title: The John Charnley Award. Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model.
abstract: In this study the efficacy of an oral bisphosphonate therapy to inhibit wear debris mediated bone resorption was evaluated in a canine total hip replacement model. Adult canines were randomized to three groups (n = 8 each) with a right uncemented total hip replacement performed on each animal. Group I (control) received no particulate debris. In Groups II and III, a mixture of 1 x 10(9) particles were introduced into the proximal femoral gap intraoperatively. The particle mixture consisted of fabricated ultra high molecular weight polyethylene (mean 2.3 microns, 90% by number), titanium alloy (mean 3.1 microns, 5%), and cobalt chrome alloy (mean 0.8 micron, 5%). Group III canines additionally received oral drug therapy (5 mg once a day, alendronate sodium) which was begun on postoperative Day 7 and continued until the time of sacrifice. Postoperatively, all animals were allowed 24 weeks of full ambulation before euthanasia. Radiographs obtained preoperatively, postoperatively, and at time of sacrifice were evaluated for periprosthetic osteolysis. Interfacial tissues were examined histologically and placed in organ culture and the supernatants were assayed for prostaglandin E2 and interleukin-1. One animal receiving debris (Group II) suffered a periprosthetic fracture and was sacrificed from the study. Radiographically, one of eight Group I (control) and six of seven canines from Group II (debris) had periprosthetic radiolucencies with endosteal scalloping develop. In contrast, only one of eight animals from Group III (debris + alendronate) had periprosthetic radiolucencies develop. Whereas tissues from control animals were mostly fibrous and acellular, tissues from both experimental groups had significant macrophage infiltration. Levels of prostaglandin E2 and interleukin-1 were elevated significantly in periprosthetic tissues from both experimental groups compared with controls. Continuous administration of alendronate effectively inhibited bone lysis for the 24-week duration of the study. This is consistent with the literature indicating that alendronate is incorporated in the mineralizing matrix making it refractory to osteoclastic resorption. This report has significant clinical implications for controlling the most common cause of implant failure.
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh, PA, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Shanbhag
authors.forename: C T
authors.initials: CT
authors.lastname: Hasselman
authors.forename: H E
authors.initials: HE
authors.lastname: Rubash
mesh_terms: D019386:Alendronate / Q000627:therapeutic use*; D000818:Animals; D001363:Awards and Prizes; D001862:Bone Resorption / Q000517:prevention & control*; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D005069:Evaluation Studies as Topic; D006622:Hip Prosthesis; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D009985:Orthopedics; D010014:Osteolysis / Q000517:prevention & control*; D011095:Polyethylenes; D011897:Random Allocation
chemical_list: D007375:Interleukin-1; D011095:Polyethylenes; D015232:Dinoprostone; D019386:Alendronate