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The presence of pseudotumours, which are soft-tissue masses relating to the hip, after metal-on-metal hip resurfacing arthroplasty has been associated with elevated levels of metal ions in serum, suggesting that pseudotumours occur when there is increased wear. We aimed to quantify the wear in vivo of implants revised for pseudotumours (eight) and of a control group of implants (22) revised for other reasons of failure. We found that the implant group with pseudotumours had a significantly higher rate of median linear wear of the femoral component at 8.1 microm/year (2.75 to 25.4) than the 1.79 microm/year (0.82 to 4.15; p = 0.002) of the non-pseudotumour group. For the acetabular component a significantly higher rate of median linear wear of 7.36 microm/year (1.61 to 24.9) was observed in the pseudotumour group compared with 1.28 microm/year (0.81 to 3.33, p = 0.001) in the other group. Wear of the acetabular component in the pseudotumour group always involved the edge of the implant, indicating that edge-loading had occurred. Our findings are the first direct evidence that pseudotumour is associated with increased wear at the metal-on-metal articulation. Furthermore, edge-loading with the loss of fluid-film lubrication may be an important mechanism of generation of wear in patients with a pseudotumour.

Despite the satisfactory short-term implant survivorship of metal-on-metal hip resurfacing arthroplasty, periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. Cytotoxic effects of cobalt or chromium have been suggested to play a role in its aetiology. The aim of this study was to investigate the effects of clinically relevant metal nanoparticles and ions on the viability of macrophages in vitro. A RAW 264.7 murine macrophage cell line was cultured in the presence of either: (1) cobalt, chromium and titanium nanoparticles sized 30-35 nm; or (2) cobalt sulphate and chromium chloride. Two methods were used to quantify cell viability: Alamar Blue assay and Live/Dead assay. The cytotoxicity was observed only with cobalt. Cobalt nanoparticles and ions demonstrated dose-dependent cytotoxic effects on macrophages in vitro: the cytotoxic concentrations of nanoparticles and ions were 1 x 10(12) particles ml(-1) and 1000 microM, respectively. The high concentration of cobalt nanoparticles required for cytotoxicity of macrophages in vitro suggests that increased production of cobalt nanoparticles in vivo, due to excessive MoM implant wear, may lead to local adverse biological effects. Therefore, cytotoxicity of high concentrations of metal nanoparticles phagocytosed by macrophages located in the periprosthetic tissues may be an important factor in pathogenesis of pseudotumours.

Locally destructive soft tissue pseudotumor has been reported in patients following metal-on-metal hip resurfacing arthroplasty (MoMHRA). A delayed hypersensitivity reaction type IV to nickel (Ni), chromium (Cr), or cobalt (Co) has been suggested to play a role in its aetiology. The aim of this study was to investigate the incidence and level of metal-induced systemic hypersensitivity in patients with MoMHRA, both with and without pseudotumor by measuring lymphocyte proliferation responses to metals. A total of 92 patients were investigated: (1) MoMHRA patients with pseudotumors (nine female, one male); (2) MoMHRA patients without pseudotumors (30 female, 30 male); and (3) age-matched control subjects without metal implants (9 female, 13 male). The venous blood samples were collected for serum Ni, Co, and Cr ion level measurements and lymphocyte transformation tests (LTT). A higher incidence and level of enhanced lymphocyte reactivity only to Ni was found in patients with MoMHRA compared to the patients without MoM implants, reflecting exposure and immune reactivity. However, lymphocyte reactivity to Co, Cr, and Ni did not significantly differ in patients with pseudotumors compared to those patients without pseudotumors. This suggests that systemic hypersensitivity type IV reactions, as measured by lymphocyte proliferation response to these metals, may not be the dominant biological reaction involved in the occurrence of the soft tissue pseudotumors. ß

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