transforming-growth-factor-beta and Osteomyelitis

Spinal fusion is a proven surgical tool for the treatment of degenerative, traumatic, neoplastic, and infectious conditions of the spine. Traditional grafting techniques using autogenous bone graft or allograft have inherent drawbacks including varying pseudoarthrosis rates and well recognized bone graft harvest site complications. Bone morphogenetic proteins (BMPs) offer the exciting prospect of enhanced union rates equal to or greater than autograft and potentially eliminate graft harvest site complications. Many studies have clearly demonstrated the efficacy of BMP products for various applications in spine surgery. BMP has proven effective in achieving union in anterior and posterior lumbar surgery and recently in anterior cervical surgery. Despite the reported success, the universal adoption of BMP is tempered by high costs and lingering safety concerns with reported complications specific to BMP use including vertebral osteolysis, ectopic bone formation, radiculitis and cervical soft tissue swelling. Ongoing clinical and basic-science research is focused on clearly defining guidelines for BMP use in spine surgery and on developing more affordable BMP formulations with dosing that predictably results in spine fusion yet minimizes the possible side effect profile.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Resorption; Bone Transplantation; Deglutition Disorders; Disease Models, Animal; Hematoma; Humans; Ilium; Middle Aged; Osteomyelitis; Plastic Surgery Procedures; Radiculopathy; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Spine; Tissue and Organ Harvesting; Transforming Growth Factor beta

The off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the treatment of mandibular bone defects was evaluated in 5 patients. The rhBMP-2 was used as an alternative to autogenous bone grafting.. A total of 5 patients had mandibular defects reconstructed with rhBMP-2, 1.5 mg/mL, soaked collagen sponges alone or in combination with bone marrow cells and allogenic cancellous bone chips. Four of the patients had mandibular continuity defects and the fifth patient had 2 large bone cavities following removal of dentigerous cysts. Radiographs and clinical examinations were used to evaluate healing. The longest patient follow-up was 22 months after reconstruction.. Radiographic and clinical assessments revealed bone regeneration and restoration of the mandibular defects in 3 of the 5 patients. The rhBMP-2 failed in 2 patients with continuity defects. Both patients with failed rhBMP-2 grafts were successfully repaired using autogenous harvested from the iliac crest.. Mandibular bone defects can be successfully reconstructed using rhBMP-2 soaked sponges with and without including bone marrow cells and allogenic bone. Further studies are needed to determine the ideal combination of components that will predictably and reliably regenerate bone in different types of bone defects.

Topics: Adult; Aged, 80 and over; Bone Marrow Transplantation; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Bone Regeneration; Bone Transplantation; Collagen; Female; Fractures, Comminuted; Humans; Jaw Cysts; Male; Mandible; Mandibular Diseases; Mandibular Fractures; Osteomyelitis; Recombinant Proteins; Tissue Engineering; Transforming Growth Factor beta

