title: Alendronate prevents collapse in mechanically loaded osteochondral grafts: a bone chamber study in rats.
abstract: BACKGROUND
  Subchondral bone necrosis is important in osteonecrosis, Mb Kienboeck, intraarticular fractures or osteochondral grafting. As revascularization follows, bone resorption may lead to collapse in load bearing areas during the remodeling. Bisphosphonates are potent osteoclast inhibitors. Our hypothesis was that local bisphosphonate treatment of an osteochondral graft, in a high load environment, would protect the subchondral bone from collapse and maintain the joint architecture during remodeling. To investigate this, we used a rat bone chamber model to subject a necrotic osteochondral graft to a large mechanical load during remodeling.
  
  
  METHODS
  Cylindrical osteochondral grafts were taken from the patellar groove of rats, one end of the cylinder being the joint surface. The grafts were frozen, thawed and treated with alendronate. The length of the cylinder was measured and the grafts were placed in the chambers, which were inserted into the proximal tibia of rats. The chambers were left to heal in for two weeks to allow establishment of a vascular supply, and then the transplanted osteochondral plugs were mechanically loaded for 4 weeks, once a day with 10 cycles of 2 MPa pressure at 0.16 Hz.
  
  
  RESULTS
  At harvest, the graft length had decreased during remodeling in 5 of the 6 untreated controls, but only in 2 out of 8 alendronate-treated rats (p = 0.05). Histologically, the bone graft in the non-treated controls was resorbed in the remodeled part of the graft, whereas in the alendronate-treated rats a dense trabecular bone was found consisting of both new bone and graft.
  
  
  CONCLUSIONS
  Local treatment of the graft with bisphosphonate diminishes the risk of collapse during revascularization and bone remodeling in a mechanically loaded osteochondral graft. This could be useful in a variety of situations when bone remodeling occurs after a necrosis close to a joint, either spontaneously after osteonecrosis or a fracture, or after surgical procedures such as mosaic-plasty or other osteochondral grafting.
authors.affiliation: Departments of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden. magnus.tagil@ort.lu.se
authors.forename: Magnus
authors.initials: M
authors.lastname: Tägil
authors.forename: Jörgen
authors.initials: J
authors.lastname: Astrand
authors.forename: Lars
authors.initials: L
authors.lastname: Westman
authors.forename: Per
authors.initials: P
authors.lastname: Aspenberg
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control*; D016025:Bone Transplantation / Q000473:pathology; D006084:Graft Rejection / Q000517:prevention & control; D010020:Osteonecrosis / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
chemical_list: D019386:Alendronate