The use of bone morphogenetic protein in spine fusion.

BACKGROUND CONTEXT Because pseudarthrosis remains a clinically significant complication after spinal arthrodesis, the role of recombinant bone morphogenetic proteins (BMPs) is continually evaluated in spine surgery. PURPOSE This article reviews the important literature in clinical research involving the use of BMPs in the augmentation of spinal fusion. STUDY DESIGN/SETTING Review article. METHODS A literature search was performed via MEDLINE through PubMed with the dates January 1960 to July 2007 using the keywords "bone morphogenetic protein, BMP, spinal arthrodesis, and/or bone healing." Pertinent preclinical and clinical publications were chosen based on relevance and quality for inclusion in this study. RESULTS Publications focused on the historical context and potential clinical applications using BMP were selected to delineate the risks, benefits, and current indications for the augmentation of spinal arthrodesis. CONCLUSIONS Although multiple commercially available recombinant BMPs have demonstrated clinical success in interbody and posterolateral fusions, the associated costs preclude its routine use in spinal arthrodesis. The spine surgeon must assess each patient individually based on age, bone quality, diagnosis, comorbidities, and risks of nonunion to determine the cost effectiveness of the use of BMP to augment spinal fusion.

[1]  S. Boden,et al.  Laparoscopic anterior spinal arthrodesis with rhBMP-2 in a titanium interbody threaded cage , 1998 .

[2]  J. Goulet,et al.  Autogenous Iliac Crest Bone Graft: Complications and Functional Assessment , 1997, Clinical orthopaedics and related research.

[3]  A Daluiski,et al.  The effect of regional gene therapy with bone morphogenetic protein-2-producing bone-marrow cells on the repair of segmental femoral defects in rats. , 1999, The Journal of bone and joint surgery. American volume.

[4]  M. Marone,et al.  Posterolateral intertransverse process spinal arthrodesis with rhBMP-2 in a nonhuman primate: important lessons learned regarding dose, carrier, and safety. , 1999, Journal of spinal disorders.

[5]  L. Anderson,et al.  Hernias through donor sites for iliac-bone grafts. , 1983, The Journal of bone and joint surgery. American volume.

[6]  S D Cook,et al.  Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates. , 1995, The Journal of bone and joint surgery. American volume.

[7]  J. Challis,et al.  Strangulated lumbar hernia and volvulus following removal of iliac crest bone graft. , 1975, Acta orthopaedica Scandinavica.

[8]  N. Crawford,et al.  Effect of Recombinant Human Bone Morphogenetic Protein-2 in an Experimental Model of Spinal Fusion in a Radiated Area , 2005, Spine.

[9]  M. Urist.  Bone: Formation by Autoinduction , 1965, Science.

[10]  G. Muschler,et al.  Evaluation of Human Bone Morphogenetic Protein 2 in a Canine Spinal Fusion Model , 1994, Clinical orthopaedics and related research.

[11]  B. Barnes,et al.  Lower Dose of rhBMP-2 Achieves Spine Fusion When Combined With an Osteoconductive Bulking Agent in Non-human Primates , 2005, Spine.

[12]  D. Silcox,et al.  Reversing the Inhibitory Effect of Nicotine on Spinal Fusion Using an Osteoinductive Protein Extract , 1998, Spine.

[13]  John R. Johnson,et al.  Posterolateral lumbar spine fusion with INFUSE bone graft. , 2007, The spine journal : official journal of the North American Spine Society.

[14]  T. Albert,et al.  Comparison of OP-1 Putty (rhBMP-7) to Iliac Crest Autograft for Posterolateral Lumbar Arthrodesis: A Minimum 2-Year Follow-up Pilot Study , 2005, Spine.

[15]  W. Hutton,et al.  Delivery of Recombinant Human Bone Morphogenetic Protein-2 Using a Compression-Resistant Matrix in Posterolateral Spine Fusion in the Rabbit and in the Non-Human Primate , 2002, Spine.

[16]  L. Lenke,et al.  Use of Bone Morphogenetic Protein-2 for Adult Spinal Deformity , 2005, Spine.

[17]  R E Booth,et al.  Harvesting Autogenous Iliac Bone Grafts: A Review of Complications and Techniques , 1989, Spine.

[18]  J M Toth,et al.  Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Without Decortication of Osseous Elements , 1997, Spine.

[19]  A. Vaccaro,et al.  Bone grafting alternatives in spinal surgery. , 2002, The spine journal : official journal of the North American Spine Society.

[20]  E. Thonar,et al.  Recombinant osteogenic protein‐1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[21]  T. Albert,et al.  A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions , 2003, European Spine Journal.

[22]  R. Delamarter,et al.  Controlling Bone Morphogenetic Protein Diffusion and Bone Morphogenetic Protein-Stimulated Bone Growth Using Fibrin Glue , 2006, Spine.

[23]  W. Hutton,et al.  Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein‐2 , 1995, Spine.

[24]  L. Titus,et al.  Recombinant human bone morphogenetic protein-2 overcomes the inhibitory effect of ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), on posterolateral lumbar intertransverse process spine fusion. , 1999, Spine.

[25]  Joseph D. Smucker,et al.  Increased Swelling Complications Associated With Off-Label Usage of rhBMP-2 in the Anterior Cervical Spine , 2006, Spine.

[26]  S. Cook,et al.  In Vivo Evaluation of Recombinant Human Osteogenic Protein (rhOP-1) Implants As a Bone Graft Substitute for Spinal Fusions , 1994, Spine.

[27]  L. Lenke,et al.  The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. , 1993, Journal of spinal disorders.

[28]  E. Schwarz,et al.  Overexpression of noggin inhibits BMP-mediated growth of osteolytic prostate cancer lesions. , 2006, Bone.

[29]  J. Wozney,et al.  Clinical evaluation of recombinant human bone morphogenetic protein-2. , 2002, Clinical orthopaedics and related research.

[30]  S. Boden,et al.  Use of Recombinant Human Bone Morphogenetic Protein-2 to Achieve Posterolateral Lumbar Spine Fusion in Humans: A Prospective, Randomized Clinical Pilot Trial 2002 Volvo Award in Clinical Studies , 2002, Spine.

[31]  V. Rosen,et al.  The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. , 1992, The Journal of bone and joint surgery. American volume.

[32]  J. Michael Kabo,et al.  Evaluation of rhBMP‐2 With an OPLA Carrier in a Canine Posterolateral (Transverse Process) Spinal Fusion Model , 1995, Spine.

[33]  F. Regan,et al.  Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement. A randomised controlled trial. , 1996, International angiology : a journal of the International Union of Angiology.

[34]  R. Mcguire,et al.  The Use of Primary Internal Fixation in Spondylolisthesis , 1993, Spine.

[35]  T. Zdeblick.  A prospective, randomized study of lumbar fusion. Preliminary results. , 1993, Spine.

[36]  G. Finerman,et al.  Regional gene therapy with a BMP‐2‐producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[37]  F. Cui,et al.  Lumbar Spinal Fusion With a Mineralized Collagen Matrix and rhBMP-2 in a Rabbit Model , 2003, Spine.

[38]  S. Glassman,et al.  Adverse Effects Associated With High-Dose Recombinant Human Bone Morphogenetic Protein-2 Use in Anterior Cervical Spine Fusion , 2006, Spine.

[39]  M. B. Coventry,et al.  Pelvic instability: a consequence of removing iliac bone for grafting. , 1972, The Journal of bone and joint surgery. American volume.

[40]  Marc Hedrick,et al.  Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue. , 2005, Tissue engineering.

[41]  Banwart Jc,et al.  Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. , 1995 .

[42]  S. Boden,et al.  Video‐Assisted Lateral Intertransverse Process Arthrodesis: Validation of a New Minimally Invasive Lumbar Spinal Fusion Technique in the Rabbit and Nonhuman Primate (Rhesus) Models , 1996, Spine.

[43]  W. Hsu,et al.  Lentiviral-mediated BMP-2 gene transfer enhances healing of segmental femoral defects in rats. , 2007, Bone.

[44]  S. Boden,et al.  The Use of rhBMP-2 in Interbody Fusion Cages: Definitive Evidence of Osteoinduction in Humans: A Preliminary Report , 2000, Spine.

[45]  A. Baltzer,et al.  Regional gene therapy to enhance bone repair , 2004, Gene Therapy.

[46]  H. Seeherman,et al.  Histomorphometric description of allograft bone remodeling and union in a canine segmental femoral defect model: A comparison of rhBMP‐2, cancellous bone graft, and absorbable collagen sponge , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[47]  W. Hutton,et al.  The use of coralline hydroxyapatite with bone marrow, autogenous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion. , 1999, Spine.

[48]  J. Grauer,et al.  Osteogenic Protein-1 Induced Gene Expression: Evaluation in a Posterolateral Spinal Pseudarthrosis Model , 2006, Spine.

[49]  W. Hutton,et al.  The Use of an Osteoinductive Growth Factor for Lumbar Spinal Fusion: Part I Biolog of Spinal Fusion , 1995 .

[50]  M. Moreland,et al.  Complications following iliac crest bone grafting. , 1986, Clinical Orthopaedics and Related Research.

[51]  Manohar M. Panjabi,et al.  Evaluation of OP-1 as a Graft Substitute for Intertransverse Process Lumbar Fusion , 2001, Spine.

[52]  C. Dickman,et al.  Anterior Lumbar Interbody Fusion Using rhBMP-2 With Tapered Interbody Cages , 2002, Journal of spinal disorders & techniques.

[53]  R. Connolly,et al.  The effect of osteogenic protein-1 in instrumented and noninstrumented posterolateral fusion in rabbits. , 2002, The spine journal : official journal of the North American Spine Society.

[54]  D. Bradford,et al.  Results of spinal arthrodesis with pedicle screw-plate fixation. , 1991, The Journal of bone and joint surgery. American volume.

[55]  P. Campbell,et al.  Effect of Regional Gene Therapy with Bone Morphogenetic Protein-2-Producing Bone Marrow Cells on Spinal Fusion in Rats , 2003, The Journal of bone and joint surgery. American volume.

[56]  A. Weckbach,et al.  Successful Transpedicular Lumbar Interbody Fusion by Means of a Composite of Osteogenic Protein-1 (rhBMP-7) and Hydroxyapatite Carrier: A Comparison With Autograft and Hydroxyapatite in the Sheep Spine , 2002, Spine.

[57]  W. Hutton,et al.  Morphology of the lumbar intertransverse process fusion mass in the rabbit model: a comparison between two bone graft materials--rhBMP-2 and autograft. , 1996, Journal of spinal disorders.

[58]  M. Magin,et al.  Improved Lumbar Vertebral Interbody Fusion Using rhOP-1: A Comparison of Autogenous Bone Graft, Bovine Hydroxylapatite (Bio-Oss), and BMP-7 (rhOP-1) in Sheep , 2001, Spine.

[59]  S. Glassman,et al.  Clinical Outcomes and Fusion Success at 2 Years of Single-Level Instrumented Posterolateral Fusions With Recombinant Human Bone Morphogenetic Protein-2/Compression Resistant Matrix Versus Iliac Crest Bone Graft , 2006, Spine.

[60]  S. Ludwig,et al.  Osteoinductive bone graft substitutes , 2000, European Spine Journal.

[61]  R. L. Reid.  Hernia through an iliac bone-graft donor site. A case report. , 1968, The Journal of bone and joint surgery. American volume.

[62]  H. Vinters,et al.  Dose-Dependent Toxicity of a Commercially Available Demineralized Bone Matrix Material , 2001, Spine.

[63]  J. McClellan,et al.  Vertebral Bone Resorption After Transforaminal Lumbar Interbody Fusion With Bone Morphogenetic Protein (rhBMP-2) , 2006, Journal of spinal disorders & techniques.

[64]  N. Anand,et al.  Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy and fusion: a case study. , 2007, The spine journal : official journal of the North American Spine Society.

[65]  J. Szatkowski,et al.  Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs) 1 1 J Bone Joint Surg Am 2003;85A:1544–52 , 2003 .

[66]  Hak-Sun Kim,et al.  Simple Carrier Matrix Modifications Can Enhance Delivery of Recombinant Human Bone Morphogenetic Protein-2 for Posterolateral Spine Fusion , 2003, Spine.