title: Combined effect of bisphosphonate and recombinant human bone morphogenetic protein 2 on bone healing of rat calvarial defects.
abstract: BACKGROUND
  This study aimed to investigate new bone formation using recombinant human bone morphogenetic protein 2 (rhBMP-2) and locally applied bisphosphonate in rat calvarial defects.
  
  
  METHODS
  Thirty-six rats were studied. Two circular 5 mm diameter bony defect were formed in the calvaria using a trephine bur. The bony defect were grafted with Bio-Oss® only (group 1, n = 9), Bio-Oss® wetted with rhBMP-2 (group 2, n = 9), Bio-Oss® wetted with rhBMP-2 and 1 mM alendronate (group 3, n = 9) and Bio-Oss® wetted with rhBMP-2 and 10 mM alendronate (group 4, n = 9). In each group, three animals were euthanized at 2, 4 and 8 weeks after surgery, respectively. The specimens were then analyzed by histology, histomorphometry and immunohistochemistry analysis.
  
  
  RESULTS
  There were significant decrease of bone formation area (p < 0.05) between group 4 and group 2, 3. Group 3 showed increase of new bone formation compared to group 2. In immunohistochemistry, collagen type I and osteoprotegerin (OPG) didn't show any difference. However, receptor activator of nuclear factor κB ligand (RANKL) decreased with time dependent except group 4.
  
  
  CONCLUSIONS
  Low concentration bisphosphonate and rhBMP-2 have synergic effect on bone regeneration and this is result from the decreased activity of RANKL of osteoblast.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, 626-787 Yangsan, Mulgeum-eup Korea.
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, 626-787 Yangsan, Mulgeum-eup Korea.|Biomedical Research Institute of Pusan National University, Yangsan, Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Song
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, 626-787 Yangsan, Mulgeum-eup Korea.
authors.forename: Chang-Joo
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, 626-787 Yangsan, Mulgeum-eup Korea.|Department of Oral and Maxillofacial Surgery, Good Gang-An Hospital, Busan, Korea.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Department of Oral Anatomy and Cell Biology, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: In-Ryoung
authors.initials: IR
authors.lastname: Kim
authors.affiliation: Department of Oral Anatomy and Cell Biology, School of Dentistry, Pusan National University, Yangsan, Korea.
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Park
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, 626-787 Yangsan, Mulgeum-eup Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Shin
keywords: Alendronate; Bisphophonate; Bone morphogenetic protein 2; Bone regeneration; Histology