title: Repeat use of human recombinant bone morphogenetic protein-2 for second level lumbar arthrodesis.
abstract: METHODS
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopedic Surgery, Rush University, Chicago, IL 60612, USA.
authors.forename: Kern
authors.initials: K
authors.lastname: Singh
authors.forename: Mark
authors.initials: M
authors.lastname: Dumonski
authors.forename: Tom
authors.initials: T
authors.lastname: Stanley
authors.forename: Ravi
authors.initials: R
authors.lastname: Ponnappan
authors.forename: Frank M
authors.initials: FM
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001174:Arthrodesis / Q000379:methods; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002417:Cattle; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery*; D011446:Prospective Studies; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins / Q000008:administration & dosage; D019233:Retreatment / Q000379:methods; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2