A retrospective clinical study.. To evaluate the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as the primary graft material for the surgical treatment of vertebral osteomyelitis.. The clinical and radiographic results using allograft, autograft, and vascularized bone flaps for the surgical treatment of osteomyelitis have been previously reported. Despite an expanding body of literature documenting the value of rhBMP-2 in spinal fusion, its application to the management of spinal infection has never before been analyzed.. Twenty patients underwent surgical treatment of vertebral osteomyelitis using rhBMP-2 and were analyzed with a mean follow-up of 40 months (range, 24-53 months). All patients were treated with anterior column debridement and instrumented reconstruction. Four (20%) patients were treated with an anterior approach alone while the remaining 16 (80%) patients underwent circumferential spinal reconstruction. Clinical outcomes were assessed by Frankel grade and Odom criteria. Radiographic fusion was characterized based on thin-section computerized tomography (CT) analysis.. Pathogens responsible for infection included Staphylococcus aureus (11; 55%), S. epidermidis (6; 30%), Bacteroides (1; 5%), and polymicrobial species (1; 5%). Infected segments of the spinal column based on region were found to be: thoracic (1; 5%), thoracolumbar (5; 25%), lumbar (11; 55%), and lumbosacral (3; 15%). The mean number of anterior and posterior segments fused was 3.3 (range, 2-5) and 6.5 (range 2-16), respectively. Forty-five percent of the subjects underwent multilevel corpectomies and fusion. All patients demonstrated clinical and radiographic evidence of spinal fusion at the time of follow-up. Patients had stable (14 patients) or improved (6 patients) Frankel grades after surgery. Odom criteria at final follow-up were: excellent (3; 15%), good (12; 60%), fair (4; 20%), and poor (1; 5%). There was no case of persistent or recurrent infection requiring revision surgery.. rhBMP-2 is a valuable graft option for the surgical treatment of vertebral osteomyelitis. When dosed in the manner reported, very high rates of fusion are achievable as is eradication of infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteroides; Bacteroides Infections; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Combined Modality Therapy; Debridement; Female; Humans; Intraoperative Complications; Magnetic Resonance Imaging; Male; Middle Aged; Osteomyelitis; Recombinant Proteins; Retrospective Studies; Spinal Diseases; Spinal Fusion; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Transforming Growth Factor beta; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Adolescent; Age Factors; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Collagen; Drug Carriers; Female; Humans; Jaw Fixation Techniques; Male; Mandible; Mandibular Diseases; Mandibular Neoplasms; Middle Aged; Oral Surgical Procedures; Osteomyelitis; Plastic Surgery Procedures; Recombinant Proteins; Surgical Sponges; Transforming Growth Factor beta

The treatment of vertebral osteomyelitis includes antibiotics with or without surgical intervention. The decision to place instrumentation into an infected spinal column remains controversial. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in patients with osteomyelitis is also extremely controversial. The authors review their experience in performing corpectomy and fusion with titanium cages and rhBMP-2 in patients with vertebral instability and/or neurological compromise due to vertebral osteomyelitis.. Data obtained in 15 patients treated between 2001 and 2005 were included in this analysis. Nine patients presented primarily with axial pain and six with radiculopathy or myelopathy. Seven patients had an associated epidural abscess. The cervical spine was affected in six patients, the thoracic spine in five, and the lumbar spine in four. All patients underwent corpectomy of the involved vertebral bodies; the authors then performed spinal reconstruction, placing a titanium cage-plate system with morcellized allograft/autograft and rhBMP-2. In 10 patients, supplemental posterolateral screw-rod fixation was conducted. A one-level corpectomy was performed in one patient, a two-level corpectomy in 13, and a six-level corpectomy in one. A morcellized allograft and rhBMP-2-filled titanium cage was used in 10 patients, and an autograft and rhBMP-2-filled cage in five patients. The most common pathogen was Staphylococcus aureus. All patients received intravenous antibiotics for at least 6 weeks postoperatively, and life-long antibiotic therapy was required in three patients with coccidiomycoses, candida, and tuberculosis osteomyelitis, respectively. There were no recurrent infections. Radiography demonstrated evidence of fusion in all patients at the last follow-up examination. The mean follow-up period was 20 months.. Corpectomy followed by titanium cage-plate reconstruction and the placement of rhBMP-2 may be a safe and effective treatment for selected patients with vertebral osteomyelitis. This surgical therapy does not appear, at least based on preliminary results, to lead to recurrent hardware infections. Based on the results obtained in this limited series, the authors found that rhBMP-2 can be used in the setting of active infection with excellent fusion rates and without complication. The morbidity associated with the autograft donor site is avoided when using cages. Antibiotic therapy tailored to the specific organism should be continued for at least 6 weeks after surgery, and life-long therapy is required in cases of fungal or tuberculosis infections.

Topics: Adult; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Screws; Combined Modality Therapy; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Orthopedic Procedures; Osteomyelitis; Postoperative Care; Retrospective Studies; Spinal Fusion; Spine; Staphylococcal Infections; Surgical Fixation Devices; Titanium; Transforming Growth Factor beta

Retrospective case series.. To present results of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in medically nonresponsive pyogenic vertebral osteomyelitis (PVO), treated by anterior/posterior debridement and instrumented fusion in the cervical, thoracic, and lumbosacral spine.. Surgical options for PVO vary, as do their outcomes, and can be complicated by recurrence, pseudarthrosis, and death. Although rhBMP-2 use in spinal fusion is increasing, its utility in PVO is unknown. Additionally, use in areas of infection is listed as a contraindication, although this is not supported by laboratory (animal) studies or clinical studies in long bones.. Between 2003 and 2005, 14 patients who underwent circumferential fusion for PVO were included in this study. Average patient age was 54 years (range, 27-77 years). Eight (57%) patients had 3 or more vertebral bodies involved. Diagnostic studies included radiographs, CT, MRI, and markers of infection [(C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood count (WBC)]. All patients underwent anterior fusion with rhBMP-2 inserted in structural allograft (11 patients) or titanium cylindrical cages (3 patients), followed by posterior instrumented fusion with autogenous iliac crest graft (8 occurring on the same day). Follow-up averaged 22 months (range, 11-30 months). All were studied with plain radiographs, including flexion-extension lateral films and fine cut CT scans with reconstruction. Pain ratings were recorded by visual analog scores (VAS).. Clinical resolution of infections, normalization of lab values, and bony fusion, based on dynamic radiographs and CT scans, were seen in all patients at latest follow-up. Staphylococcus aureus was the most frequently identified organism (8 patients). Four (29%) patients had positive blood cultures (all MRSA). Predisposing comorbidities were present in 12 patients. Six patients had epidural abscesses. Eight (57%) patients presented with neurologic deficits, ranging from paraparesis to quadriplegia. Complete recovery was seen in 7 (quadriplegia unchanged). At 1 year, mean VAS pain scores improved significantly (P < 0.05) from 7.9 (range, 3-10) to 2.8 (range, 0-6). Perioperative complications (non-BMP related) occurred in 2 patients. There were no surgically-related deaths.. rhBMP-2 use, in combination with antibiotics and circumferential instrumented fusion, provides a safe and successful surgical treatment of medically nonresponsive PVO, with solid fusions obtained, good clinical results, and no adverse side effects from the BMP.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cervical Vertebrae; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteomyelitis; Radiography; Retrospective Studies; Spinal Fusion; Thoracic Vertebrae; Transforming Growth Factor beta; Treatment Outcome

The objective of this study was to evaluate the use of adenoviral transfer of the BMP-2 gene (Ad-BMP-2) for enhancing healing in an infected defect fracture model. A femoral defect stabilized with plates and screws was surgically created in sixty-four skeletally mature New Zealand white rabbits. Experimental groups were: (1) non-infected Ad-luciferase (Ad-LUC, NONLUC), (2) non-infected Ad-BMP-2 (NONBMP), (3) infected Ad-LUC (INFLUC), and (4) infected Ad-BMP-2 (INFBMP). A sclerosing agent was applied to the ends of the bone at surgery to facilitate the development of osteomyelitis. Fracture healing was evaluated radiographically and histologically. Data were analyzed using an ANOVA, with statistical significance set as p<0.05. Rabbits in the non-infected and infected groups that were treated with Ad-BMP-2 had earlier initial- and bridging-callus formation, and a higher overall external callus grade compared to rabbits in the Ad-LUC groups. Rabbits in the Ad-LUC groups had more defect ossification compared to rabbits in the Ad-BMP-2 groups. There was a trend for rabbits in the Ad-BMP-2 group that were euthanized at 2 and 4 weeks after surgery to have more bone and cartilage compared to rabbits in the Ad-LUC group. The results of this study suggest that Ad-BMP-2 enhances the early stages of healing in an infected defect fracture. The results of our study were not as favorable as those reported in previous studies because animals healed by a large bridging callus and not by defect ossification. This could have been a result of the sclerosing agent, which may have damaged the cells in the defect.

Topics: Adenoviridae; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Disease Models, Animal; Female; Fracture Healing; Gene Transfer Techniques; Genetic Therapy; Osteomyelitis; Rabbits; Staphylococcal Infections; Transforming Growth Factor beta