Patients who suffer from severe joint destruction caused by arthritis often undergo total joint arthroplasty (TJA). A major limitation of this treatment and common long-term complication is the development of aseptic loosening of the prosthesis in as many as 20% of patients. The current paradigm to explain aseptic loosening proposes that wear debris generated from the prosthesis initiates a macrophage-mediated inflammatory response by resident macrophages, leading to osteoclast activation and bone resorption at the implant interface. This can then lead to the development of a peri-prosthetic fracture. The principal aim of fracture healing is to restore the bone to its original form and strength. However, this ultimate goal can be altered if the healing is impaired. This impairment may be due to bone disease (osteoporosis) or even the introduction of a foreign material such as PE wear debris that could have migrated from the articulating surface to the fracture site. A standard closed unilateral fracture of the right femur was performed in both normal and oestrogen deficient rats following fixation with a k-wire. Ceridust (PE wear debris) was combined with hyaluronic acid and saline and injected directly into the fracture site. Femurs were assessed using radiographs, histology and immunohistochemistry. Histological analysis revealed that complete remodelling was achieved in all control groups by 6 weeks post-fracture with mechanical strength returning to normal values. The mechanical properties of the fractures were not influenced by the presence of PE wear debris in the dose and timing examined. Histology and immunohistochemistry however, did reveal a local effect of the presence of PE wear debris. The histology adjacent to the PE particles was inferior to the controls but did not manifest itself in a reduction in the mechanical properties except in the oestrogen deficient bone at 6 weeks post-fracture. The levels of MMP-1 and TNF-?? correlated to the presence of PE particles. In this thesis, I have shown the mechanism by which bone remodelling in fracture healing could be retarded due to the presence of PE wear debris, by increased matrix degradation in both normal and oestrogen deficient animals.
| Identifer | oai:union.ndltd.org:ADTP/188070 |
| Date | January 2005 |
| Creators | Rajaratnam, Rema Antonette, Prince of Wales Clinical School, UNSW |
| Publisher | Awarded by:University of New South Wales. Prince of Wales Clinical School |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Rema Antonette Rajaratnam, http://unsworks.unsw.edu.au/copyright |
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