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Fusion Biologics

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Minimally Invasive Spine Surgery

Abstract

The biology of spinal fusion is a complex process that requires perfect coordination of multiple molecular, cellular, and structural events for a successful outcome. Although spinal fusion surgery has been performed for decades, the understanding of this process is still in a state of evolution. Current focus has been on elucidating the mechanism of fusion and finding alternatives or adjuncts to the traditionally viewed gold standard of iliac crest bone autograft. Studies of the process of bone healing and formation have described some of the critical components and, therefore, targets to harvest or replicate. The identification and successful application of growth factors found during bone healing has led to increasing interest in the molecular mechanisms of spinal fusion. These topics serve as current and future areas for investigation. Vast arrays of clinically available spinal biologics exist or are planned. It is vital that surgeons have an understanding of the basic science of spinal fusion to facilitate critical decision making when choosing, or forgoing, a bone graft alternative.

Spinal fusion is the bony union of two or more contiguous vertebrae causing elimination of motion at the respective segment(s). The biologic principles of spinal fusion are complex and multifactorial. Although it shares some fundamental attributes of long bone fracture healing, spinal fusion has its own unique considerations that are not as well understood. The steady increase in spinal fusion surgery in recent decades and the potential morbidity associated with pseudoarthrosis have brought with it an increasing interest in the biology of spinal fusion. The advent of improved animal models has helped further our knowledge and provided important agents to assist in promoting fusion. As the array of available bone graft options and alternatives increases, it is important to understand the underlying basic science to facilitate decision making and provide optimal outcome.

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References

  1. Boden SD, Schimandle JH, Hutton WC. An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine (Phila Pa 1976). 1995;20(4):412–20.

    Article  CAS  Google Scholar 

  2. Ludwig SC, Boden SD. Osteoinductive bone graft substitutes for spinal fusion: a basic science summary. Orthop Clin North Am. 1999;30(4):635–45.

    Article  CAS  PubMed  Google Scholar 

  3. Herkowitz H, Garfin SR, Eismont FJ, Bell GR, Balderston RA, editors. Rothman-Simeone the spine. 6th ed. Philadelphia: Elsevier; 2011.

    Google Scholar 

  4. Boden SD, Schimandle JH, Hutton WC, Chen MI. 1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor for lumbar spinal fusion. Part I: Biology of spinal fusion. Spine (Phila Pa 1976). 1995;20(24):2626–32.

    Article  CAS  Google Scholar 

  5. Morone MA, Boden SD, Hair G, Martin GJ, Jr., Racine M, Titus L, Hutton WC. The Marshall R. Urist Young Investigator Award. Gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2. Clin Orthop Relat Res. 1998;(351):252–65.

    Google Scholar 

  6. Bosch P, Musgrave DS, Lee JY, Cummins J, Shuler T, Ghivizzani TC, Evans T, Robbins TD, Huard. Osteoprogenitor cells within skeletal muscle. J Orthop Res. 2000;18(6):933–44.

    Article  CAS  PubMed  Google Scholar 

  7. Lee KJ, Roper JG, Wang JC. Demineralized bone matrix and spinal arthrodesis. Spine J. 2005;5(6 Suppl):217S–23.

    Article  PubMed  Google Scholar 

  8. Silber JS, Anderson DG, Daffner SD, Brislin BT, Leland JM, Hilibrand AS, Vaccaro AR, Albert TJ. Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion. Spine (Phila Pa 1976). 2003;28(2):134–9.

    Article  Google Scholar 

  9. Banwart JC, Asher MA, Hassanein RS. Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. Spine (Phila Pa 1976). 1995;20(9):1055–60.

    Article  CAS  Google Scholar 

  10. Burchardt H. The biology of bone graft repair. Clin Orthop Relat Res. 1983;174:28–42.

    PubMed  Google Scholar 

  11. Enneking WF, Burchardt H, Puhl JJ, Piotrowski G. Physical and biological aspects of repair in dog cortical-bone transplants. J Bone Joint Surg Am. 1975;57(2):237–52.

    CAS  PubMed  Google Scholar 

  12. Johnson KA, Howlett CR, Bellenger CR, Armati-Gulson P. Osteogenesis by canine and rabbit bone marrow in diffusion chambers. Calcif Tissue Int. 1988;42(2):113–8.

    Article  CAS  PubMed  Google Scholar 

  13. Paley D, Young MC, Wiley AM, Fornasier VL, Jackson RW. Percutaneous bone marrow grafting of fractures and bony defects. An experimental study in rabbits. Clin Orthop Relat Res. 1986;208:300–12.

    PubMed  Google Scholar 

  14. Tanaka K, Takemoto M, Fujibayashi S, Neo M, Shikinami Y, Nakamura T. A bioactive and bioresorbable porous cubic composite scaffold loaded with bone marrow aspirate: a potential alternative to autogenous bone grafting. Spine (Phila Pa 1976). 2011;36(6):441–7.

    Article  Google Scholar 

  15. Muschler GF, Nitto H, Boehm CA, Easley KA. Age- and gender-related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res. 2001;19(1):117–25.

    Article  CAS  PubMed  Google Scholar 

  16. Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am. 1997;79(11):1699–709.

    CAS  PubMed  Google Scholar 

  17. McLain RF, Fleming JE, Boehm CA, Muschler GF. Aspiration of osteoprogenitor cells for augmenting spinal fusion: comparison of progenitor cell concentrations from the vertebral body and iliac crest. J Bone Joint Surg Am. 2005;87(12):2655–61.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Connolly J, Guse R, Lippiello L, Dehne R. Development of an osteogenic bone-marrow preparation. J Bone Joint Surg Am. 1989;71(5):684–91.

    CAS  PubMed  Google Scholar 

  19. Minamide A, Yoshida M, Kawakami M, Yamasaki S, Kojima H, Hashizume H, Boden SD. The use of cultured bone marrow cells in type I collagen gel and porous hydroxyapatite for posterolateral lumbar spine fusion. Spine (Phila Pa 1976). 2005;30(10):1134–8.

    Article  Google Scholar 

  20. Ploumis A, Albert TJ, Brown Z, Mehbod AA, Transfeldt EE. Healos graft carrier with bone marrow aspirate instead of allograft as adjunct to local autograft for posterolateral fusion in degenerative lumbar scoliosis: a minimum 2-year follow-up study. J Neurosurg Spine. 2010;13(2):211–5.

    Article  PubMed  Google Scholar 

  21. Reid JJ, Johnson JS, Wang JC. Challenges to bone formation in spinal fusion. J Biomech. 2011;44(2):213–20.

    Article  PubMed  Google Scholar 

  22. Kasliwal MK, Deutsch H. Clinical and radiographic outcomes using local bone shavings as autograft in minimally invasive transforaminal lumbar interbody fusion. World Neurosurg. 2012;78:185–90.

    Article  PubMed  Google Scholar 

  23. Ehrler DM, Vaccaro AR. The use of allograft bone in lumbar spine surgery. Clin Orthop Relat Res. 2000;371:38–45.

    Article  PubMed  Google Scholar 

  24. Aaron AD, Wiedel JD. Allograft use in orthopedic surgery. Orthopedics. 1994;17(1):41–8.

    CAS  PubMed  Google Scholar 

  25. Komender A. Influence of preservation on some mechanical properties of human haversian bone. Mater Med Pol. 1976;8(1):13–7.

    CAS  PubMed  Google Scholar 

  26. Triantafyllou N, Sotiropoulos E, Triantafyllou JN. The mechanical properties of the lyophylized and irradiated bone grafts. Acta Orthop Belg. 1975;41 Suppl 1:35–44.

    PubMed  Google Scholar 

  27. Asselmeier MA, Caspari RB, Bottenfield S. A review of allograft processing and sterilization techniques and their role in transmission of the human immunodeficiency virus. Am J Sports Med. 1993;21(2):170–5.

    Article  CAS  PubMed  Google Scholar 

  28. An HS, 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(2):131–5.

    Article  CAS  PubMed  Google Scholar 

  29. Dodd CA, Fergusson CM, Freedman L, Houghton GR, Thomas D. Allograft versus autograft bone in scoliosis surgery. J Bone Joint Surg Br. 1988;70(3):431–4.

    CAS  PubMed  Google Scholar 

  30. Arnold PM, Robbins S, Paullus W, Faust S, Holt R, McGuire R. Clinical outcomes of lumbar degenerative disc disease treated with posterior lumbar interbody fusion allograft spacer: a prospective, multicenter trial with 2-year follow-up. Am J Orthop (Belle Mead NJ). 2009;38(7):E115–22.

    PubMed  Google Scholar 

  31. Miyazaki M, Tsumura H, Wang JC, Alanay A. An update on bone substitutes for spinal fusion. Eur Spine J. 2009;18(6):783–99. Review.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Urist MR. Bone: formation by autoinduction. Science. 1965;150(3698):893–9.

    Article  CAS  PubMed  Google Scholar 

  33. Russo R, Scarborough N. Inactivation of viruses in demineralized bone matrix. FDA workshop on tissue transplantation and reproductive tissue, Bethesda, 20–21 June 1995.

    Google Scholar 

  34. Wildemann B, Kadow-Romacker A, Haas NP, Schmidmaier G. Quantification of various growth factors in different demineralized bone matrix preparations. J Biomed Mater Res A. 2007;81(2):437–42.

    Article  CAS  PubMed  Google Scholar 

  35. Bae H, Zhao L, Zhu D, Kanim LE, Wang JC, Delamarter RB. Variability across ten production lots of a single demineralized bone matrix product. J Bone Joint Surg Am. 2010;92(2):427–35.

    Article  PubMed  Google Scholar 

  36. Boden SD, Schimandle JH, Hutton WC. 1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor for lumbar spinal fusion. Part II: Study of dose, carrier, and species. Spine (Phila Pa 1976). 1995;20(24):2633–44.

    Article  CAS  Google Scholar 

  37. Wang JC, Alanay A, Mark D, Kanim LE, Campbell PA, Dawson EG, Lieberman JR. A comparison of commercially available demineralized bone matrix for spinal fusion. Eur Spine J. 2007;16(8):1233–40.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Sassard WR, Eidman DK, Gray PM, Block JE, Russo R, Russell JL, Taboada EM. Augmenting local bone with Grafton demineralized bone matrix for posterolateral lumbar spine fusion: avoiding second site autologous bone harvest. Orthopedics. 2000;23(10):1059–64; discussion 64–5.

    CAS  PubMed  Google Scholar 

  39. Girardi FP, Cammisa Jr FP. The effect of bone graft extenders to enhance the performance of iliac crest bone grafts in instrumented lumbar spine fusion. Orthopedics. 2003;26(5 Suppl):s545–8.

    PubMed  Google Scholar 

  40. Kang J, An H, Hilibrand A, Yoon ST, Kavanagh E, Boden S. Grafton(R) & local bone has comparable outcomes to iliac crest bone in instrumented single level lumbar fusions. Spine (Phila Pa 1976). 2012;37:1083–91.

    Article  Google Scholar 

  41. Thalgott JS, Giuffre JM, 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(2):131–7.

    Article  CAS  PubMed  Google Scholar 

  42. Gazdag AR, Lane JM, Glaser D, Forster RA. Alternatives to autogenous bone graft: efficacy and indications. J Am Acad Orthop Surg. 1995;3(1):1–8.

    PubMed  Google Scholar 

  43. Rihn JA, Kirkpatrick K, Albert TJ. Graft options in posterolateral and posterior interbody lumbar fusion. Spine (Phila Pa 1976). 2010;35(17):1629–39.

    Article  Google Scholar 

  44. Cameron HU, Macnab I, Pilliar RM. Evaluation of biodegradable ceramic. J Biomed Mater Res. 1977;11(2):179–86.

    Article  CAS  PubMed  Google Scholar 

  45. Emery SE, Fuller DA, Stevenson S. Ceramic anterior spinal fusion. Biologic and biomechanical comparison in a canine model. Spine (Phila Pa 1976). 1996;21(23):2713–9.

    Article  CAS  Google Scholar 

  46. Khan SN, Fraser JF, Sandhu HS, Cammisa Jr FP, Girardi FP, Lane JM. Use of osteopromotive growth factors, demineralized bone matrix, and ceramics to enhance spinal fusion. J Am Acad Orthop Surg. 2005;13(2):129–37.

    PubMed  Google Scholar 

  47. Tay BK, Le AX, Heilman M, Lotz J, Bradford DS. Use of a collagen-hydroxyapatite matrix in spinal fusion. A rabbit model. Spine (Phila Pa 1976). 1998;23(21):2276–81.

    Article  CAS  Google Scholar 

  48. Orii H, Sotome S, Chen J, Wang J, Shinomiya K. Beta-tricalcium phosphate (beta-TCP) graft combined with bone marrow stromal cells (MSCs) for posterolateral spine fusion. J Med Dent Sci. 2005;52(1):51–7.

    PubMed  Google Scholar 

  49. Miller CP, Jegede K, Essig D, Garg H, Bible JE, Biswas D, Whang PG, Grauer JN. The efficacies of two ceramic bone graft extenders for promoting spinal fusion in a rabbit bone paucity model. Spine (Phila Pa 1976). 2012;37:642–7.

    Article  Google Scholar 

  50. Walsh WR, Vizesi F, Cornwall GB, Bell D, Oliver R, Yu Y. Posterolateral spinal fusion in a rabbit model using a collagen-mineral composite bone graft substitute. Eur Spine J. 2009;18(11):1610–20.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Wheeler DL, Jenis LG, Kovach ME, Marini J, Turner AS. Efficacy of silicated calcium phosphate graft in posterolateral lumbar fusion in sheep. Spine J. 2007;7(3):308–17.

    Article  PubMed  Google Scholar 

  52. Tanaka N, Nakanishi K, Fujimoto Y, Sasaki H, Kamei N, Hamasaki T, Yamada K, Yamamoto R, Nakamae T, Ochi M. Expansive laminoplasty for cervical myelopathy with interconnected porous calcium hydroxyapatite ceramic spacers: comparison with autogenous bone spacers. J Spinal Disord Tech. 2008;21(8):547–52.

    Article  PubMed  Google Scholar 

  53. Jenis LG, Banco RJ. Efficacy of silicate-substituted calcium phosphate ceramic in posterolateral instrumented lumbar fusion. Spine (Phila Pa 1976). 2010;35(20):E1058–63.

    Article  Google Scholar 

  54. Park JH, Choi CG, Jeon SR, Rhim SC, Kim CJ, Roh SW. Radiographic analysis of instrumented posterolateral fusion mass using mixture of local autologous bone and b-TCP (PolyBone(R)) in a lumbar spinal fusion surgery. J Korean Neurosurg Soc. 2011;49(5):267–72.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Yamada T, Yoshii T, Sotome S, Yuasa M, Kato T, Arai Y, Kawabata S, Tomizawa S, Sakaki K, Hirai T, Shinomiya K, Okawa A. Hybrid grafting using bone marrow aspirate combined with porous beta-tricalcium phosphate and trephine bone for lumbar posterolateral spinal fusion: a prospective, comparative study-versus local bone grafting. Spine (Phila Pa 1976). 2012;37:E174–9.

    Article  Google Scholar 

  56. Hsu CJ, Chou WY, Teng HP, Chang WN, Chou YJ. Coralline hydroxyapatite and laminectomy-derived bone as adjuvant graft material for lumbar posterolateral fusion. J Neurosurg Spine. 2005;3(4):271–5.

    Article  PubMed  Google Scholar 

  57. 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). 2002;27(23):2662–73.

    Article  Google Scholar 

  58. Ong KL, Villarraga ML, Lau E, Carreon LY, Kurtz SM, Glassman SD. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine (Phila Pa 1976). 2010;35(19):1794–800.

    Article  Google Scholar 

  59. Lee JW, Lee S, Lee SH, Yang HS, Im GI, Kim CS, Park JH, Kim BS. Improved spinal fusion efficacy by long-term delivery of bone morphogenetic protein-2 in a rabbit model. Acta Orthop. 2011;82(6):756–60.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Boden SD, Martin Jr GJ, Horton WC, Truss TL, Sandhu HS. Laparoscopic anterior spinal arthrodesis with rhBMP-2 in a titanium interbody threaded cage. J Spinal Disord. 1998;11(2):95–101.

    Article  CAS  PubMed  Google Scholar 

  61. Martin Jr GJ, Boden SD, Marone MA, Moskovitz PA. Posterolateral intertransverse process spinal arthrodesis with rhBMP-2 in a nonhuman primate: important lessons learned regarding dose, carrier, and safety. J Spinal Disord. 1999;12(3):179–86.

    PubMed  Google Scholar 

  62. Boden SD, Martin Jr GJ, Morone MA, Ugbo JL, Moskovitz PA. Posterolateral lumbar intertransverse process spine arthrodesis with recombinant human bone morphogenetic protein 2/hydroxyapatite-tricalcium phosphate after laminectomy in the nonhuman primate. Spine (Phila Pa 1976). 1999;24(12):1179–85.

    Article  CAS  Google Scholar 

  63. Bomback DA, Grauer JN, Lugo R, Troiano N, Patel T, Friedlaender GE. Comparison of posterolateral lumbar fusion rates of Grafton Putty and OP-1 Putty in an athymic rat model. Spine (Phila Pa 1976). 2004;29(15):1612–7.

    Article  Google Scholar 

  64. Salamon ML, Althausen PL, Gupta MC, Laubach J. The effects of BMP-7 in a rat posterolateral intertransverse process fusion model. J Spinal Disord Tech. 2003;16(1):90–5.

    Article  PubMed  Google Scholar 

  65. Taghavi CE, Lee KB, He W, Keorochana G, Murray SS, Brochmann EJ, Uludag H, Behnam K, Wang JC. Bone morphogenetic protein binding peptide mechanism and enhancement of osteogenic protein-1 induced bone healing. Spine (Phila Pa 1976). 2010;35(23):2049–56.

    Google Scholar 

  66. Boden SD, Zdeblick TA, Sandhu HS, Heim SE. The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report. Spine (Phila Pa 1976). 2000;25(3):376–81.

    Article  CAS  Google Scholar 

  67. Burkus JK, Dorchak JD, Sanders DL. Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2. Spine (Phila Pa 1976). 2003;28(4):372–7.

    Google Scholar 

  68. 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. 2004;1(1):19–23.

    Article  PubMed  Google Scholar 

  69. 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. 2007;7(3):301–7.

    Article  PubMed  Google Scholar 

  70. Singh K, Smucker JD, Gill S, Boden SD. 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(6):416–23.

    Article  PubMed  Google Scholar 

  71. Hamilton DK, Jones-Quaidoo SM, Sansur C, Shaffrey CI, Oskouian R, Jane Sr JA. Outcomes of bone morphogenetic protein-2 in mature adults: posterolateral non-instrument-assisted lumbar decompression and fusion. Surg Neurol. 2008;69(5):457–61; discussion 61–2.

    Article  PubMed  Google Scholar 

  72. Vaccaro AR, Patel T, Fischgrund J, Anderson DG, Truumees E, Herkowitz H, Phillips F, Hilibrand A, Albert TJ. A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions. Eur Spine J. 2003;12(5):495–500.

    Article  PubMed Central  PubMed  Google Scholar 

  73. Vaccaro AR, Whang PG, Patel T, Phillips FM, Anderson DG, Albert TJ, Hilibrand AS, Brower RS, Kurd MF, Appannagri A, Patel M, Fischgrund JS. 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. Spine J. 2008;8(3):457–65.

    Article  PubMed  Google Scholar 

  74. Baskin DS, Ryan P, Sonntag V, Westmark R, Widmayer MA. 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 (Phila Pa 1976). 2003;28(12):1219–24; discussion 25.

    Google Scholar 

  75. Buttermann GR. 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(3):426–35.

    Article  PubMed  Google Scholar 

  76. Xu R, Bydon M, Sciubba DM, Witham TF, Wolinsky JP, Gokaslan ZL, Bydon A. Safety and efficacy of rhBMP2 in posterior cervical spinal fusion for subaxial degenerative spine disease: analysis of outcomes in 204 patients. Surg Neurol Int. 2011;2:109.

    Article  PubMed Central  PubMed  Google Scholar 

  77. Williams BJ, Smith JS, Fu KM, Hamilton DK, Polly Jr DW, Ames CP, Berven SH, Perra JH, Knapp DR, McCarthy RE, Shaffrey CI. Does bone morphogenetic protein increase the incidence of perioperative complications in spinal fusion? A comparison of 55,862 cases of spinal fusion with and without bone morphogenetic protein. Spine (Phila Pa 1976). 2011;36(20):1685–91.

    Article  Google Scholar 

  78. Poynton AR, Lane JM. Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976). 2002;27(16 Suppl 1):S40–8.

    Article  Google Scholar 

  79. Burkus JK, Gornet MF, Glassman SD, Slosar PJ, Rosner MK, Deckey JE, Nowak J, Hatcher BM. Blood serum antibody analysis and long-term follow-up of patients treated with recombinant human bone morphogenetic protein-2 in the lumbar spine. Spine (Phila Pa 1976). 2011;36(25):2158–67.

    Article  Google Scholar 

  80. Helgeson MD, Lehman Jr RA, Patzkowski JC, Dmitriev AE, Rosner MK, Mack AW. Adjacent vertebral body osteolysis with bone morphogenetic protein use in transforaminal lumbar interbody fusion. Spine J. 2011;11(6):507–10.

    Article  PubMed  Google Scholar 

  81. 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). 2009;34(14):1480–4; discussion 5.

    Article  Google Scholar 

  82. Joseph V, Rampersaud YR. Heterotopic bone formation with the use of rhBMP2 in posterior minimal access interbody fusion: a CT analysis. Spine (Phila Pa 1976). 2007;32(25):2885–90.

    Article  Google Scholar 

  83. Glassman SD, Gum JL, Crawford 3rd CH, Shields CB, Carreon LY. Complications with recombinant human bone morphogenetic protein-2 in posterolateral spine fusion associated with a dural tear. Spine J. 2011;11(6):522–6.

    Article  PubMed  Google Scholar 

  84. Mines D, Gu Y, Kou TD, Cooper GS. Recombinant human bone morphogenetic protein-2 and pancreatic cancer: a retrospective cohort study. Pharmacoepidemiol Drug Saf. 2011;20(2):111–8.

    Article  PubMed  Google Scholar 

  85. Molina CA, Sarabia-Estrada R, Gokaslan ZL, Witham TF, Bydon A, Wolinsky JP, Sciubba DM. Delayed onset of paralysis and slowed tumor growth following in situ placement of recombinant human bone morphogenetic protein 2 within spine tumors in a rat model of metastatic breast cancer. J Neurosurg Spine. 2012;16:365–72.

    Article  PubMed  Google Scholar 

  86. Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 2011;11(6):471–91.

    Article  PubMed  Google Scholar 

  87. Comer GC, Smith MW, Hurwitz EL, Mitsunaga KA, Kessler R, Carragee EJ. Retrograde ejaculation after anterior lumbar interbody fusion with and without bone morphogenetic protein-2 augmentation: a 10-year cohort controlled study. Spine J. 2012;12(10):881–90.

    Article  PubMed  Google Scholar 

  88. Lindley EM, McBeth ZL, Henry SE, Cooley R, Burger EL, Cain CM, Patel VV. Retrograde ejaculation after anterior lumbar spine surgery. Spine (Phila Pa 1976). 2012;37(20):1785–9.

    Article  Google Scholar 

  89. Yaremchuk KL, Toma MS, Somers ML, Peterson E. Acute airway obstruction in cervical spinal procedures with bone morphogenetic proteins. Laryngoscope. 2010;120(10):1954–7.

    Article  PubMed  Google Scholar 

  90. Shields LB, Raque GH, Glassman SD, Campbell M, Vitaz T, Harpring J, Shields CB. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine (Phila Pa 1976). 2006;31(5):542–7.

    Article  Google Scholar 

  91. Dickerman RD, Reynolds AS, Morgan BC, Tompkins J, Cattorini J, Bennett M. rh-BMP-2 can be used safely in the cervical spine: dose and containment are the keys! Spine J. 2007;7(4):508–9.

    Article  PubMed  Google Scholar 

  92. Jenis LG, Banco RJ, Kwon B. A prospective study of Autologous Growth Factors (AGF) in lumbar interbody fusion. Spine J. 2006;6(1):14–20.

    Article  PubMed  Google Scholar 

  93. Sys J, Weyler J, Van Der Zijden T, Parizel P, Michielsen J. Platelet-rich plasma in mono-segmental posterior lumbar interbody fusion. Eur Spine J. 2011;20(10):1650–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Hee HT, Majd ME, Holt RT, Myers L. Do autologous growth factors enhance transforaminal lumbar interbody fusion? Eur Spine J. 2003;12(4):400–7.

    Article  PubMed Central  PubMed  Google Scholar 

  95. Huang JW, Lin SS, Chen LH, Liu SJ, Niu CC, Yuan LJ, Wu CC, Chen WJ. The use of fluorescence-labeled mesenchymal stem cells in poly(lactide-co-glycolide)/hydroxyapatite/collagen hybrid graft as a bone substitute for posterolateral spinal fusion. J Trauma. 2011;70(6):1495–502.

    Article  CAS  PubMed  Google Scholar 

  96. Min WK, Bae JS, Park BC, Jeon IH, Jin HK, Son MJ, Park EK, Kim SY. Proliferation and osteoblastic differentiation of bone marrow stem cells: comparison of vertebral body and iliac crest. Eur Spine J. 2010;19(10):1753–60.

    Article  PubMed Central  PubMed  Google Scholar 

  97. Gan Y, Dai K, Zhang P, Tang T, Zhu Z, Lu J. The clinical use of enriched bone marrow stem cells combined with porous beta-tricalcium phosphate in posterior spinal fusion. Biomaterials. 2008;29(29):3973–82.

    Article  CAS  PubMed  Google Scholar 

  98. Wang JC. Gene therapy for spinal fusion. Spine J. 2011;11(6):557–9.

    Article  PubMed  Google Scholar 

  99. Miyazaki M, Sugiyama O, Tow B, Zou J, Morishita Y, Wei F, Napoli A, Sintuu C, Lieberman JR, Wang JC. The effects of lentiviral gene therapy with bone morphogenetic protein-2-producing bone marrow cells on spinal fusion in rats. J Spinal Disord Tech. 2008;21(5):372–9.

    Article  PubMed  Google Scholar 

  100. Douglas JT, Rivera AA, Lyons GR, Lott PF, Wang D, Zayzafoon M, Siegal GP, Cao X, Theiss SM. Ex vivo transfer of the Hoxc-8-interacting domain of Smad1 by a tropism-modified adenoviral vector results in efficient bone formation in a rabbit model of spinal fusion. J Spinal Disord Tech. 2010;23(1):63–73.

    Article  PubMed Central  PubMed  Google Scholar 

  101. Miyazaki M, Sugiyama O, Zou J, Yoon SH, Wei F, Morishita Y, Sintuu C, Virk MS, Lieberman JR, Wang JC. Comparison of lentiviral and adenoviral gene therapy for spinal fusion in rats. Spine (Phila Pa 1976). 2008;33(13):1410–7.

    Article  Google Scholar 

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Correspondence to Scott D. Boden MD .

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Yalamanchili, P.K., Boden, S.D. (2014). Fusion Biologics. In: Phillips, F., Lieberman, I., Polly, D. (eds) Minimally Invasive Spine Surgery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5674-2_8

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