Asceptic loosening is the most common cause of problems leading to hip revision. This loosening may be due to micromotion, accumulation of particle debris or a combination of both leading to osteolysis (aggressive bone resorption around the implant) and eventual implant failure. Bisphosphonates are compounds that reduce bone resorption by causing ostoeclast apoptosis thereby reducing the life span of the osteoporosis and Paget's disease. We propose to test a bisphosphonate, pamidronate, in our osteolytic rat model as a possible anti-osteolytic compound. All rats will have a titanium pin implant with associated LPS exposed particles dispersed in gelatin inserted through a intercondylar drill hole into the distal femur on one side. Rats will be divided into 5 groups (10 rats each). Group one will receive no bisphosphonate, groups 2-4 will receive 100 mu1 IP infections of 0.1 mg/ml and 10.0 mg/ml every other day for ten days after surgery and group 5 will receive a one time dose of 30 mg/kg body weight mixed with gelatin that is placed inside the defect at the time of the surgery. After six weeks the animals will be sacrificed. Initial and six week radiographs, histology and histomorphometry will be used to assess the outcome of the animals. Gap sizes between the bone and implant will be measured and means compared using an ANOVA and multiple range tests.
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