Vertical Bone Augmentation Using Recombinant Bone Morphogenetic Protein, Mineralized Bone Allograft, and Titanium Mesh: A Retrospective Cone Beam Computed Tomography Study Craig M. Misch, DDS, MDS1/Ole T. Jensen, DDS, MS2/Michael A. Pikos, DDS3/Jay P. Malmquist, DMD4 Purpose: This retrospective study evaluated the use of a composite graft of recombinant human bone morphogenetic protein-2 (rhBMP-2) and particulate mineralized bone allograft protected by a titanium mesh for vertical bone augmentation. Materials and Methods: A review of data on patients from four oral and maxillofacial surgery practices in the United States who required vertical augmentation prior to implant treatment was conducted. Vertical augmentation was accomplished with rhBMP-2 in an absorbable collagen sponge (ACS) carrier and particulate allograft. Cone beam computed tomography was used to measure vertical bone gains using this technique. Results: Sixteen vertical ridge augmentation procedures were performed in 15 patients. The maximum vertical bone gains ranged from 4.4 to 16.3 mm. The average maximum vertical bone gain was 8.53 mm. The procedure allowed implant placement in all patients. Forty implants were inserted into the grafted ridges after a minimum of 6 months of healing. All implants integrated and were used for prosthetic support. Conclusion: This study suggests that rhBMP-2/ACS and particulate mineralized bone allograft protected by a titanium mesh offers favorable vertical bone gains to allow dental implant placement. Int J Oral Maxillofac Implants 2015;30:202–207. doi: 10.11607/jomi.3977 Key words: cone beam computed tomography, recombinant human bone morphogenetic protein-2, titanium mesh, vertical bone augmentation
S
everal methods and materials are available for bone augmentation in the maxilla and mandible for dental implant placement. The choice of a particular augmentation technique or graft material depends on several factors, including the anatomical region, degree of atrophy, morphology of the osseous defect, type of prosthesis planned, and clinician and patient preferences. Although there are no studies documenting that one bone augmentation technique is necessarily superior, the surgeon should strive to select a method that offers predictable results for the given clinical situation.1 1Private
Practice Limited to Oral and Maxillofacial Surgery, Sarasota, Florida, USA. 2Private Practice Limited to Oral and Maxillofacial Surgery, Denver, Colorado, USA. 3 Private Practice Limited to Oral and Maxillofacial Surgery, Tampa, Florida, USA. 4Private Practice Limited to Oral and Maxillofacial Surgery, Portland, Oregon, USA. Correspondence to: Dr Craig Misch, 120 Tuttle Ave S., Sarasota, FL 34237, USA. Fax: +941-957-6440. Email: [email protected] ©2015 by Quintessence Publishing Co Inc.
Autogenous bone grafts are often used in the treatment of large osseous defects or severe atrophy.2–4 The superior biologic properties of autogenous bone, including osteogenesis and osteoinduction, offer significant advantages in reconstructing the atrophic ridge. Large autogenous bone grafts may be used in the form of corticocancellous blocks or cancellous marrow covered with titanium mesh.2,3,5 For smaller segmental defects, the use of intraorally harvested cortical blocks or particulate autograft with titanium mesh or membranes may be considered.6–8 Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been under investigation as a replacement for autogenous bone for ridge augmentation.9–12 RhBMP-2 is a locally acting growth factor that induces bone formation at the site of application. The protein is chemotactic for mesenchymal stem cells and induces osteoprogenitor cells to differentiate into osteoblasts.13 Although absorbable collagen sponge (ACS) has been found to be an optimal carrier for the rhBMP-2 molecule, its poor scaffolding properties cannot resist flap compression. Thus, titanium mesh has been used as a method to provide space maintenance and protect the rhBMP-2/ACS graft to enable bone ingrowth.9–11 The addition of an osteoconductive matrix
202 Volume 30, Number 1, 2015 © 2015 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Misch et al
Fig 1 Failing maxillary implants.
to the rhBMP-2/ACS complex, such as particulate allograft, has also been suggested as a strategy to provide additional scaffolding and a matrix for cellular migration.9,10,14 Supplementation with a portion of particulate bone substitute may provide additional scaffolding without significantly diluting the amount of rhBMP-2.9,10,14,15 This also decreases the cost of the procedure, as less BMP is needed. The use of a commercially available rhBMP-2 product (Infuse Bone Graft, Medtronic) for ridge augmentation is considered an off-label application by the U.S. Food and Drug Administration. The off-label designation does not prevent clinicians from considering rhBMP-2/ACS for this application, but patients must be properly informed, and all adverse effects need to be well documented. This retrospective study evaluated the usefulness of a composite graft of rhBMP-2/ACS and particulate mineralized bone allograft protected by a titanium mesh for vertical bone augmentation. Cone beam computed tomography (CBCT) was used to measure vertical bone gains using this technique. The goal of the study was to determine the amount of vertical bone augmentation that may be obtained with this approach to provide clinicians with guidelines for its use.
MATERIALS AND METHODS Data were collected from four oral and maxillofacial surgery practices in the United States attended by the authors. A retrospective review was performed of patients who required vertical ridge augmentation to allow implant placement (Figs 1 and 2). No cases of extraction socket bone grafting or sinus bone grafting were included. Informed consent for the off-label use of rhBMP-2 for ridge augmentation was obtained. A CBCT scan of the maxilla or mandible was taken preoperatively to assess the ridge morphology and amount of jaw atrophy.
Fig 2 Preoperative view of the maxillary ridge defect.
Fig 3 Maxillary extraosseous vertical ridge defect.
The size of the defect and the volume of planned augmentation determined the appropriate dosage of rhBMP-2. As described by Marx et al,9 the dosage of rhBMP-2 was approximately 1.05 mg for each two-tooth edentulous span. The ACS included in the Infuse bone graft kit was evenly saturated with the reconstituted rhBMP-2 liquid (1.5 mg/mL). A minimum of 15 minutes was allowed to pass to allow binding of the growth factor to the collagen carrier. The collagen sponge was then cut into smaller pieces with scissors and mixed with particulate mineralized bone allograft (50% by volume) (MinerOss, BioHorizons). In 11 patients, platelet-rich plasma was also added to the composite graft. After local anesthesia had been induced, a crestal incision was made to extend well beyond the graft margins. Vertical releasing incisions were made as needed, and a broad-based mucoperiosteal flap was developed to completely expose the ridge deficiency and identify local anatomy (Fig 3). The 0.2-mm-thick titanium mesh was trimmed with scissors to extend beyond the planned implant sites and cover the desired area of augmentation. The mesh was formed over the ridge area, and the edges were molded to The International Journal of Oral & Maxillofacial Implants 203
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Misch et al
Fig 4 Composite graft of rhBMP-2/ACS with mineralized bone allograft and platelet concentrate contained in titanium mesh.
Fig 5 Titanium mesh with composite graft secured in the right maxilla.
Fig 6 Cross-sectional view from the preoperative CT scan.
Fig 7 Cross-sectional view from the CT scan of the healed graft reveals the reconstructed ridge.
Fig 8 The titanium mesh is removed after 6 months of healing.
the bone with a periosteal elevator. The concave portion of the mesh was then packed with the rhBMP-2/ ACS mixed with particulate allograft (Fig 4). The mesh with the composite graft was reinserted over the ridge and compressed into place. A minimum of two fixation screws were placed along the buccal cortex to secure the mesh. Additional palatal or lingual fixation screws were inserted as needed (Fig 5). In some cases, a non–cross-linked collagen membrane and/or platelet concentrate was placed over the mesh in the area of wound closure. A scalpel blade was used to incise the periosteum along the base of the facial flap and obtain release for advancement over the graft site. In the posterior mandible, lingual flap release was accomplished by dissecting it to the mylohyoid ridge and stretching the thin periosteum with a gloved finger. The flap margins were then advanced over the mesh and approximated without tension. The flaps were closed primarily with polytetraflouroethylene, polyethylene, or polyglactin 910 mattress and interrupted sutures. No soft tissue–supported prosthesis was worn over the grafted
site until the incision had healed completely. If needed and when possible, temporary tooth replacement was accomplished with a fixed provisional prosthesis. A removable Essix retainer was used as an alternative. The grafted sites were allowed to heal for at least 6 months. A CBCT scan was obtained prior to implant surgery to evaluate the graft healing and bone density and to select implants of appropriate size. The vertical bone changes were measured using the incorporated software of the CBCT scan unit. The most inferior point of the preoperative ridge deficiency was used to determine the maximum bone volume gained (Fig 6). Crosssectional images were used to identify the crest of the regenerated ridge (Fig 7). All measurements were repeated three times by one clinician (CM). The data were collected, and statistical analysis was performed. The patients then underwent a second surgery. After local anesthesia had been achieved, the surgeon used a flap design for removal of the mesh similar to that used during grafting surgery (Fig 8). The mesh and fixation screws were removed, and the fibrous tissue
204 Volume 30, Number 1, 2015 © 2015 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Misch et al
Fig 9 Dental implants are placed in the reconstructed maxilla.
that typically forms under the mesh was reflected from the underlying bone. Implant osteotomies were prepared according to the manufacturer’s drilling sequence. Dental implants were inserted and allowed to heal, with the healing period determined by quality of the bone at the site (Figs 9 and 10).
Fig 10 Occlusal view of the implants placed in the healed graft.
Table 1 Data on Patients Treated with Vertical Bone Augmentation with rhBMP-2/ACS and Mineralized Bone Allograft with Titanium Mesh Patient
Graft site
Defect type
No. of Vertical implants gain placed
RESULTS
1
Right maxilla
Extraosseous 10.6 mm
3
2
Anterior maxilla
Intraosseous
7.4 mm
1
Sixteen vertical ridge augmentation procedures were performed in 15 patients (6 men, 9 women). Eight patients required maxillary grafting (six anterior, three posterior) and seven patients needed mandibular grafts (two anterior, five posterior) (Table 1). No meshes were exposed during healing. The maximum vertical bone gains ranged from 4.4 to 16.3 mm. The average maximum vertical bone gain was 8.53 mm (standard deviation 3.5 mm). In all cases, there was a thin radiolucent space under the mesh that likely represented a layer of soft tissue. The ridge augmentation allowed implant placement in all 15 patients. Forty implants were inserted into the grafted ridges after a minimum of 6 months of healing. One patient decided not to undergo implant placement. All 40 implants integrated and were used for prosthetic support.
Right maxilla
Intraosseous
5.7 mm
3
3
Right mandible
Extraosseous
4.4 mm
3
4
Anterior mandible Extraosseous 11.2 mm
2
5
Left mandible
Intraosseous
7.1 mm
2
6
Left mandible
Extraosseous
5.3 mm
2
7
Right mandible
Extraosseous
5.1 mm
2
8
Anterior maxilla
Extraosseous
8.3 mm
4
9
Anterior maxilla
Extraosseous 10.5 mm
2
10
Left mandible
Extraosseous
8.5 mm
3
11
Anterior maxilla
Extraosseous
6.3 mm
4
12
Right maxilla
Extraosseous 11.6 mm
3
13
Anterior maxilla
Extraosseous
3.8 mm
4
14
Anterior maxilla
Extraosseous 16.3 mm
2
15
Anterior mandible Extraosseous 14.3 mm
–
DISCUSSION Osseous regeneration and repair of a defect originate primarily from the bony walls surrounding the defect. Growth factors stimulate the migration of the mesenchymal stem cells needed for tissue repair. The ingrowth of blood vessels from the surrounding bone provides a path for osteoprogenitor cells and new bone formation. As such, the morphology of a bone defect should influence the choice of material or technique. Sites with fewer surrounding osseous walls and
more pronounced atrophy are more demanding and require materials and/or techniques that offer greater biologic activity and regenerative capacity. As a general rule, vertical onlay bone augmentation is more biologically and clinically challenging than horizontal bone augmentation. Explanations for this difference would include fewer osseous walls and greater difficulty in achieving space maintenance, graft stability, and soft tissue coverage. The International Journal of Oral & Maxillofacial Implants 205
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Misch et al
Most classification systems used to describe jaw atrophy focus on the progressive pattern of ridge resorption.16,17 Recently, the Cologne Classification for Alveolar Ridge Defects18 was proposed to address the morphology of the defect as well as augmentation needs. In this classification, a ridge defect is described as horizontal, vertical, or combined. The relationship between the defect region and augmentation can be classified as internal (inside the bony contour) or external (outside the bony contour). This distinction is important, as vertical bone defects inside the bony contour are much easier to reconstruct than onlay augmentation required outside the osseous contour. Intraosseous defects have a higher regenerative capacity with better space maintenance, and soft tissue coverage is more easily achieved. Many methods are available for vertical bone augmentation, including guided bone regeneration, particulate and block bone grafting, titanium mesh grafting, interpositional grafting, and distraction osteogenesis.19,20 Some techniques offer a greater amount of bone regeneration than others. However, it is difficult to determine bone augmentation gains in many publications, as this parameter is often not measured.20 In addition, those studies that do include augmentation gains often do not define the osseous morphology of treated vertical defects (intraosseous or extraosseous). Recently, Milinkovic and Cordaro4 performed a systematic review to determine whether specific indications could be determined for different bone augmentation procedures. In partially edentulous patients requiring vertical augmentation for implant placement, the average bone gain was 3.04 mm for guided bone regeneration and simultaneous implant placement, 4.3 mm for guided bone regeneration and staged implant placement, 4.75 mm for autogenous bone blocks, and 7.08 mm for distraction osteogenesis. A limitation in the data on autogenous bone blocks arose from the combination of bone gains from smaller intraoral blocks with larger iliac crest blocks. Although distraction osteogenesis may allow for more vertical augmentation than other techniques, a large percentage of patients may require secondary augmentation prior to dental implant placement.21,22 There may also be problems with vector control, patient compliance, premature consolidation, and device instability.23 Traditionally, the titanium mesh technique used cancellous autogenous bone graft.5 This approach has been shown to produce significant vertical bone augmentation gains exceeding 10.0 mm.24,25 However, a secondary donor site, such as the iliac crest or tibia, is required, with the associated morbidity of graft harvest. Marx et al9 compared the use of autogenous cancellous bone grafts with a composite graft of rhBMP-2/ ACS, mineralized bone allograft, and platelet-rich
plasma. Both types of grafts were placed into titanium mesh cribs. Forty patients with vertical bone defects in the maxilla were randomly assigned to receive a composite graft or an autogenous graft. Although no bone volume gains were reported, the authors found similar outcomes between the groups in terms of the ability to place dental implants and implant survival. Another study evaluated the use of titanium mesh for horizontal ridge augmentation in the anterior maxilla using rhBMP-2/ACS or particulated autogenous bone harvested from the mandible.11 The authors found no significant differences in horizontal bone gain after 6 months of healing (rhBMP-2/ACS: 3.2 mm; autograft: 3.7 mm) and similar dental implant survival rates. In the current study, the vertical bone gains ranged from 4.4 to 16.3 mm. An evaluation of the sites treated reveals that the majority of the smaller gains were found in the posterior mandible (Table 1). The saddle-shaped defects in this area required less augmentation prior to implant placement. Several patients obtained vertical augmentation of more than 10.0 mm. The literature on rhBMP-2/ACS suggests that this approach may be considered as an alternative to the use of autogenous bone for ridge augmentation. From a patient’s perspective, there are significant benefits to the use of an osteoinductive growth factor, as no bone graft harvest is required, with its associated morbidity. The surgery may be performed in an office environment under sedation and local anesthesia, instead of an operating room under general anesthesia. The elimination of a graft harvest surgery and the relative technical ease of the procedure greatly reduce surgical time. However, the ability to manage the surgical flaps to attain tension-free primary closure is still required for graft success. The disadvantages of the use of rhBMP-2 compared to the use of autograft include greater postoperative edema, longer graft healing times, softer initial bone quality, and higher material costs.9,10 The use of rhBMP-2/ACS with mineralized bone allograft contained in a titanium mesh scaffold offers an alternative to managing vertical bone deficiencies in the maxilla and mandible. This study suggests that there is potential for vertical bone gains comparable to those found with autogenous bone and exceeding other augmentation techniques. Clinicians will need to weigh the higher costs of this material against the simplified technique, enhanced biologic response, and potential for reduced morbidity.
ACKNOWLEDGMENTS The authors wish to thank Ms Maggie A. Misch for her research assistance with this project. The authors reported no conflicts of interest related to this study.
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Misch et al
REFERENCES 1. Chiapasco M, Casentini P, Zaniboni M. Bone augmentation procedures in implant dentistry. Int J Oral Maxillofac Implants 2009;24:237–259. 2. Nyström E, Nilson H, Gunne J, Lundgren S. A 9-14 year follow-up of onlay bone grafting in the atrophic maxilla. Int J Oral Maxillofac Surg 2009;38:111–116. 3. Misch CM. Maxillary autogenous bone grafting. Oral Maxillofac Surg Clin North Am 2011;23:229–238. 4. Milinkovic I, Cordaro L. Are there specific indications for the different alveolar bone augmentation procedures for implant placement? A systematic review. Int J Oral Maxillofac Surg 2014;43:606–625. 5. Boyne P. Osseous Reconstruction of the Maxilla and the Mandible: Surgical Techniques Using Titanium Mesh and Bone Mineral. Chicago: Quintessence, 1997:1–100. 6. Misch CM: Comparison of intraoral donor sites for onlay grafting prior to implant placement. Int J Oral Maxillofac Implants 1997;12:767–776. 7. Pikos MA. Mandibular block autografts for alveolar ridge augmentation. Atlas Oral Maxillofac Surg Clin North Am 2005;13:91–107. 8. Urban IA, Lozada JL, Jovanovic SA, Nagursky H, Nagy K. Vertical ridge augmentation with titanium-reinforced, dense-PTFE membranes and a combination of particulated autogenous bone and anorganic bovine bone-derived mineral: A prospective case series in 19 patients. Int J Oral Maxillofac Implants 2014;29:185–193. 9. Marx RE, Armentano L, Olavarria A, Samaniego J. rhBMP-2/ACS grafts versus autogenous cancellous marrow grafts in large vertical defects of the maxilla: An unsponsored randomized open-label clinical trial. Oral Craniofac Tissue Eng 2011;1:33–41. 10. Misch CM. Bone augmentation of the atrophic posterior mandible for dental implants using rhBMP-2 and titanium mesh: Clinical technique and early results. Int J Periodontics Restorative Dent 2011;31:581–589. 11. de Freitas RM, Susin C, Spin-Neto R, et al. Horizontal ridge augmentation of the atrophic anterior maxilla using rhBMP-2/ACS or autogenous bone grafts: A proof-of-concept randomized clinical trial. J Clin Periodontol 2013;40:968–975. 12. Jensen OT, Lehman H, Ringeman JL, Casap N. Fabrication of printed titanium shells for containment of BMP-2 composite graft materials for alveolar bone reconstruction. Int J Oral Maxillofac Implants 2014;29:e103–105. 13. Wozney JM, Wikesjo UME. rhBMP-2: Biology and applications in oral and maxillofacial surgery and periodontics. In: Lynch SE, Marx RE, Nevins M, Wisner-Lynch LA (eds). Tissue Engineering, ed 2. Chicago: Quintessence, 2008:159–177.
14. Misch CM. The use of recombinant human bone morphogenetic protein-2 for the repair of extraction socket defects: A technical modification and case series report. Int J Oral Maxillofac Implants 2010;25:1246–1252. 15. Tarnow DP, Wallace SS, Testori T, Froum SJ, Motroni A, Prasad HS. Maxillary sinus augmentation using recombinant bone morphogenetic protein-2/acellular collagen sponge in combination with a mineralized bone replacement graft: A report of three cases. Int J Periodontics Restorative Dent 2010;30:139–149. 16. Lekholm U, Zarb GA. Patient selection and preparation. In: Brånemark P-I, Zarb GA, Albrektsson T (eds). Tissue-Integrated Prostheses: Osseointegration in Clinical Dentistry. Chicago: Quintessence, 1985:199–209. 17. Cawood, JI, Howell RA. A classification of the edentulous jaws. Int J Oral Maxillofac Surg 1988;17:232–236. 18. Cologne Classification for Alveolar Ridge Defects. https://www. bdizedi.org/bdiz/web.nsf/gfx/guidelines_Konsensus-Leitfaden-2013_engl.pdf/$file/guidelines_Konsensus-Leitfaden-2013_ engl.pdf 19. Tinti C, Parma-Benfenati S, Polizzi G. Vertical ridge augmentation: What is the limit? Int J Periodontics Restorative Dent 1996;16: 220–229. 20. Rocchietta I, Fontana F, Simion M. Clinical outcomes of vertical bone augmentation to enable dental implant placement: A systematic review J Clin Periodontol 2008;35(suppl 8):203–215. 21. Jensen OT, Cockrell R, Kuhike L, Reed C. Anterior maxillary alveolar distraction osteogenesis: A prospective 5-year clinical study. Int J Oral Maxillofac Implants 2002;17:52–68. 22. Esposito M, Grusovin MG, Felice P, et al. The efficacy of horizontal and vertical bone augmentation procedures for dental implants: A Cochrane systematic review. Eur J Oral Implantol 2009;2:167–184. 23. Froum SJ, Rosenberg ES, Elian N, Tarnow D, Cho SC. Distraction osteogenesis for ridge augmentation: Prevention and treatment of complications. Thirty case reports. Int J Periodontics Restorative Dent 2008;28:337–345. 24. Louis PJ, Gutta R, Said-Al-Naief N, Bartolucci AA. Reconstruction of the maxilla and mandible with particulate bone graft and titanium mesh for implant placement. J Oral Maxillofac Surg 2008;66:235–245. 25. Miyamoto I, Funaki K, Yamauchi K, Kodama T, Takahashi T. Alveolar ridge reconstruction with titanium mesh and autogenous particulate bone graft: Computed tomography-based evaluations of augmented bone quality and quantity. Clin Implant Dent Relat Res 2012;14:304–311.
The International Journal of Oral & Maxillofacial Implants 207 © 2015 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
S
everal methods and materials are available for bone augmentation in the maxilla and mandible for dental implant placement. The choice of a particular augmentation technique or graft material depends on several factors, including the anatomical region, degree of atrophy, morphology of the osseous defect, type of prosthesis planned, and clinician and patient preferences. Although there are no studies documenting that one bone augmentation technique is necessarily superior, the surgeon should strive to select a method that offers predictable results for the given clinical situation.1 1Private
Practice Limited to Oral and Maxillofacial Surgery, Sarasota, Florida, USA. 2Private Practice Limited to Oral and Maxillofacial Surgery, Denver, Colorado, USA. 3 Private Practice Limited to Oral and Maxillofacial Surgery, Tampa, Florida, USA. 4Private Practice Limited to Oral and Maxillofacial Surgery, Portland, Oregon, USA. Correspondence to: Dr Craig Misch, 120 Tuttle Ave S., Sarasota, FL 34237, USA. Fax: +941-957-6440. Email: [email protected] ©2015 by Quintessence Publishing Co Inc.
Autogenous bone grafts are often used in the treatment of large osseous defects or severe atrophy.2–4 The superior biologic properties of autogenous bone, including osteogenesis and osteoinduction, offer significant advantages in reconstructing the atrophic ridge. Large autogenous bone grafts may be used in the form of corticocancellous blocks or cancellous marrow covered with titanium mesh.2,3,5 For smaller segmental defects, the use of intraorally harvested cortical blocks or particulate autograft with titanium mesh or membranes may be considered.6–8 Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been under investigation as a replacement for autogenous bone for ridge augmentation.9–12 RhBMP-2 is a locally acting growth factor that induces bone formation at the site of application. The protein is chemotactic for mesenchymal stem cells and induces osteoprogenitor cells to differentiate into osteoblasts.13 Although absorbable collagen sponge (ACS) has been found to be an optimal carrier for the rhBMP-2 molecule, its poor scaffolding properties cannot resist flap compression. Thus, titanium mesh has been used as a method to provide space maintenance and protect the rhBMP-2/ACS graft to enable bone ingrowth.9–11 The addition of an osteoconductive matrix
202 Volume 30, Number 1, 2015 © 2015 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Misch et al
Fig 1 Failing maxillary implants.
to the rhBMP-2/ACS complex, such as particulate allograft, has also been suggested as a strategy to provide additional scaffolding and a matrix for cellular migration.9,10,14 Supplementation with a portion of particulate bone substitute may provide additional scaffolding without significantly diluting the amount of rhBMP-2.9,10,14,15 This also decreases the cost of the procedure, as less BMP is needed. The use of a commercially available rhBMP-2 product (Infuse Bone Graft, Medtronic) for ridge augmentation is considered an off-label application by the U.S. Food and Drug Administration. The off-label designation does not prevent clinicians from considering rhBMP-2/ACS for this application, but patients must be properly informed, and all adverse effects need to be well documented. This retrospective study evaluated the usefulness of a composite graft of rhBMP-2/ACS and particulate mineralized bone allograft protected by a titanium mesh for vertical bone augmentation. Cone beam computed tomography (CBCT) was used to measure vertical bone gains using this technique. The goal of the study was to determine the amount of vertical bone augmentation that may be obtained with this approach to provide clinicians with guidelines for its use.
MATERIALS AND METHODS Data were collected from four oral and maxillofacial surgery practices in the United States attended by the authors. A retrospective review was performed of patients who required vertical ridge augmentation to allow implant placement (Figs 1 and 2). No cases of extraction socket bone grafting or sinus bone grafting were included. Informed consent for the off-label use of rhBMP-2 for ridge augmentation was obtained. A CBCT scan of the maxilla or mandible was taken preoperatively to assess the ridge morphology and amount of jaw atrophy.
Fig 2 Preoperative view of the maxillary ridge defect.
Fig 3 Maxillary extraosseous vertical ridge defect.
The size of the defect and the volume of planned augmentation determined the appropriate dosage of rhBMP-2. As described by Marx et al,9 the dosage of rhBMP-2 was approximately 1.05 mg for each two-tooth edentulous span. The ACS included in the Infuse bone graft kit was evenly saturated with the reconstituted rhBMP-2 liquid (1.5 mg/mL). A minimum of 15 minutes was allowed to pass to allow binding of the growth factor to the collagen carrier. The collagen sponge was then cut into smaller pieces with scissors and mixed with particulate mineralized bone allograft (50% by volume) (MinerOss, BioHorizons). In 11 patients, platelet-rich plasma was also added to the composite graft. After local anesthesia had been induced, a crestal incision was made to extend well beyond the graft margins. Vertical releasing incisions were made as needed, and a broad-based mucoperiosteal flap was developed to completely expose the ridge deficiency and identify local anatomy (Fig 3). The 0.2-mm-thick titanium mesh was trimmed with scissors to extend beyond the planned implant sites and cover the desired area of augmentation. The mesh was formed over the ridge area, and the edges were molded to The International Journal of Oral & Maxillofacial Implants 203
© 2015 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Misch et al
Fig 4 Composite graft of rhBMP-2/ACS with mineralized bone allograft and platelet concentrate contained in titanium mesh.
Fig 5 Titanium mesh with composite graft secured in the right maxilla.
Fig 6 Cross-sectional view from the preoperative CT scan.
Fig 7 Cross-sectional view from the CT scan of the healed graft reveals the reconstructed ridge.
