transforming-growth-factor-beta and Pseudarthrosis

Cervical spine degenerative disease is one of the main causes of myelopathy. Anterior cervical discectomy and fusion (ACDF) is the most common surgical procedure used to treat cervical myelopathy. Therefore, it is important to study pseudarthrosis rates after ACDF and correlate them with the graft used.. We performed a systematic review to evaluate the relationship between pseudarthrosis after ACDF and the interbody graft used.. A total of 3732 patients were evaluated in 46 studies. The mean age of the included patients was 51.5 ± 4.18 years (range, 42-59.6 years). ACDF is most often perforemd as single-level surgery and the level most impaired is C5-C6. The use of titanium cages, zero profile, recombinant human bone morphogenetic protein 2, and carbon cages was seen as a protective factor for pseudarthrosis compared with the autograft group (control group); with an odds ratio of 0.29, 0.51, 0.03, and 0.3, respectively; the results were statistically relevant. The use of polyetheretherketone, poly(methyl methacrylate), and trabecular metal was a risk factor for development of pseudarthrosis compared with the control group, with an odds ratio of 1.7, 8.7, and 6.8, respectively; the results were statistically relevant. Radiologic follow-up was an important factor for the pseudarthrosis rate; paradoxically, a short follow-up (<1 year) had lower rates of pseudarthrosis and follow-up >2 years increased the chance of finding pseudarthrosis.. Different types of grafts lead to a significant difference in pseudarthrosis rates. Follow-up time is also an important factor that affects the rate of pseudarthrosis after ACDF.

Topics: Benzophenones; Bone Morphogenetic Protein 2; Bone Transplantation; Carbon; Cervical Vertebrae; Diskectomy; Humans; Ketones; Odds Ratio; Polyethylene Glycols; Polymers; Polymethyl Methacrylate; Postoperative Complications; Prosthesis Design; Prosthesis Implantation; Pseudarthrosis; Recombinant Proteins; Risk Factors; Spinal Cord Diseases; Spinal Diseases; Spinal Fusion; Titanium; Transforming Growth Factor beta; Transplantation, Autologous

A review of the literature concerning the use of recombinant human bone morphogenetic proteins 2 (rhBMP-2) and 7 (rhBMP-7) in spinal fusion.. To summarize the pertinent preclinical experiments that enabled regulated human clinical trials of recombinant bone morphogenetic proteins for spinal fusion and to update clinicians on the results of those trials.. More than three decades of research involving thousands of scientists and academicians throughout the world have led to the clinical use of recombinant bone morphogenetic proteins for the treatment of spinal disease.. The published and presented scientific literature and the author's personal experience were examined.. Recent clinical data support the assertion that recombinant bone morphogenetic proteins can be used as complete bone graft substitutes in spinal fusion surgery. In some circumstances, the efficacy of these factors for inducing successful fusion is superior to that of autogenous bone graft. RhBMP-2 is shown to be efficacious in several fusion applications, including intervertebral and lumbar posterolateral. Similar efficacy for rhBMP-7 has not yet been demonstrated, although relevant clinical studies are currently under way. The availability of these biologic agents will improve our ability to predictably treat spinal disease and may facilitate the further development of less invasive surgical innovations.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Transplantation; Collagen Type I; Feasibility Studies; Humans; Models, Animal; Pilot Projects; Prostheses and Implants; Pseudarthrosis; Radiography; Recombinant Proteins; Spinal Fusion; Spine; Transforming Growth Factor beta; Treatment Outcome

Prospective, single center, nonblinded radiographic analysis of anterior and posterior adult spinal deformity fusions performed with bone morphogenetic protein (rhBMP-2).. To determine the ability of rhBMP-2 to achieve multilevel spinal fusion in the deformity patient.. No previous study has evaluated rhBMP-2 for multilevel adult spinal deformity fusion with 2-year results. We postulated fusion could be achieved without distant autogenous graft harvest.. Prospective analysis was performed for 98 patients (308 levels; mean age, 51.4 years) who underwent multilevel anterior or posterior spinal fusion (PSF) with minimum 2-year follow-up (average, 2.6 years). Group 1 (10 mg/level) contained 47 patients (109 levels; 2.33 levels/patient) who underwent anterior spinal fusion (ASF): BMP on an absorbable collagen sponge (ACS) with a titanium mesh cage. Group 2 (20 mg/level) included 43 patients (156 levels; 3.63 levels/patient) with PSF: BMP on an ACS with local bone graft (LBG) and bulking agent [tricalcium phosphate/hydroxyapatite (TCP-HA)]. Group 3 (40 mg/level) contained 8 patients (43 levels; 5.38 levels/patient) with PSF: rhBMP-2 and TCP-HA with no autologous bone. Confounding negative factors were present in the study population: medical comorbidities (26%), tobacco use (17%), revision surgery (34%), previous laminectomy (51%), and preoperative pseudarthrosis (27%). Postoperative films (AP, lateral, oblique) were evaluated by independent observers. Average fusion grade was based on a published scale.. Overall fusion rate was 95%. (group 1 91%, group 2 97%, group 3 100%). No confounding factor demonstrated a detrimental statistical significance to fusion.. In multilevel ASF, BMP (10 mg/level) generates fusion without autogenous bone. In multilevel PSF, BMP (20 mg/level) with LBG and TCP-HA produced fusion. BMP (40 mg/level) and TCP-HA without LBG achieved fusion. In multilevel spinal fusion, rhBMP-2 eliminated the necessity for iliac crest bone graft and yielded an excellent fusion rate.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Dose-Response Relationship, Drug; Female; Humans; Ilium; Male; Middle Aged; Osseointegration; Osteogenesis; Prospective Studies; Pseudarthrosis; Radiography; Recombinant Proteins; Scoliosis; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Topics: Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Child; Child, Preschool; Female; Fracture Fixation, Internal; Fracture Healing; Humans; Infant; Male; Prospective Studies; Pseudarthrosis; Radiography; Recombinant Proteins; Tibial Fractures; Transforming Growth Factor beta; Treatment Outcome

Congenital tibial pseudarthrosis is a rare condition seen in neurofibromatosis type 1 (NF1), and treatment is complex. A randomized, placebo-controlled trial of bone morphogenetic protein (rhBMP-2; INFUSE bone graft) at time of tibial surgery was developed by the Neurofibromatosis Clinical Trials Consortium. Patients were randomized to receive rhBMP-2 that would, or would not, be added to the standard surgical procedure consisting of resection of pseudarthrosis tissue, insertion of a rigid intramedullary rod, and placement of autogenous iliac crest bone graft. Despite involvement of 16 centers with wide experience with NF1 orthopaedic management, only 5 patients (of 54 required) were able to be enrolled in the study during a 3-year time period. Because of the inability to recruit sufficient patients, this study was closed in June 2019, with plans to terminate. The obstacles that were encountered during the study are summarized. The authors question whether a randomized, placebo-controlled trial of a rare pediatric orthopaedic condition is possible to accomplish. Recommendations are provided to guide future studies of orthopaedic manifestations of NF1.Level of Evidence: Level V.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Humans; Neurofibromatosis 1; Orthopedic Procedures; Patient Selection; Pseudarthrosis; Randomized Controlled Trials as Topic; Rare Diseases; Recombinant Proteins; Sample Size; Tibia; Transforming Growth Factor beta

Economic modeling of data from a multicenter, prospective registry.. The aim of this study was to analyze the cost utility of recombinant human bone morphogenetic protein-2 (BMP) in adult spinal deformity (ASD) surgery.. ASD surgery is expensive and presents risk of major complications. BMP is frequently used off-label to reduce the risk of pseudarthrosis.. Of 522 ASD patients with fusion of five or more spinal levels, 367 (70%) had at least 2-year follow-up. Total direct cost was calculated by adding direct costs of the index surgery and any subsequent reoperations or readmissions. Cumulative quality-adjusted life years (QALYs) gained were calculated from the change in preoperative to final follow-up SF-6D health utility score. A decision-analysis model comparing BMP versus no-BMP was developed with pseudarthrosis as the primary outcome. Costs and benefits were discounted at 3%. Probabilistic sensitivity analysis was performed using mixed first-order and second-order Monte Carlo simulations. One-way sensitivity analyses were performed by varying cost, probability, and QALY estimates (Alpha = 0.05).. BMP was used in the index surgery for 267 patients (73%). The mean (±standard deviation) direct cost of BMP for the index surgery was $14,000 ± $6400. Forty patients (11%) underwent revision surgery for symptomatic pseudarthrosis (BMP group, 8.6%; no-BMP group, 17%; P = 0.022). The mean 2-year direct cost was significantly higher for patients with pseudarthrosis ($138,000 ± $17,000) than for patients without pseudarthrosis ($61,000 ± $25,000) (P < 0.001). Simulation analysis revealed that BMP was associated with positive incremental utility in 67% of patients and considered favorable at a willingness-to-pay threshold of $150,000/QALY in >52% of patients.. BMP use was associated with reduction in revisions for symptomatic pseudarthrosis in ASD surgery. Cost-utility analysis suggests that BMP use may be favored in ASD surgery; however, this determination requires further research.. 2.

Topics: Adult; Bone Morphogenetic Protein 2; Cost-Benefit Analysis; Humans; Postoperative Complications; Prospective Studies; Pseudarthrosis; Quality-Adjusted Life Years; Recombinant Proteins; Reoperation; Spinal Curvatures; Spinal Fusion; Spine; Transforming Growth Factor beta

Tibial pseudarthrosis associated with Neurofibromatosis type 1 (NF1) is an orthopedic condition with consistently poor clinical outcomes. Using a murine model that features localized double inactivation of the Nf1 gene in an experimental tibial fracture, we tested the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and/or the bisphosphonate zoledronic acid (ZA). Tibiae were harvested at 3 weeks for analysis, at which time there was negligible healing in un-treated control fractures (7% union). In contrast, rhBMP-2 and rhBMP-2/ZA groups showed significantly greater union (87% and 93%, p < 0.01 for both). Treatment with rhBMP-2 led to a 12-fold increase in callus bone volume and this was further increased in the rhBMP-2/ZA group. Mechanical testing of the healed rhBMP-2 and rhBMP-2/ZA fractures showed that the latter group had significantly higher mechanical strength and was restored to that of the un-fractured contralateral leg. Co-treatment with rhBMP-2/ZA also reduced fibrous tissue infiltration at the fracture site compared to rhBMP alone (p = 0.068). These data support the future clinical investigation of this combination of anabolic and anti-resorptive agents for the treatment of NF1 pseudarthrosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:930-936, 2018.

Topics: Animals; Bone Density Conservation Agents; Bone Morphogenetic Protein 2; Bony Callus; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Therapy, Combination; Female; Genes, Neurofibromatosis 1; Mice; Neurofibromatosis 1; Pseudarthrosis; Recombinant Proteins; Transforming Growth Factor beta; Zoledronic Acid

In congenital pseudarthrosis of the tibia, use of intramedullary (IM) fixation and autogenous bone graft has long been the standard of care. This study was undertaken to determine whether the addition of rhBMP-2 to this treatment method further enhances healing potential.. Twenty-one patients with congenital pseudarthrosis of the tibia were evaluated. Fifteen of these patients had neurofibromatosis type 1 (NF1). All had IM fixation and autogenous bone graft, followed by a BMP-soaked collagen sponge wrapped around both the fracture site and bone graft. A minimum 2 years' follow-up was required.. Follow-up averaged 7.2 years (range, 2.1 to 12.8 y). Sixteen of 21 tibias achieved bone union following the index surgery, at an average 6.6 months postoperatively. The 5 persistent nonunions occurred in NF1 patients. Further surgery was undertaken in these 5 NF1 patients, including the use of BMP. One of the 5 healed, 1 had persistent nonunion, and 3 eventually had amputation. Of the 16 patients who healed initially following the index surgery, 5 refractured (3 had NF1). Of these 5 patients, the IM fixation at the index surgery did not cross the ankle joint, and refracture occurred at the rod tip in 4. Three of these 5 patients healed following further surgery, 1 had persistent nonunion, and 1 had amputation. All of those with eventual amputation had NF1. No deleterious effects related to the use of BMP-2 were recognized in any patient.. The addition of rhBMP-2 appears to be helpful in shortening the time required to achieve fracture union in those who healed, but its use does not insure that healing will occur.. Level IV-therapeutic, case series.

