transforming-growth-factor-beta and Spinal-Diseases

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

Spinal arthrodesis is a major element of the spinal surgeon's practice. To attain successful fusion rates, attention must be paid to spinal segment immobilization and proper selection of bone graft. Autogenous bone graft (ie, ICBG), the "gold standard," with or without graft extenders and enhancers provides the foundation for most spinal fusions. ABG is the only graft option containing all 3 factors of new bone growth: osteoconductivity, osteoinductivity, and osteogenicity. While many bone graft alternatives function well as bone graft extenders, only growth factors proteins (ie, rhBMP-2 or OP-2) function as bone graft enhancers and substitutes. The search for optimal hybrid interbody cages, bone graft substitutes, autogenous or allogenic stem cells, and nanostructure scaffolds for release of growth factors continues.

Topics: Bone Morphogenetic Protein 2; Bone Substitutes; Bone Transplantation; Humans; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Spine; Transforming Growth Factor beta

Spinal osteobiologics have evolved substantially in this century after the development of many product categories such as growth factors, allograft, and stem cells. The indications for the use of novel biologics within spine surgery are rapidly expanding as the mechanism of each is elucidated. While the knowledge base of bone morphogenetic protein increases with each subsequent year, the application of new nanotechnology and cell-based strategies are being reported. This review will discuss the most recent data in novel osteobiologics, and where we could use future study.

Topics: Biocompatible Materials; Bone Morphogenetic Proteins; Humans; Recombinant Proteins; Spinal Diseases; Transforming Growth Factor beta

To introduce the latest advances of research on repair of the degenerative intervertebral disc with gene transduction.. The recently-published articles about the treatment of degenerative disc with gene transduction were reviewed, especially the articles published during the recent 5 years about the application of this therapy to regulating the synthesis and degradation of the extracellular matrix of the degenerative intervertebral disc.. The shape and function of the normal intervertebral disc were reported to be closely related to the synthesis and degradation of the extracellular matrix of the intervertebral disc. The extracellular matrix of the intervertebral disc was a target for the gene transduction to repair the degenerative intervertebral disc. There was a great development of the treatment with gene transduction, especially in vector choice, target gene transduction, and transgene regulation and safety.. The advances of the research have indicated that repair of the degenerative intervertebral disc with gene transduction is a key to curing the disease of the degenerative intervertebral disc.

Topics: Animals; Dependovirus; Extracellular Matrix; Genetic Therapy; Genetic Vectors; Humans; Intervertebral Disc; Rabbits; Spinal Diseases; Transduction, Genetic; Transforming Growth Factor beta

Models available for the study of intervertebral disc degeneration are designed to answer many important questions. In vitro biologic models employ a variety of cell, tissue, or organ culture techniques with culture conditions that partially mimic the cellular environment of the degenerated human intervertebral disc. In vitro biomechanical models include intervertebral disc or motion-segment loading experiments as well as finite element modeling techniques. The literature describes numerous in vivo animal models for use in the study of intervertebral disc degeneration, each of which has its own advantages and disadvantages. Human-subject studies have included the use of magnetic resonance imaging and other techniques to assess diffusion into the intervertebral disc, to measure intradiscal pressure, to conduct kinematic or stiffness studies of lumbar motion segments, and to evaluate muscular forces on the spine. Although all of these studies are helpful in answering specific questions, their relevance in assessing disc degeneration in patients with symptoms of discogenic pain must be carefully considered.

Topics: Age Factors; Aged; Animals; Biomechanical Phenomena; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Disease Models, Animal; Disease Progression; Dogs; Humans; In Vitro Techniques; Intervertebral Disc; Middle Aged; Pain; Pain Measurement; Range of Motion, Articular; Risk Factors; Severity of Illness Index; Species Specificity; Spinal Diseases; Stress, Mechanical; Transforming Growth Factor beta

In spine surgery, fixation devices that revolutionized spinal fusion are becoming mature technologies, and new tools derived from biologics are becoming more important in clinical practice. Thus, surgeons need to become more sophisticated in evaluating and using these new biologics, which are rapidly entering the market. The majority of these biologics are aimed at enhancing spinal fusion and can be called osteobiologics. Osteobiologic products vary from recombinant proteins to specially prepared allograft or autograft materials. Their financial costs are considerable, and the level of proof for the efficacy and safety of these products varies widely. In this article, I delineate useful principles that can be used to evaluate current and future generations of osteobiologic products, and I discuss the most pertinent examples of specific osteobiologics.

Topics: Biocompatible Materials; Biological Products; Bone Matrix; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Transplantation; Growth Differentiation Factor 5; Humans; Spinal Diseases; Transforming Growth Factor beta

A review was conducted.. To determine the safety profiles of human recombinant bone morphogenetic protein-2 (rhBMP-2) and osteogenic protein-1 (OP-1) used clinically in spine applications.. Safety issues associated with the use of bone morphogenetic proteins in spine applications include the possibility of bony overgrowth, interaction with exposed dura, cancer risk, systemic toxicity, reproductive toxicity, immunogenicity, local toxicity, osteoclastic activation, and effects on distal organs. These issues have been given detailed examination in both human and animal studies, and safety data are available for both rhBMP-2 and OP-1. The safety data available for OP-1 are less detailed.. The study involved reviews of published reports and the safety data submitted to the Food and Drug Administration (rhBMP-2 and OP-1) and to the European Agency for the Evaluation of Medicinal Products (OP-1), as well as personal communication with the manufacturers of rhBMP-2 (Medtronic Sofamore Danek, Memphis, TN) and OP-1 (Stryker Biotech, Hopkinton, MA).. Application of either rhBMP-2 or OP-1 to raw decorticated bony surfaces leads to new bone formation, which is desirable in the intertransverse or interbody regions. However, new bone formation also may occur if rhBMP-2 or OP-1 comes in contact with laminectomy sites or decompressed neuroforamina, and may lead to restenosis. Inadvertent placement of either rhBMP-2 or OP-1 in the spinal canal leads to formation of bone. Leakage of rhBMP-2 or OP-1 outside the fusion area may lead to adjacent-level fusion. Accurate placement of these factors and adequate retention by their carrier are highly important factors in minimizing these problems. Subdural bone formation occurs if OP-1 is implanted directly beneath the dura. Osteoclastic overstimulation does not appear to be a significant problem with rhBMP-2. However, bone resorption has been associated with OP-1 used in the setting of thoracolumbar fractures. Findings show that RhBMP-2 has an antiproliferative effect on many cancer cells, and no evidence exists that it is carcinogenic. It is unlikely that OP-1 has carcinogenic potential, although fewer data are available. Systemic and local toxicity, significant adverse effects, and harmful effects on distant organs have not been observed in either human or animal studies on rhBMP-2 and OP-1. The benign safety profile of rhBMP-2 may result from its rapid systemic clearance, which results in very little systemic exposure. Systemic exposure to OP-1 also is low. No reproductive toxicity has been observed with either rhBMP-2 or OP-1. However, there is no human safety data. Subclinical immune responses in human subjects to collagen carriers have been reported. Antibody responses to rhBMP-2 have been detected in less than 1% of spine patients. Low titer immune responses have been observed in 38% of patients treated with OP-1. There were no associated clinical adverse effects.. Given the available data, both rhBMP-2 and OP-1 appear to be safe provided they are used appropriately, placed accurately, not allowed to come into contact with decompressed areas, and contained in the region of fusion. They must be used with caution in the presence of dural defects.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Humans; Osteogenesis; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

The safety and effectiveness of osteogenic protein (OP)-1 putty (recombinant human bone morphogenetic protein-7) in promoting fusion in complex spinal cases was studied in nine cases.. The authors prospectively evaluated nine patients requiring spinal fusion in whom there were medical risk factors that would inhibit osseous fusion. Intraoperatively the OP-1 putty mixed with autologous bone was placed at the fusion site. Outcome measurement instruments were used to provide information on patient demographics, comorbidities, and pain. The Short Form (SF)-36 questionnaire and Oswestry Disability Index (ODI) were administered pre- and postoperatively. All patients underwent routine radiography of the surgery site during follow-up examination. The age of the five women and four men ranged from 21 to 74 years (mean height 1.6 m, mean weight 76.7 kg). Risk factors included mucopolysaccharide syndrome, adrenal insufficiency, rheumatoid arthritis with chronic corticosteroid use, morbid obesity, and heavy smoking. Surgery, which consisted of five cervical and four lumbar procedures, including intradural surgery in three patients, was uneventful in all cases without perioperative complication. The follow-up period ranged from 1 to 15 months (mean 5.22 months). The ODI score changed from severe disability (mean 46.89) preoperatively to minimal and moderate disability (mean 34.56) postoperatively. The SF-36 survey showed overall improved mental and physical health scores. Fusion was present in all patients with greater than 3 months follow up.. The OP-1 putty appears to be safe and effective in promoting spinal arthrodesis in patients in whom adverse medical risk factors exist.

Topics: Adult; Aged; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Female; Humans; Male; Middle Aged; Neuroprotective Agents; Prospective Studies; Radiography; Risk Factors; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Anterior intervertebral fusion increasingly is used as a treatment for discogenic or intersegmental pathologic diseases of the lumbar spine. This is in part attributable to the evolution and refinement of laparoscopic and minimally invasive surgical techniques that now can be used to access the anterior spinal column. It also is attributable to the availability of newer generation intervertebral fixation devices such as the threaded titanium cages or threaded allograft bone dowels, both of which are technically simpler to implant. Recently, limited clinical studies of intervertebral lumbar fusion have examined the use of these devices combined with osteoinductive growth factors as substitutes for autogenous bone graft. Early clinical results of lumbar fusion using threaded intervertebral implants filled with recombinant human bone morphogenetic protein-2 have been favorable. Higher fusion rates, shorter operative times, and shorter hospital stays have been reported in the initial series. Clinical trials involving larger cohorts with various spinal applications for osteoinductive molecules currently are in progress.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Growth Substances; Humans; Lumbar Vertebrae; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Titanium; Transforming Growth Factor beta

Gene therapy involves the transfer of genes to cells such that the recipient cells express these genes and thereby synthesize the ribonucleic acid and protein that they encode. Recent investigations suggest that gene therapy may have potential applications in the treatment of intervertebral disc disorders, particularly those associated with disc degeneration. The successful in vivo transfer of therapeutic genes to target cells within the intervertebral disc in clinically relevant animal models is one example of the rapid progress that is being made. The purpose of the current review is to address several important technical issues, including choice of vectors and gene delivery strategy and the characteristics of the target tissues, which are relevant to future clinical applications of gene therapy for the treatment of intervertebral disc disorders. It already is apparent from the growing literature that gene therapy has the potential of becoming a valuable clinical treatment mode for intervertebral disc disorders in the twenty-first century.

Topics: Adenoviridae; Animals; Cell Culture Techniques; Cell Transplantation; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Intervertebral Disc; Retroviridae; Spinal Diseases; Transforming Growth Factor beta

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used as an alternative bone graft in spine fusion surgery. However, clinical outcome such as effects and complications has not yet been revealed for transforaminal lumbar interbody fusion (TLIF). Although previous studies have reported some results, the evidence is weak. Therefore, the purpose of this trial is to evaluate the effectiveness and safety of Escherichia coli-derived rhBMP-2 combined with hydroxyapatite (HA) in TLIF.. This trial is designed as a prospective, assessor-blinded, open-label, multicenter, randomized controlled study. Participants will be recruited from six tertiary teaching hospitals. All randomized participants will be undergoing one- or two-level TLIF with rhBMP-2 (77 participants) as the active experimental group or with an auto-iliac bone graft (77 participants) as the control group. The primary interbody fusion rate outcome will be evaluated using computed tomography (CT) 12 months after surgery. The secondary outcomes will be as follows: clinical outcomes (visual analog scale score, EuroQol-5-dimensions-5-level score, Oswestry Disability Index score, and some surgery-related variables) and adverse effects (radiculitis, heterotrophic ossification, endplate resorption, and osteolysis). Radiological outcomes will be evaluated using simple radiography or CT. All outcomes will be measured, collected, and evaluated before surgery and at 12, 24, and 52 weeks postoperatively.. This study will be the primary of its kind to evaluate the effectiveness and safety of E. coli-derived rhBMP-2 with HA in one- or two-level TLIF. It is designed to evaluate the equivalence of the results between rhBMP-2 with HA and auto-iliac bone graft using an appropriate sample size, assessor-blinded analyses, and prospective registration to avoid bias. This study will set up clear conclusions for using E. coli-derived rhBMP-2 with HA in TLIF.. This study protocol was registered at Korea Clinical Research Information Service ( https://cris.nih.go.kr ; number identifier: KCT0005610) on 19 November 2020. And protocol version is v1.1, January 2022.

Topics: Bone Morphogenetic Protein 2; Durapatite; Escherichia coli; Humans; Lumbar Vertebrae; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

In this prospective, randomized controlled trial, our objective was to assess both the clinical and radiographic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in patients treated with an instrumented single-level posterior lumbar interbody arthrodesis with polyetheretherketone cages.. Forty patients were randomized with a 1:1 ratio. Two patients who had a two-level arthrodesis (L4-L5 and L5-S1) were excluded. Patients completed the Oswestry Disability Index, the Short Form-36, and the visual analog scale preoperatively and postoperatively at three, six, twelve, and twenty-four months. Computed tomography scans with coronal and sagittal reconstructions were made at three, six, and twelve months postoperatively. Interbody arthrodesis was performed using polyetheretherketone cages, which were filled with 8 mg of rhBMP-2 in the study group and 2.5 mL of autologous bone in the control group.. Baseline demographic data showed no significant difference between groups, except for the body mass index, which was higher in the study group (p = 0.032). There were no significant differences in the clinical results (visual analog scale, Oswestry Disability Index, and Short Form-36) between the groups at each postoperative visit. At three months, end-plate resorption was noted around the cages filled with rhBMP-2 in all patients in the study group. No cage migration or subsidence was observed. Bridging trabecular bone scale scores and bone density measures were significantly lower in the study group. Osteolysis and ectopic bone formation occurred in seven of nineteen patients in the study group and did not occur in the control group. This did not result in radicular symptoms within the time span of this study. At one year, computed tomography scans showed osseous healing in all patients. There were no revision procedures.. This trial showed no clinical difference when rhBMP-2 was used in posterior lumbar interbody arthrodesis compared with autologous bone. On computed tomography scans, fusion was equally achieved, but trabecular bone formation occurred at a slower rate and interbody bone density was lower within the first year after surgery when rhBMP-2 was used. End-plate resorption, osteolysis, and ectopic bone formation were frequently noted in the rhBMP-2 group.

Topics: Adult; Aged; Benzophenones; Biocompatible Materials; Bone Density; Bone Morphogenetic Protein 2; Bone Remodeling; Bone Transplantation; Female; Follow-Up Studies; Health Status Indicators; Humans; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Ketones; Lumbar Vertebrae; Male; Middle Aged; Polyethylene Glycols; Polymers; Prospective Studies; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Spondylolisthesis; Surveys and Questionnaires; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

Bone morphogenetic proteins BMPs, when used in spinal fusion, hasten healing and initiate distinct imaging features. We undertook a study to record and analyze the radiographic and CT changes after the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal fusion surgery.. This study included 95 patients who underwent spinal interbody fusion using rhBMP-2. The lumbar spine fusion cohort consisted of 23 patients who underwent anterior lumbar interbody fusion, 36 patients who underwent transforaminal lumbar interbody fusion, and two patients who underwent posterior lumbar interbody fusion. The remaining 34 patients underwent anterior cervical decompression and fusion.. A polyetheretherketone cage was used as an interbody spacer in 59 patients (82 levels) and an allograft bone was the spacer in 36 patients (55 levels). Patients were evaluated 2 and 6 weeks after the procedure and then 3, 6, 12, and 24 months after the procedure. All patients underwent radiography at every follow-up visit, and CT evaluation was performed in 32 patients.. Features observed on imaging that we attributed to the use of rhBMP-2 included an enhanced fusion rate and an increased incidence of prevertebral soft-tissue swelling in patients who underwent cervical fusion. Endplate resorption was observed in 100% of patients who underwent cervical fusion and in 82% of the lumbar levels. Subsidence of the cage resulting in narrowing of the disk space was seen in more than 50% of cases. Cage migration and heterotopic bone formation in the spinal canal and neural foramen occurred maximally in the lumbar spine of patients in whom a polyetheretherketone cage was placed using a transforaminal approach.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Combined Modality Therapy; Humans; Joint Instability; Male; Middle Aged; Prognosis; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome; X-Ray Film

Autogenous iliac crest bone is the gold-standard graft for spinal fusion surgery. Unfortunately, there is a frequent incidence of graft site pain that persists well into the postoperative period with complication rates reported in 2.8-39% of patients. Persistent pain lasting at least 2 years is reported in 15-39% of patients.. The objective of this work was to determine the incidence of acute and persistent pain as well as patient assessment of graft site appearance following iliac crest bone graft harvest for anterior lumbar interbody fusion (ALIF). The control arms of four randomized prospective multicenter clinical trials evaluating recombinant human bone morphogenetic protein-2 (rhBMP-2) versus autogenous iliac crest bone graft were combined. Two hundred eight patients underwent iliac crest bone graft harvest for ALIF in threaded cylindrical cages or threaded bone dowels. Patients were assessed at each postoperative visit with questionnaires evaluating graft site pain intensity, duration, and appearance.. Two hundred eight patients underwent iliac crest bone graft harvest for ALIF as the control group of four randomized prospective multicenter clinical trials evaluating rhBMP-2 versus autogenous iliac crest bone graft in threaded cylindrical cages or threaded bone dowels. Most patients in the control group had anterior iliac crest graft harvest, equally from the right and left side. Three grafts (1.4%) were taken from the posterior crest and six (2.9%) were tricortical. Follow-up was obtained at hospital discharge, 6 weeks, 3, 6, 12, and 24 months. A pain evaluation score was made up of two Visual Analog Scales: one scale measuring intensity, the other frequency of pain. For the intensity scale, a rating of "0" meant no pain and "10" was "as bad as it could be." For the frequency scale, a rating of "0" meant pain was present "none of the time" and "10" meant it was present "all the time." Combining these scales, a total score of 20 indicated the worst pain was present all the time. Patients were also questioned about the graft site appearance.. Two hundred eight patients underwent iliac crest harvest, and prospective data were available on 202 patients. At hospital discharge, 2 patients (1%) had no pain; this increased to 34 of 199 (17%) at 6 weeks postoperatively and to 85 of 199 patients (43%) at 3 months. However, 41% of patients reported pain at 6 months postoperatively (79/192), and 33% of 168 reported pain at 1 year. One hundred forty-one of 208 patients completed a survey at 24 months, with 31% reporting some level of pain. At hospital discharge, the graft site pain score ranged from 0 to 20 with a mean of 12.8, decreasing to 7.3 at 6 weeks, to 3.8 at 3 months, and to 2.9, 2.4, and 1.8 at 6, 12, and 24 months, respectively. At all time intervals, P values from t tests comparing the mean with 0 were <0.001. Graft site appearance at discharge was good in 49% of patients, fair in 40%, and poor in 11%. At 6 weeks, appearance was good in 69%, fair in 27%, and poor in 5%; at 3 months, it was good in 75%, fair in 24%, and poor in 2%; at 6 months, it was good in 82%, fair in 15%, and poor in 3%; at 12 months, it was good in 82% and fair or poor in 19%; and at 24 months, it was good in 84% and fair or poor in 16%. There was no significant difference between posterior and anterior harvest sites or bicortical grafts, and all were included in the analysis. Right or left side demonstrated no differences.. This is the first study known to the authors presenting results of prospective data collected in a multicenter study evaluating iliac crest harvest site pain, both intensity and frequency, as well as graft site appearance. The results demonstrate that 31% of patients had persistent pain at 24 months postoperatively and 16% reported fair or poor appearance of their graft site.. Persistent donor site pain remains a problem with harvest of autogenous iliac crest bone graft for spinal fusion. This prospective study, the first such study reported for ALIF, confirms that donor site pain remains a significant postoperative management problem.

Topics: Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Female; Humans; Ilium; Incidence; Lumbar Vertebrae; Male; Middle Aged; Pain, Postoperative; Patient Satisfaction; Prospective Studies; Recombinant Fusion Proteins; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Prospective, randomized, unblinded study of iliac crest bone graft (ICBG) versus recombinant human bone morphogenetic protein-2/compression resistant matrix (rhBMP-2/CRM)in a posterolateral instrumented fusion procedure.. Document initial radiographic characteristics, based on computed tomography, with rhBMP-2/CRM for posterolateral fusion at 6 and 12-month intervals.. As the acceptance of INFUSE bone graft as an ICBG replacement becomes more widespread, surgeons have begun to study applications for rhBMP-2 in posterior spinal fusion. Preclinical studies have examined variables including carrier composition, rhBMP-2 concentration, and rhBMP-2 dose. Pilot studies have been performed with encouraging initial results.. Patients with single level lumbar degenerative disease were enrolled in a randomized study of ICBG versus rhBMP-2/CRM in a posterolateral instrumented fusion procedure. Computed tomography scans at 6 and 12 months were graded as demonstrating no fusion (grade 1), partial or limited unilateral fusion (grade 2), partial or limited bilateral fusion (grade 3), solid unilateral fusion (grade 4), or solid bilateral fusion (grade 5).. At our institution, 74 patients (38 rhBMP-2/CRM, 36 ICBG) reached minimum 1-year follow-up and were included in this analysis. Mean fusion grade (scale1-5) at 6 months after surgery was 4.35 in the rhBMP-2/CRM group versus 3.09 in the ICBG group (P < 0.0001). At 1 year after surgery mean fusion grade was 4.62 in the rhBMP-2/CRM group versus 3.77 in the ICBG group (P < 0.0023).. These early results are encouraging and suggest a more rapid incorporation and development of the fusion mass with rhBMP-2/CRM than iliac crest autograft in a single level posterior instrumented fusion.

Topics: Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Calcium Phosphates; Collagen; Drug Carriers; Durapatite; Female; Follow-Up Studies; Humans; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Smoking; Spinal Diseases; Spinal Fusion; Statistics, Nonparametric; Transforming Growth Factor beta

A prospective, randomized, pilot clinical trial compared recombinant human bone morphogenetic protein-2 (rhBMP-2) with iliac crest autograft bone for the treatment of human cervical disc disease.. To examine the safety and effectiveness of using INFUSE Bone Graft (rhBMP-2 applied to an absorbable collagen sponge), as compared with an autogenous iliac crest bone graft placed inside the CORNERSTONE-SR fibular allograft, in anterior cervical discectomy and interbody fusion.. Recombinant human bone morphogenetic protein-2 is an osteoinductive protein that induces a reliable fusion in the lumbar spine, but it has not been studied in patients with degenerative cervical disc disease.. For this study, 33 patients with degenerative cervical disc disease were randomly assigned to investigational or control groups. The investigational group received a fibular allograft (CORNERSTONE-SR Allograft Ring) with an rhBMP-2-laden collagen carrier inside the graft along with an ATLANTIS anterior cervical plate. The control group received a fibular allograft with cancellous iliac crest autograft placed inside it, along with an ATLANTIS anterior cervical plate. The patients underwent plain radiographs at 6 weeks, then at 3, 6, 12, and 24 months, and CT scans at 3 and 6 months after surgery. They also completed general health profiles and self-evaluation scales. Adverse events were evaluated for severity, duration, association with the implant, and the need for a second surgical procedure.. All the patients evaluated had solid fusions 6, 12, and 24 months after surgery. There were no device-related adverse events. At 24 months, the investigational group had mean improvement superior to that of the control group in neck disability and arm pain scores (P < 0.03 each).. This pilot study demonstrates the feasibility of using rhBMP-2 safely and effectively in the cervical spine.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Cervical Vertebrae; Diskectomy; Female; Humans; Ilium; Male; Middle Aged; Osseointegration; Osteogenesis; Pilot Projects; Prospective Studies; Recombinant Proteins; Safety; Spinal Diseases; Spinal Fusion; Tomography, X-Ray Computed; Transforming Growth Factor beta; Transplantation, Autologous; Treatment Outcome

In a multicenter, prospective, randomized, nonblinded, 2-year study, 279 patients with degenerative lumbar disc disease were randomly divided into two groups that underwent interbody fusion using two tapered threaded fusion cages. The investigational group (143 patients) received rhBMP-2 on an absorbable collagen sponge, and a control group (136 patients) received autogenous iliac crest bone graft. Plain radiographs and computed tomographic scans were used to evaluate fusion at 6, 12, and 24 months after surgery. Mean operative time (1.6 hours) and blood loss (109.8 mL) were less in the investigational rhBMP-2 group than in the autograft control group (2.0 hours and 153.1 mL). At 24 months the investigational group's fusion rate (94.5%) remained higher than that of the control group (88.7%). New bone formation occurred in all investigational patients. At all intervals, mean postoperative Oswestry, back pain, and leg pain scores and neurologic status improved in both treatment groups with similar outcomes. In the control group, eight adverse events related to the iliac crest graft harvest occurred (5.9%), and at 24 months 32% of patients reported graft site discomfort and 16% were bothered by its appearance. Lumbar fusion using rhBMP-2 and a tapered titanium fusion cage can yield a solid union and eliminate the need for harvesting iliac crest bone graft.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Female; Humans; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Time Factors; Tomography, X-Ray Computed; Transforming Growth Factor beta; Transplantation, Autologous; Treatment Outcome

A prospective randomized controlled human clinical pilot trial.. To determine the feasibility of using rhBMP-2/collagen as a substitute for autogenous bone graft inside interbody fusion cages to achieve arthrodesis in humans.. Preclinical studies have shown rhBMP-2 to be an effective substitute for autogenous bone graft, but there are no studies to date documenting such efficacy for human spine fusion.. Fourteen patients with single-level lumbar degenerative disc disease refractory to nonoperative management were randomized to receive lumbar interbody arthrodesis with a tapered cylindrical threaded fusion cage filled with rhBMP-2/collagen sponge or autogenous iliac crest bone. Patients were evaluated with radiographs, sagittally reformatted computed tomography scans, and Short Form-36 and Oswestry outcome questionnaires.. All 11 patients who received rhBMP-2 were judged by three independent radiologists to have solid fusions (at 6, 12, and 24 months postimplantation), whereas only 2 of the 3 control patients, who received the standard treatment of autogenous iliac crest bone, were deemed to be fused. The Oswestry Disability Questionnaire scores of the rhBMP-2 group improved sooner (after 3 months) than those of the autograft group, with both groups demonstrating similar improvement at 6 months. Short Form 36 scores continued to improve up to 24 months.. The arthrodesis was found to occur more reliably in patients treated with rhBMP-2-filled fusion cages than in controls treated with autogenous bone graft, although the sample size was limited. There were no adverse events related to the rhBMP-2 treatment. This study is one of the first to show consistent and unequivocal osteoinduction by a recombinant growth factor in-humans.

Topics: Adolescent; Adult; Aged; Arthrodesis; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Collagen; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteogenesis; Pilot Projects; Prospective Studies; Recombinant Proteins; Spinal Diseases; Transforming Growth Factor beta; Transplantation, Autologous; Treatment Outcome

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a life-threatening, inherited, nonhypertensive arteriole disease of the brain. Therapeutic strategy for CARASIL is limited because its pathogenesis is not clear. We previously reported the first family with CARASIL in China, which involves a high-temperature requirement serine protease gene mutation (HtrA1. Food maze and water maze experiments were used in the behavioral studies. Pathological studies were carried out by arteriole labeling staining and electron microscopy. The mRNA and protein expression levels of the key factors of TGF-β/Smad signaling pathway (TGF-β, Smad2, Smad3, and Smad4) in the brain of the model mice were detected by immunohistochemistry, real-time quantitative polymerase chain reaction (RT-PCR), and Western blot assay.. The food maze and water maze experiment data showed significant differences between the Mut and wild-type (WT) mice in the first time to find food, the time to contact the escape table for the first time, and the number of times to travel in the escape table quadrant (p < 0.001). The results of vascular labeling staining showed that some small arteries in the brain of Mut mice lost normal structure. The results of electron microscopy showed that the cell morphologies in the cortex and hippocampus of Mut mice were abnormal; the number of synapses was reduced; the walls of capillaries, venules, and arterioles thickened; lumen stenosis and other abnormal phenomenon occurred; and lipofuscin deposition and autophagosomes were found in the hippocampus. Immunohistochemistry, RT-PCR, and Western Blot results showed that the mRNA and protein expression levels of TGF-β, Smad2, and Smad3 in the brain of Mut mice increased to different degrees.. The most significant innovation of this study is the first study on the pathogenesis of CARASIL disease using model animals. The Mut mice can well simulate the pathogenesis of CARASIL in behavioral and pathological aspects. The TGF-β/Smad signaling pathway, which is involved in the pathogenesis of CARASIL, is abnormally upregulated in the brain of Mut mice.

Topics: Alopecia; Animals; Cerebral Arterial Diseases; Cerebral Infarction; Cerebrovascular Disorders; Cognitive Dysfunction; High-Temperature Requirement A Serine Peptidase 1; Leukoencephalopathies; Mice; RNA, Messenger; Signal Transduction; Spinal Diseases; Transforming Growth Factor beta

Bone morphogenetic protein (BMP) is a growth factor that aids in osteoinduction and promotes bone fusion. There is a lack of literature regarding recombinant human BMP-2 (rhBMP-2) dosage in different spine surgeries. This study aims to investigate the trends in rhBMP-2 dosage and the associated complications in spinal arthrodesis.. A retrospective study was conducted investigating spinal arthrodesis using rhBMP-2. Variables including age, procedure type, rhBMP-2 size, complications, and postoperative imaging were collected. Cases were grouped into the following surgical procedures: anterior lumbar interbody fusion/extreme lateral interbody fusion (ALIF/XLIF), posterior lumbar interbody fusion/transforaminal lumbar interbody fusion (PLIF/TLIF), posterolateral fusion (PLF), anterior cervical discectomy and fusion (ACDF), and posterior cervical fusion (PCF).. A total of 1209 patients who received rhBMP-2 from 2006 to 2020 were studied. Of these, 230 were categorized as ALIF/XLIF, 336 as PLIF/TLIF, 243 as PLF, 203 as ACDF, and 197 as PCF. PCF (P < 0.001), PLIF/TLIF (P < 0.001), and PLF (P < 0.001) demonstrated a significant decrease in the rhBMP-2 dose used per level, with major transitions seen in 2018, 2011, and 2013, respectively. In our sample, 129 complications following spinal arthrodesis were noted. A significant relation between rhBMP-2 size and complication rates (χ. BMP is an effective compound in fusing adjacent spine segments. However, it carries some regional complications. We demonstrate a decreasing trend in the dose/vertebral level. A decrease rhBMP-2 dose per level correlated with a decrease in complication rates.

Topics: Bone Morphogenetic Protein 2; Cohort Studies; Diskectomy; Dose-Response Relationship, Drug; Humans; Longitudinal Studies; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.

Topics: ADAMTS Proteins; Alopecia; Animals; Benzimidazoles; Biphenyl Compounds; Cerebral Infarction; Cerebrovascular Circulation; Disease Progression; Extracellular Matrix Proteins; High-Temperature Requirement A Serine Peptidase 1; Latent TGF-beta Binding Proteins; Leukoencephalopathies; Mice; Mice, Inbred C57BL; Recombinant Proteins; Spinal Diseases; Tetrazoles; Transforming Growth Factor beta

High temperature requirement A1 (HTRA1) is a serine protease playing a modulatory role in various cell processes, particularly in the regulation of transforming growth factor-β (TGF-β) signaling. A deleterious role in late-onset cerebral small vessel diseases (CSVDs) of heterozygous HTRA1 mutations, otherwise causative in homozygosity of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, was recently suggested. However, the pathomechanism of these heterozygous mutations is still undefined. Our aim is to evaluate the expression profile and activity of HTRA1 on TGF-β signaling in fibroblasts from four subjects carrying the HTRA1 heterozygous mutations-p.E42Dfs*173, p.A321T, p.G295R, and p.Q151K. We found a 50% reduction of HTRA1 expression in HTRA1 mutation carriers compared to the control. Moreover, we showed no changes in TGF-β signaling pathway downstream intermediate, Phospho Smad2/3. However, we found overexpression of genes involved in the extracellular matrix formation in two heterozygous HTRA1 carriers. Our results suggest that each heterozygous HTRA1 missense mutation displays a different and peculiar HTRA1 expression pattern and that CSVD phenotype may also result from 50% of HTRA1 expression.

Topics: Alopecia; Cells, Cultured; Cerebral Infarction; Cerebrovascular Disorders; Female; Fibroblasts; Heterozygote; High-Temperature Requirement A Serine Peptidase 1; Humans; Leukoencephalopathies; Male; Middle Aged; Mutation; Signal Transduction; Spinal Diseases; Transcriptome; Transforming Growth Factor beta

OBJECTIVEUse of recombinant human bone morphogenetic protein-2 (rhBMP-2) in patients with spine infections is controversial. The purpose of this study was to identify long-term complications, reoperations, and healthcare utilization associated with rhBMP-2 use in patients with spine infections.METHODSThis retrospective study extracted data using ICD-9/10 and CPT codes from MarketScan (2000-2016). Patients were dichotomized into 2 groups (rhBMP-2, no rhBMP-2) based on whether rhBMP-2 was used during fusion surgery for spinal infections. Outcomes of interest were reoperation rates (index level, other levels), readmission rates, discharge disposition, length of stay, complications, and healthcare resource utilization at the index hospitalization and 1, 3, 6, 12, and 24 months following discharge. Outcomes were compared using nonparametric 2-group tests and generalized linear regression models.RESULTSThe database search identified 2762 patients with > 24 months' follow-up; rhBMP-2 was used in 8.4% of their cases. The patients' median age was 53 years, 52.43% were female, and 15.11% had an Elixhauser Comorbidity Index ≥ 3. Patients in the rhBMP-2 group had higher comorbidity indices, incurred higher costs at index hospitalization, were discharged home in most cases, and had lower complication rates than those in the no-rhBMP-2 group. There was no statistically significant between-groups difference in complication rates 1 month following discharge or in reoperation rates at 3, 6, 12, and 24 months following the procedure. Patients in the no-rhBMP-2 group incurred higher utilization of outpatient services and medication refill costs at 1, 3, 6, 12, and 24 months following surgery.CONCLUSIONSIn patients undergoing surgery for spine infection, rhBMP-2 use was associated with lower complication rates and higher median payments during index hospitalization compared to cases in which rhBMP-2 was not used. There was no significant between-groups difference in reoperation rates (index and other levels) at 3, 6, 12, and 24 months after the index operation. Patients treated with rhBMP-2 incurred lower utilization of outpatient services and overall payments. These results indicate that rhBMP-2 can be used safely in patients with spine infections with cost-effective utilization of healthcare resources and without an increase in complications or reoperation rates.

Topics: Adult; Bone Morphogenetic Protein 2; Female; Humans; Infections; Male; Middle Aged; Patient Acceptance of Health Care; Postoperative Complications; Recombinant Proteins; Reoperation; Retrospective Studies; Spinal Diseases; Spinal Fusion; Spine; Transforming Growth Factor beta

The purpose of this study was to report an independent real-life experience about the use of recombinant human bone morphogenetic protein 2 in lumbar interbody fusion with a special focus on complications. This is a retrospective single-center cohort study between 2007 and 2013 including 277 patients treated for anterior or posterior lumbar fusion with recombinant human bone morphogenetic protein 2. We report the complications occurring during the 12 first postoperative months and analyze the fusion rate on X-rays. There are 58 cases (22.8%) of clinical complications. In 15 cases (5.9%), these complications were related to the use of recombinant human bone morphogenetic protein 2. Only one patient (0.4%) required a new intervention due to recombinant human bone morphogenetic protein 2. Fusion rate at 1 year was 98%. The low rate of specific complication suggests that recombinant human bone morphogenetic protein 2 can be safe and effective in anterior and posterior interbody fusion when used with simple precautions.

Topics: Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Postoperative Complications; Radiography; Recombinant Proteins; Retrospective Studies; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Level III, Retrospective observational study.. To determine if there is an increased risk of developing cancer after exposure to high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) and if risk is dose and/or exposure-dependent.. Concerns have been raised regarding a relationship between rhBMP-2 and cancer.. A total of 642 adult deformity patients from a single institution receiving a cumulative rhBMP-2 dose ≥40 mg from July, 2002 to July, 2009 were identified. Patients with a history of surveillance, epidemiology, and end result (SEER) cancer before rhBMP-2 exposure were excluded. To determine the occurrence of a cancer event, questionnaires were mailed and telephone follow up attempted for nonresponders. Only cancers tracked by the National Cancer Institute (NCI) SEER registry were included. Observed cancer counts were compared to expected cancer counts based on general population incidence rates within 5-year age strata. Cumulative incidence competing risk (CICR) modeling was used to evaluate the association between rhBMP-2 exposure and cancer controlling for potential confounding variables.. Forty-nine patients were lost-to-follow up, leaving 593 patients (92.4%; 138 males/455 females) available for analysis. Mean age was 52.8 years at the time of first exposure. Mean cumulative rhBMP-2 dose was 113.5 mg with 85% having one exposure (range: 1-8). Mean follow-up [date of exposure to date of death (regardless of cause) or returned completed questionnaire] was 5.6 ± 1.9 years; median follow up was 5.4 years. A total of 342 patients have greater than 5-year follow up. Minimum follow up was 2.0 years or until occurrence of a SEER cancer. Our total 8-year cumulative incidence of new SEER cancer accounting for the competing risk of death was 7.4% for 30 cancers in 593 patients. Fewer cancers were observed than expected based on general population rates, though the difference was not statistically significant (expected = 34; standardized incidence ratio = 0.88, 95% confidence interval, CI = 0.60-1.26). CICR found neither cumulative rhBMP-2 dose (hazard ratio, HR = 0.995, 95% CI 0.988-1.003; P = 0.249) nor number of exposures (HR = 0.776, 95% CI 0.359-1.677; P = 0.519) increased the risk of developing a postexposure cancer after controlling for known cancer risk factors.. The incidence of a SEER cancer after rhBMP-2 exposure was similar to incidence reported by the NCI. There were no significant rhBMP-2 dose or multi-exposure related risks of developing a life-threatening cancer.. 3.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasms; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; SEER Program; Spinal Diseases; Transforming Growth Factor beta

The clinical application of recombinant bone morphogenetic protein in spinal surgery has been shown to be safe and effective. However, its use in minimally invasive spine surgery has been limited to anterior interbody fusion procedures. To date, no study has evaluated the feasibility of percutaneous posterolateral fusion in the spine utilizing recombinant bone morphogenetic protein-2 (rhBMP-2).. To evaluate the feasibility of percutaneous posterolateral fusion in the spine utilizing rhBMP-2.. Animal study.. This is an animal research model involving 32 New Zealand white rabbits stratified into 4 study groups: control, autogenous iliac crest bone graft (ICBG), demineralized bone matrix (DBM), and rhBMP-2 groups, with 8 study subjects per group. The rhBMP-2 group was subdivided into the open technique (right side) and the percutaneous technique groups (left side). Fusion was graded at 6 weeks and 3 months after plain radiography, computed tomography, and clinical assessment with the following grading system: grade A, no bone formation; grade B, non-bridging bone formation; grade C, fusion; and grade D, fusion with ectopic bone formation.. No fusion was noted in the placebo and the DBM groups. However, in the DBM group, bone formation occurred in 37.5% of the subjects. The rhBMP-2 group had a higher fusion rate compared with the ICBG group at 6 weeks and 3 months. The fusion rate for the ICBG, the rhBMP-2 (open), and the rhBMP-2 (percutaneous) groups were 37.5%, 87.5%, and 50.0% at 6 weeks and 50.0%, 100.0%, and 62.5% at 3 months, respectively. Ectopic bone formation occurred in 12.5% of the cases in the rhBMP-2 (percutaneous) group and in 25.0% of the cases in the rhBMP-2 (open) group.. Usage of rhBMP-2 is feasible for percutaneous posterolateral fusion of the lumbar spine in this animal model. However, a more precise delivery system might improve the fusion rate when the percutaneous technique is used. A significant rate of ectopic bone formation occurred when rhBMP-2 was used.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Transplantation; Disease Models, Animal; Feasibility Studies; Follow-Up Studies; Rabbits; Radiography; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Time Factors; Tomography Scanners, X-Ray Computed; Transforming Growth Factor beta

Although use of very high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) has been reported to markedly improve fusion rates in adult spinal deformity (ASD) surgery, most centers use much lower doses due to cost constraints. How effective these lower doses are for fusion enhancement remains unclear.. To assess fusion rates using relatively low-dose rhBMP-2 for ASD surgery.. This was a retrospective review of consecutive ASD patients that underwent thoracic to sacral fusion. Patients that achieved 2-year follow-up were analyzed. Impact of patient and surgical factors on fusion rate was assessed, and fusion rates were compared with historical cohorts.. Of 219 patients, 172 (78.5%) achieved 2-year follow-up and were analyzed. Using an average rhBMP-2 dose of 3.1 mg/level (average total dose = 35.9 mg/case), the 2-year fusion rate was 73.8%. Cancellous allograft, local autograft, and very limited iliac crest bone graft (<20 mL, obtained during iliac bolt placement) were also used. On multivariate analysis, female sex was associated with a higher fusion rate, whereas age, comorbidity score, deformity type, and 3-column osteotomy were not. There were no complications directly attributable to rhBMP-2.. Fusion rates for ASD using low-dose rhBMP-2 were comparable to those reported for iliac crest bone graft but lower than for high-dose rhBMP-2. Importantly, there were substantial differences between patients in the present series and those in the historical comparison groups that could not be fully adjusted for based on available data. Prospective evaluation of rhBMP-2 dosing for ASD surgery is warranted to define the most appropriate dose that balances benefits, risks, and costs.. ASD, adult spinal deformityICBG, iliac crest bone graftOR, odds ratiorhBMP-2, recombinant human bone morphogenetic protein-2RR, risk ratioTCO, 3-column osteotomy.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Female; Humans; Ilium; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta; Transplantation, Autologous; Treatment Outcome

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 U.S. Food and Drug Administration reported a higher incidence of cancer in patients who had spinal arthrodesis and were exposed to a high dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) compared with the control group in a randomized controlled trial. The purpose of this study was to determine the risk of cancer after spinal arthrodesis with BMP.. We retrospectively analyzed the incidence of cancer in 467,916 Medicare patients undergoing spinal arthrodesis from 2005 to 2010. Patients with a preexisting diagnosis of cancer were excluded. The average follow-up duration was 2.85 years for the BMP group and 2.94 years for the control group. The main outcome measure was the relative risk of developing new malignant lesions after spinal arthrodesis with or without exposure to BMP.. The relative risk of developing cancer after BMP exposure was 0.938 (95% confidence interval [95% CI]: 0.913 to 0.964), which was significant. In the BMP group, 5.9% of the patients developed an invasive cancer compared with 6.5% of the patients in the control group. The relative risk of developing cancer after BMP exposure was 0.98 in males (95% CI: 0.94 to 1.02) and 0.93 (95% CI: 0.90 to 0.97) in females. The control group showed a higher incidence of each type of cancer except pancreatic cancer.. Recent clinical use of BMP was not associated with a detectable increase in the risk of cancer within a mean 2.9-year time window.. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Topics: Age Distribution; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Case-Control Studies; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Incidence; Male; Medicare; Middle Aged; Neoplasms; Predictive Value of Tests; Recombinant Proteins; Retrospective Studies; Risk Assessment; SEER Program; Sex Distribution; Spinal Diseases; Spinal Fusion; Time Factors; Transforming Growth Factor beta; Treatment Outcome; United States

Topics: Bone Density; Bone Morphogenetic Protein 2; Bone Remodeling; Female; Humans; Lumbar Vertebrae; Male; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Topics: Bone Density; Bone Morphogenetic Protein 2; Bone Remodeling; Female; Humans; Lumbar Vertebrae; Male; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Retrospective review of prospectively collected data.. Without industry funding, the study evaluated short- and long-term complications related to off-label bone morphogenetic protein (BMP) used with transforaminal lumbar interbody fusion (TLIF) from a large consecutive series. Complications and results were analyzed by BMP dose, fusion length, and primary versus revision surgery. Based on the results, surgical technique and BMP dose recommendations were proposed.. Off-label use of BMP in TLIF, although common, has only been studied in small series and case reports using various techniques, cage types, and doses of BMP. Several of these studies have reported minimal complications. Others report problems related to BMP, which has led to questions regarding current widespread use of TLIF with BMP.. TLIF with rhBMP-2 was performed at 872 discs in 509 consecutive adults who underwent open posterior instrumented fusion and had minimum 2-year follow-up; diagnoses included degenerative disease (179), spondylolisthesis (207), deformity (123). Patient age averaged 61 years: 12% were smokers and 41% had revision surgery. TLIF was performed at 1.7 levels: single level: 229, 2 levels: 201, 3 levels: 74, 4 levels: 5. Local autograft was used for backfill around and behind each rectangular cage. Varying doses of interbody BMP were used at an average 7.3 mg per disc (range: 2-12 mg per disc).. At 5 years average follow-up, 8 patients developed pseudoarthrosis at levels of TLIF (8 of 872 discs, 0.92%). Seroma (0.4%) and ectopic bone growth (0.6%) were too infrequent to be associated with a particular BMP dose. Deep infection was 2.6% overall (1.7% of the degenerative group). Symptomatic osteolysis or cage subsidence did not occur. Significant long-term improvement was noted in clinical and functional outcomes compared with preoperation.. Five-year follow-up after TLIF with BMP, independent of industry, confirms effective arthrodesis in short and long fusions, both primary and revision. Most complications occurred in deformity patients. BMP-related complications (seroma, ectopic bone) were rare.. 3.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Screws; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Intervertebral Disc Degeneration; Logistic Models; Lumbar Vertebrae; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Recombinant Proteins; Retrospective Studies; Spinal Diseases; Spinal Fusion; Spondylolisthesis; Time Factors; Transforming Growth Factor beta; Treatment Outcome; Young Adult

Retrospective review of prospectively collected data.. To evaluate long-term clinical outcomes and complications of the transforaminal lumbar interbody fusion (TLIF) procedure from a large consecutive series, without industry funding. Clinical outcomes and complications are analyzed by diagnosis and primary versus revision surgery to assess whether TLIF with bone morphogenic protein (BMP) is appropriate for common use in deformity, spondylolisthesis, and degenerative disease.. A common method for achieving spinal arthrodesis includes TLIF with a cage and off-label interbody BMP-2, supported by posterior arthrodesis and a pedicle screw construct. There are no large studies analyzing outcomes and complications after TLIF in different diagnoses, for primary and revision surgery, leading some to question the widespread use of TLIF.. A total of 509 consecutive adults underwent open posterior instrumented fusion, augmented with TLIF at 872 discs using a cage and rhBMP-2, with minimum 2-year follow-up. Cohort diagnoses included 179 degenerative, 207 spondylolisthesis, and 123 deformity patients. Patient age averaged 61 years, 207 had undergone prior decompression or fusion surgery. All patients underwent posterior instrumented fusion and pedicle screw instrumentation at average 3.6 levels (range, 1-16); all patients had TLIF 1.7 levels (range, 1-4 levels) with BMP and autograft, stabilized with an interbody cage.. At average 59 months follow-up, 12 patients developed pseudoarthrosis, 8 at TLIF levels (8/872 discs, 0.92%) most commonly at L5-S1 (6/8). Significant clinical improvement was noted in patients with deformity, spondylolisthesis, and degenerative disease undergoing primary and revision surgery. Overall, visual analogue scale preoperative score was 6.6, at 1 year 3.8, at 2 years 3.5 (P < 0.001) and the preoperative ODI was 50.9, at 1 year 36.1, and at 2 years 35.0 (P < 0 0.001). Pain medication requirements also declined.. The efficacy of TLIF with BMP is supported in this large series with long-term follow-up, independent of industry. Reliable fusion and improved outcomes can be expected in adults undergoing TLIF for deformity, spondylolisthesis, and degenerative disease. Most complications occurred in patients with deformity.. 3.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Screws; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Intervertebral Disc Degeneration; Logistic Models; Lumbar Vertebrae; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Recombinant Proteins; Retrospective Studies; Spinal Diseases; Spinal Fusion; Spondylolisthesis; Time Factors; 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

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

Clinical, biochemical, and histologic analysis was performed after in vivo delivery of cDNA encoding various anabolic cytokines and marker genes to the lumbar epidural space of New Zealand white rabbits, using both adenoviral and adeno-associated viral vectors.. To mimic errant or misplaced doses of gene therapy to better ascertain the potential risks associated with alternative vectors and transgene products with regard to their application to problems of the intervertebral disc.. Work done with several anabolic cytokines including bone morphogenic proteins and transforming growth factors, has demonstrated the potential of gene therapy. Recently, data has been published demonstrating that improperly dosed or delivered adenoviral-mediated gene therapy within the subarachnoid space can result in significant morbidity in rabbits. There are currently no studies examining the effect of these errors within the epidural space or using an adeno-associated viral (AAV) vector.. Using either adenoviral or AAV vectors, complementary DNA (cDNA) encoding anabolic cytokines bone morphogenic protein-2 (BMP-2) and transforming growth factor-beta 1 and marker proteins LacZ and green fluorescent protein were injected into the epidural space of 37 New Zealand white rabbits at the L5/6 level. Rabbits were then observed clinically for up to 6 weeks, after which the rabbits were sacrificed in order to perform a comprehensive biochemical and histologic analysis.. Following adenoviral-mediated delivery of anabolic cytokine cDNA, up to eighty percent of rabbits demonstrated significant clinical, biochemical, and histologic morbidity. Conversely, AAV-mediated delivery of any cDNA and adenoviral-mediated delivery of marker protein cDNA resulted in no clinical, histologic, or biochemical morbidity.. Properly dosed and directed gene therapy seems to be both safe and potentially efficacious. This study suggests that side effects of gene therapy may be due to a combination of dosing, transgene product, and vector choice, and that newer AAV vectors may reduce these side-effects and decrease the risk of this technology.

Topics: Adenoviridae; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Dependovirus; Disease Models, Animal; DNA, Complementary; Epidural Space; Female; Genetic Therapy; Genetic Vectors; Green Fluorescent Proteins; Injections, Spinal; Lac Operon; Lumbar Vertebrae; Rabbits; Spinal Diseases; Transforming Growth Factor beta; Transforming Growth Factor beta1

LMP-1 is known to increase proteoglycan production through the upregulating the BMPs and it is also known that BMP-2 acts on anulus fibrosus cells and chondrocytes to increase proteoglycan production.. We carried out an experiment, the effect of AdLMP-1 transfection on AF cells and chondrocytes in the production of sulfated-glycosaminoglycans, mRNA expression (aggrecan, type I, II collagen, LMP-1, BMP-2, and BMP-7), and immunofluorescence staining. AF cells and chondrocytes were grown in monolayer and treated for 6 days with AdLMP1-green fluorescence protein (GFP) (10, 20, and 30 multiplicity of infection [MOI]). After 6 days, the sGAG content in the media was quantified using 1,9-dimethylmethylene blue staining. The mRNA expression was measured with real-time PCR after 20 MOI infection of AdLMP1-GFP. The each cells treated with 20 MOI infection of AdGFP was used as a control group for the mRNA expression. The each cell group was immunofluorescence stained with each antibodies in the chamber slide at 3 x 10(4) cells/chamber.. 1) The sGAG production was maximum in 20 MOI AdLMP1-GFP infection on the AdLMP-1 treatment for both of AF cells and chondrocytes. 2) The mRNA expression of aggrecan, type I collagen, type II collagen, LMP-1, BMP-2, and BMP-7 is increased in both AF cells and chondrocytes in 20 MOI AdLMP1-GFP infection. 3) On the immunofluorescence staining results, the positive immunofluorescence stained cell numbers are increased after 20 MOI AdLMP1-GFP infection concordant with upregulation of mRNA expression.. The AdLMP-1 treatments in AF cells and chondrocytes may be useful for cell transplantation therapy in disc degeneration.

Topics: Adaptor Proteins, Signal Transducing; Aggrecans; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Cell Transplantation; Chondrocytes; Collagen Type I; Collagen Type II; Cytoskeletal Proteins; Gene Expression Regulation; Genetic Therapy; Glycosaminoglycans; Humans; Intervertebral Disc; Intracellular Signaling Peptides and Proteins; LIM Domain Proteins; Polymerase Chain Reaction; RNA, Messenger; Spinal Diseases; Transfection; Transforming Growth Factor beta

Adult mesenchymal stem cell therapy has a potential application in the biological treatment of disc degeneration. Our objectives were: to direct adipose-derived mesenchymal stem cells (AD-MSC) from the sand rat to produce a proteoglycan and collagen type I extracellular matrix (ECM) rich in known ECM components of the annulus fibrosis of disc; and to stimulate proteoglycan production by co-culture of human annulus cells with AD-MSC.. AD-MSC were isolated and characterised by adherence to plastic, appropriate expression of cluster of differentiation (CD) markers, and differentiation to osteoblasts and chondrocytes in vitro. AD-MSC were grown in three-dimensional (3D) culture and treated with or without transforming growth factor beta (TGFbeta) to direct them to produce annulus-like ECM as determined by proteoglycan content and collagen expression. AD-MSC were co-cultured with human annulus cells and grown in 3D culture.. AD-MSC produced a proteoglycan and collagen type I rich ECM after treatment with TGFbeta in 3D culture as confirmed by a 48% increase in proteoglycan content assayed by 1,9-dimethylmethylene blue (DMB), and by immunohistochemical identification of ECM components. Co-culture of human annulus and sand rat AD-MSC in 3D culture resulted in a 20% increase in proteoglycan production compared with the predicted value of the sum of the individual cultures.. Results support the hypothesis that AD-MSC have potential in cell-based therapy for disc degeneration.

Topics: Adipose Tissue; Animals; Cell Adhesion; Cell Differentiation; Cell- and Tissue-Based Therapy; Cells, Cultured; Coculture Techniques; Collagen Type I; Extracellular Matrix; Gerbillinae; Humans; Intervertebral Disc; Mesenchymal Stem Cells; Proteoglycans; Rats; Spinal Diseases; Transforming Growth Factor beta

Case series from a single spine specialty clinic.. This study analyzed wound related or anaphylactic adverse events in patients re-exposed to rhBMP-2.. The use of recombinant bone morphogenetic protein (rhBMP-2) as a bone graft substitute is increasing. There is concern that re-exposing patients to rhBMP-2, might result in a hyper-inflammatory response causing wound problems or an allergic reaction.. Ninety-six patients who had at least 2 spine surgeries using rhBMP-2 (Infuse, Medtronic Sofamor Danek, Memphis, TN) were identified. Anteroposterior surgeries, surgeries for infection and trauma were excluded. Demographic and operative data were collected from review of medical records. Surgeries were classified into primary, revision same approach and revision different approach. Logistic regression was used to control for variables associated with increased risk of complications.. During the first exposure there were 90 primary fusions and 6 revisions with 2 wound infections requiring debridements and 9 minor wound problems. During the second exposure there were 25 primary fusions, 50 same approach first revisions, 16 different approach first revisions, 1 same approach second revision and 4 different approach second revisions. There were 5 wound infections, 11 minor wound problems and no allergic reactions. There was no significant difference in the number of complications between the first and second surgeries or between patients who had a second primary surgery, a revision through the same approach or through a different approach. There were no wound problems or allergic reactions among twelve patients who had a third surgery with rhBMP-2.. Multiple exposures to rhBMP-2, whether for a second primary surgery, revision through the same approach or revision through a different approach does not increase the risk of a wound infections/problems or result in clinically detectable allergic reactions.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Substitutes; Female; Humans; Logistic Models; Male; Recombinant Proteins; Reoperation; Spinal Diseases; Spinal Fusion; Surgical Wound Infection; Transforming Growth Factor beta; Treatment Outcome

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

Prospective analysis.. To investigate biologic influences of recombinant human bone morphogenetic protein (rhBMP)-2 on intervertebral discs after anular tears.. Treatments for intervertebral disc injury or degeneration are unsatisfactory. rhBMP-2, a high-potency osteoinductive and chondroinductive substance, is approved for use in anterior lumbar interbody fusions. rhBMP-2 stimulates the proliferation of rat disc cells and the secretion of extracellular matrix in vitro. In vivo responses in the intervertebral disc after anular tears are rarely studied.. Twenty New Zealand white rabbits received full-thickness anular tears and intradiscal injections of saline (control) and rhBMP-2 0.1 mg with and without coral grafts at L2-L3, L3-L4, and L4-L5, respectively. Three died or had infection. Therefore, 17 underwent radiography and sacrifice at 12 weeks. Spinal sections were stained with hematoxylin and eosin to examine responses to rhBMP-2.. Radiographs revealed degenerative changes, such as disc space narrowing and irregularity, subchondral sclerosis, osteophyte formation, and hypertrophy of vertebral endplates in all groups. Degeneration was more frequent and severe with rhBMP-2 with (P < 0.01) and without (P < 0.05) coral than with saline. Two rabbits receiving rhBMP-2 and coral achieved solid interbody bony fusion. New bone formation was noted in 2 controls, in 3 animals treated with rhBMP-2, and in 4 treated with rhBMP-2 and coral. Vascularity and fibroblast proliferation increased with rhBMP-2 (n = 14) and rhBMP-2 with coral (n = 9) compared with control (n = 3; P < 0.01 and P = 0.03, respectively). Inflammatory infiltrates increased with rhBMP-2 (n = 8) compared with control (n = 2; P = 0.03).. Degenerative changes were more frequent and severe in the groups treated with rhBMP-2 with or without coral in radiographic findings. In histopathologic findings, rhBMP-2 promoted hypervascularity and fibroblast proliferation of the intervertebral disc after an anular tear.

Topics: Animals; Anthozoa; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Substitutes; Cell Proliferation; Disease Models, Animal; Fibroblasts; Humans; Injections, Spinal; Intervertebral Disc; Lumbar Vertebrae; Male; Neovascularization, Physiologic; Osseointegration; Rabbits; Recombinant Proteins; Spinal Diseases; Time Factors; Transforming Growth Factor beta

Observational study with prospective CT analysis.. To assess the incidence and clinical sequelae of epidural bone formation following the adjunctive use of recombinant bone morphogenetic protein 2 (rhBMP2) with local autogenous bone graft use of (rhBMP2) in minimal access interbody (PLIF and TLIF) fusions.. The use of rhBMP2 for interbody fusion is associated with high fusion rates. However, for posterior approaches, concerns regarding heterotopic bone formation within the epidural space have been raised.. An independent CT analysis of 33 consecutive patients following minimal access lumbar fusion (PLIF [n = 10] or TLIF [n = 23]) with [n = 23] and without [n = 10] rhBMP2 was performed. Bone formation was graded in a centrifugal manner (intradiscal, anular/ALL/PLL, epidural [canal/foramen] and beyond the spine). In all BMP cases, a constant dose of 4.2 mg/disc level was administered (lowest commercially available dose). In all cases, local autograft was used. Review and assessment of prospectively collected outcomes data were performed.. Average clinical and CT (minimum 6 months) follow-up was 25.0 and 7.9 months, respectively. Bridging bone (fusion) was seen in 100% of the BMP group and 90% without BMP. Epidural bone formation occurred in 20.8% with the use of BMP (5 levels: n = 1 spinal canal and n = 4 within the foramen) compared with 8.3% (1 level: canal) without BMP. Foraminal bone formation was seen only in the TLIF group. All epidural bone formation was heterotopic, and no ectopic bone formation occurred. There were no clinical sequelae associated with heterotopic bone formation. The mean preoperative and postoperative Oswestry Disability Index was 50.2% (range, 25%-75%) and 11.3% (range, 0%-38%) respectively.. Although the adjunctive use of rhBMP2 is associated with a higher incidence of heterotopic bone, there does not seem to be any associated clinical sequelae.

Topics: Adult; Aged; Back Pain; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Disability Evaluation; Epidural Space; Female; Follow-Up Studies; Humans; Incidence; Lumbar Vertebrae; Male; Middle Aged; Minimally Invasive Surgical Procedures; Ossification, Heterotopic; Pain Measurement; Prospective Studies; Recombinant Proteins; Severity of Illness Index; Spinal Cord Diseases; Spinal Diseases; Spinal Fusion; Time Factors; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

In vivo study of the effect of injection of osteogenic protein-1 (OP-1) on a rabbit anular needle puncture model of intervertebral disc (IVD) degeneration.. To study radiographic, magnetic resonance imaging (MRI), biochemical, and histologic changes in the rabbit IVD after injection of OP-1 into the nucleus pulposus in a needle puncture disc degeneration model.. Growth factors, such as OP-1, have the ability to stimulate synthesis of proteoglycans and collagen in vitro. The in vivo injection of OP-1 into the normal rabbit IVD has increased disc height and proteoglycan content in the anulus fibrosus and nucleus pulposus. However, to our knowledge, no attempts have yet been made to determine the effects of these growth factors in an in vivo model of disc degeneration.. New Zealand adolescent white rabbits (n = 90, 8 for baseline evaluation, 82 at 8 times) received an anular puncture in 2 noncontiguous discs with an 18-gauge needle to induce disc degeneration. Four weeks later, either 5% lactose (10 microL) or OP-1 (100 microg in 10 microL 5% lactose) was injected into the center of the nucleus pulposus. The disc height was followed radiographically for up to 24 weeks after the injections. At the 2, 4, 8, 12, and 24-week times after the injection, rabbits were euthanized, and MRI of the harvested spinal columns was obtained to grade the degeneration. The discs injected with OP-1 or lactose and noninjected discs were subjected to biochemical and histologic analysis. The specimens at the 24-week time were limited to histologic evaluation.. The anular puncture with a needle induced a consistent disc narrowing within 4 weeks. The injection of OP-1 induced a restoration of disc height at 6 weeks, which was sustained for the entire experimental period, up to 24 weeks after the injection. The injection of lactose alone did not change the course of disc narrowing over the same time. MRI grading score showed significant differences between the OP-1 and lactose groups at the 8, 12, and 24-week times, suggesting an increase in water content in the nucleus pulposus of the OP-1 group. The proteoglycan content of the nucleus pulposus and anulus fibrosus was significantly higher in the OP-1 group than in the control group. The degeneration grades of the punctured discs in the OP-1 group were significantly lower than those in the lactose group.. The results of this study show the feasibility of restoring degenerative rabbit discs by a single injection of OP-1 into the nucleus pulposus. Importantly, the effects of the OP-1 injection on disc height were sustained for up to 24 weeks. The metabolic changes in the cells, following a single injection, might be sustained and, thus, induce long-term changes in disc structure. An efficacy study in large animals is required to show further that the intradiscal injection of OP-1, or bone morphogenetic proteins or growth factors with similar properties would be useful for the structural restoration of the IVD in humans.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Disease Models, Animal; Injections, Spinal; Intervertebral Disc; Rabbits; Radiography; Spinal Diseases; Transforming Growth Factor beta

Quantitative analysis of endogenous messenger ribonucleic acid (mRNA) expression of anabolic cytokines in the anulus fibrosus and nucleus pulposus tissue from the intervertebral discs of young and old rabbits was performed.. To measure the expression of anabolic cytokines bone morphogenetic protein-2 (BMP-2), BMP-7, transforming growth factor-beta (TGF-beta), and insulin-like growth factor-I (IGF-I) in the anulus fibrosus and nucleus pulposus tissue from young and old rabbits to determine if there are differences with age.. Disc degeneration increases with age and is associated with compromised disc chondrocytic function. Molecules such as BMP-2, BMP-7, TGF-beta, and IGF-I are known to up-regulate disc cell synthesis of key chondrocytic matrix molecules in vitro, and have been proposed as therapeutic agents to prevent disc degeneration. Previous studies have shown that exogenous anabolic cytokines can up-regulate disc-cell function both in vitro and in vivo, however, the endogenous expression of anabolic cytokines in the disc is still unknown.. New Zealand white rabbits aged 3 years (old) and 6 months (young) were used. Quantitative real-time polymerase chain reaction was performed to measure the mRNA levels of BMP-2, BMP-7, TGF-beta1, and IGF-I from anulus fibrosus and nucleus pulposus tissue from young and old rabbits. The discs form the young rabbits represent nondegenerated discs, and the discs from the old rabbits represent discs at the onset of degeneration.. In the nucleus pulposus, the mRNA levels, given as a ratio of old to young, were 3.6 for BMP-2 (P = 0.004), 61 for BMP-7 (P = 0.02), 4.0 for TGF-beta1 (P = 0.3), and 0.6 for IGF-I (P = 0.2). In the anulus fibrosus, the mRNA levels, given as a ratio of old to young, were 1.6 for BMP-2 (P = 0.07), 4.6 for BMP-7 (P = 0.004), 2.9 for TGF- beta1 (P = 0.01), and 2.0 for IGF-I (P = 0.1).. The disc tissue from the old rabbits as compared to the young rabbits showed, in general, significantly higher mRNA levels of endogenous BMP-2, BMP-7, and TGF-beta in both the anulus fibrosus and nucleus pulposus. The similar patterns of up-regulation in gene expression with age shown by these 3 anabolic cytokines suggest a common pathway in terms of regulation and transcription in the early stage of disc degeneration. The knowledge of the age-related pattern in endogenous gene expression of these anabolic cytokines could provide important information for clinical interventional therapy.

Topics: Aging; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Cytokines; Insulin-Like Growth Factor I; Intervertebral Disc; Rabbits; RNA, Messenger; Spinal Diseases; Transforming Growth Factor beta

To observe the effect of calcitonin on the pathology of fusion in lumbar posterior/facet spinal fusion in rabbit model.. Thirty-two male New Zealand white rabbits were used to establish spinal fusion model. Sixteen rabbits received calcitonin at a dose of 1 IU x kg(-1) x d(-1) were classified as calcitonin group, and the remaining 16 rabbits as control group. Rabbits were killed 1, 2, 4, and 8 weeks after operations. Haematoxylin-eosin staining was applied to observe the pathological process of spinal fusion. Expression of bone morphogenetic protein-2 (BMP2) was detected by immunohistochemistry.. Bone resorption and fibrovascular stroma formation were the main histological presentation 1 week after surgery. Two and 4 weeks after surgery, more cartilage formed with varying degrees of mineralization, while less trabeculae could be observed in the phase of active bone formation. No remarked margin was seen between cartilage and bone tissues. Eight weeks after surgery, trabeculae distributed widely. The pathological process of spinal fusion in calcitonin group was faster than in control group. Emery scores showed significant differences at different time points (F = 265.44, P < 0.001). Calcitonin and time had a positively synergistic effect on Emery scores, and calcitonin caused significant difference in terms of Emery scores since the second week (F = 22.43, P < 0.001). Expressions of BMP, were significantly different at different time points (F = 1186.54, P < 0.001). Also, calcitonin and time had a synergistic effect on BMP2 expression (F = 13.14, P < 0. 001).. Endochondral ossification exists in the spinal fusion process and may be the main way of ossification. Calcitonin may stimulate the expression of BMP2 and thus accelerate the process of spinal fusion.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Calcitonin; Lumbar Vertebrae; Male; Rabbits; Random Allocation; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Bone morphogenetic protein (rhBMP-2) has demonstrated an increased rate of interbody fusion when placed in the intervertebral space. Owing to this advantage, rhBMP-2 is being implanted with increasing frequency in the lumbar spine. The purpose was to quantify and describe the presence of bone resorption within the vertebral body after transforaminal lumbar interbody fusion with placement of rhBMP-2 within the disc space.. Twenty-six patients were selected from a clinical database. Patients included in the study had undergone a transforaminal lumbar interbody fusion with BMP. Interbody implants included allograft dowels or interbody cages augmented with autograft or allograft bone. A computed tomography study of the lumbar spine a minimum of 3-month postoperatively was another inclusion criterion. Osteolytic defects were grouped into 3 categories on the basis of the size and extent of involvement in the vertebral body.. A total of 32 lumbar levels were reviewed. Fourteen males and 12 females with an average age of 46.0 years were included in the study. Bone resorption defects were noted in 22 of the 32 levels reviewed (69%). The defects were characterized as mild in 50% (11 of 22), moderate in 18% (4 of 22), and severe in 31% (7 of 22).. The benefit of rhBMP-2 to promote interbody fusion in the lumbar spine has been well documented. BMP has demonstrated an increased fusion rate and the ability to produce a robust fusion mass. rh-BMP-2's osseous remodeling potential may lead to bone resorption within the vertebral body.

Topics: Adolescent; Adult; Aged; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Resorption; Female; Follow-Up Studies; Humans; Intervertebral Disc; Lumbar Vertebrae; Male; Middle Aged; Radiography; Recombinant Proteins; Retrospective Studies; Severity of Illness Index; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

Topics: Activin Receptors, Type I; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Cervical Vertebrae; Humans; Lumbar Vertebrae; Orthopedics; Prostheses and Implants; Proteins; Recombinant Proteins; Scoliosis; Spinal Cord Injuries; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

To study the therapeutic efficacy of intradiscal injection of osteogenic protein-1 (OP-1) to reduce degeneration and associated discogenic pain.. To evaluate if intradiscal injection of OP-1 can reverse disc degeneration and reduce hyperalgesia, a pain-related behavior.. We showed that induction of hyperalgesia was higher in rats exposed to compressed nucleus pulposus (NP). It has been reported that intradiscal injection of OP-1 stimulates synthesis of proteoglycans and collagen in normal intervertebral discs.. Rats were divided into several groups. In the sham group, the rings of an Ilizarov-type apparatus were only applied to the tail without compression. In the compressed NP group, the apparatus was used to apply chronically compression to the tail. Four weeks after surgery, the NP group was subdivided into 3 groups: saline-treated and OP-1-treated, which was divided into 2 groups (i.e., the continuous compression OP-1 [COP-1] group, in which compression was continuously applied to the tail for 4 weeks after OP-1 treatment and the release compression OP-1 [ROP-1] group, in which compression was released at treatment. Either physiologic saline or OP-1 was injected into the instrumented NP. The treated NP was harvested and applied to the left lumbar nerve roots 4 weeks after injection. Hyperalgesia was measured up to 3 weeks after surgery. The degree of disc degeneration and the appearance of the extracellular matrix in the intervertebral discs were evaluated by histology.. Mechanical hyperalgesia was observed in the sham and saline groups, but not in the OP-1 treated group. In the saline group, NP cells became spindle-shaped. In the OP-1 group, the NP cells became swollen with vacuolated cytoplasm, and the content of the extracellular matrix was markedly increased.. OP-1 injection into degenerative intervertebral disc resulted in the enhancement of the extracellular matrix and the inhibition of pain-related behavior.

Topics: Animals; Behavior, Animal; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Extracellular Matrix; Female; Hot Temperature; Hyperalgesia; Injections, Spinal; Intervertebral Disc; Pain; Pressure; Rats; Rats, Sprague-Dawley; Spinal Diseases; Tail; 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

Data from animals have revealed that osteogenic protein-1 induces solid intertransverse process fusion more reliably than autograft, and has motivated the question: What is the difference in the fusion bed environment engendered by the addition of osteogenic protein-1? To address this question, an established New Zealand White rabbit model of spinal arthrodesis was used to evaluate the effect of iliac crest autograft, and alternatively osteogenic protein-1, on cytokine gene expression in the developing spinal fusion mass. The autograft group and the osteogenic protein-1 group had a similar pattern of gene expression for most of the cytokines investigated, highlighting the finding that the application of one bone morphogenetic protein to the fusion bed results in nearly the same gene expression as that resulting from application of autologous bone. Some differences in cytokine expression were observed at the fusion bed with the addition of osteogenic protein-1. The increased level of expression of particular osteogenic, chondrogenic, and angiogenic growth factors at the later stages of fusion may be responsible for the improved rate of solid fusion with osteogenic protein-1 as compared with autograft alone. Sequences for bone morphogenetic protein-5 and bone morphogenetic protein-7 were determined, and their respective expression in the developing spinal fusion mass was observed for the first time.

Topics: Animals; Arthrodesis; Bone Morphogenetic Protein 5; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Transplantation; Disease Models, Animal; Female; Gene Expression Regulation; Genetic Markers; Lumbar Vertebrae; Male; Osteogenesis; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Sensitivity and Specificity; Spinal Diseases; Transforming Growth Factor beta; Transplantation, Autologous; Treatment Outcome

To investigate therapeutic efficiency of Ad/CMV- hTGF-beta1 gene for rabbit intervertebral disc degeneration model. 60 Japanese white rabbits were selected to form the 1.5-L6 Anterior-Lateral-Anulus-Fibrosus-Incision-Induced model in order to simulate human intervertebral disc degeneration. 36 rabbits, whose corresponding intervertebral discs were injected with 20 microl (10 x 10(6) pfu) of Ad/CMV- hTGF-beta1 gene, constituted the therapy group, 12 were injected with 20 microl (10 x 10(6) pfu)of Ad/CMV-LacZ gene as comparison group, while 12 were only injected with equivalent capacity of saline for empty comparison group, 3 weeks after injection, examples were taken for investigation of HE staining, MRI, Western Blotting and immunohistochemical research TGF-beta1. Wide distribution of TGF-beta1 was detected by immunohistochemical research in the degenerated annulus fibrosus after injection. Western Blotting research showed significant increase of TGF-beta1 content in intervertebral discs treated with TGF-beta1 gene than comparison groups. MRI signal transformed from low to comparatively high and that intervertebral disc pathological degree improved. Ad/CMV- hTGF-beta1 gene transfection is a potential method to increase TGF-beta1 content and reverse intervertebral disc degeneration.

Topics: Adenoviridae; Animals; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Intervertebral Disc; Lumbar Vertebrae; Rabbits; Spinal Diseases; Transfection; Transforming Growth Factor beta; Transforming Growth Factor beta1

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

To determine whether the synthesis of proteoglycan, collagen and associated ultrastructure are related to the adenovirus-mediated gene transferred to adult degenerative cells.. Adenovirus/cytomegalovirus human transforming growth factor-beta 1 (Ad/CMV-hTGF-beta 1) was used to transfect degenerative cells. Antonopulos method, Miamine method and transmission electron microscopy were conducted to study the synthesis of proteoglycan, collagen, and ultrastructure, respectively. Cell cultures were established from the nucleus pulpous and annulus fibrosus tissues, which were taken from surgery.. Nucleus pulpous and annulus fibrosus cells were efficiently transduced by the adenoviral vector carrying hTGF-beta 1 gene. The synthesis of proteoglycan and collagen increased compared with the control group (P < 0.05). The metabolism of cells was slightly improved. No significant toxic effects were found.. Expression of hTGF-beta 1 gene is efficient to accelerates proteoglycan synthesis and thus accelerates the improvement of collagen. The function and structure of degenerative cells are improved. Ad/CMV-hTGF-beta 1 may be suitable for treating disc degeneration.

Topics: Adenoviridae; Adult; Cells, Cultured; Collagen; Extracellular Matrix; Genetic Vectors; Humans; Intervertebral Disc; Proteoglycans; Spinal Diseases; Transfection; Transforming Growth Factor beta; Transforming Growth Factor beta1

Disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium analyzed for production of a range of pro-inflammatory mediators.. This study was conducted to confirm that the human intervertebral disc is capable of responding to a pro-inflammatory stimulus and to identify the principal mediators involved in any response.. Degenerate human disc tissue has been shown to spontaneously secrete a number of pro-inflammatory mediators. The importance of these molecules in the pathophysiology of symptomatic disc degeneration is increasingly recognized. Human nucleus pulposus has been shown to synthesize increased amounts of interleukin (IL)-6, prostaglandin E2 (PGE2), and nitric oxide in response to stimulation with IL-1beta. Murine nucleus pulposus synthesizes increased amounts of IL-1beta, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor in response to lipopolysaccharide stimulation. Lipopolysaccharide is a potent inducer of tumor necrosis factor-alpha (TNF-alpha), which is thought to play an important role in the pathophysiology of sciatica. To date, human nucleus pulposus has not been shown to secrete TNF-alpha in response to a pro-inflammatory stimulus.. Human disc tissue obtained from patients undergoing surgery for scoliosis, lumbar radiculopathy, and discogenic pain was cultured under basal and lipopolysaccharide-stimulated conditions and the medium subsequently analyzed for a range of pro-inflammatory mediators.. None of the specimens produced any TNF-alpha, IL-1beta, granulocyte-macrophage colony-stimulating factor, or leukotriene B4. Measurable quantities of IL-6, IL-8, PGE2, MCP-1, basic fibroblast growth factor, and trans forming growth factor-beta1 were produced by a number of specimens. Lipopolysaccharide significantly increased IL-6, IL-8, and PGE2 production in both control and degenerate disc tissue. Degenerate disc specimens responded more vigorously to lipopolysaccharide stimulation than scoliotic specimens.. We conclude that both scoliotic and degenerate human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by secreting increased amounts of IL-6, IL-8, and PGE2 but not TNF-alpha and that degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its scoliotic counterpart.

Topics: Adolescent; Adult; Chemokine CCL2; Child; Child, Preschool; Culture Techniques; Dinoprostone; Fibroblast Growth Factor 2; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Intervertebral Disc; Lipopolysaccharides; Male; Spinal Diseases; Transforming Growth Factor beta; Transforming Growth Factor beta1

An established rabbit intertransverse process lumbar fusion model was used to evaluate osteogenic protein (OP)-1 as a potential graft substitute.. To determine whether OP-1 is effective in producing intertransverse process lumbar fusion in a rabbit model.. Autogenous iliac crest bone is the gold standard in grafting material for inducing intertransverse process fusion. However, bone graft substitutes are being considered as supplementary or alternative means to achieve such fusion with less morbidity. Relatively little research has been undertaken to investigate the efficacy of OP-1 in this role.. Single-level intertransverse process lumbar fusions were performed at L5-L6 of 31 New Zealand White rabbits. These were divided into three study groups: autograft, carrier alone, and carrier with OP-1. The animals were killed 5 weeks after surgery. Resultant fusion masses were evaluated by manual palpation, radiography, biomechanical multidirectional flexibility testing, and histology.. Seven rabbits (23%) were excluded because of complications. Of the remaining 24 rabbits, 5 (63%) of the 8 in the autograft group had fusion detected by manual palpation, none (0%) of the 8 in the carrier-alone group had fusion, and all 8 (100%) in the OP-1 group had fusion. Radiographs were 55% sensitive and 92% specific for determining fusion. Biomechanical testing results correlated well with those of manual palpation. Histologically, autograft specimens were predominantly fibrocartilage, OP-1 specimens were predominantly maturing bone, and carrier-alone specimens did not show significant bone formation.. OP-1 was found to reliably induce solid intertransverse process fusion in a rabbit model at 5 weeks.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Transplantation; Disease Models, Animal; Female; Graft Survival; Lumbar Vertebrae; Postoperative Complications; Rabbits; Radiography; Recovery of Function; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

To prospectively evaluate the clinical and radiographic outcome of laparoscopic anterior lumbar interbody fusion with rhBMP-2.. It was hypothesized that discogenic pain could be treated successfully with an anterior lumbar interbody fusion performed laparoscopically using rhBMP-2 as a replacement for autogenous bone.. The traditional surgical treatment of discogenic pain involves painful incisions of muscles, with potential loss of integrity and strength. Harvesting of bone graft is associated with significant complications including persistent pain at the donor site.. Twenty-two consecutive patients were studied prospectively with the surgery performed by one surgeon. Patients were evaluated clinically and radiographically at 6 and 12 months after surgery. An unbiased radiologist read postoperative computed tomography scans for evidence of fusion.. There were 8 male (36%) and 14 female (64%) patients. The average age was 38 years (range, 21-56 years). At 6 and 12 months after surgery 95% (21 of 22) were available for follow-up; 100% were satisfied with treatment at 12 months. Concerning their symptoms, 100% reported relief of back pain, 100% had improvement of leg pain, and 100% described significant functional improvement. Improvements were seen at 6 and 12 months on Oswestry (P < 0.001), functional testing (P < 0.001), and pain analog scale (P < 0.001). Radiographic analysis showed that all of the patients had evidence of a solid fusion at 6 months after operation.. Discogenic low back pain can be effectively treated surgically with a laparoscopic anterior lumbar interbody fusion using rhBMP-2 in place of autogenous bone. The fusion occurs quickly and predictably with no adverse effects identified.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Female; Humans; Laparoscopy; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Radiography; Recombinant Proteins; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Topics: Adult; Female; Humans; Interleukin-6; Joint Diseases; Male; Middle Aged; Spinal Diseases; Transforming Growth Factor beta