Repeat use of human recombinant bone morphogenetic protein-2 for second level lumbar arthrodesis

Spine (Phila Pa 1976). 2011 Feb 1;36(3):192-6. doi: 10.1097/BRS.0b013e3181cdd396.

Abstract

Study design: Prospective randomized controlled animal model.

Objective: The purpose of this study is to determine whether the readministration of human recombinant bone morphogenetic protein-2 (rhBMP-2) induces an immune response and inhibits successful fusion in repeat posterolateral spinal surgery.

Summary of background data: Little research has been performed on the effectiveness or immunoreactivity of rhBMP-2 (Infuse, Medtronic, Memphis, TN) in the context of its reuse in posterolateral fusion spinal surgery at adjacent levels.

Methods: A total of 34 New Zealand White rabbits underwent posterior intertransverse process fusion with the use of rhBMP-2 delivered on an absorbable collagen sponge (rhBMP-2/ACS). Two rabbits were killed early leaving 32 total rabbits. Serologic studies (Type I bovine collagen and rhBMP-2 antibodies) were obtained at 2-week intervals throughout the experiment. At 10 weeks, posteroanterior radiographs confirmed solid fusion masses in all rabbits. The 32 rabbits were randomly separated into 2 groups of 16, and each group underwent an adjacent level, bilateral intertransverse process fusion with either rhBMP-2/ACS or iliac crest.

Results: There was no statistical difference in fusion rates with repeat use of rhBMP-2 (n = 15/16, 94%) or iliac crest (n = 11/16, 69%) (P = 0.17) at the adjacent level. Four rabbits (n = 4/32, 13%) developed rhBMP-2 antibodies. Of these 4 rabbits, 1 developed anti-rhBMP antibodies after the first exposure and 3 developed antibodies after the second surgery. Eight rabbits (n = 8/32, 25%) developed collagen antibodies with 7 rabbits developing antibodies after the first exposure and 1 rabbit developing antibodies after the second exposure. The development of antibodies did not effect fusion rates. No rabbit demonstrated evidence of a systemic or anaphylactic reaction to repeat exposure to rhBMP-2.

Conclusion: rhBMP-2 appears to be successful in promoting intertransverse fusions when used in both primary and repeat fusion environments. The infrequent development of antibodies to rhBMP-2 after re-exposure occurs without a predictable time course suggesting that host immunologic variation may play a role. This animal study would tend to support early clinical data emerging on the reuse of BMP-2 for lumbar fusion, suggesting an acceptable fusion rate without a high incidence of complications.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Arthrodesis / methods
  • Bone Morphogenetic Protein 2 / administration & dosage*
  • Cattle
  • Humans
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / drug effects
  • Lumbar Vertebrae / surgery*
  • Prospective Studies
  • Rabbits
  • Radiography
  • Recombinant Proteins / administration & dosage
  • Retreatment / methods
  • Spinal Fusion / methods*
  • Transforming Growth Factor beta / administration & dosage*

Substances

  • Bone Morphogenetic Protein 2
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2