Topics: Adolescent; Bone Morphogenetic Protein 2; Bone Transplantation; Child; Child, Preschool; Female; Fracture Fixation, Intramedullary; Humans; Infant; Male; Neurofibromatosis 1; Pseudarthrosis; Radiography; Recombinant Proteins; Retrospective Studies; Tibial Fractures; Transforming Growth Factor beta

There is a lack of studies reporting on rhBMP-2 application in pediatric orthopaedics, although few reports demonstrated promising results of the use of rhBMP-2 in children, especially for spine fusion and for the treatment of congenital pseudarthrosis of the tibia. The objectives of this study were (1) to examine clinical and radiographic healing after rhBMP-2 application for the treatment of congenital pseudarthrosis of the tibia (CPT) or persistent tibial nonunion in children and adolescents, and (2) to investigate the safety of rhBMP-2 use in these cases. Therefore we reviewed the medical records of ten patients with a mean age of 8.6 years (2.3-21) with CPT (n = 7) or persistent tibial nonunion for at least six months (n = 3) who had been treated with rhBMP-2. Nine of ten patients had union at final follow-up, after a mean of 72.9 months (25-127). In the CPT group, primary healing of the pseudarthrosis occurred in six of seven patients at a mean of 5.2 months (3-12). Repeat rhBMP-2 application was performed in three patients; two patients had one additional application each, and one patient had three additional applications. Complications that may be attributed to the use of rhBMP-2 were seen in two of fifteen applications, including a compartmemt syndrome and a hematoma. In this retrospective case series rhBMP-2 has been used successfully to treat CPT or persistent tibial nonunion in pediatric patients. However, prospective randomized controlled trials are warranted to investigate the long-term efficacy and safety of rhBMP-2 use in these cases.

Topics: Adolescent; Bone Morphogenetic Protein 2; Bone Transplantation; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Male; Postoperative Period; Pseudarthrosis; Recombinant Proteins; Retrospective Studies; Tibia; Tibial Fractures; Transforming Growth Factor beta; Young Adult

Retrospective case series.. The purpose of this study was to determine the fusion rate and evaluate the complications associated with the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) in posterior cervical fusion.. The rates of fusion and complications associated with the use of rhBMP-2 in posterior cervical fusion is unclear, though recent work has shown up to a 100% fusion rate.. We independently reviewed consecutive series of patients who underwent posterior cervical, occipitocervical, or cervicothoracic instrumented fusion augmented with rhBMP-2. Two surgeons at a tertiary-referral, academic medical center performed all operations, and each patient had a minimum of 2-year follow-up. Fusion status was determined by bony bridging on computed tomography scans, absence of radiolucency around instrumentation, and absence of motion on lateral flexion/extension radiographs.. Fifty-seven patients with a mean age of 56.7±13.2 years and mean follow-up of 37.7±20.6 months were analyzed. Forty-eight patients (84.2%) had undergone previous cervical surgery, and 42.1% had a preexisting nonunion. Constructs spanned 5.6±2.6 levels; 19.3% involved the occiput, whereas 61.4% crossed the cervicothoracic junction. The mean rhBMP-2 dose was 21.1±8.7 mg per operation. Iliac crest autograft was used for 29.8% of patients. Six patients (10.5%) experienced nonunion; only 2 required revision. In each case of nonunion, instrumentation crossed the occipitocervical or cervicothoracic junction. However, none of the analyzed variables was statistically associated with nonunion. Fourteen patients (24.6%) suffered complications, with 7 requiring additional surgery.. The observed fusion rate of rhBMP-2-augmented posterior cervical, occipitocervical, and cervicothoracic fusions was 89.5%. This reflects the complicated nature of the patients included in the current study and demonstrates that rhBMP-2 cannot always overcome the biomechanical challenges entailed in spanning the occipitocervical or cervicothoracic junction.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Cervical Vertebrae; Female; Humans; Longitudinal Studies; Male; Middle Aged; Postoperative Complications; Pseudarthrosis; Recombinant Proteins; Risk Factors; Spinal Diseases; Spinal Fusion; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome; Young Adult

The objective of this independent study is to determine the impact of recombinant human bone morphogenetic protein 2 (rhBMP-2) on reoperation for pseudarthrosis and/or instrumentation failure. A nested case-control study of first-time posterolateral, instrumented fusion of the lumbar spine for degenerative spinal disease was undertaken. Cases of reoperation for pseudoarthrosis and/or instrumentation failure were assigned to controls, who did not experience the primary outcome measure at the time of reoperation. Cases and controls were matched on number of interspaces fused and inclusion of interbody. Predictors of reoperation for pseudoarthrosis and/or instrumentation failure were assessed with a conditional logistical regression controlling for rhBMP-2, age, obesity, and smoking. Of the 448 patients, 155 cases of reoperation for pseudoarthrosis and/or instrumentation were matched with 293 controls. Twenty-six percent of first-time surgeries included rhBMP-2, which was statistically more commonly used in the control cohort (33.11%) versus the case cohort (12.90%) (Unadjusted odds ratio [ORunadj]=0.28) (95% confidence interval [CI]: 0.16-0.49). Following a multivariate analysis controlling for age, obesity, and smoking, the rhBMP-2 recipients incurred a 73% lower odds of reoperation for pseudoarthrosis and/or instrumentation failure (95% CI, 0.15-0.48). Neither sarcomatous nor osseous neoplasm was detected in the study population. Mean follow up did not differ between the cases (81.57±standard deviation [SD] 4.98months) versus controls (74.75±2.49month) (ORunadj=1.01) (95% CI: 1.00-1.01). rhBMP-2 in lumbar fusion constructs protects against reoperation for pseudoarthrosis and/or instrumentation failure. However, the decision to include fusion supplements should be weighted between surgical determinants and clinical outcomes.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Case-Control Studies; Cohort Studies; Female; Humans; Length of Stay; Lumbar Vertebrae; Male; Middle Aged; Prosthesis Failure; Pseudarthrosis; Random Allocation; Recombinant Proteins; Reoperation; Retrospective Studies; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Congenital tibial dysplasia is a severe pediatric condition that classically results in a persistent pseudarthrosis. A majority of these cases are associated with neurofibromatosis type I (NF1), a genetic disorder in which inactivation of the NF1 gene leads to overactivity of the Ras-MEK-MAPK (mitogen-activated protein kinase) signaling pathway. We therefore hypothesized that pharmaceutical inhibition of MEK-MAPK may be a beneficial therapeutic strategy.. Animals treated with the delivery vehicle alone, PD0325901, rhBMP-2, or the PD0325901 + rhBMP-2 combination showed union rates of 0%, 8%, 69% (p < 0.01), or 80% (p < 0.01), respectively, at twenty-one days after fracture. Mice treated with the rhBMP-2 + PD0325901 combination displayed a callus volume sixfold greater than the vehicle controls and twofold greater than the group receiving rhBMP-2 alone. Although MEK inhibition combined with rhBMP-2 led to increases in bone formation and union, the proportion of fibrous tissue in the callus was not significantly reduced.. The data suggest that MEK inhibition can promote bone formation in combination with rhBMP-2 in the context of an NF1 pseudarthrosis. However, PD0325901 did not promote substantive bone anabolism in the absence of an exogenous anabolic stimulus and did not suppress fibrosis.. This study examines a signaling pathway-based approach to treating poor bone healing in a model of NF1 pseudarthrosis.

Topics: Animals; Benzamides; Bone Morphogenetic Protein 2; Diphenylamine; Disease Models, Animal; Drug Therapy, Combination; Female; Mice; Mitogen-Activated Protein Kinase Kinases; Neurofibromatosis 1; Osteogenesis; Pseudarthrosis; Recombinant Proteins; Transforming Growth Factor beta

Twenty-four consecutive patients with cervical spondylosis who were treated with cervical corpectomy and recombinant human bone morphogenetic protein-2 (rhBMP-2) with standalone anterior instrumentation were evaluated. Mean number of levels fused was 2.4. There were significant improvements in visual analog scale neck pain and Oswestry Disability Index scores and cervical lordosis. Cervical corpectomy with a lower dose of rhBMP-2 was found to be safe and efficacious for patients who are at a higher risk for pseudarthrosis.

Topics: Aged; Bone Morphogenetic Protein 2; Cervical Vertebrae; Female; Humans; Male; Middle Aged; Pseudarthrosis; Recombinant Proteins; Spinal Fusion; Spondylosis; Transforming Growth Factor beta

Matched cohort comparison.. To compare the use of bone morphogenetic protein (BMP) or iliac crest bone graft (ICBG) on the long-term outcomes in patients undergoing long fusions to the sacrum for adult spinal deformity.. No long-term studies beyond a 2-year follow-up have been performed comparing the use of BMP versus ICBG for fusion rates in long fusions to the sacrum in adult spinal deformity.. A total of 63 consecutive patients, from 1997-2006, comprised of 31 patients in the BMP group and 32 patients in the ICBG group, operated on at a single institution with a minimum 4-year follow-up (4-14 yr) were analyzed. Inclusion criteria were ambulators who were candidates for long fusions (thoracic as the upper level) to the sacrum. Exclusion criteria were revisions, neuromuscular scoliosis, ankylosing spondylitis, and patients who had both BMP and ICBG used for fusion. Oswestry Disability Index and 3 domains of the Scoliosis Research Society score were used to assess outcomes.. The 2 groups were similar with respect to age, sex, smoking history, comorbidities, BMI, number of fusion levels and Cobb angles. Eight patients in the BMP group underwent a posterior only, whereas 23 underwent combined anterior and posterior (A/P) surgery. All 32 patients in the ICBG had A/P fusion. The average BMP level was 11.1 mg (3-36 mg). The rate pseudarthrosis was 6.4% (2/31) in the BMP and 28.1% (9/32) in the ICBG group (P = 0.04) using Fisher exact test and odds ratio = 5.67. The fusion rates for BMP group were 93.5% and 71.9% for the ICBG group. Oswestry Disability Indexes were similar between groups. However, the BMP group demonstrated superior sum composite Scoliosis Research Society scores in pain, self-image and function domains (P = 0.02).. BMP is superior to ICBG in achieving fusion in long constructs in adult deformity surgery. The rate of pseudarthrosis was significantly higher in the ICBG group than BMP group. The concentration and dosage of recombinant human bone morphogenetic protein 2 (rhBMP-2) used seems to have an effect on the rate of fusion and pseudarthrosis rate because no patient receiving more than 5 mg per level had apparent or detected pseudarthroses (n = 20/20).. 3.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Transplantation; Cohort Studies; Disability Evaluation; Follow-Up Studies; Humans; Ilium; Middle Aged; Pseudarthrosis; Radiography; Recombinant Proteins; Sacrum; Scoliosis; Spinal Fusion; Spine; Time Factors; Transforming Growth Factor beta; Treatment Outcome

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue-specific lesions associated with local double-inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre-expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1(flox/flox) and Nf1(flox/-) mice. The effects of the presence of Nf1(null) cells were extensively examined. Cultured Nf1(null)-committed osteoprogenitors from neonatal calvaria failed to differentiate and express mature osteoblastic markers, even with recombinant bone morphogenetic protein-2 (rhBMP-2) treatment. Similarly, Nf1(null)-inducible osteoprogenitors obtained from Nf1 MyoDnull mouse muscle were also unresponsive to rhBMP-2. In both closed and open fracture models in Nf1(flox/flox) and Nf1(flox/-) mice, local AdCre injection significantly impaired bone healing, with fracture union being <50% that of wild type controls. No significant difference was seen between Nf1(flox/flox) and Nf1(flox/-) mice. Histological analyses showed invasion of the Nf1(null) fractures by fibrous and highly proliferative tissue. Mean amounts of fibrous tissue were increased upward of 10-fold in Nf1(null) fractures and bromodeoxyuridine (BrdU) staining in closed fractures showed increased numbers of proliferating cells. In Nf1(null) fractures, tartrate-resistant acid phosphatase-positive (TRAP+) cells were frequently observed within the fibrous tissue, not lining a bone surface. In summary, we report that local Nf1 deletion in a fracture callus is sufficient to impair bony union and recapitulate histological features of clinical CPT. Cell culture findings support the concept that Nf1 double inactivation impairs early osteoblastic differentiation. This model provides valuable insight into the pathobiology of the disease, and will be helpful for trialing therapeutic compounds.

Topics: Acid Phosphatase; Animals; Bone Morphogenetic Protein 2; Cell Differentiation; Cell Lineage; Cell Proliferation; Disease Models, Animal; Female; Fibrosis; Fracture Healing; Gene Deletion; HEK293 Cells; Humans; Integrases; Isoenzymes; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscles; Neurofibromatosis 1; Neurofibromin 1; Osteoblasts; Osteoclasts; Osteogenesis; Pseudarthrosis; Recombinant Proteins; Reproducibility of Results; Tartrate-Resistant Acid Phosphatase; Tibia; Transforming Growth Factor beta

The US Food and Drug Administration has approved recombinant human bone morphogenetic protein 2 (rhBMP-2) (Infuse Bone Graft; Medtronic Sofamor Danek, Minneapolis, MN) as an alternative to autogenous bone graft for sinus augmentations and for localized alveolar ridge augmentations for defects associated with extraction sockets. The objective of this analysis was to characterize adverse events reported after the use of rhBMP-2 in oral and maxillofacial procedures.. The US Food and Drug Administration's Manufacturer and User Facility Device Experience database contains reports of adverse events involving medical devices. The publicly available version of the database was searched for reports for the brand name Infuse Bone Graft. Descriptive statistics were used to summarize the procedures and adverse events.. As of April 30, 2011, the Manufacturer and User Facility Device Experience database contained 83 reports of adverse events after oral and maxillofacial operations involving rhBMP-2. Of these reports, 55 (66.3%) described off-label uses, such as reconstruction of the mandible after fracture or cancer or alveolar cleft repair. The most commonly reported adverse events included local reactions, graft failure, infections, and other wound complications. Of the reports, 25 (30.1%) stated that the patient required additional surgery to address the reported adverse event.. Serious adverse events, some of which may require a second operation, can occur after the use of rhBMP-2 in oral and maxillofacial procedures. In this analysis graft, failure and pseudarthrosis were more commonly reported after off-label uses of rhBMP-2 than approved uses.

Topics: Adverse Drug Reaction Reporting Systems; Alveolar Process; Bone Morphogenetic Protein 2; Cleft Palate; Databases as Topic; Drug Monitoring; Graft Survival; Humans; Mandibular Fractures; Mandibular Neoplasms; Off-Label Use; Oral Surgical Procedures; Plastic Surgery Procedures; Pseudarthrosis; Recombinant Proteins; Reoperation; Surgical Wound Infection; Transforming Growth Factor beta; United States; United States Food and Drug Administration

Topics: Bone Morphogenetic Proteins; Cervical Vertebrae; Deglutition Disorders; Diskectomy; Edema; Female; Humans; Ketones; Male; Polyethylene Glycols; Postoperative Complications; Prostheses and Implants; Pseudarthrosis; Recombinant Proteins; Spinal Fusion; Titanium; Transforming Growth Factor beta

The goal of this study was to demonstrate the incidence of fusion and soft-tissue swelling in multilevel anterior cervical discectomies and fusions (ACDFs) using polyetheretherketone (PEEK) spacers with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated in a Type I collagen sponge and titanium plates.. A single surgeon performed 30 multilevel ACDFs using PEEK spacers with an rhBMP-2 impregnated collagen sponge (0.4 ml, or the equivalent of 0.6 mg rhBMP-2). Soft-tissue swelling was assessed using cervical spine radiographs on postoperative Day 1 and at 2, 6, and 10 weeks and 6 months after surgery. Incidence of dysphagia was assessed with the Cervical Spine Research Society Swallowing-Quality of Life tool. Clinical success was evaluated with the Neck Disability Index, neck pain scores, and arm pain scores. Final fusion was assessed with CT by an independent neuroradiologist.. Patients were followed for 6 months unless they had an incomplete fusion; those patients were reassessed at 9 months. Twenty-four patients underwent 2-level ACDFs and 6 underwent 3-level ACDFs were performed on patients with the following risk factors for pseudarthrosis: smoking (33%), diabetes (13%), and obesity (body mass index ≥ 30 [43%]). Seventeen percent of the patients had multiple risk factors. Soft-tissue swelling peaked at 2 weeks regardless of level of surgery or number of levels treated surgically and decreased to near preoperative levels by 6 months. At 2 weeks, Swallowing-Quality of Life evaluation showed 19% of patients frequently choking on food, 4.8% frequently choking when drinking, and 47.6% with frequent food sticking in the throat. Scores continued to improve, and at 6 months, 0% had frequent choking on food, 6.7% had frequent difficulty drinking, and 6.7% had frequent food sticking in the throat. The Neck Disability Index, neck pain, and arm pain scores all improved progressively over 6 months. Incidence of fusion was 95% at 6 months and 100% at 9 months. There were no rehospitalizations or reoperations for soft-tissue swelling or dysphagia.. Multilevel ACDF procedures using PEEK grafts and rhBMP-2 can be performed safely in patients with multiple risk factors for pseudarthrosis with excellent fusion outcomes.

Topics: Adult; Aged; Benzophenones; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cervical Vertebrae; Deglutition Disorders; Diskectomy; Dose-Response Relationship, Drug; Edema; Female; Humans; Ketones; Male; Middle Aged; Polyethylene Glycols; Polymers; Postoperative Complications; Prostheses and Implants; Pseudarthrosis; Recombinant Proteins; Reoperation; Retrospective Studies; Risk Factors; Spinal Fusion; Titanium; Tomography, X-Ray Computed; Transforming Growth Factor beta

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the treatment of congenital pseudarthrosis of the tibia has been investigated in only one previous study, with promising results. The aim of this study was to determine whether rhBMP-2 might improve the outcome of this disorder. We reviewed the medical records of five patients with a mean age of 7.4 years (2.3 to 21) with congenital pseudarthrosis of the tibia who had been treated with rhBMP-2 and intramedullary rodding. Ilizarov external fixation was also used in four of these patients. Radiological union of the pseudarthrosis was evident in all of them at a mean of 3.5 months (3.2 to 4) post-operatively. The Ilizarov device was removed after a mean of 4.2 months (3.0 to 5.3). These results indicate that treatment of congenital pseudarthrosis of the tibia using rhBMP-2 in combination with intramedullary stabilisation and Ilizarov external fixation may improve the initial rate of union and reduce the time to union. Further studies with more patients and longer follow-up are necessary to determine whether this surgial procedure may significantly enhance the outcome of congenital pseudarthrosis of the tibia, considering the refracture rate (two of five patients) in this small case series.

Topics: Ankle Joint; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Child, Preschool; Combined Modality Therapy; External Fixators; Female; Follow-Up Studies; Fracture Fixation, Intramedullary; Fracture Healing; Humans; Ilizarov Technique; Knee Joint; Male; Pseudarthrosis; Radiography; Range of Motion, Articular; Recombinant Proteins; Retrospective Studies; Tibial Fractures; Transforming Growth Factor beta; Treatment Outcome; Young Adult

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix®; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 µg rhBMP-2 on ACS (positive control), TrioMatrix®, Grafton® (Osteotech, Inc., Eatontown, NJ), and DBX® (Synthes, Inc., West Chester, PA). Both TrioMatrix® and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton®, and DBX® groups. Notably, the use of TrioMatrix® as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix®. Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Substitutes; Collagen; Disease Models, Animal; Durapatite; Fracture Healing; Glycerol; Humans; Lumbar Vertebrae; Nanocomposites; Osteitis; Postoperative Complications; Pseudarthrosis; Rats; Rats, Nude; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta; X-Ray Microtomography

Topics: Administration, Topical; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Child; Child, Preschool; Female; Fracture Fixation, Intramedullary; Humans; Infant; Intercellular Signaling Peptides and Proteins; Male; Pseudarthrosis; Recombinant Proteins; Retrospective Studies; Tibia; Tibial Fractures; Transforming Growth Factor beta

Results recently reported in the literature have raised some concerns regarding the use of recombinant human bone morphogenetic protein (rhBMP-2) in the cervical spine.. We undertook a radiological and clinical review of cervical fusions performed at our institution with polyetheretherketone (PEEK) interbody cage and rhBMP-2.. Observational study.. Perioperative clinical and radiologic data of all patients who underwent an anterior cervical discectomy and fusion using PEEK and rhBMP-2 for cervical spondylotic radiculopathy or myelopathy were collected.. Images were examined for fusion, heterotopic ossification, end-plate resorption, subsidence, and segmental sagittal alignment.. All patients underwent detailed postoperative radiologic analysis using a computed tomography (CT) scan obtained at least 6 months postoperatively and plain X-rays obtained at regular intervals.. Twenty-two patients had 38 levels fused using PEEK and varying doses of rhBMP-2. No anterior cervical swelling requiring additional procedures or longer than anticipated hospital stays occurred. Pseudoarthrosis, shown as a horizontal radiolucent fissure through the midportion of the PEEK cage on CT, occurred in four patients. Excessive bone growth into the spinal canal or foramina occurred in 26 (68%) patients but did not result in neurologic sequelae. Cystic regions in the core of the PEEK spacer were seen in most patients, with 15 levels (39%) having cysts measuring 3mm or greater. Moderate or severe osteolysis of the end plates occurred in 57% of levels, and this led to subsidence of the construct and loss of some of the segmental sagittal alignment (ie, lordosis) that had been achieved with surgery.. The unlimited supply of PEEK spacers and rhBMP-2 and their ease of use make them attractive platforms to achieve fusion. This study has demonstrated that the fusion process using rhBMP-2 is a dynamic one, with osteolysis dominating the initial phase, leading to end-plate resorption and consequently loss of some of the disc space height and sagittal alignment that was achieved with surgery. There is a high incidence of bone growth beyond the core of the PEEK spacer and cystic regions within the cage. Given our experience, we currently reserve the use of PEEK and rhBMP-2 for use in those patients who are at greatest risk of pseudoarthrosis.

Topics: Adult; Aged; Benzophenones; Bone Cysts; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Cervical Vertebrae; Female; Humans; Ketones; Male; Middle Aged; Osseointegration; Ossification, Heterotopic; Osteolysis; Polyethylene Glycols; Polymers; Postoperative Complications; Prosthesis Failure; Pseudarthrosis; Radiography; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta

