transforming-growth-factor-beta and Spinal-Cord-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

Topics: Animals; Cervical Cord; Gliosis; Interleukin-17; Neuroinflammatory Diseases; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Spinal Cord; Spinal Cord Compression; Spinal Cord Diseases; Spinal Cord Injuries; Transcriptome; Transforming Growth Factor beta

Few studies have examined the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) in 2-level anterior cervical discectomy and fusion (ACDF). The purpose of this study was to compare the outcomes in a series of patients with CSM treated with 2-level ACDF with or without rhBMP-2.. The retrospective study included a total of 146 patients with CSM. The rhBMP-2 group consisted of 73 patients who underwent 2-level ACDF with rhBMP-2. A total of 73 patients who also received 2-level ACDF with autogenous ICBG alone were included in the matched-pair ICBG group with a ratio of 1:1, based on age, sex, and BMI. All data, including fusion rate and time, VAS, JOA score, operative date, and complications, were assessed.. With respect to the length of hospital stay, operative times, and blood loss, there were no significant difference between the 2 groups. However, the rhBMP-2 group presented a shorter fusion time (P<0.013) and higher fusion rate (P<0.036) than the ICBG group. In the rhBMP-2 group, 22% required additional treatment for complications compared to 18% of patients in the ICBG group, which showed no significant difference (P=0.543).. The application of rhBMP-2 in 2-level ACDF showed higher fusion rates, shorter fusion time, and similar function outcomes compared to those who received ACDF with ICBG alone.

Topics: Aged; Bone Morphogenetic Protein 2; Bone Transplantation; Cervical Vertebrae; Diskectomy; Female; Humans; Ilium; Length of Stay; Male; Middle Aged; Radiography; Recombinant Proteins; Retrospective Studies; Smoking; Spinal Cord Diseases; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Considerable attention has focused on concerns of increased complications with recombinant human bone morphogenetic protein-2 (rhBMP-2) use for anterior cervical fusion, but few reports have assessed its use for posterior cervical fusions.. To assess the safety, efficacy, and dosing of rhBMP-2 as an adjunct for instrumented posterior cervical arthrodesis.. All patients treated by the senior author with posterior cervical or cervicothoracic instrumented fusion using rhBMP-2 from 2003 to 2008 with a minimum of 2 years of follow-up were included. Diagnosis, levels fused, rhBMP-2 dose, complications, and fusion were assessed.. Fifty-three patients with a mean age of 55.7 years (range, 2-89 years) and an average follow-up of 40 months (range, 25-80 months) met inclusion criteria. Surgical indications included basilar invagination (n = 6), fracture (n = 6), atlantoaxial instability (n = 16), kyphosis/kyphoscoliosis (n = 22), osteomyelitis (n = 1), spondylolisthesis (n = 1), and cyst (n = 1). Fifteen patients had confirmed rheumatoid disease. The average rhBMP-2 dose was 1.8 mg per level, with a total of 282 levels treated (average, 5.3 levels; SD, 2.8 levels). Among 53 patients, only 2 complications (3.8%) were identified: a superficial wound infection and an adjacent-level degeneration. No cases of dysphagia or neck swelling requiring treatment were identified. At the last follow-up, all patients had achieved fusion.. Despite many of the patients in the present series having complex pathology and/or rheumatoid arthritis, a 100% fusion rate was achieved. Collectively, these data suggest that use of rhBMP-2 as an adjunct for posterior cervical fusion is safe and effective at an average dose of 1.8 mg per level.

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

We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years. Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (> 10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height. Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support.

Topics: Adolescent; Adult; Aged; Bone Matrix; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Cervical Vertebrae; Female; Humans; Intervertebral Disc Displacement; Lumbar Vertebrae; Male; Middle Aged; Pain Measurement; Postoperative Complications; Prospective Studies; Radiography; Recombinant Proteins; Reoperation; Scoliosis; Spinal Cord Diseases; Spinal Fusion; Spondylolisthesis; Transforming Growth Factor beta; Treatment Outcome

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 acute experimental autoimmune encephalomyelitis (EAE), demyelination is induced by myelin-specific CD4(+) T lymphocytes and myelin-specific antibodies. Recovery from the disease is initiated by cytokines which suppress T cell expansion and the production of myelin-toxic molecules by macrophages. Th2/3 cell-derived signals may also be involved in central nervous system (CNS) repair. Remyelination is thought to be initiated by the recruitment and differentiation of oligodendrocyte precursor cells (OPC) in demyelinated CNS lesions. Here, we report that unlike Th1 cytokines (TNF-alpha, IFN-gamma), the Th2/3 cytokine TGF-beta induces primary microglia from C57BL/6 mice to secrete a chemotactic factor for primary OPC. We identified this factor to be the hepatocyte growth factor (HGF). Our studies show that TGF-beta-1-2-3 as well as IFN-beta induce HGF secretion by microglia and that antibodies to the HGF receptor c-Met abrogate OPC chemotaxis induced by TGF-beta2-treated microglia. In addition we show spinal cord lesions in EAE induced in SJL/J mice to contain both OPC and HGF producing macrophages in the recovery phase, but not in the acute stage of disease. Taken these findings, TGF-beta may play a pivotal role in remyelination by inducing microglia to release HGF which is both a chemotactic and differentiation factor for OPC.

Topics: Animals; Blotting, Western; Cells, Cultured; Chemotaxis; Encephalomyelitis, Autoimmune, Experimental; Female; Gene Expression; Hepatocyte Growth Factor; Immunohistochemistry; Macrophages; Mice; Microglia; Microscopy, Confocal; Oligodendroglia; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-met; Remission, Spontaneous; Spinal Cord Diseases; Stem Cells; Transforming Growth Factor beta