Development and Initial Testing of a Rat Model for Particle-Induced Impaired Implant Fixation

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PROQUEST: 820921619

Abstract

Aseptic loosening is considered as one of the main causes of the failure of total hip and knee arthoplasties. Peri-prosthetic osteolysis, which is initiated by particulate wear from the artificial joint surface, is one of the most usual causes leading to aseptic loosening. From a study in 2005, it is projected that, by 2030, the annual demand for hip and knee revision procedures in the US will greatly increase. So, there is an urgent need to study the prevention and treatment of particle-induced implant loosening. Although current prevention and treatment are focused on using anti-catabolic agent, such as biosphosphonates, and antagonist of pro-inflammatory cytokines, anabolic agents are considered as promising candidates for this therapy. Sclerostin antibody is an anabolic agent and has shown its enhancement in the implant fixation and fracture healing. Therefore, the main specific aims of this dissertation were to develop and validate an animal model of particle-induced implant loosening, and to apply this model for testing the effect of sclerostin antibody in the prevention of particle-induced implant loosening. We started the dissertation with a methodology study to test whether an automated uCT-based bone-implant contact can be used as one criterion to validate our model. We showed that this measurement can not accurately predict bone-implant contact though it can be used as a direct of mechanical fixation. Then, this dissertation continued with a specific aim looking at the effect of polyethylene particles on the osteogenic potential of bone marrow. We found that polyethylene particles inhibited the proliferation of osteoprogenitor in the overall bone marrow though did not change the activity of single osteoprogenitor. Next, in the study for specific aim 3, we developed an animal model of particle-induced implant loosening, and validated the model from histological characteristics, \iCT bone architectures, mechanical implant fixation, serum biomarkers of bone turnover and histomorphometry. At the end, in the study for specific aim 4, we showed that sclerostin antibody could prevent particle-induced implant loosening by increasing bone formation and inhibiting bone resorption. It could be a general therapy for inflammation-related bone disease.

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