Skip to main content

Advertisement

SpringerLink
Log in

A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

  • Original Article
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to an increasing interest in the potential for their use in fusion surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety of one such BMP—osteogenic protein 1, in the form of OP-1 putty—combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements followed by intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and radiographically using static and dynamic radiographs to assess their fusion status. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. In addition to bridging bone, less than or equal to 5° of angular motion and less than or equal to 2 mm of translation were required to classify the patients as successfully fused, as per the definition of successful fusion provided by the FDA for use in clinical trials involving investigational devices to attain spinal fusion. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed 9 of the 12 patients (75%) obtained at least a 20% improvement in their preoperative Oswestry score, while 6 of 11 patients (55%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in 10 of the 11 patients (91%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was approximately 45%. The lack of adverse events related to the OP-1 putty implant in this study is in agreement with other studies supporting the safety of bone morphogenetic proteins in spinal surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  1. Albert TJ, Pinto M, Denis F (2000) Management of symptomatic lumbar pseudarthrosis with anteroposterior fusion. A functional and radiographic outcome study. Spine 25:123–129; discussion 130

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. Barrick WT, Schofferman JA, Reynolds JB, et al (2000) Anterior lumbar fusion improves discogenic pain at levels of prior posterolateral fusion. Spine 25:853–857

    Article  CAS  PubMed  Google Scholar 

  4. Beirne JC, Barry HJ, Brady FA, Morris VB (1996) Donor site morbidity of the anterior iliac crest following cancellous bone harvest. Int J Oral Maxillofac Surg 25:268–271

    CAS  PubMed  Google Scholar 

  5. Boden SD (1998) The biology of posterolateral lumbar spinal fusion. Orthop Clin North Am 29:603–619

    CAS  PubMed  Google Scholar 

  6. Boden SD (2000) Biology of lumbar spine fusion and use of bone graft substitutes: present, future, and next generation. Tissue Eng 6:383–399

    Article  CAS  PubMed  Google Scholar 

  7. Boden SD, Sumner DR (1995) Biologic factors affecting spinal fusion and bone regeneration. Spine 20:102S–112S

    CAS  PubMed  Google Scholar 

  8. Brantigan JW (1994) Pseudarthrosis rate after allograft posterior lumbar interbody fusion with pedicle screw and plate fixation. Spine 19:1271–1279; discussion 1280

    CAS  PubMed  Google Scholar 

  9. 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

    CAS  PubMed  Google Scholar 

  10. Brown CW, Orme TJ, Richardson HD (1986) The rate of pseudarthrosis (surgical nonunion) in patients who are smokers and patients who are nonsmokers: a comparison study. Spine 11:942–943

    CAS  PubMed  Google Scholar 

  11. 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 

  12. Cameron HU, Bridges A (1985) Pseudoarthrosis in lumbar spine fusion. Prog Clin Biol Res 187:479–484

    CAS  PubMed  Google Scholar 

  13. 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 

  14. Chirossel JP, Gay E, Boutrand JP, Jenny P, Turner-Domergue M (2000) Stryker Spine PEEK and titanium cages: interbody fusion with OP-1 (BMP-7) vs autograft in a sheep model. EuroSpine 2000, Antwerp, 10–14 October

    Google Scholar 

  15. Cohen DB, Chotivichit A, Fujita T, et al (2000) Pseudarthrosis repair. Autogenous iliac crest versus femoral ring allograft. Clin Orthop 371:46–55

    PubMed  Google Scholar 

  16. Cook SD (1999) Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites. Orthopedics 22:669–671

    CAS  PubMed  Google Scholar 

  17. Cook SD, Baffes GC, Wolfe MW, Sampath TK, Rueger DC (1993) Recombinant human osteogenic protein-1 (rhOP01) heals segmental long bone defects in non-human primates. Presented at the 60th Annual meeting of the American Academy of Orthopaedic Surgeons. San Francisco

  18. Cook SD, Dalton JE, Tan EH, Whitecloud TS, Rueger DC (1994) In vivo evaluation of recombinant human osteogenic protein (rhOP-1) implants as a bone graft substitute for spinal fusion. Spine 19:1655–1663

    CAS  PubMed  Google Scholar 

  19. Cunningham BW, Kanayama M, Parker LM, et al (1999) Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. Spine 24:509–518

    Google Scholar 

  20. Cunningham BW, Shimanoto N, Sefter JC, et al (2000) Posterolateral spinal arthrodesis using osteogenic protein-1: an in-vivo time-course study using a canine model. NASS New Orleans

  21. de la Torre JI, Tenenhaus M, Gallagher PM, Sachs SA (1999) Harvesting iliac bone graft: decreasing the morbidity. Cleft Palate Craniofac J 36:388–390

    PubMed  Google Scholar 

  22. DePalma AF, Rothman RH (1968) The nature of pseudoarthrosis. Clin Orthop 59:113–118

    PubMed  Google Scholar 

  23. 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

    CAS  PubMed  Google Scholar 

  24. France JC, Yaszemski MJ, Lauerman WC, et al (1999) A randomized prospective study of posterolateral lumbar fusion. Outcomes with and without pedicle screw instrumentation. Spine 24:553–560

    Google Scholar 

  25. Friedlaender GE, Perry CR, Cole JD, et al (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 83:S151–S158

    Google Scholar 

  26. Gertzbein SD, Hollopeter MR, Hall S (1998) Pseudarthrosis of the lumbar spine. Outcome after circumferential fusion. Spine 23:2352–2356; discussion 2356–2357

    Article  CAS  PubMed  Google Scholar 

  27. Grauer JN, Patel TC, Erulkar JS, Troiano MW, Panjabi MM, Friedlaender GE (2000) Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion. Spine 26:127–133

    Article  Google Scholar 

  28. Greenough CG, Peterson MD, Hadlow S, Fraser RD (1998) Instrumented posterolateral lumbar fusion. Results and comparison with anterior interbody fusion. Spine 23:479–486

    CAS  PubMed  Google Scholar 

  29. Heggeness MH, Esses SI (1991) Classification of pseudarthroses of the lumbar spine. Spine 16:S449–S454

    CAS  PubMed  Google Scholar 

  30. 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 

  31. Jacobson JA, Starok M, Pathria MN, Garfin SR (1997) Pseudarthrosis: US evaluation after posterolateral spinal fusion: work in progress. Radiology 204:853–858

    CAS  PubMed  Google Scholar 

  32. Kanayama M, Cunningham BW, Weis JC, Parker LM, Kaneda K, McAfee PC (1998) The effects of rigid spinal instrumentation and solid bony fusion on spinal kinematics. A posterolateral spinal arthrodesis model. Spine 23:767–773

    Article  CAS  PubMed  Google Scholar 

  33. Kimura I, Shingu H, Murata M, Hashiguchi H (2001) Lumbar posterolateral fusion alone or with transpedicular instrumentation in L4–L5 degenerative spondylolisthesis. J Spinal Disord 14:301–310

    Article  CAS  PubMed  Google Scholar 

  34. Kuntz KM, Snider RK, Weinstein JN, Pope MH, Katz JN (2000) Cost-effectiveness of fusion with and without instrumentation for patients with degenerative spondylolisthesis and spinal stenosis. Spine 25:1132–1139

    Article  CAS  PubMed  Google Scholar 

  35. Magin MN (2001) Enhancement of lumbar vertebral interbody fusion by human recombinant osteogenic protein-1 (BMP-7), in a sheep model. Spine 26:469–478

    CAS  PubMed  Google Scholar 

  36. Magin M, Delling G (2001) Improved lumbar vertebral interbody fusion using rhOP-1. Spine 26:469–478

    CAS  PubMed  Google Scholar 

  37. McCulloch JA (1998) Microdecompression and uninstrumented single-level fusion for spinal canal stenosis with degenerative spondylolisthesis. Spine 23:2243–2252

    Article  CAS  PubMed  Google Scholar 

  38. Nachemson A, Zdeblick TA, O'Brien JP (1996) Lumbar disc disease with discogenic pain. What surgical treatment is most effective? Spine 21:1835–1838

    CAS  PubMed  Google Scholar 

  39. Nork SE, Hu SS, Workman KL, Glazer PA, Bradford DS (1999) Patient outcomes after decompression and instrumented posterior spinal fusion for degenerative spondylolisthesis. Spine 24:561–569

    Article  PubMed  Google Scholar 

  40. Paramore CG, Lauryssen C, Rauzzino J, et al (1999) The safety of OP-1 for lumbar fusion with decompression—a canine study. Neurosurgery 44:1151–1156

    CAS  PubMed  Google Scholar 

  41. Patel TC, Erulkar JS, Grauer JS (2000) OP-1 overcomes the inhibitory effects of nicotine on lumbar fusion. NASS, New Orleans

  42. Quagliano PV, Hayes CW, Palmer WE (1993) Vertebral pseudoarthrosis associated with diffuse idiopathic skeletal hyperostosis. Skeletal Radiol 23:353–355

    Google Scholar 

  43. Raiszadeh R, Heggeness M, Esses SI (2000) Thoracolumbar pseudarthrosis. Am J Orthop 29:513–520

    CAS  PubMed  Google Scholar 

  44. Rechtine GR, Sutterlin CE, Wood GW, Boyd RJ, Mansfield FL (1996) The efficacy of pedicle screw/plate fixation on lumbar/lumbosacral autogenous bone graft fusion in adult patients with degenerative spondylolisthesis. J Spinal Disord 9:382–391

    CAS  PubMed  Google Scholar 

  45. Robertson PA, Wray AC (2001) Natural history of posterior iliac crest bone graft donation for spinal surgery: a prospective analysis of morbidity. Spine 26:1473–1476

    CAS  PubMed  Google Scholar 

  46. Rothman RH, Booth R (1975) Failures of spinal fusion. Orthop Clin North Am 6:299–304

    CAS  PubMed  Google Scholar 

  47. Salkeld SL, Patron LP, Barrack RL, Cook SD (2001) The effect of osteogenic protein-1 on the healing of segmental bone defects treated with autograft or allograft bone. J Bone Joint Surg Am 83:803–816

    Google Scholar 

  48. Schnee CL, Freese A, Weil RJ, Marcotte PJ (1997) Analysis of harvest morbidity and radiographic outcome using autograft for anterior cervical fusion. Spine 22:2222–2227

    Article  CAS  PubMed  Google Scholar 

  49. Steinmann JC, Herkowitz HN (1992) Pseudarthrosis of the spine. Clin Orthop 284:80–90

    Google Scholar 

  50. Summers BM, Eisenstein SM (1989) Donor site pain from the ilium. A complication of lumbar spine fusion. J Bone Joint Surg Br 71:677–680

    CAS  PubMed  Google Scholar 

  51. Younger EM, Chapman MW (1989) Morbidity at bone graft donor sites. J Orthop Trauma 3:192–195

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Thomas Jefferson University, The Rothman Institute, 925 Chestnut St, 5th Floor, Philadelphia, PA 19107, USA

    Alexander R. Vaccaro, Alan Hilibrand & Todd J. Albert

  2. Commonwealth Orthopaedics & Rehabilitation, Fairfax, Virginia, USA

    Tushar Patel

  3. Department of Orthopaedic Surgery, William Beaumont Hospital, Southfield, Michigan, USA

    Jeffrey Fischgrund

  4. Department of Orthopaedic Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia, USA

    D. Greg Anderson

  5. Adjunct Faculty Bioengineering Center, Wayne State University, William Beaumont Hospital, Southfield, Michigan, USA

    Eeric Truumees

  6. Department of Orthopaedic Surgery, William Beaumont Hospital, Royal Oak, Michigan, USA

    Harry Herkowitz

  7. Department of Orthopaedic Surgery, University of Chicago, Louis A. Weiss Memorial Hospital, Chicago, Illinois, USA

    Frank Phillips

Authors
  1. Alexander R. Vaccaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tushar Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey Fischgrund
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Greg Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eeric Truumees
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Harry Herkowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Frank Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alan Hilibrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Todd J. Albert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander R. Vaccaro.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vaccaro, A.R., Patel, T., Fischgrund, J. et al. 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 12, 495–500 (2003). https://doi.org/10.1007/s00586-003-0561-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-003-0561-8

Keywords

Search

Navigation