title: Reduction of instability-induced bone resorption using bisphosphonates: high doses are needed in rats.
abstract: Bone resorption associated with prosthetic loosening can be reduced by giving bisphosphonates since they bind to bone surfaces and inactivate osteoclasts when bisphosphonate-containing bone is resorbed. During loosening, an increase in osteoclastic activity can be triggered by mechanical instability, fluid pressure or wear particles. We used a rat model in which a titanium surface can be made to slide over a bone surface and cause instability-induced bone resorption. 111 rats were operated on with a plate implant and treated with alendronate or clodronate injections in different doses or saline controls. After 4 weeks of osseointegration, the plate was moved during 2 weeks and the findings evaluated with histomorphometry. The percentage of persisting bone-metal contact and the soft tissue area at the interface were measured to estimate bone loss. Low or intermediate doses of the bisphosphonates increased the ash weight of untraumatized bone, but did not inhibit resorption at the unstable interface. Only rats treated with the highest doses of alendronate or clodronate had more bone-metal contact than controls. Instability-induced bone resorption therefore seems to be reduced by bisphosphonates, but higher doses are needed to obtain this effect than to reduce bone resorption associated with normal remodeling of untraumatized bone.
authors.affiliation: Department of Orthopedics, Lund University Hospital, Sweden. Jorgen.Astrand@ort.lu.se
authors.forename: Jörgen
authors.initials: J
authors.lastname: Astrand
authors.forename: Per
authors.initials: P
authors.lastname: Aspenberg
mesh_terms: D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D001860:Bone Plates; D001862:Bone Resorption / Q000517:prevention & control*; D004002:Clodronic Acid / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007593:Joint Instability / Q000517:prevention & control*; D008297:Male; D016348:Osseointegration / Q000187:drug effects*; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D019736:Prostheses and Implants; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013977:Tibia / Q000601:surgery
chemical_list: D004164:Diphosphonates; D004002:Clodronic Acid; D019386:Alendronate