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DENTAL IMPLANTS

Ridge Preservation Using Demineralized


Bone Matrix Gel With Recombinant Human
Bone Morphogenetic Protein-2 After Tooth
Extraction: A Randomized Controlled
Clinical Trial
Yu-Jin Kim, DDS,* Jeong-Yol Lee, DDS, PhD,y Jong-Eun Kim, DDS,z Jung-Chul Park, DDS, PhD,x
Sang-Wan Shin, DDS, PhD,jj and Kyoo-Sung Cho, DDS, PhD{
Purpose: The aim of the present randomized controlled trial was to determine the safety and efficacy of
injectable demineralized bone matrix (DBM) gel combined with recombinant human bone morphogenetic
protein-2 (rhBMP-2) on alveolar ridge preservation after tooth extraction.
Materials and Methods: A total of 69 patients were randomly assigned to either a test group (n = 35) or
a control group (n = 34). In the test group, DBM, together with rhBMP-2 (0.05 mg/mL; rhBMP-2/DBM) was
transplanted into the extraction sockets. The control group received DBM alone. The safety of rhBMP-2/
DBM was evaluated by oral examination, serum chemistry, and hematologic examination. The radio-
graphic changes in alveolar bone height and width were measured using computed tomography scans per-
formed immediately after transplant and again 3 months thereafter.
Results: Healing was uneventful in all subjects, with no anticipated adverse events and no clinically sig-
nificant changes in the serum chemistry and hematologic findings. No meaningful immune response was
found among the study groups. No significant difference was found in the radiographic changes of alveolar
bone height and width (P > .05).
Conclusions: This new injectable biomaterial can be used easily and safely in clinical applications.
Ó 2014 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg -:e1-e10, 2014
Demineralized bone matrix (DBM) is made from collagen matrix.1 During this process, a group of pro-
donated human bone from which the inorganic min- teins becomes sequestered in the residual inorganic
eral has been removed, leaving behind the organic bone matrix; these proteins have been termed ‘‘bone

*Resident, Department of Periodontology, Research Institute for The present study was supported by a faculty research grant from
Periodontal Regeneration, College of Dentistry, Yonsei University, Yonsei University College of Dentistry for 2011 (grant 6-2011-0051).
Seoul, Korea. Drs Kim, Shin, and Cho contributed equally to this work and they
yProfessor, Department of Prosthodontics, Institute for Clinical are co-corresponding authors.
Dental Research, Korea University Guro Hospital, Korea University, Address correspondence and reprint requests to Dr Cho: Depart-
Seoul, Korea. ment of Periodontology, Research Institute for Periodontal Regener-
zResident, Department of Prosthodontics, Institute for Clinical ation, College of Dentistry, Yonsei University, 50 Yonsei-ro,
Dental Research, Korea University Guro Hospital, Korea University, Seodaemun-gu, Seoul 120-752, Korea; e-mail: kscho@yuhs.ac
Seoul, Korea. Received October 3 2013
xClinical Research Assistant Professor, Department of Accepted January 24 2014
Periodontology, Research Institute for Periodontal Regeneration, Ó 2014 American Association of Oral and Maxillofacial Surgeons
College of Dentistry, Yonsei University, Seoul, Korea. 0278-2391/14/00148-7$36.00/0
jjProfessor, Department of Prosthodontics, Institute for Clinical http://dx.doi.org/10.1016/j.joms.2014.01.022
Dental Research, Korea University Guro Hospital, Korea University,
Seoul, Korea.
{Professor, Department of Periodontology, Research Institute for
Periodontal Regeneration, College of Dentistry, Yonsei University,
Seoul, Korea.

e1
e2 EFFECT OF RHBMP-2/DBM GEL IN ALVEOLAR RIDGE PRESERVATION

morphogenetic proteins’’ (BMPs) by Urist.2 Owing to extraction have been performed. Hence, the present
the osteogenetic characteristics of native BMPs, DBM study was designed to determine the effect of DBM
has been classified as an osteoinductive material,3 combined with rhBMP-2 in an injectable gel form
and it has been routinely used to promote bone regen- (rhBMP-2/DBM) for alveolar ridge preservation after
eration, not only in orthopedic surgery, but also in exodontia. The aims of our RCT were to assess the
dental implant surgery.4,5 safety of rhBMP-2/DBM in human subjects; and to eval-
However, controversy exists regarding the osteoin- uate the radiographic changes in the alveolar ridge
ductive potential of DBM. Although it has been shown after transplantation of either DBM alone or rhBMP-
in animal studies that DBM implants placed in mid- 2/DBM gel into extraction sockets.
diaphyseal defects and extraction sockets have failed
to induce new bone formation,6,7 Landsberg et al8
found that DBM did promote bone formation in de-
Materials and Methods
fects adjacent to dental implants. Even the results of STUDY POPULATION AND DESIGN
meta-analyses of previous clinical trials have been The present single-blind, prospective, and parallel-
controversial. Reynolds et al9 reported a beneficial ef- arm RCT was conducted at 2 centers in the Republic
fect of DBM, and Laurell et al10 stated that its use might of Korea from April 2011 to March 2013, and the study
not be beneficial. This apparent lack of consistency in protocol was approved by the institutional review
the ability of DBM to induce bone regeneration could board at each of the 2 study centers (approval nos.
be attributable to variations in the donor characteris- 2-2010-0004, MD09019). The present study was con-
tics. A few studies have found that donor age, physi- ducted with the approval of the Korean Food and
ology, and pharmacologic status11,12 could be Drug Association. This clinical trial was registered at
contributing factors to the variable osteoinductive http://cris.nih.go.kr/cris/index.jsp.
capacity of DBM. Furthermore, the processing and All patients aged 20 to 70 years, who required single
sterilization protocols used have differed according tooth extraction in the anterior region and alveolar
to the bone bank used, which might have influenced ridge preservation were candidates for the present
the quality of the final product by affecting the DBM study. At the first visit, the patients were asked for their
particle size,13 just as would the acid exposure times informed consent before enrollment in our study.
during the demineralization procedure. Therefore, The inclusion criteria were systemically healthy sub-
the use of DBM in clinics, with the associated benefi- jects who required extraction of a single-rooted non-
cial release of native BMPs, has been limited owing molar tooth and residual extraction sockets with less
to their variable concentration within, or inadequate than 50% bone loss in all dimensions. The exclusion
recovery from, bone. criteria were the presence of severe periodontitis or
Recombinant technologies have been used to pro- acute infections at tooth extraction; pregnancy or
vide controlled concentrations of BMPs, resulting in planning to become pregnant within 1 year of the
the development of recombinant human BMP experiment; recent myocardial infarction or uncon-
(rhBMP), which expresses osteoinductive proper- trolled bleeding disorders; the presence of mental ill-
ties.14-16 It has been shown that when rhBMP-2 is suc- nesses or suspected mental illnesses; hypersensitivity
cessfully loaded into inactive DBM, the addition of to bone graft materials; and the presence of clinically
rhBMP-2 directly to inactive DBM provides consistent significant or unstable systemic diseases affecting
bone induction.17 Furthermore, a few other studies bone or soft tissue growth, or other renal, hepatic,
have found that DBM is a suitable carrier for rhBMP-2.18 endocrine, hematologic, and autoimmune diseases.
The mechanism underlying these useful effects of Randomization was performed using a computer-
DBM as a carrier for rhBMP-2 is not clear; however, it generated randomization list. The randomization
seems that the collagenous substrate that remains after code was opened only at surgery (visit 2), and the pa-
hydrochloric acid extraction of the mineral fraction2 tients were randomly allocated to either the test or the
might provide a sustained pattern of release of the control group. The test group received rhBMP-2/DBM
osteoinductive protein19 and serve as a scaffold for (Rafugen DBM Gel plus rhBMP-2, 0.05 mg/mL; Korea
the proliferation and differentiation of osteoproge- Bone Bank, Seoul, Korea). The control group received
nitor cells.20 Moreover, the manufacture of DBM into DBM alone into the extraction socket immediately af-
a putty- or paste-type form provides easy handling ter tooth removal.
without scattering, which might facilitate its retention
in the grafted area.
To the best of our knowledge, no well-controlled, PREPARATION OF RHBMP-2/DBM
randomized clinical trials (RCTs) of the utility of After cleaning the cortical bones with distilled water
DBM combined with rhBMP-2 and modified into an and grinding them to a particle size of 0.5 to 1.0 mm,
injectable gel form for ridge preservation after tooth the lipid and fat were removed in 70% ethanol and 3%
KIM ET AL e3

FIGURE 1. Clinical photographs of the surgical procedure. A, Residual root of the mandibular second premolar. B, Extraction site after atrau-
matic exodontia. C, Placement of recombinant human bone morphogenetic protein-2/demineralized bone matrix into the socket (which was
ultimately covered with a collagen membrane). D, Primary coverage was achieved.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preservation. J Oral Maxillofac Surg 2014.
e4 EFFECT OF RHBMP-2/DBM GEL IN ALVEOLAR RIDGE PRESERVATION

FIGURE 2. A, Superimposition of the Digital Imaging and Communications in Medicine data of 2 computed tomography images at B, baseline
and C, 3 months after transplantation of maxillary left canine to determine whether any changes had occurred in the measurement parameters
between the 2 points.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preservation. J Oral Maxillofac Surg 2014.

hydrogen peroxide for 2 hours. The bone specimens mixture of DBM and porcine collagen gel (Rafugen
were decalcified in 0.6 N hydrochloric acid for DBM Gel, Korea Bone Bank, Seoul, Korea), and the
72 hours, lyophilized at 70 C under vacuum condi- mixture of rhBMP-2–coated DBM, collagen gel, and
tions, and then stored at room temperature. CMC (Rafugen BMP-2 DBM Gel, Korea Bone Bank)
A 1-mL volume of Chinese hamster ovary cells were injectable using a syringe. Both types of gel
expressing rhBMP-2 (0.05 mg/mL) was dispersed in were stored at 4 C until clinical use.
1 mL of DBM and stored at 70 C overnight. It was
then freeze dried at 70 C under vacuum conditions.
The freeze-dried powder was stored at 4 C until cli- SURGICAL TREATMENT
nical use. After administration of local anesthesia, crestal and in-
To facilitate the handling and reliable delivery of trasulcular incisions were made to the adjacent teeth in
DBM,21 porcine collagen gel and carboxy-methyl- all patients to expose the involved teeth and alveolar
cellulose (CMC) were applied to the matrix. Both crest. Extractions were performed as atraumatically as
DBM alone and rhBMP-2/DBM were mixed with 3% possible. The teeth were sectioned if necessary to pre-
porcine collagen type I gel and 5.7% CMC. The serve all of the socket’s bony walls. The extraction
KIM ET AL e5

FIGURE 3. Radiographic, computed tomography (CT) measurements of the cross-sectional area, height, and width of alveolar bone at base-
line (within 4 days after transplantation or demineralized bone matrix (DBM) or recombinant human bone morphogenetic protein-2/DBM) and
3 months later. A, First, point d was marked at the same point of the apex of the extraction socket on the representative CT scans taken at baseline
and 3 months after transplantation. Second, line a’ connected points a and d, taking into consideration the axis of the extraction socket. Third,
points b and c were marked at the same distance from line a’. Fourth, line b’ connected points b and c. Fifth, line c’ was drawn perpendicular to
line a’ from the most superior point of the buccal alveolar bone. Finally, the bone height was defined as the distance between point a and line c’.
B, First, line g was drawn perpendicular to line a’ from the most superior point of the lingual alveolar bone. Second, the alveolar bone width was
measured at 1, 3, and 5 mm below line g.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preservation. J Oral Maxillofac Surg 2014.

sockets were thoroughly debrided to remove all the soft careful bleeding control with gauze. A collagen mem-
tissue. The test material was delivered through a syringe brane (Bio-Gide; Geistlich Biomaterials, Wolhusen,
and packed into the socket by 1 designated dentist Switzerland) was tucked under the flaps and sutured
at each of the 2 centers. It was passively packed after over the materials using the mattress suture technique.

FIGURE 4. Patient flow diagram. DBM, demineralized bone matrix; rhBMP-2, recombinant human bone morphogenetic protein-2.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preservation. J Oral Maxillofac Surg 2014.
e6 EFFECT OF RHBMP-2/DBM GEL IN ALVEOLAR RIDGE PRESERVATION

Table 1. AGE AND GENDER DISTRIBUTIONS IN


tests were performed at the screening and final visits,
BOTH GROUPS and the formation of antibodies to rhBMP-2 was evalu-
ated using an enzyme-linked immunosorbent assay
Control Experimental All (Automatic Microplate Reader, VERSAmax; Molecular
Variable Group Group Patients Devices, Sunnyvale, CA).
Patients 34 35 69 RADIOGRAPHIC ANALYSIS
Gender
Male 19 15 34 Computed tomography (CT; HiSpeed Advantage;
Female 15 20 35 GE Medical Systems, Milwaukee, WI; and SOMATOM
Mean age (yr) 51.18  10.14 50.37  13.45 Sensation 16; Siemens, Erlangen, Germany) was used
Age group to investigate the following parameters: alveolar
<50 yr 13 14 27 bone height (1 measurement) and bone width (3 mea-
50-59 yr 15 12 27 surements at 1, 3, and 5 mm below the superior point
>60 yr 6 9 15 of the lingual alveolar bone of the extraction sockets).
These measurements were taken from the baseline CT
Data presented as n or mean  standard deviation.
scans (ie, within 4 days after transplantation) and at 3
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preserva-
tion. J Oral Maxillofac Surg 2014.
months thereafter. The data were processed in Digital
Imaging and Communications in Medicine (DICOM)
Primary closure was obtained using periosteal releasing format, and the area of interest was reconstructed
incisions, if possible; minor exposure was accepted using the OnDemand 3-dimensional software
(Fig 1). (Cybermed, Seoul, Korea). The OnDemand ‘‘fusion’’
The medication prescribed to all subjects included function, a visualization tool that uses a registration
antibiotics (500 mg amoxicillin 3 times daily for 5 technique to combine and display the image data,
days) and analgesics (200 mg ibuprofen 3 times daily was implemented to superimpose the original DICOM
for 5 days). The patients wore temporary prostheses data of the 2 CT scans. The 2 data sets were aligned and
after the surgery for esthetic reasons, taking care to then manually checked to confirm a perfect match
avoid pressure on the wound area. The sutures were (Fig 2). Subsequently, the bone height and bone width
removed after 7 days, and the subjects were followed responses (3-month value minus the baseline value for
up 1 and 3 months thereafter. both; Fig 3) were calculated using the same reference
points and lines.
SAFETY ASSESSMENT
STATISTICAL ANALYSIS
The oral wounds at the treated sites were examined
at each visit, including at baseline and days 2 and 14 The major effects of the bone graft materials were
and 1 and 3 months postoperatively, to monitor the assessed by comparing the alveolar bone height at
occurrence of any of the commonly seen postopera- baseline and 3 months after transplantation between
tive complications associated with the augmentation the control and experimental groups. Furthermore,
procedure (ie, pain, discomfort, swelling, fever, and the minor effects of the bone graft materials and
wound dehiscence). Serum chemistry and hematology changes in alveolar bone width at 1, 3, and 5 mm
below the superior point of the lingual alveolar bone
immediately after ridge preservation and at 3 months
Table 2. EVALUATION OF SAFETY OF after transplantation were compared between the con-
RHBMP-2/DBM (IE, THE IMMUNE RESPONSE) trol and experimental groups.
The mean  standard deviation of the test parame-
3-mo Evaluation ters was calculated using the Statistical Analysis Sys-
Experimental Group Control Group tem, version 9.1.3 (SAS Institute, Cary, NC). For each
parameter, the difference between the 2 groups was
Baseline Negative Positive Negative Positive compared using the Wilcoxon rank sum test. The
paired t test was used to determine the significance
Negative 31 (91.18) 2 (5.88) 29 (90.63) 0 (0.00) of the changes. P < .05 was considered statisti-
Positive 0 (0.00) 1 (2.94) 0 (0.00) 3 (9.38) cally significant.
Data presented as n (%).
P = .4965, Fisher’s exact test. Results
Abbreviations: DBM, demineralized bone matrix; rhBMP-2,
recombinant human bone morphogenetic protein. Patient flow through the study is shown in Figure 4.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preserva- A total of 78 patients were initially screened, and 69
tion. J Oral Maxillofac Surg 2014. eligible patients were randomly allocated at surgery
KIM ET AL e7

FIGURE 5. Cross-sectional images of the grafted areas. Computed tomography scans at A,C, baseline and B,D, 3 months after transplantation
for the demineralized bone matrix (DBM)-only (maxillary right second premolar) and recombinant human bone morphogenetic protein-2/DBM
(maxillary left canine) groups.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preservation. J Oral Maxillofac Surg 2014.

(visit 2) into the test group (n = 35) or control group data of another 6 patients were not of diagnostic qual-
(n = 34). Six subjects were withdrawn or lost during ity, their clinical parameters were included in the
the follow-up period (Table 1). Although the radiologic safety assessment.
e8 EFFECT OF RHBMP-2/DBM GEL IN ALVEOLAR RIDGE PRESERVATION

Table 3. RADIOGRAPHIC EVALUATION OF CHANGES IN ALVEOLAR BONE HEIGHT IN BOTH GROUPS

Alveolar Bone Height


Height Change
Baseline 3 mo

Group Mean  SD Median Range Mean  SD Median Range Mean  SD Median Range

Experimental 20.98  7.74 21.14 9.54-39.58 19.81  7.73 19.03 7.29-37.17 1.17  0.82 1.19 2.71 to
(n = 29) 0.00
Control 21.83  6.89 22.12 11.79-35.75 20.32  6.92 20.29 10.14-35.75 1.50  1.07 1.41 4.45 to
(n = 30) 0.00

P = .1844, Wilcoxon rank sum test.


Abbreviation: SD, standard deviation.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preservation. J Oral Maxillofac Surg 2014.

SAFETY ASSESSMENT mean change in alveolar bone height, which was eval-
Healing was uneventful in all subjects, with no se- uated by comparing the CT scans taken immediately
vere adverse events. No clinically significant changes and 3 months after transplantation, was 1.50 
were found in the blood count, blood chemistry, or uri- 1.07 mm in the control group and 1.17  0.82 mm
nalysis results. The presence of antibodies to DBM in the experimental group. Both groups exhibited a
alone and the rhBMP-2/DBM gel was found in 34 significant vertical height reduction from baseline to
experimental patients and 32 control patients the final examination, and no statistically significant
receiving bone graft material into extraction sockets. difference was found between the 2 groups (P >
Of the 34 patients receiving the rhBMP-2/DBM gel, 1 .05; Table 3).
(5.88%) developed antibodies compared with 0 of 32 Changes in the alveolar bone width were also
(0%) in the control group; the difference was not statis- measured to determine the minor effects of the bone
tically significant (P = .4965; Table 2). grafts on the preservation of alveolar bone. At 1 mm
below the baseline, a 1.21  1.31 mm change was
RADIOGRAPHIC ANALYSIS seen in the bone width of the control group
and 1.06  1.26 mm in the experimental group. The
Representative cross-sectional CT images of both
corresponding values were 0.58  0.68 and 0.43 
experimental groups are shown in Figure 5. The

Table 4. RADIOGRAPHIC EVALUATION OF CHANGES IN ALVEOLAR BONE WIDTH IN BOTH GROUPS

Alveolar Bone Width


Width Change
Baseline At 3 mo
P
Group Mean  SD Median Range Mean  SD Median Range Mean  SD Median Range Value*

At 1 mm .4574
Experimental 7.61  2.71 7.78 1.49-12.25 6.56  2.73 6.28 1.10-11.32 1.06  1.26 0.57 5.58 to 0.00
(n = 29)
Control 8.39  2.00 8.29 5.50-13.01 7.18  2.04 7.51 4.29-12.76 1.21  1.31 0.94 6.78 to 0.00
(n = 30)
At 3 mm .1758
Experimental 8.06  2.22 7.66 4.63-12.30 7.63  2.22 6.96 4.49-11.38 0.43  0.71 0.16 3.28 to 0.00
(n = 29)
Control 8.57  2.44 8.36 4.97-14.16 7.98  2.34 7.68 4.30-14.04 0.58  0.68 0.34 2.67 to 0.00
(n = 30)
At 5 mm .6939
Experimental 8.31  2.42 7.70 4.28-13.15 8.08  2.41 7.41 4.28-12.57 0.23  0.45 0.00 2.23 to 0.00
(n = 29)
Control 8.56  2.59 8.45 4.65-15.31 8.19  2.49 7.76 4.25-14.74 0.37  0.61 0.00 2.24 to 0.00
(n = 30)

Abbreviation: SD, standard deviation.


* Wilcoxon rank sum test.
Kim et al. Effect of rhBMP-2/DBM Gel in Alveolar Ridge Preservation. J Oral Maxillofac Surg 2014.
KIM ET AL e9

0.71 mm at 3 mm below the baseline and 0.37  0.61 can have the potential to affect the safety or efficacy
and 0.23  0.45 mm at 5 mm below the baseline. of the rhBMP-2. In some studies, no difference was
Therefore, both groups exhibited significant horizontal observed in the adverse event rates between the
width reduction between the baseline and final examina- antibody-positive patients and antibody-negative pa-
tion, with no statistically significant difference between tients, including adverse events.26 These findings are
the 2 groups (P > .05; Table 4). similar to those of previous studies using rhBMP-2/
absorbable collagen sponge,27,28 suggesting that no
specific toxicity is related to this study device.
Discussion
However, several reports have been published of
In the present study, the application of rhBMP-2 complications occurring after the application of
using injectable DBM gel into the extraction socket rhBMP-2. Therefore, additional evaluation of the
successfully preserved the volume of the alveolar changes in antibody titer should be conducted to
ridge, and its clinical safety was well demonstrated. monitor the long-term safety of this product.
In addition, no adverse reactions to the graft material, The major limitation of the present study was the
including rhBMP-2, were observed. lack of a negative control group in which patients
The experimental model in the ridge preservation received no graft after extraction. However, the original
procedure after extraction is a well-established study purpose of our clinical trial was to compare the clinical
design and has been used in a number of studies.22 and radiographic changes of the 2 transplanted mate-
In the present study, the extraction sockets with rials within the extraction socket and to investigate
buccal bone loss less than 50% were included, and their safety and efficacy using an injectable application.
Fiorellini et al23 included sockets with more than Therefore, it was beyond the scope of our study to
50% of buccal bone loss, termed the ‘‘postextraction ascertain the effect of the DBM applications compared
buccal wall defect model.’’ Both study models are with the outcomes for an untreated extraction socket.
well established; however, the latter is more focused The results from the present study have substantially
on the evaluation of efficacy than the former. The pri- shown that both materials are equally safe.
mary aim of the present study was to evaluate the local In conclusion, the results from this randomized,
and systemic safety and the efficacy of the rhBMP-2/ controlled, multicenter clinical study have shown
DBM gel. However, the evaluation of the efficacy of that the application of rhBMP-2/DBM or DBM gel is
rhBMP-2/DBM gel using the aforementioned buccal safe to use clinically for preservation of the alveolar
wall defect model could be investigated in ridge, and no difference in the dimensional changes
future studies. was observed between the 2 groups.
The rhBMP-2/DBM gel did not show a significant dif-
ference from DBM alone in terms of the alveolar bone
References
width and height. We hypothesized that this phenom-
enon could be attributed to the relatively lower dos- 1. Maddox E, Zhan M, Mundy GR, et al: Optimizing human demin-
ages of rhBMP-2 than those in previous studies.23,24 eralized bone matrix for clinical application. Tissue Eng 6:441,
2000
Controversies regarding the proper dosage of rhBMP- 2. Urist MR: Bone: Formation by autoinduction. Science 150:893,
2 for maxillofacial application and uncertainty of 1965
possible adverse events from the higher dosage appli- 3. Zhou S, Yates KE, Eid K, et al: Demineralized bone promotes
chondrocyte or osteoblast differentiation of human marrow
cation still exist.25 In the present study, we used a stromal cells cultured in collagen sponges. Cell Tissue Bank 6:
lower dosage of rhBMP-2 than used in previous studies 33, 2005
and maximum precaution was undertaken to ensure 4. Kubler N, Michel C, Zoller J, et al: Repair of human skull defects
using osteoinductive bone alloimplants. J Craniomaxillofac Surg
the safety of the materials. The results from the present 23:337, 1995
study have shown that rhBMP-2/DBM gel and DBM 5. Rosenthal RK, Folkman J, Glowacki J: Demineralized bone im-
alone were well tolerated both locally and systemi- plants for nonunion fractures, bone cysts, and fibrous lesions.
Clin Orthop Relat Res 364:61, 1999
cally, with no adverse events, and we have shown 6. Schwartz Z, Mellonig JT, Carnes DL Jr, et al: Ability of commercial
that resorption of the alveolar ridge was successfully demineralized freeze-dried bone allograft to induce new bone
prevented. Furthermore, the technical feasibility of de- formation. J Periodontol 67:918, 1996
7. Becker W, Becker BE, Caffesse R: A comparison of demineralized
vice implantation was also achieved. freeze-dried bone and autologous bone to induce bone forma-
During the 3-month follow-up period, the patients tion in human extraction sockets. J Periodontol 65:1128, 1994
experienced neither unexpected adverse events nor 8. Landsberg CJ, Grosskopf A, Weinreb M: Clinical and biologic ob-
servations of demineralized freeze-dried bone allografts in
clinically significant changes in the blood count, blood augmentation procedures around dental implants. Int J Oral
chemistry, or urinalysis results. Moreover, no signifi- Maxillofac Implants 9:586, 1994
cant immune response to rhBMP-2 was seen. Of the 9. Reynolds MA, Aichelmann-Reidy ME, Branch-Mays GL, et al: The
efficacy of bone replacement grafts in the treatment of peri-
34 patients receiving the rhBMP-2/DBM gel, 1 odontal osseous defects: A systematic review. Ann Periodontol
(5.88%) developed antibodies. Antibody formation 8:227, 2003
e10 EFFECT OF RHBMP-2/DBM GEL IN ALVEOLAR RIDGE PRESERVATION

10. Laurell L, Gottlow J, Zybutz M, et al: Treatment of intrabony de- 20. Han B, Yang Z, Nimni M: Effects of moisture and temperature on
fects by different surgical procedures: A literature review. J Pe- the osteoinductivity of demineralized bone matrix. J Orthop Res
riodontol 69:303, 1998 23:855, 2005
11. Schwartz Z, Somers A, Mellonig JT, et al: Ability of commercial 21. Gruskin E, Doll BA, Futrell FW, et al: Demineralized bone matrix
demineralized freeze-dried bone allograft to induce new bone in bone repair: History and use. Adv Drug Deliv Rev 64:1063,
formation is dependent on donor age but not gender. J Periodon- 2012
tol 69:470, 1998 22. Vittorini Orgeas G, Clementini M, De Risi V, et al: Surgical tech-
12. Jergesen HE, Chua J, Kao RT, et al: Age effects on bone induction by niques for alveolar socket preservation: A systematic review. Int
demineralized bone powder. Clin Orthop Relat Res 268:253, 1991 J Oral Maxillofac Implants 28:1049, 2013
13. Vail TB, Trotter GW, Powers BE: Equine demineralized bone ma- 23. Fiorellini JP, Howell TH, Cochran D, et al: Randomized study
trix: Relationship between particle size and osteoinduction. Vet evaluating recombinant human bone morphogenetic protein-
Surg 23:386, 1994 2 for extraction socket augmentation. J Periodontol 76:605,
14. Lee JH, Kim CS, Choi KH, et al: The induction of bone formation 2005
in rat calvarial defects and subcutaneous tissues by recombinant 24. Misch CM: The use of recombinant human bone morphogenetic
human BMP-2, produced in Escherichia coli. Biomaterials 31: protein-2 for the repair of extraction socket defects: A technical
3512, 2010 modification and case series report. Int J Oral Maxillofac Im-
15. Jang JW, Yun JH, Lee KI, et al: Osteoinductive activity of biphasic plants 25:1246, 2010
calcium phosphate with different rhBMP-2 doses in rats. Oral 25. Zara JN, Siu RK, Zhang X, et al: High doses of bone morphoge-
Surg Oral Med Oral Pathol Oral Radiol Endod 113:480, 2012 netic protein 2 induce structurally abnormal bone and inflamma-
16. Kim JW, Jung IH, Lee KI, et al: Volumetric bone regenerative ef- tion in vivo. Tissue Eng Part A 17:1389, 2011
ficacy of biphasic calcium phosphate-collagen composite block 26. Burkus JK, Gornet MF, Glassman SD, et al: Blood serum
loaded with rhBMP-2 in vertical bone augmentation model of a antibody analysis and long-term follow-up of patients
rabbit calvarium. J Biomed Mater Res A 100:3304, 2012 treated with recombinant human bone morphogenetic
17. Schwartz Z, Somers A, Mellonig JT, et al: Addition of human re- protein-2 in the lumbar spine. Spine (Phila Pa 1976) 36:
combinant bone morphogenetic protein-2 to inactive commer- 2158, 2011
cial human demineralized freeze-dried bone allograft makes an 27. Garrett MP, Kakarla UK, Porter RW, et al: Formation of painful se-
effective composite bone inductive implant material. J Periodon- roma and edema after the use of recombinant human bone
tol 69:1337, 1998 morphogenetic protein-2 in posterolateral lumbar spine fusions.
18. Niederwanger M, Urist MR: Demineralized bone matrix supplied Neurosurgery 66:1044, 2010
by bone banks for a carrier of recombinant human bone 28. van den Bergh JP, ten Bruggenkate CM, Groeneveld HH, et al: Re-
morphogenetic protein (rhBMP-2): A substitute for autogeneic combinant human bone morphogenetic protein-7 in maxillary
bone grafts. J Oral Implantol 22:210, 1996 sinus floor elevation surgery in 3 patients compared to autoge-
19. Winn SR, Uludag H, Hollinger JO: Carrier systems for bone morpho- nous bone grafts: A clinical pilot study. J Clin Periodontol 27:
genetic proteins. Clin Orthop Relat Res 367(suppl):S95, 1999 627, 2000

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