MECHANISM OF ASEPTIC LOOSENING--AN IN VITRO STUDY

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The long term objective of this project is to improve cemented arthroplasty longevity by avoiding or delaying the occurrence of aseptic loosening which would: 1) broaden the indications for cemented arthroplasty to younger individuals, 2) avoid or delay the need for revision surgery in all patients, 3) improve results in those patients who have poor bone quality or quantity. To obtain this objective, the specific goal of this project is to improve our understanding of the mechanism of aseptic loosening. This will be an in - vitro study involving two groups of experiments over a five year period. In the first group, we will determine the role for each cell type present at the bone-cement interface (i.e. osteoblast, osteoclast, macrophage) in the bone resorption that leads to aseptic loosening by coculturing macrophages exposed to PMMA particles with: 1. rat calvaria and measuring 45 Ca release, 2. osteoclasts cultured on dentin strips and measuring numbers of excavations in bone via scanning E.M., 3. first with osteoblasts and then adding the new secondarily conditioned media to: a. rat calvaria and measuring 45 Ca release, and to; b. osteoclasts cultured on dentin strips and measuring numbers of excavations in bone via scanning E.M. In the second groups of studies, we will determine the relative role of each of the three major bone resorbing mediators in bone resorption at the interface by repeating the experiments in group 1 and attempting to block 45 Ca release or osteoclast excavations with; 1. indomethacin (block prostaglandin E2 synthesis), 2. antibodies to tumor necrosis factor and 3. antibodies to interleukin 1.