Does a pro-angiogenic state exist in the bone-implant interface of aseptically loosened joint prosthesis?

Neovascularization is indispensable to both bone remodeling and the develop ment of chronic inflammation. A pro-angiogenic state in the periprosthetic tissue may augment the inflammatory response to wear debris. To investigate if a pro-angiogenic state exists in the bone-implant interface of aseptica lly loosened joint prosthesis, the expression of vascular endothelial growt h factor (VEGF) and its receptor Flk-1/KDR were studied by immunohistochemi stry. The VEGF-Flk/KDR pathway has been implicated as a key signaling requi rement for pathological angiogenesis. The level of vascularization in perip rosthetic tissue was semi-quantitatively compared to osteoarthritic (OA) an d rheumatoid arthritic (RA) synovium. The level of vascularization in areas of periprosthetic tissue with heavy or low/moderate wear debris were also compared semi-quantitatively by image analysis. High levels of VEGF expression (16/16 cases) particularly in the implant sy novial-like lining layer together with Flk-1/KDR expression by endothelial cells (13/16), suggests that neovascularization is occurring. Morphometric comparison of periprosthetic tissue with RA and OA synovium revealed no sig nificant difference in microvessel density, but did reveal significantly in creased microvessel area in RA synovium (P\gt 0.05). Areas of high wear deb ris infiltrate also contained a significantly smaller microvessel area (P\g t 0.01). Suggesting that wear debris may cause behavioral modification of m icrovessels. Modifying angiogenesis in the periprosthetic tissue could be a potential therapeutic target in reducing inflammation. (C) 2001 Kluwer Aca demic Publishers.