Alan S. Herford

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.

Immediate distraction osteogenesis: the sandwich technique in combination with rhBMP-2 for anterior maxillary and mandibular defects.

AbstractThe goal of this study was to demonstrate the technique and effectiveness of incorporating recombinant human bone morphogenetic protein-2 (rhBMP-2) to the established sandwich osteotomy technique. Although the success of the sandwich osteotomy procedure has been well documented, we hope to show that the addition of rhBMP-2 will enhance bone formation.We performed a sandwich osteotomy technique in patients who had been treated initially by grafting with suboptimal results. Only defects involving the anterior maxilla (3 patients) or the anterior mandible (1 patient) were included. There were 4 patients, 2 men and 2 women, with an age range of 19 to 62 years. The causes of the ridge deficiencies ranged from pathology to trauma. The height (distance) of distracted transport bone segment was measured. The amount of relapse was measured 6 months after the surgery.All patients exhibited a significant increase in bone height. The amount distracted was 6.75 mm (range, 5–11 mm). The amount of relapse was 8.5% (range, 0%–18%). Dental implants were placed in the reconstructed ridges in all patients. There were no instances of permanent paresthesia. Two patients had exposure of a portion of the hardware, which healed uneventfully.The sandwich osteotomy technique has proven to be an effective method for augmenting deficient alveolar ridges. The addition of rhBMP-2 may aid in its success rate by promoting osteogenesis at the osteotomy site, especially in multiple-operated patients where other traditional techniques have failed to gain the desired ridge height.

Recombinant human bone morphogenetic protein type 2 application for a possible treatment of bisphosphonates-related osteonecrosis of the jaw.

Abstract Bisphosphonates are a class of agents used for treating osteoporosis and malignant bone metastases treatment. Osteonecrosis of the jaws is the main complication in a subset of patients receiving these drugs. Based on a growing number of case reports and institutional reviews, bisphosphonate therapy can cause exposed and necrotic bone that is isolated to the jaw. This clinical investigation is aimed at analyzing the clinical effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) application in patients affected by bisphosphonates-related osteonecrosis of the jaws undergoing surgery for necrotic bone removal. A case review was made of 20 patients. The rhBMP-2 in all the cases reported here was used alone with the collagen carrier without concomitant bone materials. The cases involved osteonecrotic lesions of the upper and lower jaws. A total dose of 4 to 8 mg of rhBMP-2 was delivered to the surgical site in concentrations of 1.5 mg/mL (depending on the size of lesion). Patients were followed up over a period ranging 6 to 12 months. Patients had successful healing of the necrotic area. New bone formation in the surgical area could be clinically evaluated by palpation at the end of 3 to 4 months and confirmed by radiographic examination at the end of 12 months. This study indicated that the use of rhBMP-2 without concomitant bone grafting materials was useful in promoting healing of bisphosphonates-related osteonecrosis of the jaws. The use of growth factors, particularly rhBMP-2, should be considered a therapeutic choice in patients affected by osteonecrosis of the jaws related to bisphosphonate therapy.

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.

Recombinant human bone morphogenetic protein type 2 jaw reconstruction in patients affected by giant cell tumor.

Giant cell tumor (GCT) is a relatively common skeletal tumor. Mandibular localization of this tumor is usually treated with resection of the tumor area. 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 (hip graft), 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 aims to underline the effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) in a collagen carrier with concomitant bone grafting material in the restoration of continuity critical-size defects after GCT resection in the mandible. The rhBMP-2 was used with absorbable collagen sponge. A total dose of 4 to 8 mg of rhBMP-2 was delivered to the surgical site in concentrations of 1.5 mg/mL. The patient was followed up over a period from 6 to 18 months. Occlusal function was initially restored with conventional prosthesis. 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 results clearly indicated that the use of rhBMP-2 without concomitant bone grafting materials in large critical-size mandibular defects secondary to GCT produced excellent regeneration of the area, establishing the basis for the return of prosthodontic function.

rhBMP-2 as an Option for Reconstructing Mandibular Continuity Defects

c T r B b s b andibular continuity defects are frequently caused by umor removal or significant trauma. The reconstruction f these defects can be challenging. For defects with xtensive hard and soft tissue loss, microvascular freeissue transfer often provides an excellent reconstrucive option. However, significant site morbidity, as well s nonideal bone stock for implant placement, can ocur. For mandibular continuity defects not associated ith significant soft tissue loss, nonvascularized autogeous bone has been shown to provide excellent results. he advantages compared with microvascular free-tisue transfer include a more limited donor site and the bility to provide excellent height and width for subseuent dental implants. Autogenous bone grafting is considered the reference tandard for reconstructing mandibular defects. Limits xist, however, to the amount of bone that can be arvested, and autogenous grafts have additional moridity risks associated with the secondary harvest site. Successful reconstruction of segmental defects ust include restoration of both bone height and idth to enable secondary prosthetic rehabilitation. he limitations of autogenous grafting include 1) a imited number of donor sites in the human skeleton, ) a finite quantity of available bone, and 3) surgical orbidity. Associated morbidities include pain, parsthesia, gait disturbances, scarring, and infection. Certain naturally occurring growth factors have beome available for clinical use. One such growth actor, recombinant human bone morphogenetic proein 2 (rhBMP-2), has been shown to lead to de novo one formation. In 2000, the Food and Drug Adminstration (FDA) approved rhBMP-2 for spinal fusion, nd in 2004, the growth factor was approved for use

Histomorphometric Evaluation of Anorganic Bovine Bone Coverage to Reduce Autogenous Grafts Resorption: Preliminary Results

Physiologic resorption due to remodeling processes affects autogenous corticocancellous grafts in the treatment of atrophic jawbone alveolar ridges. Such a situation in the past made overgrafting of the recipient site mandatory to get enough bone support to dental implants in order to perform a prosthetic rehabilitation. Anorganic bovine bone, conventionally used to treat alveolar bone deficiencies in implant surgery, showed a high osteoconductive property thanks to its micro and macrostructure very similar to that of human hydroxyapatite. An original technique provides for the application of a thin layer of anorganic bovine bone granules and a collagen membrane on the top of the corticocancellous onlay bone grafts to reduce in a remarkable way the graft resorption due to remodeling. The results of a clinical prospective study and a histomorphometric analysis done on autogenous grafts harvested from the iliac crest showed that the proposed technique is able to maintain the original bone volume of the corticocancellous blocks.

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.

Protein-Signaled Guided Bone Regeneration Using Titanium Mesh and Rh-BMP2 in Oral Surgery: A Case Report Involving Left Mandibular Reconstruction after Tumor Resection

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive protein approved for use in oral and maxillofacial defect reconstruction. Growth factors act as mediators of cellular growth on morphogenesis and mythogenesis phases. Utilized as recombinant proteins, these growth factors need the presence of local target cells capable of obtaining the required results. This cell population may be present at the wound site or added to scaffolding material before implantation at the surgical site. The aim of this study is to evaluate the clinical and radiographic results of a reported case with a large bone defect, treated with an absorbable collagen sponge, rhBMP-2 and a titanium plate and mesh. The Authors want to report a case which shows the resulting effectiveness of the rhBMP2 action regarding a large, mandibular defect reconstruction. This case also shows how the removal of a rare tumor such as a ghost cell tumor of the jaw may be treated without harvesting bone from another body site. A quick diagnosis of the lesions is important in order to perform the most suitable treatment. The Authors also underline the clinical and histological steps to insure the correct treatment is carried out to solve the case. Moreover, from results obtained from this case, it is possible to highlight several clinical benefits for the patient by adding rhBMP-2 to the common allograft to not only have alveolar reconstruction defects and sinus floor augmentation, but also to have alveolar cleft reconstruction and to treat segmental defects.

Complications in Bone Grafting

Autogenous bone grafts continue to have wide use for reconstructing alveolar defects because of the many advantages associated with them. Although complications are low, the harvesting of bone grafts does have the risk of morbidity, which varies based on the harvest site chosen. Patients should be informed of possible complications associated with bone harvest as well as complications that many develop at the grafted site.