The use of bone morphogenetic protein in lumbar spine surgery.

Lumbar spinal fusion is an integral component of the surgical management of degenerative disease, trauma, deformity, tumor, and infection of the spine. Pseudarthrosis can, in turn, lead to persistent pain, failure of the instrumentation, and the need for revision surgery. It is a challenge to obtain a solid osseous fusion; therefore, both mechanical and biological variables should be optimized. Mechanical stability is optimized by using pedicle screws and rods for rigid fixation until there is osseous fusion. Internal fixation improves the fusion rates compared with those associated with lumbar fusion without instrumentation, but it does not ensure a 100% fusion rate. Autogenous bone graft has been used to optimize the biological environment and is considered the “gold standard” for fusion in lumbar spine surgery; however, pseudarthrosis rates of up to 55% have been reported even with use of autogenous bone graft1,2. In addition, up to 25% of patients have reported substantial and persistent morbidity associated with the harvesting of autogenous iliac crest bone3-8. There is a limited supply of autogenous iliac crest, and it may not be available for a patient requiring revision surgery. Biologics have been used as alternatives to, or enhancements of, autograft in lumbar fusion surgery over the last decade. One of the most studied and frequently used biological alternatives to autograft is bone morphogenetic protein (BMP). In this paper, we review the types of BMP used in lumbar spine surgery, the clinical results and complications associated with BMP use, and their economic impact. BMP was discovered by Marshall Urist in 19659. It is a group of growth factor proteins within the transforming growth factor-β (TGF-β) superfamily of growth factors10. Through molecular cloning techniques and recombinant expression, osteoinductive BMP molecules have been identified and have …

[1]  T. Smoljanović,et al.  Significance of Early CT Evaluation after Lumbar Interbody Fusions Using Recombinant Human Bone Morphogenetic Protein-2 , 2009, American Journal of Neuroradiology.

[2]  R. Vaidya,et al.  Complications in the Use of rhBMP-2 in PEEK Cages for Interbody Spinal Fusions , 2008, Journal of spinal disorders & techniques.

[3]  John R. Johnson,et al.  The perioperative cost of Infuse bone graft in posterolateral lumbar spine fusion. , 2008, The spine journal : official journal of the North American Spine Society.

[4]  T. Albert,et al.  The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study. , 2008, The spine journal : official journal of the North American Spine Society.

[5]  J. Harms,et al.  [A one-stager procedure in operative treatment of spondylolistheses: dorsal traction-reposition and anterior fusion (author's transl)]. , 2008, Zeitschrift fur Orthopadie und ihre Grenzgebiete.

[6]  S. Glassman,et al.  Adverse Events in Patients Re-Exposed to Bone Morphogenetic Protein for Spine Surgery , 2008, Spine.

[7]  J. Steib.  Re: Mahar A, Kim S, Wedermeyer M, et al. Short segmental fixation of lumbar burst fractures using pedicle fixation at level of the fracture. Spine 2007;32:1503-7. , 2008, Spine.

[8]  S. Vukicevic,et al.  Regeneration of the skeleton by recombinant human bone morphogenetic proteins. , 2007, Collegium antropologicum.

[9]  K. Lewandrowski,et al.  Vertebral osteolysis after posterior interbody lumbar fusion with recombinant human bone morphogenetic protein 2: a report of five cases. , 2007, The spine journal : official journal of the North American Spine Society.

[10]  T. Albert,et al.  10. BMP-2 Causes Increased Postoperative Radiculitis Following TLIF , 2007 .

[11]  S. Boden,et al.  The Efficacy of rhBMP-2 for Posterolateral Lumbar Fusion in Smokers , 2007, Spine.

[12]  R. Vaidya,et al.  Interbody fusion with allograft and rhBMP-2 leads to consistent fusion but early subsidence. , 2007, The Journal of bone and joint surgery. British volume.

[13]  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.

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

[15]  Joseph D. Smucker,et al.  Use of Recombinant Human Bone Morphogenetic Protein-2 as an Adjunct in Posterolateral Lumbar Spine Fusion: A Prospective CT-Scan Analysis at One and Two Years , 2006, Journal of spinal disorders & techniques.

[16]  H. Yoshikawa,et al.  Bone Morphogenetic Proteins in Bone Stimulate Osteoclasts and Osteoblasts During Bone Development , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  D. Togawa,et al.  A Prospective Randomized Study of Posterolateral Lumbar Fusion Using Osteogenic Protein-1 (OP-1) Versus Local Autograft With Ceramic Bone Substitute: Emphasis of Surgical Exploration and Histologic Assessment , 2006, Spine.

[18]  J. Burkus,et al.  Influence of rhBMP-2 on the Healing Patterns Associated With Allograft Interbody Constructs in Comparison With Autograft , 2006, Spine.

[19]  F. Watzinger,et al.  Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation , 2006 .

[20]  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.

[21]  K. Bulsara,et al.  Safety of transforaminal lumbar interbody fusion and intervertebral recombinant human bone morphogenetic protein-2. , 2005, Journal of neurosurgery. Spine.

[22]  J. Burkus,et al.  CT evaluation of lumbar interbody fusion: current concepts. , 2005, AJNR. American journal of neuroradiology.

[23]  John R. Johnson,et al.  Initial Fusion Rates With Recombinant Human Bone Morphogenetic Protein-2/Compression Resistant Matrix and a Hydroxyapatite and Tricalcium Phosphate/Collagen Carrier in Posterolateral Spinal Fusion , 2005, Spine.

[24]  H. Seeherman,et al.  Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. , 2005, Cytokine & growth factor reviews.

[25]  J. Burkus,et al.  Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery. , 2005, The Journal of bone and joint surgery. American volume.

[26]  W. Hutton,et al.  Comparison of Healos/Bone Marrow to INFUSE(rhBMP-2/ACS) With a Collagen-Ceramic Sponge Bulking Agent as Graft Substitutes for Lumbar Spine Fusion , 2005, Spine.

[27]  Safdar N. Khan,et al.  Use of Osteopromotive Growth Factors, Demineralized Bone Matrix, and Ceramics to Enhance Spinal Fusion , 2005, The Journal of the American Academy of Orthopaedic Surgeons.

[28]  Kevin T Foley,et al.  Minimally Invasive Transforaminal Lumbar Interbody Fusion (TLIF): Technical Feasibility and Initial Results , 2005, Journal of spinal disorders & techniques.

[29]  T. Albert,et al.  A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions , 2005, European Spine Journal.

[30]  T. Albert,et al.  A Pilot Study Evaluating the Safety and Efficacy of OP-1 Putty (rhBMP-7) as a Replacement for Iliac Crest Autograft in Posterolateral Lumbar Arthrodesis for Degenerative Spondylolisthesis , 2004, Spine.

[31]  C. Branch,et al.  Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. , 2004, The spine journal : official journal of the North American Spine Society.

[32]  S. Stralka,et al.  A cost analysis of bone morphogenetic protein versus autogenous iliac crest bone graft in single-level anterior lumbar fusion. , 2003, Orthopedics.

[33]  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.

[34]  H. Sandhu.  Bone Morphogenetic Proteins and Spinal Surgery , 2003, Spine.

[35]  T. Albert,et al.  Donor Site Morbidity After Anterior Iliac Crest Bone Harvest for Single-Level Anterior Cervical Discectomy and Fusion , 2003, Spine.

[36]  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.

[37]  R. Balderston,et al.  Clinical and Radiographic Outcomes of Anterior Lumbar Interbody Fusion Using Recombinant Human Bone Morphogenetic Protein-2 , 2002, Spine.

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

[39]  James D. Kang,et al.  3:51 Recombinant human bone morphogenic protein–2 for posterolateral spine fusion , 2002 .

[40]  D. Polly,et al.  Economic Evaluation of Bone Morphogenetic Protein Versus Autogenous Iliac Crest Bone Graft in Single-Level Anterior Lumbar Fusion: An Evidence-Based Modeling Approach , 2002, Spine.

[41]  P. Holtom,et al.  Comparison of Anterior and Posterior Iliac Crest Bone Grafts in Terms of Harvest-Site Morbidity and Functional Outcomes , 2002, The Journal of bone and joint surgery. American volume.

[42]  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.

[43]  A. Minamide,et al.  Evaluation of Carriers of Bone Morphogenetic Protein for Spinal Fusion , 2001, Spine.

[44]  M. Salamon,et al.  The Role of Human Bone Morphogenetic Proteins in Spinal Fusion , 2000, The Journal of the American Academy of Orthopaedic Surgeons.

[45]  S. Boden,et al.  Posterolateral Lumbar Intertransverse Process Spine Arthrodesis With Recombinant Human Bone Morphogenetic Protein 2/Hydroxyapatite‐Tricalcium Phosphate After Laminectomy in the Nonhuman Primate , 1999, Spine.

[46]  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.

[47]  Paramore Cg.  The safety of OP-1 for lumbar fusion with decompression-- a canine study. , 1999 .

[48]  J. Wozney,et al.  Safety of Recombinant Human Bone Morphogenetic Protein‐2 After Spinal Laminectomy in the Dog , 1999, Spine.

[49]  W C Lauerman,et al.  A randomized prospective study of posterolateral lumbar fusion. Outcomes with and without pedicle screw instrumentation. , 1999, Spine.

[50]  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.

[51]  M. Mackay,et al.  1997 Volvo Award Winner in Clinical Studies: Degenerative Lumbar Spondylolisthesis With Spinal Stenosis: A Prospective, Randomized Study Comparing Decompressive Laminectomy and Arthrodesis With and Without Spinal Instrumentation , 1997, Spine.

[52]  R. Delamarter,et al.  Effective Doses of Recombinant Human Bone Morphogenetic Protein‐2 in Experimental Spinal Fusion , 1996, Spine.

[53]  A. Scutt,et al.  Subtle differences in the mitogenic effects of recombinant human bone morphogenetic proteins −2 to −7 on DNA synthesis on primary bone-forming cells and identification of BMP-2/4 receptor , 1996, Calcified Tissue International.

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

[55]  Marc A. Asher,et al.  Iliac Crest Bone Graft Harvest Donor Site Morbidity: A Statistical Evaluation , 1995, Spine.

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

[57]  V. Rosen,et al.  Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[58]  V. Rosen,et al.  Growth factors influencing bone development , 1990, Journal of Cell Science.

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

[60]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988, Science.

[61]  V. Rosen,et al.  Purification and characterization of other distinct bone-inducing factors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[62]  M. Urist,et al.  Bone: Formation by Autoinduction , 1965, Science.

[63]  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.

[64]  J. Szatkowski,et al.  Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). , 2003, The Journal of bone and joint surgery. American volume.

[65]  B. Cunningham,et al.  Osseointegration of autograft versus osteogenic protein-1 in posterolateral spinal arthrodesis: emphasis on the comparative mechanisms of bone induction. , 2002, The spine journal : official journal of the North American Spine Society.

[66]  M. Hadley,et al.  The safety of OP-1 for lumbar fusion with decompression-- a canine study. , 1999, Neurosurgery.

[67]  V. Rosen,et al.  Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. , 1998, Clinical orthopaedics and related research.

[68]  V. Rosen,et al.  Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo. , 1996, Growth factors.

[69]  H. Chambers,et al.  Complications of iliac crest bone graft harvesting. , 1996, Clinical orthopaedics and related research.

[70]  D. Kingsley,et al.  The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. , 1994, Genes & development.

[71]  R. Kaufman,et al.  Expression and characterization of bone morphogenetic protein-2 in Chinese hamster ovary cells. , 1992, Growth factors.

[72]  M. Chapman,et al.  Morbidity at bone graft donor sites. , 1989, Journal of orthopaedic trauma.