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


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.

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    • "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. "
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    07/2015; 2015(355, supplement):320713. DOI:10.1155/2015/320713
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    • "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. "
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    • "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. "
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