title: Recombinant human bone morphogenic protein-2-enhanced anterior spine fusion without bone encroachment into the spinal canal: a histomorphometric study in a thoracoscopically instrumented porcine model.
abstract: METHODS
  A thoracoscopically assisted 5-level anterior spinal fusion and instrumentation model analyzing new bone formation when using recombinant human bone morphogenic protein-2 (rhBMP-2) with a collagen hydroxyapatite-tricalcium phosphate (HA/TCP) composite sponge carrier.
  
  
  OBJECTIVE
  To determine whether new bone formation extends beyond the posterior confines of the vertebral body encroaching into the spinal canal when rhBMP-2 is used to enhance anterior fusion.
  
  
  BACKGROUND
  A possible concern regarding the use of rhBMP-2 to enhance spinal fusion is the risk of unwanted bone formation leading to inadvertent fusion of adjacent levels or compression of neural elements. The safety of rhBMP-2 in one spinal application does not ensure similar results in other applications. Therefore, the expanded use of rhBMP-2 should occur only after carefully monitored preclinical and clinical studies for each new application.
  
  
  METHODS
  Eighteen pigs underwent thoracoscopically-assisted instrumentation and fusion of 5 contiguous levels (T5-T10) and randomly assigned to 4 treatment groups: group 1 (n = 6): rh-BMP-2 on a HA/TCP-collagen sponge (Medtronic Sofamor Danek, Memphis, TN); group 2 (n = 4): iliac crest autograft; group 3 (n = 4): empty; group 4 (n = 4): HA/TCP-collagen sponge (Medtronic Sofamor Danek) only. In groups 1 and 4, the HA/TCP collagen sponge was morselized into small granules and pushed through a bone delivery funnel for implantation into the disc. At 4 months after surgery, spines were sectioned longitudinally through the midsagittal plane and underwent undecalcified processing. Bone formation extending beyond the margins of the original discectomy and the confines of vertebral body were evaluated histomorphometrically at each operative level.
  
  
  RESULTS
  Recombinant human bone morphogenic protein-2 on a HA/TCP-collagen sponge induced significant new bone formation extending anterior to the confines of the vertebral body compared with the other treatment groups (P < 0.05). In addition, rhBMP-2 on a HA/TCP-collagen sponge induced significant new bone formation extending posterior to the original margins of the discectomy (P < 0.05). However, there was no new bone formation beyond the confines of the posterior vertebral body. The total bone volume in the rhBMP-2-HA/TCP-collagen sponge group was significantly greater compared with all other groups in both the discectomy fusion area and beyond the discectomy area (P < 0.05).
  
  
  CONCLUSIONS
  Recombinant human bone morphogenic protein-2 on a HA/TCP-collagen sponge enhanced anterior spinal fusion and induced significant new bone formation extending beyond the margins of the original discectomy and anterior vertebral body, most likely secondary to migration of some morselized carrier fragments from the disc space. However, the new bone formation did not extend beyond the posterior confines of the vertebral body to encroach into the spinal canal because of the intact posterior anulus and/or posterior longitudinal ligament.
authors.affiliation: Texas Scottish Rite Hospital for Children, Dallas, Texas 75219, USA. hong.zhang@tsrh.org
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sucato
authors.forename: Robert D
authors.initials: RD
authors.lastname: Welch
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013115:Spinal Canal / Q000166:cytology / Q000187:drug effects*; D013123:Spinal Fusion / Q000295:instrumentation / Q000379:methods*; D013552:Swine; D013906:Thoracoscopy / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta