title: Development of a New Zealand white rabbit model of spinal pseudarthrosis repair and evaluation of the potential role of OP-1 to overcome pseudarthrosis.
abstract: METHODS
  Posterolateral lumbar fusions were performed in nicotine-exposed, New Zealand white rabbits. Animals that developed a pseudarthrosis were then regrafted with no graft, autograft, or osteogenic protein-1 (OP-1).
  
  
  OBJECTIVE
  To establish a model of pseudarthrosis repair and to evaluate the ability of OP-1 to induce fusion in this model.
  
  
  BACKGROUND
  OP-1 has been shown to have a 100% fusion rate in an established rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion.
  
  
  METHODS
  Forty-four New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To maximize the incidence of pseudarthroses, nicotine was administered to all rabbits. At 5 weeks, the spines were explored, and all pseudarthroses were redecorticated and grafted with no graft, autograft, or OP-1. At 10 weeks, the rabbits were killed and fusions masses were assessed with manual palpation, radiography, computed tomography, and/or histology.
  
  
  RESULTS
  Nine rabbits (20%) were lost to complications. Thirty-four (94%) had pseudarthroses on exploration at 5 weeks. By manual palpation at 10 weeks, 1 of 10 (10%) pseudarthroses that received no graft fused, 5 of 12 (42%) pseudarthroses that received autograft fused, and 9 of 11 (82%) pseudarthroses that received OP-1 fused. Computed tomography and histology further characterized the fusion masses.
  
  
  CONCLUSIONS
  This study establishes a model for treatment of pseudarthroses. OP-1, which has previously been shown to have 100% fusion rate in animal models, outperformed autograft and induced fusion in 82% of rabbits.
authors.affiliation: Rothman Institute at Jefferson University, Philadelphia, PA, USA. jonathan.grauer@yale.edu
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Grauer
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Vaccaro
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kato
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kwon
authors.forename: John M
authors.initials: JM
authors.lastname: Beiner
authors.forename: Tushar C
authors.initials: TC
authors.lastname: Patel
authors.forename: Alan S
authors.initials: AS
authors.lastname: Hilibrand
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Albert
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D003367:Cotinine / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007085:Ilium / Q000637:transplantation; D015918:Infusion Pumps, Implantable; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery*; D009538:Nicotine / Q000097:blood / Q000633:toxicity*; D011183:Postoperative Complications / Q000209:etiology / Q000601:surgery*; D011542:Pseudarthrosis / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins / Q000627:therapeutic use; D016037:Single-Blind Method; D013122:Spinal Diseases / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D013123:Spinal Fusion; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D014945:Wound Healing
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D009538:Nicotine; D003367:Cotinine