Fig 8 The titanium mesh is removed after 6 months of healing.
the bone with a periosteal elevator. The concave portion of the mesh was then packed with the rhBMP-2/ ACS mixed with particulate allograft (Fig 4). The mesh with the composite graft was reinserted over the ridge and compressed into place. A minimum of two fixation screws were placed along the buccal cortex to secure the mesh. Additional palatal or lingual fixation screws were inserted as needed (Fig 5). In some cases, a non–cross-linked collagen membrane and/or platelet concentrate was placed over the mesh in the area of wound closure. A scalpel blade was used to incise the periosteum along the base of the facial flap and obtain release for advancement over the graft site. In the posterior mandible, lingual flap release was accomplished by dissecting it to the mylohyoid ridge and stretching the thin periosteum with a gloved finger. The flap margins were then advanced over the mesh and approximated without tension. The flaps were closed primarily with polytetraflouroethylene, polyethylene, or polyglactin 910 mattress and interrupted sutures. No soft tissue–supported prosthesis was worn over the grafted
site until the incision had healed completely. If needed and when possible, temporary tooth replacement was accomplished with a fixed provisional prosthesis. A removable Essix retainer was used as an alternative. The grafted sites were allowed to heal for at least 6 months. A CBCT scan was obtained prior to implant surgery to evaluate the graft healing and bone density and to select implants of appropriate size. The vertical bone changes were measured using the incorporated software of the CBCT scan unit. The most inferior point of the preoperative ridge deficiency was used to determine the maximum bone volume gained (Fig 6). Crosssectional images were used to identify the crest of the regenerated ridge (Fig 7). All measurements were repeated three times by one clinician (CM). The data were collected, and statistical analysis was performed. The patients then underwent a second surgery. After local anesthesia had been achieved, the surgeon used a flap design for removal of the mesh similar to that used during grafting surgery (Fig 8). The mesh and fixation screws were removed, and the fibrous tissue
204 Volume 30, Number 1, 2015 © 2015 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.
Misch et al
Fig 9 Dental implants are placed in the reconstructed maxilla.
that typically forms under the mesh was reflected from the underlying bone. Implant osteotomies were prepared according to the manufacturer’s drilling sequence. Dental implants were inserted and allowed to heal, with the healing period determined by quality of the bone at the site (Figs 9 and 10).
Fig 10 Occlusal view of the implants placed in the healed graft.
Table 1 Data on Patients Treated with Vertical Bone Augmentation with rhBMP-2/ACS and Mineralized Bone Allograft with Titanium Mesh Patient
Graft site
Defect type
No. of Vertical implants gain placed
RESULTS
1
Right maxilla
Extraosseous 10.6 mm
3
2
Anterior maxilla
Intraosseous
7.4 mm
1
Sixteen vertical ridge augmentation procedures were performed in 15 patients (6 men, 9 women). Eight patients required maxillary grafting (six anterior, three posterior) and seven patients needed mandibular grafts (two anterior, five posterior) (Table 1). No meshes were exposed during healing. The maximum vertical bone gains ranged from 4.4 to 16.3 mm. The average maximum vertical bone gain was 8.53 mm (standard deviation 3.5 mm). In all cases, there was a thin radiolucent space under the mesh that likely represented a layer of soft tissue. The ridge augmentation allowed implant placement in all 15 patients. Forty implants were inserted into the grafted ridges after a minimum of 6 months of healing. One patient decided not to undergo implant placement. All 40 implants integrated and were used for prosthetic support.
Right maxilla
Intraosseous
5.7 mm
3
3
Right mandible
Extraosseous
4.4 mm
3
4
Anterior mandible Extraosseous 11.2 mm
2
5
Left mandible
Intraosseous
7.1 mm
2
6
Left mandible
Extraosseous
5.3 mm
2
7
Right mandible
Extraosseous
5.1 mm
2
8
Anterior maxilla
Extraosseous
8.3 mm
4
9
Anterior maxilla
Extraosseous 10.5 mm
2
10
Left mandible
Extraosseous
8.5 mm
3
11
Anterior maxilla
Extraosseous
6.3 mm
4
12
Right maxilla
Extraosseous 11.6 mm
3
13
Anterior maxilla
Extraosseous
3.8 mm
4
14
Anterior maxilla
Extraosseous 16.3 mm
2
15
Anterior mandible Extraosseous 14.3 mm
–
DISCUSSION Osseous regeneration and repair of a defect originate primarily from the bony walls surrounding the defect. Growth factors stimulate the migration of the mesenchymal stem cells needed for tissue repair. The ingrowth of blood vessels from the surrounding bone provides a path for osteoprogenitor cells and new bone formation. As such, the morphology of a bone defect should influence the choice of material or technique. Sites with fewer surrounding osseous walls and
more pronounced atrophy are more demanding and require materials and/or techniques that offer greater biologic activity and regenerative capacity. As a general rule, vertical onlay bone augmentation is more biologically and clinically challenging than horizontal bone augmentation. Explanations for this difference would include fewer osseous walls and greater difficulty in achieving space maintenance, graft stability, and soft tissue coverage. The International Journal of Oral & Maxillofacial Implants 205
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Misch et al
Most classification systems used to describe jaw atrophy focus on the progressive pattern of ridge resorption.16,17 Recently, the Cologne Classification for Alveolar Ridge Defects18 was proposed to address the morphology of the defect as well as augmentation needs. In this classification, a ridge defect is described as horizontal, vertical, or combined. The relationship between the defect region and augmentation can be classified as internal (inside the bony contour) or external (outside the bony contour). This distinction is important, as vertical bone defects inside the bony contour are much easier to reconstruct than onlay augmentation required outside the osseous contour. Intraosseous defects have a higher regenerative capacity with better space maintenance, and soft tissue coverage is more easily achieved. Many methods are available for vertical bone augmentation, including guided bone regeneration, particulate and block bone grafting, titanium mesh grafting, interpositional grafting, and distraction osteogenesis.19,20 Some techniques offer a greater amount of bone regeneration than others. However, it is difficult to determine bone augmentation gains in many publications, as this parameter is often not measured.20 In addition, those studies that do include augmentation gains often do not define the osseous morphology of treated vertical defects (intraosseous or extraosseous). Recently, Milinkovic and Cordaro4 performed a systematic review to determine whether specific indications could be determined for different bone augmentation procedures. In partially edentulous patients requiring vertical augmentation for implant placement, the average bone gain was 3.04 mm for guided bone regeneration and simultaneous implant placement, 4.3 mm for guided bone regeneration and staged implant placement, 4.75 mm for autogenous bone blocks, and 7.08 mm for distraction osteogenesis. A limitation in the data on autogenous bone blocks arose from the combination of bone gains from smaller intraoral blocks with larger iliac crest blocks. Although distraction osteogenesis may allow for more vertical augmentation than other techniques, a large percentage of patients may require secondary augmentation prior to dental implant placement.21,22 There may also be problems with vector control, patient compliance, premature consolidation, and device instability.23 Traditionally, the titanium mesh technique used cancellous autogenous bone graft.5 This approach has been shown to produce significant vertical bone augmentation gains exceeding 10.0 mm.24,25 However, a secondary donor site, such as the iliac crest or tibia, is required, with the associated morbidity of graft harvest. Marx et al9 compared the use of autogenous cancellous bone grafts with a composite graft of rhBMP-2/ ACS, mineralized bone allograft, and platelet-rich
plasma. Both types of grafts were placed into titanium mesh cribs. Forty patients with vertical bone defects in the maxilla were randomly assigned to receive a composite graft or an autogenous graft. Although no bone volume gains were reported, the authors found similar outcomes between the groups in terms of the ability to place dental implants and implant survival. Another study evaluated the use of titanium mesh for horizontal ridge augmentation in the anterior maxilla using rhBMP-2/ACS or particulated autogenous bone harvested from the mandible.11 The authors found no significant differences in horizontal bone gain after 6 months of healing (rhBMP-2/ACS: 3.2 mm; autograft: 3.7 mm) and similar dental implant survival rates. In the current study, the vertical bone gains ranged from 4.4 to 16.3 mm. An evaluation of the sites treated reveals that the majority of the smaller gains were found in the posterior mandible (Table 1). The saddle-shaped defects in this area required less augmentation prior to implant placement. Several patients obtained vertical augmentation of more than 10.0 mm. The literature on rhBMP-2/ACS suggests that this approach may be considered as an alternative to the use of autogenous bone for ridge augmentation. From a patient’s perspective, there are significant benefits to the use of an osteoinductive growth factor, as no bone graft harvest is required, with its associated morbidity. The surgery may be performed in an office environment under sedation and local anesthesia, instead of an operating room under general anesthesia. The elimination of a graft harvest surgery and the relative technical ease of the procedure greatly reduce surgical time. However, the ability to manage the surgical flaps to attain tension-free primary closure is still required for graft success. The disadvantages of the use of rhBMP-2 compared to the use of autograft include greater postoperative edema, longer graft healing times, softer initial bone quality, and higher material costs.9,10 The use of rhBMP-2/ACS with mineralized bone allograft contained in a titanium mesh scaffold offers an alternative to managing vertical bone deficiencies in the maxilla and mandible. This study suggests that there is potential for vertical bone gains comparable to those found with autogenous bone and exceeding other augmentation techniques. Clinicians will need to weigh the higher costs of this material against the simplified technique, enhanced biologic response, and potential for reduced morbidity.
ACKNOWLEDGMENTS The authors wish to thank Ms Maggie A. Misch for her research assistance with this project. The authors reported no conflicts of interest related to this study.
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Misch et al
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