Philip J. Boyne

Reconstruction of Mandibular Continuity Defects With Bone Morphogenetic Protein-2 (rhBMP-2)

PURPOSE Several autogenous bone grafting techniques are available for the restoration of large continuity defects of the mandible. However, these procedures are associated with limitations involving postoperative morbidity, difficulty in ambulation, and pain. The development of a technique of surgical reconstruction not involving autogenous bone would offer new opportunities for facial bone reconstruction, particularly of the mandible. This study was instituted to observe the effect of rhBMP-2 in a collagen carrier without concomitant bone grafting material in the restoration of continuity critical-sized defects of the mandible. MATERIALS AND METHODS A case review was made of 14 patients who were selected from a larger group having received BMP-2 in different categories of mandibular defects. The rhBMP-2 in all the cases reported here was used alone with the collagen carrier without concomitant bone materials. The cases involved lesions of the body and angle of the mandible in 2 categories: 1) defects resulting from neoplastic diseases, and 2) defects secondary to osteomyelitis (related to bisphosphonates or irradiation). A total dose of 4 to 8 mg of rhBMP-2 was delivered to the surgical site in concentrations of 1.5 mg per cc (depending on the size of lesion). Cases were followed over a period from 6 to 18 months. Occlusal function was restored with implant-borne or conventional prosthesis. RESULTS All of the cases reported here had successful osseous restoration of the edentulous area followed by prosthetic treatment. Bone formation in the surgical area could be palpated at the end of 3 to 4 months and identified radiographically at the end of 5 to 6 months. The maintenance of a periosteal envelope was effected by the use of a superiorly placed minibar in the upper portion of the defect, or with the use of titanium mesh superiorly. This metallic tenting up to the mucosa is thought to be necessary to maintain the space for osseous regeneration. CONCLUSION This study indicated that the use of rhBMP-2 without concomitant bone grafting materials in large critical sized mandibular defects produced excellent regeneration of the area establishing the basis for the return of prosthodontic function. This study tends to support the use of cytokines, particularly rhBMP-2, in osseous regeneration or repair of facial bones. The technique describes a new alternative to various types of autogenous bone grafting procedures for the treatment of critical sized bony lesions of the mandible.

Pivotal, Randomized, Parallel Evaluation of Recombinant Human Bone Morphogenetic Protein-2/Absorbable Collagen Sponge and Autogenous Bone Graft for Maxillary Sinus Floor Augmentation

PURPOSE The purpose of this prospective study was to evaluate the safety and effectiveness of recombinant human morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS) compared with an autogenous bone graft when used for 2-stage maxillary sinus floor augmentation. The study assessed new bone formation, placement integration, and functional loading after 6 months and long term for 2 years. MATERIALS AND METHODS A total of 160 subjects were randomized, enrolled, and followed from January 1999 to February 2004 at 21 centers in the United States. The subjects with less than 6 mm of native bone height were treated with 1.50 mg/mL rhBMP-2/ACS or with an autograft. The height and density measurements were quantified by computed tomography scans. Core biopsies were obtained at dental implant placement and used for histological analysis. Safety was evaluated by oral examinations, radiographs, serum chemistries, and hematology. RESULTS A significant amount of new bone was formed by 6 months postoperatively in each group. The mean change in bone height in the rhBMP-2/ACS subjects was 7.83 +/- 3.52 mm versus 9.46 +/- 4.11 mm for the bone graft subjects. At 6 months after dental restoration, the induced bone in the rhBMP-2/ACS group was significantly denser than that in the bone graft group. No marked differences were found in the histologic parameters evaluated between the 2 groups. The new bone was comparable to the native bone in density and structure in both groups. The success rate for the rhBMP-2/ACS group was 79% (64 of 81 subjects), and 201 of 251 implants placed in the bone graft group and 199 of 241 implants placed in the rhBMP-2/ACS group were integrated, retained, and functional at 6 months after loading. No adverse events were deemed related to the rhBMP-2/ACS treatment. The autograft group was noted to have a 17% rate of long-term parasthesia, pain, or gait disturbance related to the bone graft harvest. CONCLUSIONS The results of our multicenter, randomized, prospective, clinical trial have shown the effectiveness and safety of rhBMP-2/ACS compared with bone graft for sinus floor augmentation. The studys primary endpoint was exceeded, and the implants placed in rhBMP-2/ACS and bone graft groups performed similarly after functional loading.

