title: rhBMP-2 enhances the bone healing response in a diabetic rat segmental defect model.
abstract: OBJECTIVE
  Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to enhance new bone formation in fracture and bone defect models in both normal and diabetic rats. Effects of rhBMP-2 in a segmental femoral defect model in diabetes mellitus (DM) BB Wistar rats have not been reported.
  
  
  METHODS
  Collagen sponge soaked with either buffer or rhBMP-2 was inserted in a mid-diaphyseal 3.0-mm defect fixed with polyimide plate and stainless steel screws, in 62 DM BB Wistar rats. Progress of new bone formation in the defect was monitored with serial radiographs every 2 weeks. Histomorphometric analysis of the new bone formation was done on undecalcified sections of the extracted femurs at 3 and 6 weeks post surgery. Further analysis of the new bone was done by assessment of neoangiogenesis using immunohistochemical staining for Platelet endothelial cell adhesion molecule-1. Mechanical testing was performed at 9 weeks to assess the new bone with respect to 4 different parameters of mechanical and structural properties of bone.
  
  
  RESULTS
  Radiographs assessed over a 6-point grading system showed statistically significant improvement in scores in rhBMP-2-treated rats at 6 weeks (P < 0.001). Histomorphometric analysis showed statistically significant increase in area of new bone formation between rats treated with rhBMP-2 compared with buffer at both 3 and 6 weeks (P < 0.001). On Platelet endothelial cell adhesion molecule-1 staining at 3 weeks, the mean number of vessels in rhBMP-2-treated DM rats was 12.76 +/- 5.43/mm(2) compared with 4.49 +/- 1.89/mm(2) in buffer treated DM rats (P = 0.034). On mechanical testing, all 4 DM/buffer rats had nonunion. In DM/rhBMP-2 rats, the torque to failure and torsional rigidity values were 393.57 +/- 233.3 (P < 0.03) and 29,711 +/- 6224 (P < 0.002), respectively.
  
  
  CONCLUSIONS
  Clearly, although DM has a known impact on osseous healing, its negative effects are ameliorated with the application of the rhBMP-2-collagen carrier and demonstrates the potential clinical role of this adjunct in the clinical arena.
authors.affiliation: Department of Orthopedics, University of Medicine and Dentistry, Newark, NJ 07103, USA.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Azad
authors.forename: Eric
authors.initials: E
authors.lastname: Breitbart
authors.forename: Loay
authors.initials: L
authors.lastname: Al-Zube
authors.forename: Sloane
authors.initials: S
authors.lastname: Yeh
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Connor
authors.forename: Sheldon S
authors.initials: SS
authors.lastname: Lin