title: Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength.
abstract: OBJECTIVE
  Bone morphogenic proteins (BMPs) can be used in non-unions to replace autograft. BMPs induce osteoblasts and (less well known) also osteoclasts, which can in turn be controlled by a bisphosphonate. In the present study, our aim was to improve the biological effect of autologous bone graft by adding an anabolic BMP, with or without bisphosphonates, in an open-fracture model prone to non-union.
  
  
  METHODS
  Rat femurs were osteotomized and fixed with an intramedullary K-wire. Autograft was placed at the osteotomy, mixed with either saline or BMP-7. After 2 weeks, the rats had a single injection of saline or of a bisphosphonate (zoledronate). The rats were killed after 6 weeks and the femurs were evaluated by radiography, micro-CT, histology, and 3-point bending test.
  
  
  RESULTS
  All fractures healed. The callus volume was doubled in the BMP-treated femurs (p < 0.01) and increased almost 4-fold in the femurs treated with both BMP and systemic zoledronate (p < 0.01) compared to autograft. In mechanical testing, the autograft group reached approximately half the strength of the contralateral, non-osteotomized femur (p < 0.001). By adding BMP to the autograft, the strength was doubled (p < 0.001) and with both BMP and systemic zoledronate, the strength was increased 4-fold (p < 0.001) compared to autograft alone.
  
  
  CONCLUSIONS
  The combination of BMP and bisphosphonate as an adjunct to autograft is superior to autograft alone or combined with BMP. The combination may prove valuable in the treatment of non-unions.
authors: Department of Orthopaedics, Clinical Sciences, Lund University, Lund, Sweden. per_bosemark@yahoo.se
authors: Per
authors: P
authors: Bosemark
authors: Hanna
authors: H
authors: Isaksson
authors: Michelle M
authors: MM
authors: McDonald
authors: David G
authors: DG
authors: Little
authors: Magnus
authors: M
authors: Tägil
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D016025:Bone Transplantation / Q000379:methods*; D002146:Bony Callus / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology; D004164:Diphosphonates / Q000627:therapeutic use*; D005269:Femur / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology; D017759:Fractures, Malunited / Q000188:drug therapy / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D010027:Osteotomy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid