Safety Of Bone Morphogenetic Protein Research Articles

Comparative Clinical Effectiveness and Safety of Bone Morphogenetic Protein Versus Autologous Iliac Crest Bone Graft in Lumbar Fusion: A Meta-analysis and Systematic Review.

This is a systematic literature review and meta-analysis. We aimed to evaluate the efficacy and safety of recombinant human bone morphogenetic protein (RhBMP) and autologous iliac crest bone graft (ICBG) in lumbar fusion. RhBMP has been emphasized in lumbar fusion due to high fusion success rate. However, ICBG remains the criterion standard graft approach for lumbar fusion. The safety and effectiveness of rhBMP are controversial. Prospective randomized controlled trials were searched from PubMed, EMBASE, and Cochrane Central Register of Controlled Trails by using Medical Subject Headings terms "bone morphogenetic protein,' "bone transplantation,' and "spinal fusion.' Two independent investigators screened eligible studies, assessed the bias of original articles, extracted data including fusion success, Oswestry disability index improvement, improved short form 36 questionnaire scores, adverse events and re-operation, and a subgroup analysis. The GRADE approach was used to grade quality of evidence. Twenty randomized controlled trials (2185 patients) met the inclusion criteria. There were higher fusion success rate (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.88-7.63, P = 0.0002), better improvement of Oswestry Disability Index (mean difference 1.54, 95% CI 0.18-2.89, P = 0.03), and lower re-operation rate (OR 0.59, 95% CI 0.43-0.80, P = 0.0007) in rhBMP group. Heterogeneity was obvious in fusion success rate (I = 58%); hence, a subgroup analysis, based on protein type (rhBMP-2 or rhBMP-7), was performed, which suggested that only rhBMP-2 was better than ICBG for lumbar fusion. There was no difference in the incidence of adverse events between rhBMP and ICBG (OR 0.91, 95% CI 0.70-1.18, P = 0.47). In lumbar fusion, rhBMP-2 exhibited a higher fusion success rate and reduced the risk of re-operation. No difference in complication rate is between rhBMP (rhBMP-2 and rhBMP-7) and ICBG. We suggest rhBMP especially rhBMP-2 as an effective substitute for ICBG for lumbar fusion. 1.

A comprehensive assessment of the risk of bone morphogenetic protein use in spinal fusion surgery and postoperative cancer diagnosis.

The risk of postoperative cancer following the use of recombinant human bone morphogenetic protein (BMP)-2 in spinal fusion is one potential complication that has received significant interest. Until recently, there has been little clinical evidence to support the assertion of potential cancer induction after BMP use in spinal surgery. This report aims to summarize the findings from clinical data available to date from the Yale University Open Data Access (YODA) project as well as more recently published large database studies regarding the association of BMP use in spinal fusion and the risk of postoperative cancer. A detailed review was based on online databases, primary studies, FDA reports, and bibliographies of key articles for studies that assessed the efficacy and safety of BMP in spinal fusion. In an analysis of the YODA project, one meta-analysis detected a statistically significant increase in cancer occurrence at 24 months but not at 48 months, and the other meta-analysis did not detect a significant increase in postoperative cancer occurrence. Analysis of 3 large health care data sets (Medicare, MarketScan, and PearlDiver) revealed that none were able to detect a significant increase in risk of malignant cancers when BMP was used compared with controls. The potential risk of postoperative cancer formation following the use of BMP in spinal fusion must be interpreted on an individual basis for each patient by the surgeon. There is no conclusive evidence that application of the common formulations of BMP during spinal surgery results in the formation of cancer locally or at a distant site.

Bone Morphogenetic Protein in Spine Surgery: Current and Future Uses

The clinical use of bone morphogenetic protein (BMP) in spinal fusion surgery has recently become controversial. After its approval by the US FDA in July 2002, BMP was adopted by many spine surgeons as a replacement for the more traditional iliac crest bone graft to avoid the complications associated with bone graft harvest. However, as broad clinical use escalated, reports increased of potentially serious complications associated with BMP. Controversy continues, particularly regarding the safety of BMP and whether it should routinely replace iliac crest bone graft for spinal fusion surgery.

A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to a multitude of investigations into their use as bone graft substitutes in spinal surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety and efficacy of BMP-7 (osteogenic protein 1, OP-1), in the form of a putty, combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent a laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements, followed by an intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and SF-36 outcome forms, and radiographically using static and dynamic radiographs to assess their fusion status over a 2-year period. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed eight of the nine evaluable patients (89%) obtained at least a 20% improvement in their preoperative Oswestry score, while five of ten patients (50%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in seven of the ten patients (70%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the statistical superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was 45%. There were no adverse events related to the OP-1 putty implant in this study, which supports findings in other studies suggesting the safety of bone morphogenetic proteins in spinal surgery.

Summary Statement: Safety of Bone Morphogenetic Proteins for Spine Fusion

As any new technology approaches widespread clinical use, the safety profile must be of paramount concern. This article reviews the available safety data for the various bone morphogenetic protein programs. On the basis of available information, each BMP requires its own safety profile of local, regional, and systemic side effects. When used properly, BMPs currently appear to be extremely safe for spine fusion.