, it could be specu- the lack of statistical significance between the two
lated that GTR and PRP exert a similar effect in aug- treatment groups should not be interpreted as the
menting the regenerative effects of BPBM in treating two treatment modalities being equivalent. In general,
intrabony defects. Although the mechanism by which for two treatment modalities to be statistically equiv-
GTR promotes periodontal regeneration is believed to alent, a larger sample size is required than the one in
be well understood,40 the exact role played by PRP in a study to demonstrate superiority.
the regenerative process is less clear. It is possible that Hypothesizing that the differences observed be-
the PGFs present in PRP promote the growth and differ- tween experimental and control sites in the current
entiation of the periodontal ligament and alveolar bone study were statistically significant, one should also
cells, and that effect would result in the fast regenera- evaluate the results in terms of the clinical significance
tion of the periodontal unit. Another possible mecha- of combining PRP with BPBM/GTR in the treatment of
nism of action for PRP may be related to the physical intrabony defects. Clinical significance is a more sub-
characteristics of its fibrin component. Once the PRP jective issue than statistical significance, and, there-
preparation is coagulated, it assumes a sticky consis- fore, it may be a matter of interpretation. One way
tency because of its high fibrin content. The fibrin com- to frame clinical significance in light of the data pre-
ponent of PRP works as a hemostatic agent aiding in sented in this article is for the therapist to decide
stabilizing the graft material and the blood clot;41,42 it whether the time and cost involved in preparing PRP
may also adhere to the root surface and impede the ap- is justifiable by achieving greater probing depth reso-
ical migration of epithelial cells and connective tissue lution, clinical attachment gain, and defect fill that is

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Xenograft and GTR With or Without PRP in Intrabony Defects Volume 80 • Number 6

not >1 mm compared to not using PRP. Preparation of derived and insulin-like growth factors on periodontal
the PRP adds another step to the periodontal surgery wound healing. J Periodontol 1991;62:458-467.
appointment and increases the time of the entire pro- 6. Giannobile WV, Finkelman RD, Lynch SE. Compari-
son of canine and non-human primate animal models
cedure by 20 to 30 minutes. Under the supervision of a for periodontal regenerative therapy. Results following
dental surgeon, a properly trained surgical assistant a single administration of PDGF/IGF-I. J Periodontol
can prepare PRP. In addition to time, there are costs 1994;65:1158-1168.
associated with disposable items and equipment ac- 7. Rutherford RB, Niekrash CE, Kennedy JE, Charette
quisition and maintenance. Although assigning a pre- MF. Platelet-derived and insulin-like growth factors
stimulate periodontal attachment in monkeys. J Peri-
cise monetary value to the preparation of PRP in a
odontal Res 1992;27:285-290.
periodontal practice scenario is a complex exercise 8. Rutherford RB, Ryan ME, Kennedy JE, Tucker MM,
that is outside the scope of this study, it is fair to state Charette MF. Platelet-derived growth factor and dex-
that such a cost is not insignificant. Given the fact that amethasone combined with a collagen matrix induce
PDGF for periodontal applications can be obtained regeneration of the periodontium in monkeys. J Clin
from other sources, such as those generated via ge- Periodontol 1993;20:537-544.
9. Sigurdsson TJ, Lee MB, Kubota K, Turek TJ, Wozney
netic engineering,14 a comparison between PRP and JM, Wikesjö UM. Periodontal repair in dogs: Recombi-
PDGF with regard to its effectiveness and the cost/ nant human bone morphogenetic protein-2 significantly
benefit ratio would be of interest. Taken together, it enhances periodontal regeneration. J Periodontol
could be argued that the cost/benefit ratio of adding 1995;66:131-138.
PRP to BPBM/GTR is high and difficult to justify. 10. Ripamonti U, Heliotis M, van den Heever B, Reddi AH.
Bone morphogenetic proteins induce periodontal re-
CONCLUSIONS generation in the baboon (Papio ursinus). J Periodon-
tal Res 1994;29:439-445.
The data reported herein suggest that PRP does not 11. Sigurdsson TJ, Nygaard L, Tatakis DN, Fu E, Turek
augment the effects of BPBM/GTR in the regenerative TJ, Jin L, Wozney JM, Wikesjö UM. Periodontal repair
treatment of intrabony defects in humans. It also sug- in dogs: Evaluation of rhBMP-2 carriers. Int J Peri-
gests that PRP does not enhance defect fill in intrabony odontics Restorative Dent 1996;16:524-537.
12. King GN, King N, Cruchley AT, Wozney JM, Hughes
defects treated with the BPBM/GTR combination. It
FJ. Recombinant human bone morphogenetic protein-
must be emphasized that this study used a relatively 2 promotes wound healing in rat periodontal fenestra-
small sample size. Hypothetically, if similar studies tion defects. J Dent Res 1997;76:1460-1467.
with a larger sample size (‡61 paired defects) were 13. Howell TH, Fiorellini JP, Paquette DW, Offenbacher S,
performed and the results were the same as in the cur- Giannobile WV, Lynch SE. A phase I/II clinical trial to
rent clinical trial, the differences between the experi- evaluate a combination of recombinant human-derived
growth factor-BB and recombinant human insulin-like
mental and control groups would be statistically growth factor-I in patients with periodontal disease.
significant. However, even in that hypothetical sce- J Periodontol 1997;68:1186-1193.
nario, the clinical benefits of adding PRP to BPBM 14. Nevins M, Giannobile WV, McGuire MK, et al. Platelet-
and GTR would be marginal at best. derived growth factor stimulates bone fill and rate of
attachment level gain: Results of a large multicenter
ACKNOWLEDGMENT randomized controlled trial. J Periodontol 2005;76:
2205-2215.
The authors report no conflicts of interest related to 15. McClain PK, Schallhorn RG. Combined osseous composite
this study. grafting, root conditioning, and guided tissue regeneration.
Int J Periodontics Restorative Dent 1993;13:9-27.
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