title: Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density: a bone chamber study in rats.
abstract: OBJECTIVE
  The remodeling of morselized bone grafts in revision surgery can be enhanced by an anabolic substance such as a bone morphogenetic protein (BMP). On the other hand, BMPs boost catabolism and might cause a premature resorption, both of the graft and of the new-formed bone. Bisphosphonates inactivate osteoclasts and can be used to control the resorption. We studied a combination of both drugs as a local admix to a cancellous allograft.
  
  
  METHODS
  Cancellous bone allografts were harvested and freeze-dried. Either saline, BMP-7, the bisphosphonate zoledronate, or a combination of BMP-7 and zoledronate were added in solution. The grafts were placed in bone conduction chambers and implanted in the proximal tibia of 34 rats. The grafts were harvested after 6 weeks and evaluated by histomorphometry.
  
  
  RESULTS
  Bone volume/total volume (BV/TV) was 50% in the grafts treated with the combination of BMP-7 and zoledronate and 16% in the saline controls (p < 0.001). In the zoledronate group BV/TV was 56%, and in the BMP group it was 14%. The ingrowth distance of new bone into the graft was 3.5 mm for the combination of BMP-7 and zoledronate and 2.6 mm in the saline control (p = 0.002). The net amount of retained remodeled bone was more than 4 times higher when BMP-7 and zoledronate were combined than in the controls.
  
  
  CONCLUSIONS
  An anabolic drug like BMP-7 can be combined with an anti-catabolic bisphosphonate as local bone graft adjunct, and the combination increases the amount of remaining bone after remodeling is complete.
authors: Department of Orthopedics, Clinical Sciences Lund, Lund University, Sweden.
authors: Ola
authors: O
authors: Belfrage
authors: Gunnar
authors: G
authors: Flivik
authors: Martin
authors: M
authors: Sundberg
authors: Uldis
authors: U
authors: Kesteris
authors: Magnus
authors: M
authors: Tägil
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage*; D016025:Bone Transplantation; D015194:Diffusion Chambers, Culture; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D055419:Bone Morphogenetic Protein 7; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid