- Department of Neurosurgery, The Albert Einstein College of Medicine, Bronx, New York, 10461, and Chief of Neurosurgical Spine/Education; Department of Neuroscience, Winthrop University Hospital, Mineola, NY 11501, USA
Nancy E. Epstein
Department of Neurosurgery, The Albert Einstein College of Medicine, Bronx, New York, 10461, and Chief of Neurosurgical Spine/Education; Department of Neuroscience, Winthrop University Hospital, Mineola, NY 11501, USA
DOI:10.4103/2152-7806.109452Copyright: © 2013 Epstein NE This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Epstein NE. Commentary on research of bone morphogenetic protein discussed in review article: Genetic advances in the regeneration of the intervertebral disc. Surg Neurol Int 22-Mar-2013;4:
How to cite this URL: Epstein NE. Commentary on research of bone morphogenetic protein discussed in review article: Genetic advances in the regeneration of the intervertebral disc. Surg Neurol Int 22-Mar-2013;4:. Available from: http://sni.wpengine.com/surgicalint_articles/commentary-on-research-of-bone-morphogenetic-protein-discussed-in-review-article-genetic-advances-in-the-regeneration-of-the-intervertebral-disc/
Background:In Maerz, Herkowitz and Baker's review, Molecular and Genetic Advances in the Regeneration of the Intervertebral Disc, they also included an assessment of both in vivo and in vitro complications attributed to Bone Morphogenetic Protein ((BMP): BMP-2, BMP-7). This topic is of particular interest to spinal surgeons, as INFUSE/BMP (Medtronic, Memphis, TN, USA) is utilized, mostly off-label in the cervical, thoracic, and lumbar spine, where it has been associated with significant perioperative and postoperative complications.
Methods:BMP-2 and BMP-7 are the only human recombinant growth factors approved by the Food and Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) in combination with the Lumbar Tapered Fusion Device (LT Cage: Medtronic, Memphis, TN, USA). BMP, however, is more typically utilized “off-label” in many other areas of the spine, where it has been associated with numerous complications.
Results:Maerz, et al. documented multiple in vivo and in vitro laboratory-based animal studies dating back to the early 2000's in which BMP (INFUSE is the clinically available product: Medtronic, Memphis, TN) contributed to multiple complications, especially when utilized at higher doses. These complications included; inflammation/inflammatory processes, increased vascularity, fibroblastic proliferation, and catabolism.
Conclusion:Maerz, et al. reviewed the increased risks associated with utilizing high dose BMP=INFUSE in spinal surgery, particularly when utilized “off-label”. The authors clearly indicate that BMP/INFUSE should be further investigated (based on the old and new findings) to better determine/confirm its safety, efficacy, and dosing.
Keywords: Animal laboratory studies, bone morphogenetic protein, clinical, infuse, intervertebral disc, regeneration, spinal surgery
Maerz, Herkowitz, and Baker have written an excellent review article, Molecular and Genetic Advances in the Regeneration of the Intervertebral Disc.[
Maerz, et al. noted that BMP-2 and BMP-7 (OP-1) are the only human recombinant growth factors (osteoinductive properties) approved by the Food and Drug Administration (FDA).[
IN VITRO, BMP-2 PROMOTES EXPRESSION OF CHONDROGENIC, NOT OSTEOGENIC PHENOTYPES OF HUMAN INTERVERTEBRAL DISC CELLS
BMP-2, in vitro, upregulates multiple genes and enhances the expression of many proteins. In 2003, Kim, et al. observed how BMP-2 promotes the expression of “chondrogenic, not osteogenic, phenotypes of human intervertebral disc cells,” resulting in greater proteoglycan synthesis, the up-regulation of articular chondrocytes, and intervertebral disc cells (IVD).[
In 2011, McCanless, et al. evaluated the in vitro impact of BMP-2 on cell proliferation/extracellular matrix (ECM) synthesis of the nucleus pulposus (NP)-like differentiated mesenchymal stem cells (MSCs).[
In an in vivo animal model in 2011, Huang, et al. showed that rhBMP-2 promoted more degenerative changes in the disc vs. controls, while also resulting in other complications; “increased inflammation, vascularity, and fibroblastic proliferation in rhBMP-2-treated animals compared with saline-treated animals.”[
In 2004, Wang, et al. noted that the in vitro applications of BMP-14 (GDF-5) induced cellular activation/proliferation in primary IVD cells, promoting collagen synthesis. Higher doses produced inflammatory reactions in the adjacent vertebrae and connective tissue that infiltrated the nucleus. This indicated that “the positive effect of GDF-5 may depend on dosing, and that multiple treatments can cause catabolic and/or inflammatory processes.”[
In 2004, Walsh, et al. further demonstrated that one injection of insulin-like growth factor-1 (IGF-1) into a degenerate murine disc resulted in increased cell density and proliferation at 1 week, while multiple injections resulted in inflammatory reactions in adjacent vertebrae, indicating a dose-dependent response.[
In their review article, Maerz, et al. discussed how BMP/INFUSE, particularly when applied at higher dosages in vitro and in vivo models, resulted in multiple adverse reactions.[
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