Use Of rhBMP Research Articles

Complications Associated With the Use of Bone Morphogenetic Protein in Pediatric Patients

Recombinant human bone morphogenetic protein (rhBMP) has been found to be a powerful adjunct to healing nonunions and obtaining fusions. Despite the apparent clinical efficacy and good safety profile reported with rhBMP use in adults, there is little data regarding the safety of this product in pediatric patients. We evaluated the use of rhBMP-2 in pediatric patients to determine if any complications were associated with its use. We performed a retrospective review of 81 patients, all less then 18 years old, in whom rhBMP-2 was used. Theoretical complications associated with rhBMP-2 use were compiled based on a review of the published literature on rhBMP-2. A review of each patient's chart and radiographs was performed to record the occurrences of complications, which may have been associated with the use of rhBMP-2. A total of 16 complications were found, which may have been attributed to the use of rhBMP-2. There were no incidences of systemic toxicity associated with rhBMP-2 use. Nine patients were noted to have some local operative site problem, 3 deep infections were noted, 1 patient was found to have a postoperative compartment syndrome, 2 patients were found to have neurologic complications (1 with progressive myelopathy and 1 with weakness and dural fibrosis), and 1 patient with neurofibromatosis and previously diagnosed intracranial gliomas was found to have subsequent enlargement of these gliomas. In reviewing these complications, only the case of dural fibrosis and subsequent weakness was thought to possibly be directly related to the use of rhBMP-2. We found few complications in pediatric patients, which were felt to be directly attributable to the use of rhBMP-2. As such, rhBMP-2 use seems to be relatively safe in this young patient population. Due to the current use of this product in pediatric patients in an "off-label" fashion, we recommend a thorough discussion of the possible risks and benefits of this product with the family before its use. Therapeutic studies-Level IV.

Is It Safe to Use Recombinant Human Bone Morphogenetic Protein in Posterior Cervical Fusion?

A retrospective chart review of all patients who underwent posterior cervical fusion during a 1-year time period. To analyze the safety profile of recombinant human bone morphogenetic protein (rhBMP)-2 in posterior cervical fusion. Use of rhBMP-2 in anterior cervical spine surgery has been associated with complications including postoperative edema, dysphagia, and hematoma formation. No literature exists regarding the safety of rhBMP-2 use for posterior cervical fusion. We reviewed all posterior cervical fusions performed during 1 year at our hospital following institutional review board permission. A total of 83 patients underwent posterior cervical fusion. Sixty-seven (81%) did not receive rhBMP (control group), whereas 16 (19%) underwent fusion with rhBMP. The most common reason for the use of rhBMP was a failure of an anterior cervical fusion resulting in persistent neck pain, myelopathy, or radiculopathy. The average dose of rhBMP used was 1.3 mL per level. Immediate postoperative medical complications occurred in 5 (7%) in the control group and 2 (13%) in the rhBMP group. A new neurologic deficit after surgery was found in 3 (4%) in the control group and 1 (6%) in the rhBMP group. Wound infection requiring further surgery occurred in 8 (12%) in the control group, and in none in the rhBMP group. One (6%) patient in the rhBMP group had significant postoperative neck swelling, but improved with steroid treatment over 1 week, and without any compromise of vital neck structures. No postoperative hematomas were seen in either group. Chi2 analysis revealed that no complication variable reached significance (P < 0.05) when the 2 groups were compared. rhBMP can safely be used in patients undergoing posterior cervical fusion, as it does not produce complications at the rate previously seen with its use in the anterior cervical spine.

P.415 Bone formation with immobilized rhBMP-2

Bone morphogenetic proteins (BMPs) have been commonly used as a graft substitute in spinal fusion. Although the U.S. Food and Drug Administration issued a warning on life-threatening complications of recombinant human BMPs (rhBMPs) in cervical spine fusion in 2008, their off-label use has been continued. This investigation aimed to review the evidence for the use of rhBMP-2 and rhBMP-7 in anterior cervical spine fusions.A comprehensive search was performed through Ovid (MEDLINE), PubMed, and Embase. The risk of bias assessment was according to the recommended criteria by the Cochrane Back and Neck group and MINORS (Methodological Index for Non-Randomized Studies). A wide array of radiographic and clinical outcomes including the adverse events were collated.Eighteen articles (1 randomized and 17 nonrandomized) were eligible for inclusion. The fusion rate was higher with use of rhBMP in most studies and our meta-analysis of the pooled data from 4782 patients confirmed this finding (odds ratio, 5.45; P < 0.00001). Altogether, the rhBMP and control groups were comparable in patient-reported outcomes. However, most studies tended to show a significantly higher incidence of overall complication rate, dysphagia/dysphonia, cervical swelling, readmission, wound complications, neurologic complications, and ossification.Application of rhBMPs in cervical spine fusion yields a significantly higher fusion rate with similar patient-reported outcomes, yet increased risk of life-threatening complications. Thus, we do not recommend the use of rhBMP in anterior cervical fusions.