Recombinant Human Bone Morphogenetic Protein-2-Induced Radiculitis in Elective Minimally Invasive Transforaminal Lumbar Interbody Fusions

Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Spine (Impact Factor: 2.3). 07/2009; 34(14):1480-4; discussion 1485. DOI: 10.1097/BRS.0b013e3181a396a1
Source: PubMed


Retrospective single center analysis.
The purpose of our study is to quantify the development of a postoperative radiculitis in our minimally invasive transforaminal lumbar interbody fusion patient population.
The application of recombinant human Bone Morphogenetic Protein-2 (BMP) in spinal surgery has allowed for greater success in spinal fusions. This has led to the FDA approving its use in anterior lumbar interbody fusion. However, its well-recognized benefits have generated its "off-label" use in the cervical, thoracic, and lumbar spine. Despite its benefits, the adverse effects of its inflammatory properties are just starting to get recognized. Some clear adverse reactions have been documented in the literature in the cervical spine. However, we feel that these inflammatory properties may be present in the lumbar spine as well.
We performed a retrospective chart review of 43 patients who had undergone a minimally invasive transforaminal lumbar interbody fusions. Thirty-five of these patients had BMP and 8 patients did not have BMP. We documented whether there was a preoperative radiculopathy present and whether a radiculopathy was present postoperative. We reviewed radiographic postoperative imaging to establish a structural cause for any radiculopathy. If new or increasing radicular symptoms were present, we attempted to assess the duration of these symptoms.
Our analysis, showed that 0 of the 8 patients of the non-BMP group had new radicular symptoms that were not attributed to structural causes. In the BMP group, 4 of the 35 patients (11.4%) had new radicular symptoms without structural etiology.
Our analysis suggest that patients undergoing minimally invasive transforaminal lumbar interbody fusions procedures have a higher incidence of developing new radicular symptoms that could be attributed to BMP.

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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. Reports that likely had the greatest visibility included the FDA Public Health Notification [4], study of Cahill et al. [5] in the Journal of the American Medical Association, an entire issue of The Spine Journal dedicated to the use of BMP [9], a US Senate Finance Committee report [24], and the reanalysis of pivotal trial data through the Yale University Open Data Access Project [25] [26]. "
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    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.
    Full-text · Article · Dec 2014 · The spine journal: official journal of the North American Spine Society
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    • "The clinical availability of rhBMP-2 has had a profound impact on the field of spinal surgery. The ability of rhBMP- 2 to modulate mesenchymal cell differentiation through a complex signaling cascade allows increased osteoblast formation and improved osteogenesis and bone healing [19] [21]. However, this advancement has not occurred without significant adverse side effects [10]. "
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    ABSTRACT: BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is commonly used to augment posterior and interbody spinal fusion techniques and has many reported side effects. Neuroforaminal heterotopic ossification (HO) is a known cause of postoperative leg pain, but the pathohistologic composition of this material is not well understood. PURPOSE: The purpose of this article was to report the histologic composition of a case of HO and lumbar radiculopathy after transforaminal lumbar interbody fusion with rhBMP-2. STUDY DESIGN/SETTING: This is a case report. PATIENT SAMPLE: This is a single patient case report. OUTCOME MEASURES: The outcomes considered were physician-recorded clinical, physiological, and functional measures. METHODS: A retrospective review of a single patient was performed. Clinical, radiographic, and pathologic specimens were reviewed and are reported. RESULTS: A 69-year-old woman presented with low back pain and right leg radicular pain associated with L4-L5 stenosis and a recurrent facet cyst. After attempted nonsurgical care, she underwent an L4-L5 revision decompression with interbody and posterolateral fusions including off-label rhBMP-2. Postoperatively, her symptoms resolved for approximately 7 months but then returned in association with right L4-L5 foraminal HO. The ectopic tissue was notably larger than suggested by preoperative computed tomographic scan. It was decompressed, which then improved her symptoms. Histologic examination of the specimen revealed three discrete tissue types: a nonspecific fibrovascular stroma; immature osteoid and woven bone; and chondrocyte metaplasia with chondrocyte clustering. CONCLUSIONS: Neuroforaminal HO formation is a reported side effect associated with the off-label use of rhBMP-2 for posterior lumbar interbody fusion. The mechanism of formation and the composition of this material are not well understood but may involve a chondrocyte differentiation pathway.
    Full-text · Article · Nov 2013 · The spine journal: official journal of the North American Spine Society
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