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Effect of Mixture of Recombinant Human Bone Morphogenic Protein-2 and Demineralized Bone Matrix in Lateral Lumbar Interbody Fusion

  • Jun Ik Son (Department of Neurosurgery, Chung-Ang University Hospital, College of Medicine, Chung-Ang University) ;
  • Young-Seok Lee (Department of Neurosurgery, Chung-Ang University Hospital, College of Medicine, Chung-Ang University) ;
  • Myeong Jin Ko (Department of Neurosurgery, Chung-Ang University Hospital, College of Medicine, Chung-Ang University) ;
  • Seong-Hyun Wui (Department of Neurosurgery, Chung-Ang University Gwangmyeong Hospital, College of Medicine, Chung-Ang University) ;
  • Seung Won Park (Department of Neurosurgery, Chung-Ang University Gwangmyeong Hospital, College of Medicine, Chung-Ang University)
  • Received : 2023.06.27
  • Accepted : 2023.10.11
  • Published : 2024.05.01

Abstract

Objective : This study aims to determine the optimal dose of recombinant-human bone morphogenic protein-2 (rhBMP-2) for successful bone fusion in minimally invasive lateral lumbar interbody fusion (MIS LLIF). Previous studies show that rhBMP is an effective alternative to autologous iliac crest bone graft, but the optimal dose remains uncertain. The study analyzes the fusion rates associated with different rhBMP doses to provide a recommendation for the optimal dose in MIS LLIF. Methods : Ninety-three patients underwent MIS LLIF using demineralized bone matrix (DBM) or a mixture of rhBMP-2 and DBM as fusion material. The group was divided into the following three groups according to the rhBMP-2 usage : group A, only DBM was used (n=27); group B, 1 mg of rhBMP-2 per 5 mL of DBM paste (n=41); and group C, 2 mg of rhBMP-2 per 5 mL of DBM paste (n=25). Demographic data, clinical outcomes, postoperative complication and fusion were assessed. Results : At 12 months post-surgery, the overall fusion rate was 92.3% according to Bridwell fusion grading system. Groups B and C, who received rhBMP-2, had significantly higher fusion rates than group A, who received only DBM. However, there was no significant increase in fusion rate when the rhBMP-2 dosage was increased from group B to group C. The groups B and C showed significant improvement in back pain and Oswestry disability index compared to the group A. The incidence of screw loosening was decreased in groups B and C, but there was no significant difference in the occurrence of other complications. Conclusion : Usage of rhBMP-2 in LLIF surgery leads to early and increased final fusion rates, which can result in faster pain relief and return to daily activities for patients. The benefits of using rhBMP-2 were not significantly different between the groups that received 1 mg/5 mL and 2 mg/5 mL of rhBMP-2. Therefore, it is recommended to use 1 mg of rhBMP-2 with 5 mL of DBM, taking both economic and clinical aspects into consideration.

Keywords

References

  1. Adams CL, Ogden K, Robertson IK, Broadhurst S, Edis D : Effectiveness and safety of recombinant human bone morphogenetic protein-2 versus local bone graft in primary lumbar interbody fusions. Spine (Phila Pa 1976) 39 : 164-171, 2014 https://doi.org/10.1097/BRS.0000000000000089
  2. Arrington ED, Smith WJ, Chambers HG, Bucknell AL, Davino NA : Complications of iliac crest bone graft harvesting. Clin Orthop Relat Res (329) : 300-309, 1996
  3. Bisschop A, van Engelen SJ, Kingma I, Holewijn RM, Stadhouder A, van der Veen AJ, et al. : Single level lumbar laminectomy alters segmental biomechanical behavior without affecting adjacent segments. Clin Biomech (Bristol, Avon) 29 : 912-917, 2014 https://doi.org/10.1016/j.clinbiomech.2014.06.016
  4. 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
  5. Boden SD, Wiesel SW : Lumbosacral segmental motion in normal individuals. Have we been measuring instability properly? Spine (Phila Pa 1976) 15 : 571-576, 1990 https://doi.org/10.1097/00007632-199006000-00026
  6. Boerckel JD, Kolambkar YM, Dupont KM, Uhrig BA, Phelps EA, Stevens HY, et al. : Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials 32 : 5241-5251, 2011 https://doi.org/10.1016/j.biomaterials.2011.03.063
  7. 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
  8. Burkus JK, Heim SE, Gornet MF, Zdeblick TA : Is INFUSE bone graft superior to autograft bone? An integrated analysis of clinical trials using the LT-CAGE lumbar tapered fusion device. J Spinal Disord Tech 16 : 113-122, 2003 https://doi.org/10.1097/00024720-200304000-00001
  9. Carreon LY, Glassman SD, Djurasovic M, Campbell MJ, Puno RM, Johnson JR, et al. : RhBMP-2 versus iliac crest bone graft for lumbar spine fusion in patients over 60 years of age: a cost-utility study. Spine (Phila Pa 1976) 34 : 238-243, 2009 https://doi.org/10.1097/BRS.0b013e31818ffabe
  10. Choudhri TF, Mummaneni PV, Dhall SS, Eck JC, Groff MW, Ghogawala Z, et al. : Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 4: radiographic assessment of fusion status. J Neurosurg Spine 21 : 23-30, 2014 https://doi.org/10.3171/2014.4.SPINE14267
  11. Chun DS, Baker KC, Hsu WK : Lumbar pseudarthrosis: a review of current diagnosis and treatment. Neurosurg Focus 39 : E10, 2015
  12. Desai A, Bekelis K, Ball PA, Lurie J, Mirza SK, Tosteson TD, et al. : Variation in outcomes across centers after surgery for lumbar stenosis and degenerative spondylolisthesis in the spine patient outcomes research trial. Spine (Phila Pa 1976) 38 : 678-691, 2013 https://doi.org/10.1097/BRS.0b013e318278e571
  13. Haid RW Jr, Branch CL Jr, Alexander JT, Burkus JK : Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. Spine J 4 : 527-538; discussion 538-539, 2004 https://doi.org/10.1016/j.spinee.2004.04.001
  14. Han S, Park B, Lim JW, Youm JY, Choi SW, Kim DH, et al. : Comparison of fusion rate between demineralized bone matrix versus autograft in lumbar fusion : meta-analysis. J Korean Neurosurg Soc 63 : 673-680, 2020 https://doi.org/10.3340/jkns.2019.0185
  15. Hofstetter CP, Hofer AS, Levi AD : Exploratory meta-analysis on dose-related efficacy and morbidity of bone morphogenetic protein in spinal arthrodesis surgery. J Neurosurg Spine 24 : 457-475, 2016 https://doi.org/10.3171/2015.4.SPINE141086
  16. Iii WS, Orias AAE, Shifflett GD, Lee JYB, Siemionow K, Gandhi S, et al. : Image-based markers predict dynamic instability in lumbar degenerative spondylolisthesis. Neurospine 17 : 221-227, 2020 https://doi.org/10.14245/ns.1938440.220
  17. Kaiser MG, Groff MW, Watters WC 3rd, Ghogawala Z, Mummaneni PV, Dailey AT, et al. : Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: bone graft extenders and substitutes as an adjunct for lumbar fusion. J Neurosurg Spine 21 : 106-132, 2014 https://doi.org/10.3171/2014.4.SPINE14325
  18. Kim JW, Park SW, Kim YB, Ko MJ : The effect of postoperative use of teriparatide reducing screw loosening in osteoporotic patients. J Korean Neurosurg Soc 61 : 494-502, 2018 https://doi.org/10.3340/jkns.2017.0216
  19. Ko MJ, Park SW, Kim YB : Effect of cage in radiological differences between direct and oblique lateral interbody fusion techniques. J Korean Neurosurg Soc 62 : 432-441, 2019 https://doi.org/10.3340/jkns.2018.0142
  20. Lee KK, Teo EC : Effects of laminectomy and facetectomy on the stability of the lumbar motion segment. Med Eng Phys 26 : 183-192, 2004 https://doi.org/10.1016/j.medengphy.2003.11.006
  21. Lytle EJ, Slavnic D, Tong D, Bahoura M, Govila L, Gonda R, et al. : Minimally effective dose of bone morphogenetic protein in minimally invasive lumbar interbody fusions: six hundred ninety patients in a dose-finding longitudinal cohort study. Spine (Phila Pa 1976) 44 : 989-995, 2019 https://doi.org/10.1097/BRS.0000000000002993
  22. Ozkaynak E, Schnegelsberg PN, Jin DF, Clifford GM, Warren FD, Drier EA, et al. : Osteogenic protein-2. A new member of the transforming growth factor-beta superfamily expressed early in embryogenesis. J Biol Chem 267 : 25220-25227, 1992 https://doi.org/10.1016/S0021-9258(19)74028-9
  23. Pearson HB, Dobbs CJ, Grantham E, Niebur GL, Chappuis JL, Boerckel JD : Intraoperative biomechanics of lumbar pedicle screw loosening following successful arthrodesis. J Orthop Res 35 : 2673-2681, 2017 https://doi.org/10.1002/jor.23575
  24. Raizman NM, O'Brien JR, Poehling-Monaghan KL, Yu WD : Pseudarthrosis of the spine. J Am Acad Orthop Surg 17 : 494-503, 2009 https://doi.org/10.5435/00124635-200908000-00003
  25. Rihn JA, Makda J, Hong J, Patel R, Hilibrand AS, Anderson DG, et al. : The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion: a clinical and radiographic analysis. Eur Spine J 18 : 1629-1636, 2009 https://doi.org/10.1007/s00586-009-1046-1
  26. Singh K, Nandyala SV, Marquez-Lara A, Cha TD, Khan SN, Fineberg SJ, et al. : Clinical sequelae after rhBMP-2 use in a minimally invasive transforaminal lumbar interbody fusion. Spine J 13 : 1118-1125, 2013 https://doi.org/10.1016/j.spinee.2013.07.028
  27. Slosar PJ, 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 7 : 301-307, 2007 https://doi.org/10.1016/j.spinee.2006.10.015
  28. Vaidya R, Weir R, Sethi A, Meisterling S, Hakeos W, Wybo CD : Interbody fusion with allograft and rhBMP-2 leads to consistent fusion but early subsidence. J Bone Joint Surg Br 89 : 342-345, 2007 https://doi.org/10.1302/0301-620X.89B3.18270
  29. Wozney JM : Overview of bone morphogenetic proteins. Spine (Phila Pa 1976) 27(16 Suppl 1) : S2-S8, 2002 https://doi.org/10.1097/00007632-200208151-00002