Comparative study.. To compare the radiographic outcome of patients undergoing long spinal deformity surgery to the sacrum/ilium, using either rhBMP-2 without iliac crest bone graft (ICBG) or ICBG without rhBMP-2.. rhBMP-2 has been shown to be more effective in promoting successful bone union in patients undergoing single level lumbar spinal fusion than ICBG. However, to the best of our knowledge, there are no studies that compare the efficacy of rhBMP-2 versus ICBG in long spinal deformity surgery.. To obtain uniform background, we selected patients with adult spinal deformity who underwent primary spinal fusion from the thoracic spine to the sacrum/ilium and had a minimum 2-year follow-up. Fifty-five consecutive patients, consisting of 32 patients who underwent a fusion using ICBG without rhBMP-2 (ICBG group) and 23 patients who underwent a fusion using rhBMP-2 without ICBG (BMP group) were analyzed.. The 2 groups were similar with respect to age, gender, smoking history, comorbidity, and body mass index. The average number of vertebrae fused (11.3 in both groups) and the degree of preoperative deformity (major Cobb angle 58.3 degrees in ICBG group vs. 54.2 degrees in BMP group) were also similar in both groups. All but 2 patients had both anterior and posterior surgery. Both groups were similar in terms of final deformity correction. The average total amount of rhBMP-2 used in the BMP group was 119.2 mg (anterior 11.6 mg/level; posterior 10.0 mg/level). Of the 32 patients in the ICBG group, 9 patients (28.1%) developed a pseudarthrosis, while only 1 of 23 patients (4.3%) in the BMP group developed a pseudarthrosis with the caveat that the follow-up period was shorter in the BMP group (average follow-up of 4.9 vs. 2.7 years).. The pseudarthrosis rate in the BMP group compares favorably to pseudarthrosis rate in ICBG group, suggesting that the use of rhBMP-2 without iliac harvesting leads to a competitive fusion rate in long adult spinal deformity surgery, while avoiding ICBG harvest site morbidity.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Female; Humans; Ilium; Male; Middle Aged; Postoperative Complications; Pseudarthrosis; Recombinant Proteins; Sacrum; Scoliosis; Spinal Fusion; Transforming Growth Factor beta

Scaphoid fractures have the highest prevalence of non-union in the human body, but little is known about the osteogenic potential of cells at the pseudoarthrosis. It was our goal to determine whether cells isolated from non-unions could be stimulated to differentiate into osteoblasts and produce bone in vitro. Fifteen human scaphoid non-unions were excised during surgery and bone from either side of the non-union and the fibrocartilagenous central regions were harvested. Osteoblastic populations were subcultured from these. The number of bone nodules (colonies of osteoblast cells that produced bone) from all three regions was similar to the number of nodules derived from iliac bone cultures from the same patients. Treatment of cells with rhBMP-2 resulted in a 3- to 10-fold increase in bone nodule formation in vitro from cells derived from the non-unions. These data demonstrate that cells at the pseudoarthrosis have osteogenic capability and can be stimulated by rhBMP-2, possibly increasing the ability to heal.

Topics: Adolescent; Adult; Alkaline Phosphatase; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cell Culture Techniques; Cell Proliferation; Female; Fracture Healing; Humans; Male; Middle Aged; Osteocalcin; Osteogenesis; Pseudarthrosis; Recombinant Proteins; Scaphoid Bone; Transforming Growth Factor beta; Young Adult

The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated.. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM).. rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion.. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology.. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups.. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Substitutes; Bone Transplantation; Chemistry, Pharmaceutical; Disease Models, Animal; Drug Carriers; Female; Humans; Ilium; Lumbar Vertebrae; Nicotine; Osseointegration; Pseudarthrosis; Rabbits; Recombinant Proteins; Spinal Fusion; Time Factors; Tomography, X-Ray Computed; Transforming Growth Factor beta; Transplantation, Autologous

We describe a 13-year-old boy with atrophic tibial pseudarthrosis associated with neurofibromatosis who had undergone nine unsuccessful operations. Eventually, union was obtained by the use of bone morphogenetic protein 7 in conjunction with intramedullary stabilisation and autologous bone graft.

Topics: Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Combined Modality Therapy; Fibula; Follow-Up Studies; Fractures, Bone; Humans; Infant; Male; Neurofibromatoses; Pseudarthrosis; Radiography; Tibia; Tibial Fractures; Transforming Growth Factor beta

This is a prospective cohort study examining the results and radiographic characteristics of anterior lumbar interbody fusion (ALIF) using femoral ring allografts (FRAs) and recombinant human bone morphogenetic protein-2 (rhBMP-2). This was compared to a historical control ALIF using FRAs with autologous iliac crest bone graft (ICBG).. To determine whether the use of rhBMP-2 can enhance fusion ALIF with stand-alone FRAs.. ALIF is a well-accepted procedure in reconstructive spine surgery. Advances in spinal surgery have produced a multitude of anterior interbody implants. The rhBMP-2 has promoted fusion in patients undergoing ALIF with cages and threaded allograft dowels. The FRA still remains a traditional alternative for anterior support. However, as a stand-alone device, the FRA has fallen into disfavor because of high rates of pseudarthrosis. With the advent of rhBMP-2, the FRA may be more attractive because of its simplicity and remodeling potential. It is important to understand the implications when rhBMP-2 is used with such structural allografts.. A total of 36 consecutive patients who underwent ALIF with stand-alone FRAs by a single surgeon (E.G.D.) at 1 institute were included. A cohort of 9 consecutive patients who received FRAs filled with rhBMP-2 was followed prospectively. After noticing suboptimal results, the senior author terminated this method of lumbar fusion. A total of 27 prior consecutive patients who received FRAs filled with autogenous ICBG were used for comparison. Analyzing sequential radiographs, flexion-extension radiographs, and computerized tomography with multiplanar reconstructions determined nonunions. Minimum follow-up was 24 months.. Pseudarthrosis was identified in 10 of 27 (36%) patients who underwent stand-alone ALIF with FRAs and ICBG. Nonunion rate was higher among patients who received FRAs with rhBMP-2 (i.e., 5 of 9 [56%]). Statistical significance was not established because of the early termination of the treatment group (P > 0.3). Of interest, radiographs and computerized tomography revealed early and aggressive resorption of the FRAs when used with rhBMP-2. This preceded graft fracture and even disintegration, resulting in instability and eventual nonunion.. The use of rhBMP-2 did not enhance the fusion rate in stand-alone ALIF with FRAs. In fact, the trend was toward a higher nonunion rate with rhBMP-2, although this was not significant with the numbers available. This result appears to be caused by the aggressive resorptive phase of allograft incorporation, which occurs before the osteoinduction phase.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Cohort Studies; Female; Femur; Humans; Lumbar Vertebrae; Male; Middle Aged; Osseointegration; Prospective Studies; Pseudarthrosis; Radiography; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta; Transplantation, Homologous

Molecular study of gene expression in rabbit lumbar pseudarthrosis repairs using reverse transcriptase polymerase chain reaction.. To evaluate differential gene expression of no graft, autograft, and osteogenic protein-1 treated pseudarthroses.. Osteogenic protein-1 is a potential bone graft alternative that has achieved high fusion rates in a rabbit lumbar fusion model, including in the repair of nicotine-induced pseudarthroses. A previous study established a correlation between osteogenic protein-1 fusion outcomes and an enhanced level of cytokine gene expression. The expression of such cytokines is known to be decreased in nicotine-exposed rabbit fusion masses.. Messenger ribonucleic acid was isolated from nicotine-exposed New Zealand white rabbit lumbar pseudarthroses following attempted no graft, autograft, and osteogenic protein-1 pseudarthrosis repairs. Reverse transcriptase polymerase chain reaction was used to assess the expression of angiogenin, angiopoietin, intercellular adhesion molecule, platelet-derived growth factor-beta, vascular endothelial growth factor, bone morphogenetic proteins 2 and 7, type I collagen, and osteonectin. Glyceraldehyde-3-phosphate dehydrogenase was used as a constitutively expressed control.. Levels of gene expression in the osteogenic protein-1 group were higher than those of the autograft group, which were higher than the no graft group for the majority of the genes studied.. In the rabbit pseudarthrosis model, gene expression data supported the hypothesis that successful pseudarthrosis repair is related to the induction of osteogenic and angiogenic cytokines by osteogenic protein-1.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Gene Expression Regulation; Lumbar Vertebrae; Pseudarthrosis; Rabbits; Spinal Fractures; Spinal Fusion; Transforming Growth Factor beta

Direct mandibular reconstruction with an autologous bone transplant was compared with an osteoinductive implant following an extensive continuity resection of the lower jaw in Göttinger mini-pigs.. In nine full-grown mini-pigs a one-sided continuity defect (5 cm) was created in the lower jaw. In four animals it was filled with a 50 x 25 x 15 mm(3) collagenous carrier enhanced by rhBMP-2 (400 micro g/cm(3) rhBMP-2). In two animals only the carrier was implanted as a control. Three animals received the resected autologous bone as a free transplant. Bone regeneration and consolidation of the defects was analyzed radiographically and histologically.. Following implantation of the osteoinductive implant, complete osseous consolidation of the continuity defect in the lower jaw was observed in all animals. The defects were completely filled with a biomechanically stable bone which showed signs of functional adaptation. The replantation of the orthotopic autologous bone did not lead to functional stability quickly enough. In the periphery only an incomplete bony bridge was formed which was interrupted by large pseudarthrosis. No consolidation of the defects was found in the control group (carrier alone).. Direct reconstruction of an extensive, biomechanically loaded defect with an osteoinductive implant proved to be the superior method. The osseous regeneration observed shows an immediate functional orientation. The necessity for extensive adaptive remodeling is thus minimized.

Topics: Animals; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Coated Materials, Biocompatible; Collagen; Mandible; Mandibular Prosthesis; Mandibular Prosthesis Implantation; Osseointegration; Pseudarthrosis; Swine; Swine, Miniature; Transforming Growth Factor beta

Posterolateral lumbar fusions were performed in nicotine-exposed, New Zealand white rabbits. Animals that developed a pseudarthrosis were then regrafted with no graft, autograft, or osteogenic protein-1 (OP-1).. To establish a model of pseudarthrosis repair and to evaluate the ability of OP-1 to induce fusion in this model.. OP-1 has been shown to have a 100% fusion rate in an established rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion.. Forty-four New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To maximize the incidence of pseudarthroses, nicotine was administered to all rabbits. At 5 weeks, the spines were explored, and all pseudarthroses were redecorticated and grafted with no graft, autograft, or OP-1. At 10 weeks, the rabbits were killed and fusions masses were assessed with manual palpation, radiography, computed tomography, and/or histology.. Nine rabbits (20%) were lost to complications. Thirty-four (94%) had pseudarthroses on exploration at 5 weeks. By manual palpation at 10 weeks, 1 of 10 (10%) pseudarthroses that received no graft fused, 5 of 12 (42%) pseudarthroses that received autograft fused, and 9 of 11 (82%) pseudarthroses that received OP-1 fused. Computed tomography and histology further characterized the fusion masses.. This study establishes a model for treatment of pseudarthroses. OP-1, which has previously been shown to have 100% fusion rate in animal models, outperformed autograft and induced fusion in 82% of rabbits.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Cotinine; Drug Evaluation, Preclinical; Female; Humans; Ilium; Infusion Pumps, Implantable; Lumbar Vertebrae; Nicotine; Postoperative Complications; Pseudarthrosis; Rabbits; Radiography; Recombinant Proteins; Single-Blind Method; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta; Transplantation, Autologous; Wound Healing

Pseudarthrosis remains a significant problem in spinal fusion. The objective of our study was to investigate the effects of autologous growth factors (AGF) in instrumented transforaminal lumbar interbody spinal fusion (TLIF). A prospective review was carried out of 23 patients who underwent TLIF with application of AGF, with a minimum 2-year follow-up. Comparison with our historical cohort (without AGF application) was performed. Mean age at surgery was 44.3 years in the AGF treatment group. Twelve had a positive smoking history. Fourteen had undergone previous spinal surgeries. Thirteen received one-level fusions and ten received two-level fusions. The radiographic results showed a fusion rate of 100% in one-level fusions and 90% in two-level fusions. There was no significant difference in pseudarthrosis rates between the AGF treatment group and historical cohort. Excluding the cases with pseudarthrosis, there was faster bony healing in patients who had been treated with AGF application. This study indicates that although AGF may demonstrate faster fusions, it does not result in an overall increase in spinal fusion rates. Further studies are needed before AGF can routinely be used as an adjunct in spinal fusion.

Topics: Adult; Bone Transplantation; Cohort Studies; Female; Follow-Up Studies; Growth Substances; Humans; Intervertebral Disc; Lumbar Vertebrae; Male; Platelet-Derived Growth Factor; Prospective Studies; Pseudarthrosis; Radiography; Spinal Diseases; Spinal Fusion; Time Factors; Transforming Growth Factor beta; Wound Healing