On the inflammatory response in metal-on-metal implants.

backgroundMetal-on-metal implants are a special form of hip endoprostheses that despite many advantages can entail serious complications due to release of wear particles from the implanted material. Metal wear particles presumably activate local host defence mechanisms, which causes a persistent inflammatory response with destruction of bone followed by a loosening of the implant. To better characterize this inflammatory response and to link inflammation to bone degradation, the local generation of proinflammatory and osteoclast-inducing cytokines was analysed, as was systemic T cell activation.

methodsBy quantitative RT-PCR, gene expression of cytokines and markers for T lymphocytes, monocytes/macrophages and osteoclasts, respectively, was analysed in tissue samples obtained intraoperatively during exchange surgery of the loosened implant. Peripheral T cells were characterized by cytofluorometry before surgery and 7 to 10 days thereafter.

resultsAt sites of osteolysis, gene expression of cathepsin K, CD14 and CD3 was seen, indicating the generation of osteoclasts, and the presence of monocytes and of T cells, respectively. Also cytokines were highly expressed, including CXCL8, IL-1ß, CXCL2, MRP-14 and CXCL-10. The latter suggest T cell activation, a notion that could be confirmed by detecting a small, though conspicuous population of activated CD4+ cells in the peripheral blood T cells prior to surgery.

conclusionOur data support the concept that metallosis is the result of a local inflammatory response, which according to histomorphology and the composition of the cellular infiltrate classifies as an acute phase of a chronic inflammatory disease. The proinflammatory environment, particularly the generation of the osteoclast-inducing cytokines CXCL8 and IL1-ß, promotes bone resorption. Loss of bone results in implant loosening, which then causes the major symptoms of metallosis, pain and reduced range of motion.