title: Healing of rat femoral segmental defect with bone morphogenetic protein-2: a dose response study.
abstract: OBJECTIVE
  Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is becoming a common clinical approach to enhance bone repair. There is little or no information in the literature on the dose of rhBMP-2 required for effective healing of critical-sized defects such as those associated with trauma. In this study, we used a segmental defect model to assess the dose response of rhBMP-2 using quantitative and qualitative endpoints.
  
  
  METHODS
  Femoral defects in rats were replaced with absorbable collagen sponges carrying rhBMP-2 (0, 1, 5, 10 or 20 μg; N=5). At 4-weeks new bone formation was assessed using quantitative (radiography and microcomputed tomography) and qualitative (histology and backscattered-SEM) endpoints statistically compared.
  
  
  RESULTS
  rhBMP-2 showed increased bridging in the gap. Quantitative evaluation presented a bi-phasic dose response curve. Histological assessment revealed that with rhBMP-2 the defect showed the presence of spongy bone with the trabeculae layered with active osteoblasts and osteoclasts. The density and compactness of the bone varied with the dose of rhBMP-2.
  
  
  CONCLUSIONS
  Our findings revealed that all doses of rhBMP-2 result in new bone formation. However, there is an optimum dose of 12 μg of rhBMP-2 for bone repair in this model, above which and below which less stimulation of bone occurs.
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Angle
authors.forename: K
authors.initials: K
authors.lastname: Sena
authors.forename: D R
authors.initials: DR
authors.lastname: Sumner
authors.forename: W W
authors.initials: WW
authors.lastname: Virkus
authors.forename: A S
authors.initials: AS
authors.lastname: Virdi
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects*; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen