Current Updates on Bone Grafting Biomaterials and Recombinant Human Growth Factors Implanted Biotherapy for Spinal Fusion: A Review of Human Clinical Studies

Author(s): Guanbao Li*, Pinquan Li, Qiuan Chen, Hnin Ei Thu, Zahid Hussain.

Journal Name: Current Drug Delivery

Volume 16 , Issue 2 , 2019

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Graphical Abstract:


Abstract:

Background: Owing to their great promise in the spinal surgeries, bone graft substitutes have been widely investigated for their safety and clinical potential. By the current advances in the spinal surgery, an understanding of the precise biological mechanism of each bone graft substitute is mandatory for upholding the induction of solid spinal fusion.

Objective: The aim of the present review is to critically discuss various surgical implications and level of evidence of most commonly employed bone graft substitutes for spinal fusion.

Method: Data was collected via electronic search using “PubMed”, “SciFinder”, “ScienceDirect”, “Google Scholar”, “Web of Science” and a library search for articles published in peer-reviewed journals, conferences, and e-books.

Results: Despite having exceptional inherent osteogenic, osteoinductive, and osteoconductive features, clinical acceptability of autografts (patient’s own bone) is limited due to several perioperative and postoperative complications i.e., donor-site morbidities and limited graft supply. Alternatively, allografts (bone harvested from cadaver) have shown great promise in achieving acceptable bone fusion rate while alleviating the donor-site morbidities associated with implantation of autografts. As an adjuvant to allograft, demineralized bone matrix (DBM) has shown remarkable efficacy of bone fusion, when employed as graft extender or graft enhancer. Recent advances in recombinant technologies have made it possible to implant growth and differentiation factors (bone morphogenetic proteins) for spinal fusion.

Conclusion: Selection of a particular bone grafting biotherapy can be rationalized based on the level of spine fusion, clinical experience and preference of orthopaedic surgeon, and prevalence of donor-site morbidities.

Keywords: Spinal fusion, neurosurgical procedure, autograft, allograft, demineralized bone matrix, growth factor proteins.

[1]
Nyström, B. Spinal fusion in the treatment of chronic low back pain: Rationale for improvement. Open Orthop. J., 2012, 6, 478-481.
[2]
Nyström, B.; Weber, H.; Schillberg, B.; Taube, A. Symptoms and signs possibly indicating segmental, discogenic pain. A fusion study with 18 years of follow-up. Scand. J. Pain, 2017, 16, 213-220.
[3]
Machado, G.C.; Ferreira, P.H.; Yoo, R.; Harris, I.A.; Pinheiro, M.B.; Koes, B.W.; van Tulder, M.W.; Rzewuska, M.; Maher, C.G.; Ferreira, M.L. Surgical options for lumbar spinal stenosis. Cochrane Database Syst. Rev., 2016, 11, CD012421.
[4]
Boden, S.D. Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute. Spine. Phila Pa, 1976, 2002(27), S26-S31.
[5]
Jacobs, W.; Van der Gaag, N.A.; Tuschel, A.; de Kleuver, M.; Peul, W.; Verbout, A.J.; Oner, F.C. Total disc replacement for chronic back pain in the presence of disc degeneration. Cochrane Database Syst. Rev., 2012, 9, CD008326.
[6]
Cammisa, F.P.; Lowery, G.; Garfin, S.R.; Geisler, F.H.; Klara, P.M.; McGuire, R.A.; Sassard, W.R.; Stubbs, H.; Block, J.E. Two-year fusion rate equivalency between Grafton DBM gel and autograft in posterolateral spine fusion: A prospective controlled trial employing a side-by-side comparison in the same patient. Spine. Phila Pa, 1976, 2004(29), 660-666.
[7]
McGregor, A.H.; Probyn, K.; Cro, S.; Doré, C.J.; Burton, A.K.; Balagué, F.; Pincus, T.; Fairbank, J. Rehabilitation following surgery for lumbar spinal stenosis. Cochrane Database Syst. Rev., 2013, 12, CD009644.
[8]
Zaina, F.; Tomkins-Lane, C.; Carragee, E.; Negrini, S. Surgical versus non-surgical treatment for lumbar spinal stenosis. Cochrane Database Syst. Rev., 2016, 29, CD010264.
[9]
Machado, G.C.; Ferreira, P.H.; Harris, I.A.; Pinheiro, M.B.; Koes, B.W.; van Tulder, M.; Rzewuska, M.; Maher, C.G.; Ferreira, M.L. Effectiveness of surgery for lumbar spinal stenosis: A systematic review and meta-analysis. PLoS One, 2015, 10, e0122800.
[10]
Ammendolia, C.; Stuber, K.J.; Rok, E.; Rampersaud, R.; Kennedy, C.A.; Pennick, V.; Steenstra, I.A.; de Bruin, L.K.; Furlan, A.D. Nonoperative treatment for lumbar spinal stenosis with neurogenic claudication. Cochrane Database Syst. Rev., 2013, 8, CD010712.
[11]
Ammendolia, C.; Stuber, K.; Tomkins-Lane, C.; Schneider, M.; Rampersaud, Y.R.; Furlan, A.D.; Kennedy, C.A. What interventions improve walking ability in neurogenic claudication with lumbar spinal stenosis? A systematic review. Eur. Spine J., 2014, 23, 1282-1301.
[12]
Rajaee, S.S.; Bae, H.W.; Kanim, L.E.; Delamarter, R.B. Spinal fusion in the United States: Analysis of trends from 1998 to 2008. Spine. Phila Pa, 1976, 2012(37), 67-76.
[13]
Yavin, D.; Casha, S.; Wiebe, S.; Feasby, T.E.; Clark, C.; Isaacs, A.; Holroyd-Leduc, J.; Hurlbert, R.J.; Quan, H.; Nataraj, A.; Sutherland, G.R.; Jette, N. Lumbar fusion for degenerative disease: A systematic review and meta-analysis. Neurosurgery, 2017, 80, 701-715.
[14]
Duarte, R.M.; Vaccaro, A.R. Spinal infection: State of the art and management algorithm. Eur. Spine J., 2013, 22, 2787-2799.
[15]
Dahners, L.E.; Mullis, B.H. Effects of nonsteroidal anti-inflammatory drugs on bone formation and soft-tissue healing. J. Am. Acad. Orthop. Surg., 2004, 12, 139-143.
[16]
Malloy, K.M.; Hilibrand, A.S. Autograft versus allograft in degenerative cervical disease. Clin. Orthop. Relat. Res., 2002, (394), 27-38.
[17]
Fei, Q.; Li, J.; Lin, J.; Li, D.; Wang, B.; Meng, H.; Wang, Q.; Su, N.; Yang, Y. Risk factors for surgical site infection after spinal surgery: A meta-analysis. World Neurosurg., 2016, 95, 507-515.
[18]
Olsen, M.A.; Nepple, J.J.; Riew, K.D.; Lenke, L.G.; Bridwell, K.H.; Mayfield, J.; Fraser, V.J. Risk factors for surgical site infection following orthopaedic spinal operations. J. Bone Joint Surg. Am., 2008, 90, 62-69.
[19]
Meng, F.; Cao, J.; Meng, X. Risk factors for surgical site infections following spinal surgery. J. Clin. Neurosci., 2015, 22, 1862-1866.
[20]
Shields, L.B.E.; Clark, L.; Glassman, S.D.; Shields, C.B. Decreasing hospital length of stay following lumbar fusion utilizing multidisciplinary committee meetings involving surgeons and other caretakers. Surg. Neurol. Int., 2017, 8, 5.
[21]
McGregor, A.H.; Probyn, K.; Cro, S.; Doré, C.J.; Burton, A.K.; Balagué, F.; Pincus, T.; Fairbank, J. Rehabilitation following surgery for lumbar spinal stenosis. Cochrane Database Syst. Rev., 2013, 12, CD009644.
[22]
Giannoudis, P.V.; Dinopoulos, H.; Tsiridis, E. Bone substitutes: An update. Injury, 2005, 36, S20-S27.
[23]
Burwell, R.G. The function of bone marrow in the incorporation of bone graft. Clin. Orth. Rel. Res., 1985, 200, 125-141.
[24]
Salama, R.; Weissman, S.L. The clinical use of combined xenografts of bone and autologous red marrow. A preliminary report. J. Bone Joint Surg, 1978, 60, 111-115.
[25]
Begley, C.T.; Doherty, M.J.; Hankey, D.P.; Wilson, D.J. The culture of human osteoblasts upon bone graft substitutes. Bone, 1993, 14, 661-666.
[26]
Connolly, J.F.; Guse, R.; Tiedeman, J.; Dehne, R. Autologous marrow injection as a substitute for operative grafting of tibial nonunions. Clin. Orth., 1991, 266, 259-270.
[27]
Gibson, S.; McLeod, I.; Wardlaw, D.; Urbaniak, S. Allograft versus autograft in instrumented posterolateral lumbar spinal fusion: A randomized control trial. Spine. Phila Pa, 1976, 2002(27), 1599-1603.
[28]
Samartzis, D.; Shen, F.H.; Goldberg, E.J.; An, H.S. Is autograft the gold standard in achieving radiographic fusion in one-level anterior cervical discectomy and fusion with rigid anterior plate fixation? Spine. Phila Pa, 1976, 2005(30), 1756-1761.
[29]
Samartzis, D.; Shen, F.H.; Matthews, D.K.; Yoon, S.T.; Goldberg, E.J.; An, H.S. Comparison of allograft to autograft in multilevel anterior cervical discectomy and fusion with rigid plate fixation. Spine J., 2003, 3, 451-459.
[30]
Liao, Z.; Wang, C.H.; Cui, W.L. Comparison of allograft and autograft in lumbar fusion for lumbar degenerative diseases: A systematic review. J. Invest. Surg., 2016, 29, 373-382.
[31]
Tuchman, A.; Brodke, D.S.; Youssef, J.A.; Meisel, H.J.; Dettori, J.R.; Park, J.B.; Yoon, S.T.; Wang, J.C. Iliac crest bone graft versus local autograft or allograft for lumbar spinal fusion: A systematic Review. Global Spine J., 2016, 6, 592-606.
[32]
France, J.C.; Schuster, J.M.; Moran, K.; Dettori, J.R. Iliac crest bone graft in lumbar fusion: The effectiveness and safety compared with local bone graft, and graft site morbidity comparing a single-incision midline approach with a two-incision traditional approach. Global Spine J., 2015, 5, 195-206.
[33]
Radcliff, K.; Hwang, R.; Hilibrand, A.; Smith, H.E.; Gruskay, J.; Lurie, J.D.; Zhao, W.; Albert, T.; Weinstein, J. The effect of iliac crest autograft on the outcome of fusion in the setting of degenerative spondylolisthesis: A subgroup analysis of the Spine Patient Outcomes Research Trial (SPORT). J. Bone Joint Surg. Am., 2012, 94, 1685-1692.
[34]
Tuchman, A.; Brodke, D.S.; Youssef, J.A.; Meisel, H.J.; Dettori, J.R.; Park, J.B.; Yoon, S.T.; Wang, J.C. Autograft versus allograft for cervical spinal fusion: A systematic review. Global Spine J., 2017, 7, 59-70.
[35]
Montgomery, D.M.; Aronson, D.D.; Lee, C.L.; LaMont, R.L. Posterior spinal fusion: Allograft versus autograft bone. J. Spinal Disord., 1990, 3, 370-375.
[36]
Wang, Y.; Zhang, Y.G.; Zhao, S.K.; Xiao, S.H.; Liu, Z.S.; Liu, B.W. Freeze-dried allograft of posterior spinal fusion in patients with scoliosis. Zhonghua Wai Ke Za Zhi, 2004, 42, 1178-1181.
[37]
Bishop, R.C.; Moore, K.A.; Hadley, M.N. Anterior cervical interbody fusion using autogeneic and allogeneic bone graft substrate: A prospective comparative analysis. J. Neurosurg., 1996, 85, 206-210.
[38]
Young, W.F.; Rosenwasser, R.H. An early comparative analysis of the use of fibular allograft versus autologous iliac crest graft for interbody fusion after anterior cervical discectomy. Spine, 1993, 18, 1123-1124.
[39]
Savolainen, S.; Usenius, J.P.; Hernesniemi, J. Iliac crest versus artificial bone grafts in 250 cervical fusions. Acta Neurochir., (Wien), 1994, 129, 54-57.
[40]
Zhang, Z.H.; Yin, H.; Yang, K.; Zhang, T.; Dong, F.; Dang, G.; Lou, S.Q.; Cai, Q. Anterior intervertebral disc excision and bone grafting in cervical spondylotic myelopathy. Spine. (Phila Pa 1976), 1983, 8, 16-19.
[41]
Zdeblick, T.A.; Ducker, T.B. The use of freeze-dried allograft bone for anterior cervical fusions. Spine. Phila Pa, 1976, 1991(16), 726-729.
[42]
Jorgenson, S.S.; Lowe, T.G.; France, J.; Sabin, J. A prospective analysis of autograft versus allograft in posterolateral lumbar fusion in the same patient. A minimum of 1-year follow-up in 144 patients. Spine. Phila Pa, 1976, 1994(19), 2048-2053.
[43]
An, H.S.; Lynch, K.; Toth, J. Prospective comparison of autograft vs allograft for adult posterolateral lumbar spine fusion: Differences among freeze-dried, frozen, and mixed grafts. J. Spinal Disord., 1995, 8, 131-135.
[44]
Aurori, B.F.; Weierman, R.J.; Lowell, H.A.; Nadel, C.I.; Parsons, J.R. Pseudarthrosis after spinal fusion for scoliosis. A comparison of autogeneic and allogeneic bone grafts. Clin. Orthop. Relat. Res., 1985, (199), 153-158.
[45]
Dodd, C.A.; Fergusson, C.M.; Freedman, L.; Houghton, G.R.; Thomas, D. Allograft versus autograft bone in scoliosis surgery. J. Bone Joint Surg. Br., 1988, 70, 431-434.
[46]
Parthiban, J.K.; Singhania, B.K.; Ramani, P.S. A radiological evaluation of allografts (ethylene oxide sterilized cadaver bone) and autografts in anterior cervical fusion. Neurol. India, 2002, 50, 17-22.
[47]
Suchomel, P.; Barsa, P.; Buchvald, P.; Svobodnik, A.; Vanickova, E. Autologous versus allogenic bone grafts in instrumented anterior cervical discectomy and fusion: A prospective study with respect to bone union pattern. Eur. Spine J., 2004, 13, 510-515.
[48]
Buttermann, G.R. Prospective nonrandomized comparison of an allograft with bone morphogenic protein versus an iliac-crest autograft in anterior cervical discectomy and fusion. Spine J., 2008, 8, 426-435.
[49]
Kao, F.C.; Niu, C.C.; Chen, L.H.; Lai, P.L.; Chen, W.J. Maintenance of interbody space in one- and two-level anterior cervical interbody fusion: Comparison of the effectiveness of autograft, allograft, and cage. Clin. Orthop. Relat. Res., 2005, (430), 108-116.
[50]
Cammisa, F.P., Jr; Lowery, G.; Garfin, S.R.; Geisler, F.H.; Klara, P.M.; McGuire, R.A.; Sassard, W.R.; Stubbs, H.; Block, J.E. Two-year fusion rate equivalency between Grafton DBM gel and autograft in posterolateral spine fusion: A prospective controlled trial employing a side-by-side comparison in the same patient. Spine. Phila Pa, 1976, 2004(29), 660-666.
[51]
Price, C.T.; Connolly, J.F.; Carantzas, A.C.; Ilyas, I. Comparison of bone grafts for posterior spinal fusion in adolescent idiopathic scoliosis. Spine. (Phila Pa 1976), 2003, 28, 793-798.
[52]
Berven, S.; Tay, B.K.; Kleinstueck, F.S.; Bradford, D.S. Clinical applications of bone graft substitutes in spine surgery: Consideration of mineralized and demineralized preparations and growth factor supplementation. Eur. Spine J., 2001, 10, S169-S177.
[53]
Chalmers, J.; Gray, D.H.; Rush, J. Observations on the induction of bone in soft tissues. J. Bone Joint Surg. Br., 1975, 57, 36-45.
[54]
Dahners, L.E.; Jacobs, R.R. Long bone defects treated with demineralized bone. South. Med. J., 1985, 78, 933-934.
[55]
Han, B.; Tang, B.; Nimni, M.E. Quantitative and sensitive in vitro assay for osteoinductive activity of demineralized bone matrix. J. Orthop. Res., 2003, 21, 648-654.
[56]
Oakes, D.A.; Lee, C.C.; Lieberman, J.R. An evaluation of human demineralized bone matrices in a rat femoral defect model. Clin. Orthop. Relat. Res., 2003, (413), 281-290.
[57]
Takikawa, S.; Bauer, T.W.; Kambic, H.; Togawa, D. Comparative evaluation of the osteoinductivity of two formulations of human demineralized bone matrix. J. Biomed. Mater. Res. A, 2003, 65, 37-42.
[58]
Peterson, B.; Whang, P.G.; Iglesias, R.; Wang, J.C.; Lieberman, J.R. Osteoinductivity of commercially available demineralized bone matrix. Preparations in a spine fusion model. J. Bone Joint Surg. Am., 2004, 86-A, 2243-2250.
[59]
Lee, Y.P.; Jo, M.; Luna, M.; Chien, B.; Lieberman, J.R.; Wang, J.C. The efficacy of different commercially available demineralized bone matrix substances in an athymic rat model. J. Spinal Disord. Tech., 2005, 18, 439-444.
[60]
Wildemann, B.; Kadow-Romacker, A.; Haas, N.P.; Schmidmaier, G. Quantification of various growth factors in different demineralized bone matrix preparations. J. Biomed. Mater. Res. A, 2007, 81, 437-442.
[61]
Brown, M.D.; Malinin, T.; Davis, P.B. A roentgenographic evaluation of frozen allografts versus autografts in anterior cervical spine fusions. Clin. Orthop. Relat. Res., 1976, 119, 231-236.
[62]
Urist, M.R. Bone: Formation by autoinduction. Science, 1965, 150, 893-899.
[63]
Buring, K.; Urist, M.R. Effects of ionizing radiation on the bone induction principle in the matrix of bone implants. Clin. Orthop. Relat. Res., 1967, 55, 225-234.
[64]
Dubuc, F.L.; Urist, M.R. The accessibility of the bone induction principle in surface-decalcified bone implants. Clin. Orthop. Relat. Res., 1967, 55, 217-223.
[65]
Urist, M.R.; Silverman, B.F.; Büring, K.; Dubuc, F.L.; Rosenberg, J.M. The bone induction principle. Clin. Orthop. Relat. Res., 1967, (53), 243-283.
[66]
Jones, C.B. Biological basis of fracture healing. J. Orthop. Trauma, 2005, 19, S1-S3.
[67]
Guizzardi, S.; Di Silvestre, M.; Scandroglio, R.; Ruggeri, A.; Savini, R. Implants of heterologous demineralized bone matrix for induction of posterior spinal fusion in rats. Spine, 1992, 17, 701-707.
[68]
Bae, H.W.; Zhao, L.; Kanim, L.E.; Wong, P.; Delamarter, R.B.; Dawson, E.G. Intervariability and intravariability of bone morphogenetic proteins in commercially available demineralized bone matrix products. Spine. (Phila Pa 1976), 2006, 31, 1299-1306.
[69]
An, H.S.; Simpson, J.M.; Glover, J.M.; Stephany, J. Comparison between allograft plus demineralized bone matrix versus autograft in anterior cervical fusion. A prospective multicentre study. Spine. (Phila Pa 1976), 1995, 20, 2211-2216.
[70]
Vaidya, R.; Carp, J.; Sethi, A.; Bartol, S.; Craig, J.; Les, C.M. Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. Eur. Spine J., 2007, 16, 1257-1265.
[71]
Park, H.W.; Lee, J.K.; Moon, S.J.; Seo, S.K.; Lee, J.H.; Kim, S.H. The efficacy of the synthetic interbody cage and Grafton for anterior cervical fusion. Spine. (Phila Pa 1976), 2009, 34, E591-E595.
[72]
Topuz, K.; Colak, A.; Kaya, S.; Simşek, H.; Kutlay, M.; Demircan, M.N.; Velioğlu, M. Two-level contiguous cervical disc disease treated with peek cages packed with demineralized bone matrix: results of 3-year follow-up. Eur. Spine J., 2009, 18, 238-243.
[73]
Moon, H.J.; Kim, J.H.; Kim, J.H.; Kwon, T.H.; Chung, H.S.; Park, Y.K. The effects of anterior cervical discectomy and fusion with stand-alone cages at two contiguous levels on cervical alignment and outcomes. Acta Neurochir. , 2011, 153, 559-565. [Wien].
[74]
Demircan, M.N.; Kutlay, A.M.; Colak, A.; Kaya, S.; Tekin, T.; Kibici, K.; Ungoren, K. Multilevel cervical fusion without plates, screws or autogenous iliac crest bone graft. J. Clin. Neurosci., 2007, 14, 723-728.
[75]
Kang, J.; An, H.; Hilibrand, A.; Yoon, S.T.; Kavanagh, E.; Boden, S. Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. Spine. (Phila Pa 1976), 2012, 37, 1083-1091.
[76]
Vaccaro, A.R.; Stubbs, H.A.; Block, J.E. Demineralized bone matrix composite grafting for posterolateral spinal fusion. Orthopedics, 2007, 30, 567-570.
[77]
Sassard, W.R.; Eidman, D.K.; Gray, P.M.; Block, J.E.; Russo, R.; Russell, J.L.; Taboada, E.M. Augmenting local bone with Grafton demineralized bone matrix for posterolateral lumbar spine fusion: Avoiding second site autologous bone harvest. Orthopedics, 2000, 23, 1059-1064.
[78]
Schizas, C.; Triantafyllopoulos, D.; Kosmopoulos, V.; Tzinieris, N.; Stafylas, K. Posterolateral lumbar spine fusion using a novel demineralized bone matrix: A controlled case pilot study. Arch. Orthop. Trauma Surg., 2008, 128, 621-625.
[79]
Epstein, N.E.; Epstein, J.A. SF-36 outcomes and fusion rates after multilevel laminectomies and 1 and 2-level instrumented posterolateral fusions using lamina autograft and demineralized bone matrix. J. Spinal Disord. Tech., 2007, 20, 139-145.
[80]
Thalgott, J.S.; Giuffre, J.M.; Klezl, Z.; Timlin, M. Anterior lumbar interbody fusion with titanium mesh cages, coralline hydroxyapatite, and demineralized bone matrix as part of a circumferential fusion. Spine J., 2002, 2, 63-69.
[81]
Girardi, F.P.; Cammisa, F.P. The effect of bone graft extenders to enhance the performance of iliac crest bone grafts in instrumented lumbar spine fusion. Orthopedics, 2003, 26, s545-s548.
[82]
Thalgott, J.S.; Giuffre, J.M.; Fritts, K.; Timlin, M.; Klezl, Z. Instrumented posterolateral lumbar fusion using coralline hydroxyapatite with or without demineralized bone matrix, as an adjunct to autologous bone. Spine J., 2001, 1, 131-137.
[83]
Epstein, N.E. Fusion rates and SF-36 outcomes after multilevel laminectomy and noninstrumented lumbar fusions in a predominantly geriatric population. J. Spinal Disord. Tech., 2008, 21, 159-164.
[84]
Wozney, J.M. Overview of bone morphogenetic proteins. Spine. (Phila Pa 1976), 2002, 27, S2-S8.
[85]
Mehler, M.F.; Mabie, P.C.; Zhang, D.; Kessler, J.A. Bone morphogenetic proteins in the nervous system. Trends Neurosci., 1997, 20, 309-317.
[86]
Zhang, H.; Wang, F.; Ding, L.; Zhang, Z.; Sun, D.; Feng, X.; An, J. 2.; Zhu, Y. A meta analysis of lumbar spinal fusion surgery using bone morphogenetic proteins and autologous iliac crest bone graft. PLoS One, 2014, 9, e97049.
[87]
Noshchenko, A.; Hoffecker, L.; Lindley, E.M.; Burger, E.L.; Cain, C.M.; Patel, V.V. Perioperative and long-term clinical outcomes for bone morphogenetic protein versus iliac crest bone graft for lumbar fusion in degenerative disk disease: Systematic review with meta-analysis. J. Spinal Disord. Tech., 2014, 27, 117-135.
[88]
Chen, Z.; Ba, G.; Shen, T.; Fu, Q. Recombinant human bone morphogenetic protein-2 versus autogenous iliac crest bone graft for lumbar fusion: A meta-analysis of ten randomized controlled trials. Arch. Orthop. Trauma Surg., 2012, 132, 1725-1740.
[89]
Ye, F.; Zeng, Z.; Wang, J.; Liu, H.; Wang, H.; Zheng, Z. Comparison of the use of rhBMP-7 versus iliac crest autograft in single-level lumbar fusion: A meta-analysis of randomized controlled trials. J. Bone Miner. Metab., 2018, 36, 119-127.
[90]
Baskin, D.S.; Ryan, P.; Sonntag, V.; Westmark, R.; Widmayer, M.A. A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate. Spine, 2003, 28, 1219-1224.
[91]
Shields, L.B.; Raque, G.H.; Glassman, S.D.; Campbell, M.; Vitaz, T.; Harpring, J.; Shields, C.B. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine, 2006, 31, 542-547.
[92]
Vaidya, R.; Carp, J.; Sethi, A.; Bartol, S.; Craig, J.; Les, C.M. Complications of anterior cervical discectomy and fusion using recombinant human bone morphogenetic protein-2. Eur. Spine J., 2007, 16, 1257-1265.
[93]
Boden, S.D.; Zdeblick, T.A.; Sandhu, H.S.; Heim, S.E. The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: A preliminary report. Spine, 2000, 25, 376-381.
[94]
Burkus, J.K.; Dorchak, J.D.; Sanders, D.L. Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2. Spine, 2003, 28, 372-377.
[95]
Burkus, J.K.; Gornet, M.F.; Dickman, C.A.; Zdeblick, T.A. Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J. Spinal Disord. Tech., 2002, 15, 337-349.
[96]
Burkus, J.K.; Transfeldt, E.E.; Kitchel, S.H.; Watkins, R.G.; Balderston, R.A. Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine, 2002, 27, 2396-2408.
[97]
Slosar, P.J.; Josey, R.; Reynolds, J. Accelerating lumbar fusions by combining rhBMP-2 with allograft bone: A prospective analysis of interbody fusion rates and clinical outcomes. Spine J., 2007, 7, 301-307.
[98]
McClellan, J.W.; Mulconrey, D.S.; Forbes, R.J.; Fullmer, N. Vertebral bone resorption after transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J. Spinal Disord. Tech., 2006, 19, 83-486.
[99]
Pradhan, B.B.; Bae, H.W.; Dawson, E.G.; Patel, V.V.; Delamarter, R.B. Graft resorption with the use of bone morphogenetic protein: Lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2. Spine J., 2006, 31, E277-E284.
[100]
Dimar, J.R.; Glassman, S.D.; Burkus, K.J.; Carreon, L.Y. 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. Spine, 2006, 31, 2534-2539.
[101]
Park, D.K.; Kim, S.S.; Thakur, N.; Boden, S.D. Use of recombinant human bone morphogenetic protein-2 with local bone graft instead of iliac crest bone graft in posterolateral lumbar spine arthrodesis. Spine. (Phila Pa 1976), 2013, 38, E738-E747.
[102]
Singh, K.; Smucker, J.D.; Gill, S.; Boden, S.D. 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. J. Spinal Disord. Tech., 2006, 19, 416-423.


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VOLUME: 16
ISSUE: 2
Year: 2019
Page: [94 - 110]
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DOI: 10.2174/1567201815666181024142354
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