Animal studies of application of rhBMP-2 in maxillofacial reconstruction

A pilot study in adult male Macaca fascicularis (rhesus) monkeys was undertaken to observe the effect of two dose ranges of recombinant human BMP-2 on bone regeneration following bilateral hemimandibulectomies. The mandibulectomies consisted of 2.2 centimeter resections through the entire thickness of the mandible with the remaining bone segments maintained in a distracted position by orthopaedic mesh (TiMesh). In three animals, the dose range on one mandibulectomy site in each animal was 0.8 mg BMP-2 per cc with the contralateral defect receiving 0.2 mg of the rhBMP-2. The carrier was a collagen I sponge (Helistat). These animals were sacrificed at five months postoperatively. In an additional four animals, a dose of 0.4 mg per cc was used on one site with a particulate autogenous graft of cortical cancellous bone used as a control on the contralateral defect. After four months, the reconstructed areas were re-exposed and implanted with root-form Steri-oss implants (Steri-Oss). These implants were brought into occlusion at the end of an additional four month period and are being evaluated for a period of 6 months of function. In all seven animals, the alveolar ridges were regenerated completely with restoration of contour and cortical bone. In the three animals euthanized at five months, histomorphmeic analysis revealed excellent calcified bone matrix to marrow spaces ratios. The result of this work indicates that recombinant human BMP-2 can bring about osseous regeneration of critical sized hemimandibulectomy defects in rhesus monkeys.

A technique for osseous restoration of deficient edentulous maxillary ridges

A technique for maxillary bone grafting to augment the atrophic ridge is presented, and the results from 15 cases followed from three to ten years are briefly described. Loss of postoperative ridge height ranged from 10-20% in this sample. It appears that the tendencies to postoperative resorption that occur when autogenous particulate cancellous bone grafts are employed to restore atrophic mandibles are not operative in the maxilla.

Use of a Porcine Collagen Matrix as an Alternative to Autogenous Tissue for Grafting Oral Soft Tissue Defects

PURPOSE Soft tissue grafting is often required to correct intraoral mucosal deficiencies. Autogenous grafts have disadvantages including an additional harvest site with its associated pain and morbidity and, sometimes, poor quality and limited amount of the graft. Porcine collagen matrices have the potential to be helpful for grafting of soft tissue defects. PATIENTS AND METHODS Thirty consecutive patients underwent intraoral grafting to re-create missing soft tissue. Defects ranged in size from 50 to 900 mm(2). Porcine collagen matrices were used to reconstruct missing tissue. Indications included preprosthetic (22), followed by tumor removal (5), trauma (2), and release of cheek ankylosis (1). RESULTS The primary efficacy parameters evaluated were the degree of lateral and/or alveolar extension and the evaluation of re-epithelialization and shrinkage of the grafted area. Overall, the percentage of shrinkage of the graft was 14% (range, 5%-20%). The amount of soft tissue extension averaged 3.4 mm (range, 2-10 mm). The secondary efficacy parameters included hemostatic effect, pain evaluation, pain and discomfort, and clinical evaluation of the grafted site. All patients reported minimal pain and swelling associated with the grafted area. No infections were noted. CONCLUSION This porcine collagen matrix provides a biocompatible surgical material as an alternative to an autogenous transplant, thus obviating the need to harvest soft tissue autogenous grafts from other areas of the oral cavity.

Clinical, Histologic, and Histomorphometric Evaluation of Mineralized Solvent-dehydrated Bone Allograft (Puros) in Human Maxillary Sinus Grafts

Demineralized freeze-dried bone allografts (DFDBA) have been successfully used alone or in composite grafts for many decades. Little research has been done on the effect of retaining the mineral content of bone allografts. This study histologically and histomorphometrically evaluated a new mineralized bone allograft material placed in human atrophic maxillary sinuses. Seven partially edentulous patients requiring sinus grafts before implant placement were selected for this study Their age range was 56 to 81 years (mean 67.7 years). Test grafts consisted of a mineralized solvent-dehydrated cancellous bone allograft, and control grafts were a composite of DFDBA and deproteinized bovine bone xenograft (1:1). Bilateral cases (n = 3) received both test and control grafts on opposite sides, and unilateral cases received either a test (n = 3) or control (n = 1) graft only. At 10 months, core biopsies were taken from each graft site, and dental implants were placed into the augmented bone. All bone grafts resulted in new bone formation and all implants osseointegrated. Test grafts resorbed and were replaced by newly formed bone significantly faster and in greater quantities than were control grafts. No complications with grafts or implants were noted. Both test and control grafts achieved excellent results. The faster bone formation observed with the test graft may be due, in part, to its smaller particle size compared with the bovine portion of the control graft. Test grafts were either replaced by new bone or displayed new bone-to-particle surface contact in higher percentages than did control grafts. No differences in osseointegration or graft stability were noted 2 years after the study.

Free grafting of traumatically displaced or resected mandibular condyles

A technique of free grafting of the mandibular condyle with a vertical ramus osteotomy is advocated in cases presenting with markedly displaced fracture dislocation of the condyle, in reconstruction of the TMJ after mandibular resection, and in providing access for vascular surgery approaches to the treatment of carotid aneurysms. The technique of free transplantation of the condyle did not result in any aseptic necrosis or any arthritic changes in 35 patients observed over a period of 3 to 15 years. All patients had excellent TMJ function.

Implant Success in Distracted Bone Versus Autogenous Bone-Grafted Sites

Endosseous implants are the treatment of choice for restoring function and reconstructing most edentulous areas of the maxilla and mandible. In general, alveolar bone defects can be reconstructed by either distraction osteogenesis or autogenous bone grafting. After alveolar reconstruction, endosseous implants are used to support and retain the prosthesis for restoration of form and function. Eighty-two consecutive patients requiring alveolar augmentation prior to implant placement were evaluated. All patients were given treatment options for reconstructing their alveolar defects, which included autogenous bone grafting vs distraction osteogenesis. Sixty-five patients received autogenous grafts (anterior iliac crest: 44; retromolar: 17; tibia: 2; chin: 2), and 17 patients underwent distraction osteogenesis prior to implant placement. A total of 184 implants were placed in the autogenous bone-grafted sites and 56 implants in the distracted bone sites. Implants placed in sites restored with autogenous bone grafts had an implant success rate of 97% (178/184), whereas implants placed in distracted bone sites had a success rate of 98% (55/56). In the autogenous grafted group, 3 implants failed in the posterior mandible, one in the anterior maxilla, one in the anterior mandible, and one in the posterior maxilla. In the distraction group, one implant failed in the posterior mandible. Both techniques are associated with good success rates. There was no statistical difference between implant success in autogenous bone vs distracted bone sites in this group of patients.

Bone Regeneration Using rhBMP-2 Induction in Hemimandibulectomy Type Defects of Elderly Sub-Human Primates

Our previous work has shown that total osseous reconstruction of large discontinuity hemimandibulectomy, critical-sized defects can be achieved easily in 8-year-old Macaca fascicularis monkeys (Boyne 1996). However the literature has indicated that animal aging decreases the BMP induction of stem cells in rats and in other rodent species. It was necessarily important that the rhBMP-2 be demonstrated in non-human primates to determine if this reduction in effectiveness also existed in the higher animals phylogenetically. The purpose of this study was to operate aged non-human primates duplicating the model used in middle-aged animals to demonstrate regeneration of hemimandibulectomy defects. This age group could be extrapolated to the 80-year-old clinic patient. Six non-human primates aged 20 years were rendered edentulous posteriorly and the mandibles allowed to heal. Three months postoperatively bilateral hemimandibulectomies were performed. The defects received BMP in a collagen sponge (Helistat) using a dose level of 0.75 mg of rhBMP-2. After the manner previously reported by Boyne (1996, 1999), at the end of four months the surgical sites were exposed by mucoperiosteal flap demonstrating complete regeneration of the critical-sized defects. The animals received two dental implants in restored areas. The implants were brought into function approximately four months later, and were allowed to function for eight months in all cases. The results indicate that the regeneration of mandibular critical-sized defects by the use of rhBMP-2 in aged animals is comparable to that of the middle-aged group. This study indicates that aged non-human primates, chronologically comparable to 80-year-old humans, respond as favorably to rhBMP-2 as do the middle-aged animals. Extrapolating the results to the clinical level, one would expect that rhBMP-2 would produce a comparable result in the regeneration of large hemimandibulectomy-type defects in clinical human patients.

Effect of teeth with periradicular lesions on adjacent dental implants

OBJECTIVES It is generally accepted that dental implants should not be placed in infected sites. However, the effect of periradicular infections of natural teeth on adjacent osseointegrated implants is less understood. The purpose of this study was to evaluate effects of periradicular lesions on osseointegration of existing implants. Study design Forty titanium solid root-form implants were placed close to premolars in dogs. After healing following implant placement, the adjacent premolars were treated in 1 of 4 ways: group A, no treatment of the adjacent premolar; group B, induction of a periradicular lesion followed by nonsurgical root canal therapy of the premolar; group C, induction of a periradicular lesion followed by nonsurgical root canal therapy of the premolar and surgical detoxification of the implant surface; and group D, induction of periradicular lesion and no treatment of the tooth. After 7(1/2) months, block sections were prepared and the percentage of osseointegration was analyzed histomorphometrically. RESULTS The average integration for implants in groups A-B was 54%, 74%, 56%, and 68%, respectively. One-way analysis of variance demonstrated no difference between the 4 groups ( P =.518). CONCLUSIONS The results of this study indicate that teeth with periradicular lesions do not adversely affect adjacent titanium solid root-form implants.