Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease

  • Hyun, Seung-Jae (Department of Neurosurgery, Spine Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Yoon, Seung Hwan (Department of Neurosurgery, Inha University College of Medicine) ;
  • Kim, Joo Han (Department of Neurosurgery, Korea University Guro Hospital, Korea University College of Medicine) ;
  • Oh, Jae Keun (Department of Neurosurgery, Spine Center, Hallym University Sacred Heart Hospital) ;
  • Lee, Chang-Hyun (Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Shin, Jun Jae (Department of Neurosurgery, Yongin Severance Hospital, Spine and Spinal Cord Institute, Yonsei University College of Medicine) ;
  • Kang, Jiin (Department of Neurosurgery, Yongin Severance Hospital, Spine and Spinal Cord Institute, Yonsei University College of Medicine) ;
  • Ha, Yoon (Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine)
  • Received : 2020.12.02
  • Accepted : 2021.01.27
  • Published : 2021.07.01
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Abstract

Objective : This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). Methods : This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. Results : The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. Conclusion : This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI16C0751).

References

  1. Boden SD, Kang J, Sandhu H, Heller JG : 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. Spine (Phila Pa 1976) 27 : 2662-2673, 2002 https://doi.org/10.1097/00007632-200212010-00005
  2. Bormann N, Schwabe P, Smith MD, Wildemann B : Analysis of parameters influencing the release of antibiotics mixed with bone grafting material using a reliable mixing procedure. Bone 59 : 162-172, 2014 https://doi.org/10.1016/j.bone.2013.11.005
  3. Brantigan JW, Steffee AD, Geiger JM : A carbon fiber implant to aid interbody lumbar fusion. Mechanical testing. Spine (Phila Pa 1976) 16(6 Suppl) : S277-S282, 1991 https://doi.org/10.1097/00007632-199106001-00020
  4. Brekke JH, Toth JM : Principles of tissue engineering applied to programmable osteogenesis. J Biomed Mater Res 43 : 380-398, 1998 https://doi.org/10.1002/(SICI)1097-4636(199824)43:4<380::AID-JBM6>3.0.CO;2-D
  5. Burkus JK, Gornet MF, Dickman CA, Zdeblick TA : Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages. J Spinal Disord Tech 15 : 337-349, 2002 https://doi.org/10.1097/00024720-200210000-00001
  6. Carragee EJ, Chu G, Rohatgi R, Hurwitz EL, Weiner BK, Yoon ST, et al. : Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis. J Bone Joint Surg Am 95 : 1537-1545, 2013 https://doi.org/10.2106/JBJS.L.01483
  7. Chang HK, Huang M, Wu JC, Huang WC, Wang MY : Less opioid consumption with enhanced recovery after surgery transforaminal lumbar interbody fusion (TLIF): a comparison to standard minimally-invasive TLIF. Neurospine 17 : 228-236, 2020 https://doi.org/10.14245/ns.1938422.211
  8. Chen NF, Smith ZA, Stiner E, Armin S, Sheikh H, Khoo LT : Symptomatic ectopic bone formation after off-label use of recombinant human bone morphogenetic protein-2 in transforaminal lumbar interbody fusion. J Neurosurg Spine 12 : 40-46, 2010 https://doi.org/10.3171/2009.4.SPINE0876
  9. Choudhry OJ, Christiano LD, Singh R, Golden BM, Liu JK : Bone morphogenetic protein-induced inflammatory cyst formation after lumbar fusion causing nerve root compression. J Neurosurg Spine 16 : 296-301, 2012 https://doi.org/10.3171/2011.11.SPINE11629
  10. Cooper GS, Kou TD : Risk of cancer after lumbar fusion surgery with recombinant human bone morphogenic protein-2 (rh-BMP-2). Spine (Phila Pa 1976) 38 : 1862-1868, 2013 https://doi.org/10.1097/BRS.0b013e3182a3d3b4
  11. Deutsch H : High-dose bone morphogenetic protein-induced ectopic abdomen bone growth. Spine J 10 : e1-e4, 2010 https://doi.org/10.1016/j.spinee.2009.10.016
  12. Epstein NE : Basic science and spine literature document bone morphogenetic protein increases cancer risk. Surg Neurol Int 5(suppl 15) : S552-S560, 2014
  13. Gitelman SE, Kobrin MS, Ye JQ, Lopez AR, Lee A, Derynck R : Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo. J Cell Biol 126 : 1595-1609, 1994 https://doi.org/10.1083/jcb.126.6.1595
  14. Gruskin E, Doll BA, Futrell FW, Schmitz JP, Hollinger JO : Demineralized bone matrix in bone repair: history and use. Adv Drug Deliv Rev 64 : 1063-1077, 2012 https://doi.org/10.1016/j.addr.2012.06.008
  15. Guerado E, Fuerstenberg CH : What bone graft substitutes should we use in post-traumatic spinal fusion? Injury 42 Suppl 2 : S64-S71, 2011 https://doi.org/10.1016/j.injury.2011.06.200
  16. Han B, Yang Z, Nimni M : Effects of moisture and temperature on the osteoinductivity of demineralized bone matrix. J Orthop Res 23 : 855-861, 2005 https://doi.org/10.1016/j.orthres.2004.11.007
  17. Haws BE, Khechen B, Patel DV, Yoo JS, Guntin JA, Cardinal KL, et al. : Impact of iliac crest bone grafting on postoperative outcomes and complication rates following minimally invasive transforaminal lumbar interbody fusion. Neurospine 16 : 772-779, 2019 https://doi.org/10.14245/ns.1938006.003
  18. Katayama Y, Matsuyama Y, Yoshihara H, Sakai Y, Nakamura H, Imagama S, et al. : Clinical and radiographic outcomes of posterolateral lumbar spine fusion in humans using recombinant human bone morphogenetic protein-2: an average five-year follow-up study. Int Orthop 33 : 1061-1067, 2009 https://doi.org/10.1007/s00264-008-0600-5
  19. Kim DJ : Autogenous bone graft and bone substitutes. J Korean Soc Spine Surg 15 : 54-65, 2008 https://doi.org/10.4184/jkss.2008.15.1.54
  20. Lad SP, Bagley JH, Karikari IO, Babu R, Ugiliweneza B, Kong M, et al. : Cancer after spinal fusion: the role of bone morphogenetic protein. Neurosurgery 73 : 440-449, 2013 https://doi.org/10.1227/NEU.0000000000000018
  21. Ma GW : Posterior lumbar interbody fusion with specialized instruments. Clin Orthop Relat Res (193) : 57-63, 1985
  22. Massaad E, Fatima N, Kiapour A, Hadzipasic M, Shankar GM, Shin JH : Polyetheretherketone versus titanium cages for posterior lumbar interbody fusion: meta-analysis and review of the literature. Neurospine 17 : 125-135, 2020 https://doi.org/10.14245/ns.2040058.029
  23. May RD, Frauchiger DA, Albers CE, Hofstetter W, Gantenbein B : Exogenous stimulation of human intervertebral disc cells in 3-dimensional alginate bead culture with BMP2 and L51P: cytocompatibility and effects on cell phenotype. Neurospine 17 : 77-87, 2020 https://doi.org/10.14245/ns.2040002.001
  24. McKay WF, Peckham SM, Badura JM : A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE bone graft). Int Orthop 31 : 729-734, 2007 https://doi.org/10.1007/s00264-007-0418-6
  25. Mindea SA, Shih P, Song JK : Recombinant human bone morphogenetic protein-2-induced radiculitis in elective minimally invasive transforaminal lumbar interbody fusions: a series review. Spine (Phila Pa 1976) 34 : 1480-1484; discussion 1485, 2009 https://doi.org/10.1097/BRS.0b013e3181a396a1
  26. Mummaneni PV, Pan J, Haid RW, Rodts GE : Contribution of recombinant human bone morphogenetic protein-2 to the rapid creation of interbody fusion when used in transforaminal lumbar interbody fusion: a preliminary report. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004. J Neurosurg Spine 1 : 19-23, 2004 https://doi.org/10.3171/spi.2004.1.1.0019
  27. Niederwanger M, Urist MR : Demineralized bone matrix supplied by bone banks for a carrier of recombinant human bone morphogenetic protein (rhBMP-2): a substitute for autogeneic bone grafts. J Oral Implantol 22 : 210-215, 1996
  28. Overley SC, McAnany SJ, Anwar MA, Merrill RK, Lovy A, Guzman JZ, et al. : Predictive factors and rates of fusion in minimally invasive transforaminal lumbar interbody fusion utilizing rhBMP-2 or mesenchymal stem cells. Int J Spine Surg 13 : 46-52, 2019 https://doi.org/10.14444/6007
  29. Rihn JA, Patel R, Makda J, Hong J, Anderson DG, Vaccaro AR, et al. : Complications associated with single-level transforaminal lumbar interbody fusion. Spine J 9 : 623-629, 2009 https://doi.org/10.1016/j.spinee.2009.04.004
  30. Sampath TK, Maliakal JC, Hauschka PV, Jones WK, Sasak H, Tucker RF, et al. : Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem 267 : 20352-20362, 1992 https://doi.org/10.1016/S0021-9258(19)88709-4
  31. Schmidmaier G, Herrmann S, Green J, Weber T, Scharfenberger A, Haas NP, et al. : Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation. Bone 39 : 1156-1163, 2006 https://doi.org/10.1016/j.bone.2006.05.023
  32. Shahlaie K, Kim KD : Occipitocervical fusion using recombinant human bone morphogenetic protein-2: adverse effects due to tissue swelling and seroma. Spine (Phila Pa 1976) 33 : 2361-2366, 2008 https://doi.org/10.1097/BRS.0b013e318183971d
  33. Smucker JD, Rhee JM, Singh K, Yoon ST, Heller JG : Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine. Spine (Phila Pa 1976) 31 : 2813-2819, 2006 https://doi.org/10.1097/01.brs.0000245863.52371.c2
  34. Takeda M : Experience in posterior lumbar interbody fusion: unicortical versus bicortical autologous grafts. Clin Orthop Relat Res (193) : 120-126, 1985
  35. Urist MR : Bone: formation by autoinduction. Science 150 : 893-899, 1965 https://doi.org/10.1126/science.150.3698.893
  36. Urist MR, Strates BS : Bone formation in implants of partially and wholly demineralized bone matrix. Including observations on acetone-fixed intra and extracellular proteins. Clin Orthop Relat Res 71 : 271-278, 1970
  37. Villavicencio AT, Burneikiene S, Nelson EL, Bulsara KR, Favors M, Thramann J : Safety of transforaminal lumbar interbody fusion and intervertebral recombinant human bone morphogenetic protein-2. J Neurosurg Spine 3 : 436-443, 2005 https://doi.org/10.3171/spi.2005.3.6.0436
  38. Winn SR, Uludag H, Hollinger JO : Carrier systems for bone morphogenetic proteins. Clin Orthop Relat Res (367 Suppl) : S95-S106, 1999 https://doi.org/10.1097/00003086-199910001-00010
  39. Yan L, Chang Z, He B, Liu T, Wang X, Guo H, et al. : Efficacy of rhBMP-2 versus iliac crest bone graft for posterior C1-C2 fusion in patients older than 60 years. Orthopedics 37 : e51-e57, 2014 https://doi.org/10.3928/01477447-20131219-17