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

Acta Orthop. 2011 Apr;82(2):228-33. doi: 10.3109/17453674.2011.566138. Epub 2011 Mar 24.


Background and purpose: 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.

Interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Morphogenetic Protein 7 / administration & dosage*
  • Bone Transplantation*
  • Diffusion Chambers, Culture
  • Diphosphonates / administration & dosage*
  • Female
  • Humans
  • Imidazoles / administration & dosage*
  • Osteogenesis / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Transplantation, Autologous
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Bone Morphogenetic Protein 7
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid