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Bone morphogenetic protein 7 and autologous bone graft in revision surgery for non-union after lumbar interbody fusion

  • Orthopaedic Surgery
  • Published:
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Abstract

Background

Potential adverse and unknown long-term effects as well as additional costs limit the use of BMPs (Bone morphogenetic proteins) in primary fusion procedures. However, the proven osteoinductive properties render BMPs attractive for the attempt to reach fusion of symptomatic non-unions. The aim of this study is to evaluate the fusion rate and potential disadvantages of eptotermin alfa (rhBMP-7) used with autologous bone graft in revision procedures for lumbar pseudoarthrosis.

Materials and methods

At our institution, rhBMP-7 has been used to improve fusion rates in revision surgery for symptomatic pseudoarthrosis during the past 10 years. Eighty-four fusion procedures using rhBMP-7 between 08/2003 and 07/2011 were revisions due to symptomatic lumbar pseudoarthrosis. The surgical approach was posterior in three and combined anterior–posterior in 71 patients. Of those, 74 patients had either reached fusion or had follow-up of at least 39.5 months (range 21–80 months) in the case of pseudoarthrosis. These 74 patients have been included in a retrospective follow-up study.

Results

In 60 patients (81.1 %) the rhBMP-7 procedure was successful. In 14 patients, pseudoarthrosis persisted or fusion was questionable. Of those patients 12 accounted for persisting L5–S1 non-union. Persisting non-unions were found in 26.7 % of the study after four or more segment instrumentations compared to the 16.9 % after mono-, bi-, or three-segment instrumentation, and in four of 14 patients with spondylodesis of three or more levels above a pseudoarthrotic lumbosacral junction. Adverse effects related to the use of eptotermin alfa were rare in this group with symptomatic ectopic bone formation in one patient.

Conclusions

Using rhBMP-7 with autologous bone graft in revisions for lumbar pseudoarthrosis via an anterior approach is safe and can lead to fusion even under unfavorable biomechanical conditions. However, successful outcome depends on the individual constellation. Treatment of non-unions of the lumbosacral junction remains especially difficult in cases with solid fusions above those pseudoarthrotic levels.

Level of evidence

4; retrospective follow-up study.

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References

  1. Boos N, Webb JK (1997) Pedicle screw fixation in spinal disorders: a European view. Eur Spine J 6:2–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bridwell KH, Sedgewick TA, O’Brien MF, Lenke LG, Baldus C (1993) The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord 6:461–472

    Article  CAS  PubMed  Google Scholar 

  3. Fischgrund JS, Mackay M, Herkowitz HN, Brower R, Montgomery DM, Kurz LT (1997) 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. Spine 22:2807–2812

    Article  CAS  PubMed  Google Scholar 

  4. Kornblum MB, Fischgrund JS, Herkowitz HN, Abraham DA, Berkower DL, Ditkoff JS (2004) Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective long-term study comparing fusion and pseudarthrosis. Spine 29:726–733

    Article  PubMed  Google Scholar 

  5. Martin BI, Mirza SK, Comstock BA, Gray DT, Kreuter W, Deyo RA (2007) Reoperation rates following lumbar spine surgery and the influence of spinal fusion procedures. Spine 32:382–387

    Article  PubMed  Google Scholar 

  6. Videbaek TS, Christensen FB, Soegaard R, Hansen ES, Hoy K, Helmig P, Niedermann B, Eiskjoer SP, Bünger CE (2006) Circumferential fusion improves outcome in comparison with instrumented posterolateral fusion: long-term results of a randomized clinical trial. Spine 31:2875–2880

    Article  PubMed  Google Scholar 

  7. Rihn JA, Patel R, Makda J, Hong J, Anderson DG, Vaccaro AR, Hilibrand AS, Albert TJ (2009) Complications associated with single-level transforaminal lumbar interbody fusion. Spine J 9:623–629

    Article  PubMed  Google Scholar 

  8. Potter BK, Freedman BA, Verwiebe EG, Hall JM, Polly DW Jr, Kuklo TR (2005) Transforaminal lumbar interbody fusion: clinical and radiographic results and complications in 100 consecutive patients. J Spinal Disord Tech 18:337–346

    Article  PubMed  Google Scholar 

  9. Hackenberg L, Halm H, Bullmann V, Vieth V, Schneider M, Liljenqvist U (2005) Transforaminal lumbar interbody fusion: a safe technique with satisfactory three to five year results. Eur Spine J 14:551–558

    Article  PubMed  PubMed Central  Google Scholar 

  10. Herkowitz HN, Kurz LT (1991) Degenerative lumbar spondylolisthesis with spinal stenosis. A prospective study comparing decompression with decompression and intertransverse process arthrodesis. J Bone Joint Surg Am 73:802–808

    CAS  PubMed  Google Scholar 

  11. Cook SD, Dalton JE, Tan EH, Whitecloud TS, Rueger DC (1995) In vivo evaluation of demineralized bone matrix as a bone graft substitute for posterior spinal fusion. Spine 20:877–886

    Article  CAS  PubMed  Google Scholar 

  12. Cunningham BW, Kanayama M, Parker LM, Weis JC, Sefter JC, Fedder IL, McAfee PC (1999) Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. A comparative endoscopic study using the Bagby and Kuslich interbody fusion device. Spine 24:509–518

    Article  CAS  PubMed  Google Scholar 

  13. Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF, Zych GA, Calhoun JH, LaForte AJ, Yin S (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 83-A:151–158

    Google Scholar 

  14. Grauer JN, Patel TC, Erulkar JS, Troiano NW, Panjabi MM, Friedlaender GE (2001) 2000 Young Investigator Research Award winner. Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion. Spine 26:127–133

    Article  CAS  PubMed  Google Scholar 

  15. Magin MN, Delling G (2001) Improved lumbar vertebral interbody fusion using rhOP-1: a comparison of autogenous bone graft, bovine hydroxylapatite (Bio-Oss), and BMP-7 (rhOP-1) in sheep. Spine 26:469–478

    Article  CAS  PubMed  Google Scholar 

  16. Banwart JC, Asher MA, Hassanein RS (1995) Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. Spine 20:1055–1060

    Article  CAS  PubMed  Google Scholar 

  17. Fernyhough JC, Schimandle JJ, Weigel MC, Edwards CC, Levine AM (1992) Chronic donor site pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion. Spine 17:1474–1480

    Article  CAS  PubMed  Google Scholar 

  18. European Medicines Agency (2009) European public assessment report (EPAR) for Opgenra. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000819/human_med_000950.jsp&mid=WC0b01ac058001d124. Accessed 2009. (Updated 29 September 2011)

  19. Vaccaro AR, Patel T, Fischgrund J, Anderson DG, Truumees E, Herkowitz HN, Phillips F, Hilibrand A, Albert TJ, Wetzel T, McCulloch JA (2004) A pilot study evaluating safety and efficacy of OP-1 putty (rhBMP-7) as a replacement for iliac crest autograft in posterolateral lumbar arthrodesis for degenerative spondylolisthesis. Spine 29:1885–1892

    Article  PubMed  Google Scholar 

  20. Carragee EJ, Hurwitz EL, Weiner BK (2011) A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J 11:471–491

    Article  PubMed  Google Scholar 

  21. Chrastil J, Low JB, Whang PG, Patel AA (2013) Complications associated with the use of the recombinant human bone morphogenetic proteins for posterior interbody fusions of the lumbar spine. Spine 38:E1020–1027

    Article  PubMed  Google Scholar 

  22. Brantigan JW, Steffee AD (1993) A carbon fiber implant to aid interbody lumbar fusion. Two-year clinical results in the first 26 patients. Spine 18:2106–2107

    Article  CAS  PubMed  Google Scholar 

  23. Santos ER, Goss DG, Morcom RK, Fraser RD (2003) Radiologic assessment of interbody fusion using carbon fiber cages. Spine 28:997–1001

    PubMed  Google Scholar 

  24. Buttermann GR, Glazer PA, Hu SS, Bradford DS (1997) Revision of failed lumbar fusions. A comparison of anterior autograft and allograft. Spine 22:2748–2755

    Article  CAS  PubMed  Google Scholar 

  25. Carpenter CT, Dietz JW, Leung KY, Hanscom DA, Wagner TA (1996) Repair of a pseudarthrosis of the lumbar spine. A functional outcome study. J Bone Joint Surg Am 78:712–720

    CAS  PubMed  Google Scholar 

  26. Carreon LY, Glassman SD, Schwender JD, Subach BR, Gornet MF, Ohno S (2008) Reliability and accuracy of fine-cut computed tomography scans to determine the status of anterior interbody fusions with metallic cages. Spine J 8:998–1002

    Article  PubMed  Google Scholar 

  27. Fogel GR, Toohey JS, Neidre A, Brantigan JW (2008) Fusion assessment of posterior lumbar interbody fusion using radiolucent cages: X-ray films and helical computed tomography scans compared with surgical exploration of fusion. Spine J 8:570–577

    Article  PubMed  Google Scholar 

  28. Sponseller PD, Zimmerman RM, Ko PS, Pull Ter Gunne AF, Mohamed AS, Chang TL, Kebaish KM (2010) Low profile pelvic fixation with the sacral alar iliac technique in the pediatric population improves results at two-year minimum follow-up. Spine 15:1887–1892

    Article  Google Scholar 

  29. Tsuchiya K, Bridwell KH, Kuklo TR, Lenke LG, Baldus C (2006) Minimum 5-year analysis of L5-S1 fusion using sacropelvic fixation (bilateral S1 and iliac screws) for spinal deformity. Spine 1:303–308

    Article  Google Scholar 

  30. Morone MA, Boden SD, Hair G, Martin GJ Jr, Racine M, Titus L, Hutton WC (1998) 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 351:252–265

    Article  PubMed  Google Scholar 

  31. Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Park JY, He TC (2008) Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 85-A:1544–1552

    Google Scholar 

  32. Meisel HJ, Schnöring M, Hohaus C, Minkus Y, Beier A, Ganey T, Mansmann U (2008) Posterior lumbar interbody fusion using rhBMP-2. Eur Spine J 17:1735–1744

    Article  PubMed  PubMed Central  Google Scholar 

  33. McClellan JW, Mulconrey DS, Forbes RJ, Fullmer N (2006) Vertebral bone resorption after transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J Spinal Disord Tech 19:483–486

    Article  PubMed  Google Scholar 

  34. Knox JB, Dai JM, Orchowski J (2011) Osteolysis in transforaminal lumbar interbody fusion with bone morphogenetic protein-2. Spine 36:672–676

    Article  PubMed  Google Scholar 

  35. Lewandrowski KU, Nanson C, Calderon R (2007) Vertebral osteolysis after posterior interbody lumbar fusion with recombinant human bone morphogenetic protein 2: a report of five cases. Spine J 7:609–614

    Article  PubMed  Google Scholar 

  36. Helgeson MD, Lehman RA Jr, Patzkowski JC, Dmitriev AE, Rosner MK, Mack AW (2011) Adjacent vertebral body osteolysis with bone morphogenetic protein use in transforaminal lumbar interbody fusion. Spine J. 11:507–510

    Article  PubMed  Google Scholar 

  37. Mannion RJ, Nowitzke AM, Wood MJ (2011) Promoting fusion in minimally invasive lumbar interbody stabilization with low-dose bone morphogenic protein-2–but what is the cost? Spine J. 11:527–533

    Article  PubMed  Google Scholar 

  38. Vaidya R (2009) Transforaminal interbody fusion and the “off label” use of recombinant human bone morphogenetic protein-2. Spine J. 9:667–669

    Article  PubMed  Google Scholar 

  39. Crandall DG, Revella J, Patterson J, Huish E, Chang M, McLemore R (2013) Transforaminal Lumbar Interbody Fusion With rhBMP-2 in Spinal Deformity, Spondylolisthesis, and Degenerative Disease-Part 2: BMP Dosage-Related Complications and Long-term Outcomes in 509 Patients. Spine 38:1137–1145

    Article  PubMed  Google Scholar 

  40. Laursen M, Hoy K, Hansen ES, Gelineck J, Christensen FB, Bünger CE (1999) Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results. Eur Spine J 8:485–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Akamaru T, Suh D, Boden SD, Kim HS, Minamide A, Louis-Ugbo J (2003) Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion. Spine 28:429–434

    PubMed  Google Scholar 

  42. Joseph V, Rampersaud YR (2007) Heterotopic bone formation with the use of rhBMP2 in posterior minimal access interbody fusion: a CT analysis. Spine 32:2885–2890

    Article  PubMed  Google Scholar 

  43. Wong DA, Kumar A, Jatana S, Ghiselli G, Wong K (2008) Neurologic impairment from ectopic bone in the lumbar canal: a potential complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2). Spine J 8:1011–1018

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department for Spinal Surgery and Paraplegiology, Zentralklinik Bad Berka, Robert-Koch-Allee 9, 99438, Bad Berka, Germany

    Stephan Werle, Kais AbuNahleh & Heinrich Boehm

  2. Department for Spinal Surgery, Asklepios Clinic Lindau, Friedrichshafener Strasse 82, 88131, Lindau, Germany

    Stephan Werle

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Correspondence to Stephan Werle.

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All authors certify that they have NO affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus, membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Obtaining the informed consent from involved patients was waived by the Institutional Review Board. All procedures involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments. The study was approved by the Institutional Review Board.

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Werle, S., AbuNahleh, K. & Boehm, H. Bone morphogenetic protein 7 and autologous bone graft in revision surgery for non-union after lumbar interbody fusion. Arch Orthop Trauma Surg 136, 1041–1049 (2016). https://doi.org/10.1007/s00402-016-2485-x

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