title: The effect of soaking allograft in bisphosphonate: a pilot dose-response study.
abstract: BACKGROUND
  Long-term survival of uncemented total joint replacements relies on osseointegration. With reduced bone stock impacted morselized allograft enhances early implant fixation but is subject to resorption.
  
  
  OBJECTIVE
  We therefore asked whether soaking morselized allograft in different concentrations of bisphosphonate before impaction would enhance fixation.
  
  
  METHODS
  In each of 10 dogs, we implanted four unloaded titanium implants surrounded by a 2.5-mm gap into the proximal humerus, two implants in each humerus. The gap was filled with impacted morselized allograft soaked in saline or a low-, middle-, or high-dose bisphosphonate solution (0.005, 0.05, or 0.5 mg zoledronate/mL). At 4 weeks, the implants were evaluated by histomorphometric analysis and mechanical pushout test.
  
  
  RESULTS
  The low dose of zoledronate increased new bone formation in the allograft but the high dose decreased new bone formation. The high dose of zoledronate resulted in the greatest inhibition of allograft resorption, whereas the low dose of zoledronate resulted in the lowest inhibition of allograft resorption. Implants surrounded allograft soaked in the low dose of zoledronate or saline had better fixation for all three mechanical parameters compared with implants surrounded by allograft soaked in the middle or high dose of zoledronate.
  
  
  CONCLUSIONS
  These data suggest bisphosphonate may enhance osseointegration of allografted implants and emphasize the need for preclinical testing of antiresorptive therapies.
authors.affiliation: Orthopaedic Research Laboratory, Aarhus University Hospital, Norrebrogade 44, Building 1A, DK-8000 Aarhus C, Denmark. Thomas.Jakobsen@ki.au.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Jakobsen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Baas
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bechtold
authors.forename: Brian
authors.initials: B
authors.lastname: Elmengaard
authors.forename: Kjeld
authors.initials: K
authors.lastname: Søballe
mesh_terms: D000818:Animals; D019643:Arthroplasty, Replacement / Q000379:methods*; D001696:Biomechanical Phenomena; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D016025:Bone Transplantation; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006811:Humerus / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D007093:Imidazoles / Q000008:administration & dosage*; D016348:Osseointegration / Q000187:drug effects*; D010865:Pilot Projects; D019736:Prostheses and Implants; D011474:Prosthesis Design; D014025:Titanium / Q000737:chemistry; D014184:Transplantation, Homologous; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D014025:Titanium