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Lately, concerns have arisen following the use of large metal-on-metal bearings in hip replacements owing to reports of catastrophic soft-tissue reactions resulting in implant failure and associated complications. This review examines the literature and contemporary presentations on current clinical dilemmas in metal-on-metal hip replacement.

Metal-on-metal total hip replacement has been targeted at younger patients with anticipated long-term survival, but the effect of the production of metal ions is a concern because of their possible toxicity to cells. We have reviewed the results of the use of the Ultima hybrid metal-on-metal total hip replacement, with a cemented polished tapered femoral component with a 28 mm diameter and a cobalt-chrome (CoCr) modular head, articulating with a 28 mm CoCr acetabular bearing surface secured in a titanium alloy uncemented shell. Between 1997 and 2004, 545 patients with 652 affected hips underwent replacement using this system. Up to 31 January 2008, 90 (13.8%) hips in 82 patients had been revised. Pain was the sole reason for revision in 44 hips (48.9%) of which 35 had normal plain radiographs. Peri-prosthetic fractures occurred in 17 hips (18.9%) with early dislocation in three (3.3%) and late dislocation in 16 (17.8%). Infection was found in nine hips (10.0%). At operation, a range of changes was noted including cavities containing cloudy fluid under pressure, necrotic soft tissues with avulsed tendons and denuded osteonecrotic upper femora. Corrosion was frequently observed on the retrieved cemented part of the femoral component. Typically, the peri-operative findings confirmed those found on pre-operative metal artefact reduction sequence MRI and histological examination showed severe necrosis. Metal artefact reduction sequence MRI proved to be useful when investigating these patients with pain in the absence of adverse plain radiological features.

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.

Previous research has shown an increase in chromosomal aberrations in patients with worn implants. The type of aberration depended on the type of metal alloy in the prosthesis. We have investigated the metal-specific difference in the level of DNA damage (DNA stand breaks and alkali labile sites) induced by culturing human fibroblasts in synovial fluid retrieved at revision arthroplasty. All six samples from revision cobalt-chromium metal-on-metal and four of six samples from cobalt-chromium metal-on-polyethylene prostheses caused DNA damage. By contrast, none of six samples from revision stainless-steel metal-on-polyethylene prostheses caused significant damage. Samples of cobalt-chromium alloy left to corrode in phosphate-buffered saline also caused DNA damage and this depended on a synergistic effect between the cobalt and chromium ions. Our results further emphasise that epidemiological studies of orthopaedic implants should take account of the type of metal alloy used.

Wear debris was extracted from 21 worn hip and knee replacements. Its mutagenic effects were tested on human cells in tissue culture using the micronucleus assay and fluorescent in situ hybridisation. The extracted wear debris increased the level of micronuclei in a linear dose-dependent manner but with a tenfold difference between samples. The concentration of titanium +/- vanadium and aluminium within the wear debris was linearly related both to the level of centromere-positive micronuclei in tissue culture, indicating an aneuploid event, and to the level of aneuploidy in vivo in peripheral blood lymphocytes. The concentration of cobalt and chromium +/- nickel and molybdenum in the wear debris correlated with the total index of micronuclei in tissue culture, both centromere-positive and centromere-negative i.e. both chromosomal breakage and aneuploidy events. The results show that wear debris can damage chromosomes in a dose-dependent manner which is specific to the type of metal. The results from studies in vitro correlate with those in vivo and suggest that the wear debris from a worn implant is at least partly responsible for the chromosomal damage which is seen in vivo.

The long-term biological effects of wear debris are unknown. We have investigated whether there is any evidence of cumulative mutagenic damage in peripheral blood lymphocytes of patients undergoing revision arthroplasty of predominantly metal-on-plastic total hip replacements compared with those at primary arthroplasty. There was a threefold increase in aneuploidy and a twofold increase in chromosomal translocations which could not be explained by the confounding variables of smoking, gender, age and diagnostic radiographs. In the patients with TiVaAl prostheses there was a fivefold increase in aneuploidy but no increase in chromosomal translocations. By contrast, in patients with cobalt-chrome prostheses there was a 2.5-fold increase in aneuploidy and a 3.5-fold increase in chromosomal translocations. In six patients with stainless-steel prostheses there was no increase in either aneuploidy or chromosomal translocations. Our results suggest that future epidemiological studies of the putative long-term risks of joint replacement should take into account the type of alloy used in the prosthesis.

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1beta, IL-6 and PGE2 in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant.

In a post-mortem study, we compared subjects with metal implants with and without visible wear with an age-matched control group to determine the extent and effects of dissemination of wear debris. In subjects with stainless-steel and cobalt-chrome prostheses metal was found in local and distant lymph nodes, bone marrow, liver and spleen. The levels were highest in subjects with loose, worn joint prostheses and the main source of the debris was the matt coating. Metal levels were also raised in subjects with implants without visible wear and, to a less extent, in those with dynamic hip screws. Necrosis of lymph nodes was seen in those cases with the most wear, and potential damage to more distant organs such as the bone marrow, liver and spleen in the long term cannot be discounted. The consequences for the immune system and the role of metal dissemination in the possible induction of neoplasia are discussed.

The production of particulate wear debris is a recognised complication of joint arthroplasty, but interest has concentrated on local tissue reactions and a possible association with implant loosening. The fate of wear products in the body remains unknown, although some of the metals used in the construction of orthopaedic implants are known to have toxic and oncogenic properties. We report histological and electron-microscopic evidence from two cases which shows that metallic debris can be identified in the lymphoreticular tissues of the body distant from the hip some years after joint replacement. The increase in the use of total arthroplasty in younger patients, the development of new alloys and the use of porous coatings must raise concern for the long-term effects of the accumulation of wear debris in the body.