Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion

Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Spine (Impact Factor: 2.3). 04/2006; 31(5):542-7. DOI: 10.1097/01.brs.0000201424.27509.72
Source: PubMed

ABSTRACT A retrospective review of patients who underwent an anterior cervical fusion using recombinant human bone morphogenetic protein (rhBMP)-2 with an absorbable collagen sponge (INFUSE; Medtronic Sofamor Danek, Minneapolis, MN).
To ascertain the complication rate after the use of high-dose INFUSE in anterior cervical fusions.
The rhBMP-2 has been primarily investigated in lumbar spine fusions, where it has significantly enhanced the fusion rate and decreased the length of surgery, blood loss, and hospital stay.
We present 151 patients who underwent either an anterior cervical discectomy and fusion (n = 138) or anterior cervical vertebrectomy and fusion (n = 13) augmented with high-dose INFUSE between July 2003 and March 2004. The rhBMP-2 (up to 2.1 mg/level) was used in the anterior cervical discectomy and fusions.
A total of 35 (23.2%) patients had complications after the use of high-dose INFUSE in the cervical spine. There were 15 patients diagnosed with a hematoma, including 11 on postoperative day 4 or 5, of whom 8 were surgically evacuated. Thirteen individuals had either a prolonged hospital stay (> 48 hours) or hospital readmission because of swallowing/breathing difficulties or dramatic swelling without hematoma.
A significant rate of complications resulted after the use of a high dose of INFUSE in anterior cervical fusions. We hypothesize that in the cervical area, the putative inflammatory effect that contributes to the effectiveness of INFUSE in inducing fusion may spread to adjacent critical structures and lead to increased postoperative morbidity. A thorough investigation is warranted to determine the optimal dose of rhBMP-2 that will promote cervical fusion and minimize complications.

Download full-text


Available from: Lisa B E Shields, Sep 27, 2015
1 Follower
200 Reads
  • Source
    • "However, there are problems associated with its clinical application such as the large doses of BMPs required (2.1–12.0 mg), a short half-life in vivo, and high cost [19] [20] [21]. To overcome these shortcomings, investigators have been looking for alternative drugs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Biphasic calcium phosphate (BCP) scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN-) eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation.
    07/2015; 2015(355, supplement):320713. DOI:10.1155/2015/320713
  • Source
    • "The figure is annotated by the publication dates of studies by Shields et al. [18], Pradhan [19], Lewandrowski et al. [20], Vaidya et al. [21], and Buttermann [22], which were among the first case series to report wound complication, osteolysis, and dysphagia with BMP in anterior cervical fusion. Those by Mindea et al. [6], Wong et al. [7], Joseph and Rampersaud [23], and Carragee et al. [10] were the first to raise concerns about postoperative radiculitis and retrograde ejaculation with lumbar fusions involving BMP. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Use of Bone Morphogenetic Protein (BMP) as an adjunct to spinal fusion surgery proliferated following Food and Drug Administration (FDA) approval in 2002. Major safety concerns emerged in 2008. To examine whether published concerns about the safety of BMP altered clinical practice. Analysis of the National Inpatient Sample from 2002 through 2012. Adults (age >20) undergoing an elective fusion operation for common degenerative diagnoses, identified using codes from the International Classification of Diseases, 9(th)revisions, Clinical Modification (ICD-9-CM). Proportion of cervical and lumbar fusion operations, over time, that involved BMP. We aggregated the data into a monthly time series and reported the proportion of cervical and lumbar fusion operations, over time, that involved BMP. Auto Regressive Integrated Moving Average, a regression model for time series data, was used to test whether there was a statistically significant change in the overall rate of BMP use following a FDA Public Health Notification in 2008. The study was funded by federal research grants, and no investigator had any conflict of interests. Use of BMP in spinal fusion procedures increased rapidly until 2008, involving up to 45.2% of lumbar and 13.5% of cervical fusions. BMP use significantly decreased following the 2008 FDA Public Health Notification and revelations of financial payments to surgeons involved in the pivotal FDA approval trials. For lumbar fusion, the average annual increase was 7.9 percentage points per year from 2002 to 2008, followed by an average annual decrease of 11.7 percentage points thereafter (p = <0.001). Use of BMP in cervical fusion increased 2.0% per year until the FDA Notification, followed by a 2.8% per year decrease (p = 0.035). Use of BMP in spinal fusion surgery declined subsequent to published safety concerns and revelations of financial conflicts-of-interest for investigators involved in the pivotal clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.
    The spine journal: official journal of the North American Spine Society 12/2014; 15(4). DOI:10.1016/j.spinee.2014.12.010 · 2.43 Impact Factor
  • Source
    • "More recently, BMP-2 has demonstrated to be effective at lower in vivo doses (verbal communication, Medtronic). The potential off-label risks of BMP-2 have been documented in the literature and include: ectopic bone formation [26], swelling/hematoma [27], neoplasia [28], and wound problems; [29] this should be taken into consideration when using these therapies off-label. As basic science researchers, translational scientists and surgeons further understand the temporospatial orchestration of growth factor/cytokines during fracture healing, more precise delivery, timing and dosing of these factors could be delivered to these defects. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Reconstruction of critical-size bony defects remains a challenge to surgeons despite recent technological advances. Current treatments include distraction osteogenesis, cancellous autograft, induced membranes (Masquelet procedure), polymeric membranes, and titanium-mesh cages filled with bone graft. In this article, the authors presents two cases in which critical-sized defects were reconstructed using a meshed fascial autograft encasing reamer-irrigator-aspirator (RIA) autograft and cancellous allograft. This article will discuss the clinical outcomes of the technique, comparison to other current techniques, and technical insight into the potential biological mechanism.
    Patient Safety in Surgery 12/2014; 8(1):40. DOI:10.1186/s13037-014-0040-7
Show more