title: Effects of alendronate on particle-induced osteolysis in a rat model.
abstract: BACKGROUND
  Particle-induced osteolysis is currently a major problem affecting the long-term survivorship of total joint replacements. Alendronate is a third-generation bisphosphonate that blocks osteoclastic bone resorption. The objective of this study was to determine whether alendronate could prevent particle-induced osteolysis or restore (reverse) bone loss in established osteolysis.
  
  
  METHODS
  A rat model of particle-induced osteolysis was used. A specially designed polyethylene implant was placed in the proximal part of the right tibia of seventy-two animals. Following four weeks of healing, the animals were randomized into control groups, a prevention group, or a treatment group. In the prevention group, animals received intra-articular injections of high-density polyethylene particles (mean size, 2 m; all <10 m) at four, six, and eight weeks postoperatively. Alendronate (0.01 mg/kg/day) was administered concomitantly through an implantable pump from the fourth week through the tenth week. In the treatment group, animals were also exposed to polyethylene particles at four, six, and eight weeks, to establish bone loss, but they received alendronate subsequently, from the tenth week through the sixteenth week, to treat the bone loss. Positive (particle-only) and negative (saline-solution-only) control groups were assessed as well. Tissues were harvested at ten weeks in the prevention group and at sixteen weeks in the treatment group. Histological analyses and histomorphometric determinations of the periprosthetic bone volume were carried out.
  
  
  RESULTS
  Histological examination showed a rim of new bone (neocortex) around the implant in the untreated and saline-solution-treated control animals (no polyethylene particles). Treatment with saline solution (no polyethylene particles) did not affect periprosthetic bone. Animals exposed to polyethylene particles had bone loss. In those that received alendronate, the bone loss was either prevented or reversed, and the quantity of neocortical and trabecular bone was increased compared with that of the controls. Alendronate effectively preserved periprosthetic bone in both the prevention and treatment groups. In the prevention arm, the mean periprosthetic bone volume of the neocortex and the surrounding trabecular bone, as determined with histomorphometry, was 21.5% +/- 6.5% in the saline-solution-treated controls (no particles), 13.1% +/- 5.9% in the particle-treated animals, and 32.6% +/- 6.4% in the alendronate-treated animals (p < 0.001). In the treatment arm, the mean periprosthetic bone volume was 27.2% +/- 5.6% in the saline-solution-treated controls, 17.7% +/- 6.2% in the particle-treated animals, and 30.2% +/- 5.9% in the alendronate-treated animals (p = 0.002).
  
  
  CONCLUSIONS
  In our model, the intra-articular injection of polyethylene particles caused substantial bone loss around a loaded implant. Alendronate effectively prevented and treated the particle-induced periprosthetic bone loss.
authors.affiliation: The Hospital for Special Surgery, New York, NY 10021, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Millett
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Allen
authors.forename: Mathias P G
authors.initials: MP
authors.lastname: Bostrom
mesh_terms: D019386:Alendronate / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control; D001842:Bone and Bones / Q000473:pathology; D004195:Disease Models, Animal; D007270:Injections, Intra-Articular; D008297:Male; D010014:Osteolysis / Q000188:drug therapy / Q000517:prevention & control*; D020959:Polyethylene; D019736:Prostheses and Implants / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020959:Polyethylene; D019386:Alendronate