title: Effect of bone morphogenetic protein-2, demineralized bone matrix and systemic parathyroid hormone (1-34) on local bone formation in a rat calvaria critical-size defect model.
abstract: OBJECTIVE
  To determine the potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) soak-loaded on to an absorbable collagen sponge (ACS) to induce local bone formation compared with the clinical reference demineralized bone matrix (DBM) and to investigate potential additive/synergistic effects of exogenous parathyroid hormone (PTH).
  
  
  METHODS
  Critical-size (8 mm), through-through calvaria osteotomy defects in 160 adult male Sprague-Dawley rats were randomized to receive one of eight interventions: rhBMP-2/ACS, DBM, ACS, or serve as controls (empty defects) combined or not with systemic PTH. Ten animals from each group were followed for 4 and 8 wks for radiographic and histometric analysis. Multivariable analysis was used to assess the effect of experimental intervention and healing time on local bone formation.
  
  
  RESULTS
  In the multivariable analysis, rhBMP-2/ACS exhibited significantly greater histologic bone formation than control (β ± SE: 54.76 ± 5.85, p < 0.001) and ACS (β ± SE: 9.14 ± 3.31, p = 0.007) whereas DBM showed significantly less bone formation than control (β ± SE: -32.32 ± 8.23, p < 0.001). Overall, PTH did not show a significant effect on bone formation (β ± SE: 2.72 ± 6.91, p = 0.70). No significant differences in histological defect closure were observed between 4 and 8 wks for all but the control group without PTH.
  
  
  CONCLUSIONS
  rhBMP-2/ACS significantly stimulates local bone formation whereas bone formation appears significantly limited by DBM. Systemic application of PTH provided no discernible additive/synergistic effects on local bone formation.
authors.affiliation: Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR), Departments of Periodontics and Oral Biology, Georgia Health Sciences University, Augusta, GA 30912, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Stancoven
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: D R
authors.initials: DR
authors.lastname: Dixon
authors.forename: J C
authors.initials: JC
authors.lastname: McPherson
authors.forename: F C
authors.initials: FC
authors.lastname: Bisch
authors.forename: U M E
authors.initials: UM
authors.lastname: Wikesjö
authors.forename: C
authors.initials: C
authors.lastname: Susin
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D018775:Bone Demineralization Technique; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000601:surgery*; D001857:Bone Matrix / Q000637:transplantation*; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D003094:Collagen; D003399:Craniotomy / Q000379:methods; D004337:Drug Carriers; D004357:Drug Synergism; D006801:Humans; D008297:Male; D008859:Microscopy, Polarization; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D011859:Radiography; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects*; D013997:Time Factors; D014021:Tissue Preservation / Q000379:methods; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen