title: Combined effects of zoledronate and mechanical stimulation on bone adaptation in an axially loaded mouse tibia.
abstract: BACKGROUND
  local bisphosphonate delivery may be a solution to prevent periprosthetic bone loss and improve orthopedic implants fixation. In load-bearing implants, periprosthetic bone is exposed to high mechanical demands, which in normal conditions induce an adaptation of bone. In this specific mechanical situation, the modulation of the bone response by bisphosphonate remains uncertain.
  
  
  METHODS
  we assessed the combined effects of zoledronate and mechanical loading on bone adaptation using an in-vivo axial compression model of the mouse tibia and injections of zoledronate. Bone structure was quantified with in-vivo microCT before and after the period of stimulation and the mechanical properties of the tibias were evaluated with 3 point-bending tests after sacrifice.
  
  
  RESULTS
  axial loading induced a localized increase of cortical thickness and bone area. Zoledronate increased cortical thickness, bone perimeter, and bone area. At the most loaded site of the tibia, the combined effect of zoledronate and mechanical stimulation was significantly smaller than the sum of the individual effects measured at the same site in the control groups.
  
  
  CONCLUSIONS
  the results of this study suggested that a negative interaction between zoledronate and mechanical loading might exist at high level of strain.
authors.affiliation: Laboratory of Biomechanical Orthopedics, Ecole Polytechnique Fédérale de Lausanne, Switzerland; Laboratory of Bone Imaging, Schulich School of Engineering, University of Calgary, Canada.
authors.forename: V A
authors.initials: VA
authors.lastname: Stadelmann
authors.forename: N
authors.initials: N
authors.lastname: Bonnet
authors.forename: D P
authors.initials: DP
authors.lastname: Pioletti
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001842:Bone and Bones / Q000503:physiopathology*; D019245:Compressive Strength; D004164:Diphosphonates / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019736:Prostheses and Implants; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D016474:Weight-Bearing; D055114:X-Ray Microtomography / Q000379:methods; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid