title: Systemic zoledronate treatment both prevents resorption of allograft bone and increases the retention of new formed bone during revascularization and remodelling. A bone chamber study in rats.
abstract: BACKGROUND
  In osteonecrosis the vascular supply of the bone is interrupted and the living cells die. The inorganic mineral network remains intact until ingrowing blood vessels invade the graft. Accompanying osteoclasts start to resorb the bone trabeculae and gradually replace the bone. If the osteonecrosis occurs in mechanically loaded parts, like in the subchondral bone of a loaded joint, the remodelling might lead to a weakening of the bone and, in consequence to a joint collapse. Systemic bisphosphonate treatment can reduce the resorption of necrotic bone. In the present study we investigate if zoledronate, the most potent of the commercially available bisphosphonates, can be used to reduce the amount or speed of bone graft remodeling.
  
  
  METHODS
  Bone grafts were harvested and placed in a bone chamber inserted into the tibia of a rat. Host tissue could grow into the graft through openings in the chamber. Weekly injections with 1.05 microg zoledronate or saline were given subcutaneously until the rats were harvested after 6 weeks. The specimens were fixed, cut and stained with haematoxylin/eosin and used for histologic and histomorphometric analyses.
  
  
  RESULTS
  By histology, the control specimens were almost totally resorbed in the remodeled area and the graft replaced by bone marrow. In the zoledronate treated specimens, both the old graft and new-formed bone remained and the graft trabeculas were lined with new bone. By histomorphometry, the total amount of bone (graft+ new bone) within the remodelled area was 35 % (SD 13) in the zoledronate treated grafts and 19 % (SD 12) in the controls (p = 0.001). Also the amount of new bone was increased in the treated specimens (22 %, SD 7) compared to the controls (14 %, SD 9, p = 0.032).
  
  
  CONCLUSIONS
  We show that zoledronate can be used to decrease the resorption of both old graft and new-formed bone during bone graft remodelling. This might be useful in bone grafting procedure but also in other orthopedic conditions, both where necrotic bone has to be remodelled i.e. after osteonecrosis of the knee and hip and in Perthes disease, or in high load, high turnover conditions like delayed union, periprosthetic osteolysis or bone lengthening operations. In our model an increased net formation of new bone was found which probably reflects that new bone formed was retained by the action of the bisphosphonates rather than a true anabolic effect.
authors.affiliation: Department of Orthopaedics, Lund University Hospital, SE-221 85 Lund, Sweden. Jorgen.Astrand@ort.lu.se
authors.forename: Jörgen
authors.initials: J
authors.lastname: Astrand
authors.forename: Anna Kajsa
authors.initials: AK
authors.lastname: Harding
authors.forename: Per
authors.initials: P
authors.lastname: Aspenberg
authors.forename: Magnus
authors.initials: M
authors.lastname: Tägil
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000517:prevention & control*; D016025:Bone Transplantation / Q000295:instrumentation / Q000379:methods*; D001842:Bone and Bones / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D015194:Diffusion Chambers, Culture; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000033:anatomy & histology / Q000502:physiology / Q000601:surgery; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid