title: rhBMP-2 delivered in a calcium phosphate cement accelerates bridging of critical-sized defects in rabbit radii.
abstract: BACKGROUND
  Treatment of segmental bone loss remains a challenge in skeletal repairs. This study was performed to evaluate the efficacy of the use of recombinant bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate cement (alpha bone substitute material [alpha-BSM]) to bridge critical-sized defects in the rabbit radius.
  
  
  METHODS
  Unilateral 20-mm mid-diaphyseal defects were created in the radii of thirty-six skeletally mature New Zealand White rabbits. The defects in twelve rabbits each were filled with 0.166 mg/mL rhBMP-2/alpha-BSM cement, 0.033 mg/mL rhBMP-2/alpha-BSM cement, or buffer/alpha-BSM cement. Six rabbits from each group were killed at four weeks, and six were killed at eight weeks. Serial radiographs were made to monitor defect-bridging and residual alpha-BSM carrier. A semiquantitative histological scoring system was used to evaluate defect-bridging. Histomorphometry was used to quantify residual alpha-BSM; trabecular bone area; trabecular bone volume fraction; and cortical length, width, and area.
  
  
  RESULTS
  At four weeks, there had been more rapid resorption of alpha-BSM and filling of the defects with trabecular bone in the group treated with 0.166 mg/mL rhBMP-2/alpha-BSM than in the other two groups. Histomorphometry confirmed an increased trabecular area and volume fraction in this group compared with the other two groups. In both rhBMP-2/alpha-BSM-treated groups, the majority of the trabecular bone was formed by a direct process adjacent to the resorbing alpha-BSM. At eight weeks, complete cortical bridging and regeneration of the marrow space were present in all of the defects treated with 0.166 mg/mL rhBMP-2/alpha-BSM. That group also had reduced residual alpha-BSM and trabecular area and volume, compared with the other two groups, at eight weeks as a result of a rapid remodeling process.
  
  
  CONCLUSIONS
  Treatment of a critical-sized defect in a rabbit radius with 0.166 mg/mL rhBMP-2/alpha-BSM injectable cement can result in bridging with cortical bone and a regenerated bone-marrow space by eight weeks. Site-specific remodeling appears to be responsible for corticalization and marrow regeneration.
  
  
  CONCLUSIONS
  RhBMP-2 delivered in a calcium phosphate cement may be useful to achieve bridging of critical-sized defects in patients. Its injectable properties may allow minimally invasive use. Delayed percutaneous administration would also be possible when augmentation is desired following an initial surgical procedure or when soft-tissue injuries preclude adequate initial treatment.
authors.affiliation: Department of Surgery, School of Medicine, Oregon Health Sciences University, Portland, Oregon, USA. hseeherman@wyeth.com
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Seeherman
authors.forename: Kodi
authors.initials: K
authors.lastname: Azari
authors.forename: Sean
authors.initials: S
authors.lastname: Bidic
authors.forename: Leif
authors.initials: L
authors.lastname: Rogers
authors.forename: X Jian
authors.initials: XJ
authors.lastname: Li
authors.forename: Jeffrey O
authors.initials: JO
authors.lastname: Hollinger
authors.forename: John M
authors.initials: JM
authors.lastname: Wozney
mesh_terms: D000818:Animals; D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000008:administration & dosage*; D002130:Calcium Phosphates / Q000008:administration & dosage; D004195:Disease Models, Animal; D010014:Osteolysis / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D011859:Radiography; D011884:Radius; D011994:Recombinant Proteins / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
chemical_list: D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C020243:calcium phosphate