transforming-growth-factor-beta and Deglutition-Disorders

A prospective, randomized, placebo-controlled, double-blind trial.. The aim of this study was to investigate whether the local administration of depomedrol decreases the severity of dysphagia after anterior cervical discectomy and fusion (ACDF) surgery using bone morphogenetic protein (BMP).. Although recombinant human BMP-2 is effective in promoting arthrodesis, many physicians avoid using it in anterior cervical spine fusions due to concern for increased incidence of dysphagia, significant pre-vertebral swelling, and airway compromise. Pilot studies have shown that the local application of depomedrol may decrease the incidence of postoperative dysphagia. We performed a prospective, randomized trial to evaluate the efficacy of local depomedrol application in reducing the severity of postoperative dysphagia following anterior cervical fusions using low-dose rhBMP-2. We hypothesized that locally administered depomedrol reduces dysphagia following such surgeries.. Fifty patients between 18 and 70 years of age, undergoing 1, 2, and 3-level ACDFs, were randomized to 1 of 2 groups: BMP-2 with depomedrol or BMP-2 with saline. Patients were followed for 4 weeks postoperatively by the study administrator. Dysphagia was measured at 5 time intervals (postoperative days 1, 4, 7, 14, and 28) using a 4-point Modified Dysphagia Scoring System. Additional data regarding overall length of hospital stay and the administration of dysphagia-directed treatments were also recorded.. Twenty-seven patients were randomized to the treatment (depomedrol) group and 23 were randomized to the control (saline) group. The 2 groups were nearly identical in terms of their demographic and operative characteristics. Patients receiving depomedrol experienced decreased dysphagia incidence and magnitude at all time intervals, with differences reaching statistical significance on postoperative days 4, 7, 14, and 28 (P < 0.05).. This study provides Level 1 evidence that locally administered depomedrol on a collagen sponge significantly decreases postoperative dysphagia incidence and magnitude following anterior cervical spine fusion using low-dose rhBMP-2.. 1.

Topics: Anti-Inflammatory Agents; Bone Morphogenetic Protein 2; Cervical Vertebrae; Deglutition Disorders; Double-Blind Method; Female; Humans; Male; Methylprednisolone; Methylprednisolone Acetate; Middle Aged; Postoperative Complications; Prospective Studies; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta

Independent, retrospective clinical record review with a concurrent control.. To identify whether rhBMP-2 is associated with an increased incidence of clinically relevant postoperative prevertebral swelling problems in patients undergoing anterior cervical fusions.. Bone Morphogenetic Protein-2 (rhBMP-2) is FDA approved as a bone graft substitute in anterior lumbar interbody fusions. rhBMP-2 has also been used "off-label" in anterior cervical fusions. We suspected that rhBMP-2 might increase the incidence of adverse swelling events.. A total of 234 consecutive patients (ages 12-82 years) undergoing anterior cervical fusion with and without rhBMP-2 over a 2-year period at one institution comprised the study population. The incidence of clinically relevant prevertebral swelling was calculated. The populations were compared and statistical significance was determined.. A total of 234 patients met the study criteria, 69 of whom underwent anterior cervical spine fusions using rhBMP-2; 27.5% of those patients in the rhBMP-2 group had a clinically significant swelling event versus only 3.6% of patients in the non-rhBMP-2 group. This difference was statistically significant (P < 0.0001) and remained so after controlling for other significant predictors of swelling.. Off-label use of rhBMP-2 in the anterior cervical spine is associated with an increased rate of clinically relevant swelling events.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cervical Vertebrae; Child; Deglutition Disorders; Edema; Female; Humans; Incidence; Male; Middle Aged; Neck; Postoperative Complications; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta

Previous studies have called into question the safety of using rhBMP-2 in anterior cervical fusion due to the possibility of airway compromise and dysphagia. A retrospective chart review identified a significant increase in the severity of dysphagia after II-level ACDF with rhBMP-2 compared to patients who did not receive rhBMP-2. To date, this topic has not been studied prospectively.. Compare the incidence of dysphagia following anterior cervical discectomy and fusion (ACDF) when recombinant human bone morphogenetic protein-2 (rhBMP-2) is used with allograft compared to allograft alone.. Prospective cohort study.. A total of 114 patients completed a baseline SWAL-QOL survey and met the inclusion criteria. Thirty-nine patients underwent I- or II-level ACDF with allograft plus 0.5mg rhBMP-2/level. 44 patients underwent ACDF with allograft alone. Thirty-one patients undergoing a lumbar decompression were enrolled in a third cohort to control for dysphagia secondary to intubation.. The primary outcome measure was the 14-point SWAL-QOL dysphagia questionnaire. Other patient factors obtained from anesthesia and operative records were examined to evaluate their potential relationship to postoperative dysphagia.. The 14-point SWAL-QOL questionnaire was administered at multiple time points (pre-op, post-op 7 days, 6 weeks, 6 months, and at least 1 year). Multivariable repeated-measures analysis was applied to data.. Baseline adjusted SWAL-QOL means 7 days after surgery were significantly different between the three study groups. These differences resolved by 6 weeks postoperative, beyond which point there were no differences. At final follow-up, baseline adjusted SWAL-QOL means at 1 year were similar for the three study groups.. This single-center study of anterior cervical surgery demonstrated that the addition of rhBMP-2 to an ACDF increased postoperative dysphagia at 7 days after surgery, but these patients recover to levels comparable to those who underwent ACDF without rhBMP-2 or lumbar surgery within 6 weeks.

Topics: Bone Morphogenetic Protein 2; Cervical Vertebrae; Deglutition Disorders; Diskectomy; Humans; Postoperative Complications; Prospective Studies; Quality of Life; Recombinant Proteins; Retrospective Studies; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Reported complications of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in anterior cervical discectomy and fusion (ACDF) cases include dysphagia and cervical swelling. However, dysphagia often occurs after multilevel ACDF procedures performed with allograft (without BMP) as well. To date, there has been no large study comparing the dysphagia rates of patients who have undergone multilevel ACDF using allograft spacers with those who underwent ACDF using polyetheretherketone (PEEK) cages filled with rhBMP2. The authors report one of the first such comparisons between these 2 patient cohorts.. The authors retrospectively reviewed 150 patient records. Group 1 (BMP group) consisted of 100 patients who underwent multilevel ACDF with PEEK cages filled with rhBMP-2 and instrumented with a cervical plate. Group 2 (allograft group) included a matched control cohort of 50 patients who underwent multilevel ACDF with allograft spacers and anterior plate fixation (without rhBMP-2). Patient demographics were not significantly different between the groups. Fusion was assessed by means of dynamic radiographs and/or CT at routine intervals. Complications, dysphagia incidence, standardized dysphagia score, Nurick grades, and fusion rates were assessed.. The mean follow-up for the BMP group (Group 1) was 35 months while the mean follow-up for the allograft group (Group 2) was 25 months. There was a complication rate of 13% in the BMP group compared with 8% in the allograft group (p < 0.005). There was no significant difference in overall dysphagia incidence between the BMP group and the allograft group (40% vs 44%, respectively; p > 0.05). However, there was a significant difference in the severity of dysphagia (using the SWAL-QOL dysphagia scoring system) between the 2 groups: 0.757 for the BMP group versus 0.596 for the allograft group (p < 0.005). In subgroup analysis, the use of rhBMP-2 significantly increased the severity of dysphagia in patients undergoing 2-level ACDF (p < 0.005). However, the severity of dysphagia did not differ significantly between groups when 3- or 4-level ACDF cases were compared. There was no pseudarthrosis in Group 1 (the BMP group) compared with a 16% pseudarthrosis rate in Group 2 (the allograft group) (p < 0.05). There was a weak correlation between the total rhBMP-2 dose and the dysphagia score (Kendall tau rank correlation coefficient 0.166, p = 0.046).. The use of rhBMP-2 in patients undergoing 2-level ACDF significantly increases the severity of dysphagia (dysphagia score) without affecting the overall incidence of dysphagia. However, there is no statistically significant difference in the incidence or severity of dysphagia between patients undergoing 3-level or 4-level ACDF treated with PEEK/rhBMP-2 and those treated with only allograft. The use of rhBMP-2 appears to reduce the risk of pseudarthrosis. This benefit is most pronounced in patients who undergo 4-level ACDF and are smokers.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Plates; Bone Transplantation; Cervical Vertebrae; Deglutition Disorders; Diskectomy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

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

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

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

Topics: Adult; Aged; Aged, 80 and over; Benzophenones; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Cervical Vertebrae; Collagen Type I; Deglutition Disorders; Diskectomy; Drug Carriers; Female; Hematoma; Humans; Ketones; Male; Middle Aged; Orthopedic Fixation Devices; Polyethylene Glycols; Polymers; Postoperative Complications; Range of Motion, Articular; Recombinant Proteins; Safety; Seroma; Spinal Fusion; Titanium; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

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

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

The goal in this study was to demonstrate the safety and efficacy of anterior cervical discectomy and fusion ([ACDF]; single- or multilevel procedure) performed using titanium plates and polyetheretherketone (PEEK) spacers filled with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated in a type I collagen sponge to achieve fusion.. The authors retrospectively reviewed 200 patients who underwent a single- or multilevel ACDF with titanium plate fixation and PEEK spacer filled with a collagen sponge impregnated with low-dose rhBMP-2. Clinical outcomes were assessed using pre- and postoperative Nurick grades and the Odom criteria. Radiographic outcomes were assessed using dynamic radiographs and computed tomography (CT) scans.. The follow-up period ranged from 8 to 36 months (mean 16.7 months). A single-level ACDF was performed in 96 patients, 2-level ACDF in 62 patients, 3-level ACDF in 36 patients, and 4-level ACDF in 6 patients. Long-term follow-up was available for 193 patients. The Odom outcomes were rated as good to excellent in 165 patients (85%), fair in 24 (12.4%), and poor in 4 (2%). Among patients with myelopathy, Nurick grades improved from a preoperative mean of 1.42 to a postoperative mean of 0.26. All patients (100%) achieved solid radiographic fusion on dynamic radiographs and CT scans. Fourteen patients (7%) in this series experienced clinically significant dysphagia, and 4 (2%) required repeated operation for hematoma or seroma.. An ACDF performed using a PEEK spacer filled with rhBMP-2 leads to good to excellent clinical outcomes and solid fusion, even in multilevel cases and in patients who are smokers. The incidence of symptomatic dysphagia may be decreased with a lower dose of rhBMP-2 that is placed only within the PEEK spacer.

Topics: Adult; Aged; Aged, 80 and over; Benzophenones; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Cervical Vertebrae; Collagen Type I; Deglutition Disorders; Diskectomy; Drug Carriers; Female; Follow-Up Studies; Hematoma; Humans; Ketones; Longitudinal Studies; Male; Middle Aged; Orthopedic Fixation Devices; Polyethylene Glycols; Polymers; Postoperative Complications; Range of Motion, Articular; Recombinant Proteins; Retrospective Studies; Safety; Seroma; Spinal Fusion; Titanium; Tomography, X-Ray Computed; Transforming Growth Factor beta; Treatment Outcome

The use of bone morphogenetic protein-2 (rhBMP-2) in spinal fusion has increased dramatically since an FDA approval for its use in anterior lumbar fusion with the LT cage. There are several reports of its use in transforaminal lumbar interbody fusion, posterolateral fusion, and anterior cervical fusion. Reports on adverse effects of rhBMP-2 when used in spinal fusion are scarce in literature. An Institutional Review Board approved retrospective study was conducted in patients undergoing anterior spinal fusion and instrumentation following diskectomy at a single center. Forty-six consecutive patients were included. Twenty-two patients treated with rhBMP-2 and PEEK cages were compared to 24 in whom allograft spacers and demineralized bone matrix was used. Patients filled out Cervical Oswestry Scores, VAS for arm pain, neck pain, and had radiographs preoperatively as well at every follow up visit. Radiographic examination following surgery revealed end plate resorption in all patients in whom rhBMP-2 was used. This was followed by a period of new bone formation commencing at 6 weeks. In contrast, allograft patients showed a progressive blurring of end plate-allograft junction. Dysphagia was a common complication and it was significantly more frequent and more severe in patients in whom rhBMP-2 was used. Post operative swelling anterior to the vertebral body on lateral cervical spine X-ray was significantly larger in the rhBMP-2 group when measured from 1 to 6 weeks after which it was similar. These effects are possibly due to an early inflammatory response to rhBMP-2 and were observed to be dose related. With the parameters we used, there was no significant difference in the clinical outcome of patients in the two groups at 2 years. The cost of implants in patients treated with rhBMP-2 and PEEK spacers was more than three times the cost of allograft spacers and demineralized bone matrix in 1, 2, and 3-level cases. Despite providing consistently good fusion rates, we have abandoned using rhBMP-2 and PEEK cages for anterior cervical fusion, due to the side effects, high cost, and the availability of a suitable alternative.

Topics: Adult; Aged; Arthrodesis; Bone Matrix; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Cervical Vertebrae; Deglutition Disorders; Diskectomy; Female; Hoarseness; Humans; Internal Fixators; Male; Middle Aged; Pain, Postoperative; Prostheses and Implants; Radiography; Recombinant Proteins; Retrospective Studies; Spinal Fusion; Transforming Growth Factor beta; Transplantation, Homologous