BIOLOGICAL ISSUES IN METAL-METAL ARTHROPLASTY

Published in the Biomaterials Forum
Thomas P. Schmalzried, M.D.
Patricia Campbell, Ph.D. ' Frank W. Chan, Ph.D.

Metal-metal technology for total hip replacements has become a viable alternative bearing combination to metal-conventional polyethylene articulating couples since polyethylene wear particle-induced osteolysis was identified in the early 1990s as the leading problem in total hip arthroplasty. Extensive research and development has provided the orthopaedic community with an increased understanding of the engineering issues related to good metal-metal wear performance.4 Despite this and state-of-the-art manufacturing leading to reproducible, low-wearing metal-metal couples, the biological issues of this technology remain in the spotlight.

The wear rate of metal-metal hips is a fraction of the wear rate of metal-conventional ultra-high molecular weight polyethylene (UHMWPE) implants.25,29 However, the cobalt chromium alloy (CoCr) particles found within macrophages around metal-metal total hips are in the nanometer-size range, one order of magnitude smaller than typical polyethylene particles.6 Because smaller particles will have relatively larger surface area, there may be potential clinical ramifications as total particle surface area can possibly influence dissolution rate and biological activity. Surface area has been identified as a variable affecting the macrophage response to particles.28

The focus of concern, therefore, has been the wear particles generated from the intended motion of the joint, the ball moving relative to the socket. Practically, however, numerous wear particles can also be generated from other, non-articulating surfaces in what is referred to as mode four wear.21 This includes particles generated from relative motion due to loosening, modular connections, and neck-socket impingement, which can be orders of magnitude greater than that generated by a well-functioning hip articulation. Studies have shown that mode four wear can potentially cause adverse local and systemic tissue reactions31 including rapid osteolysis26, resulting in the need for revision despite little wear of the primary metal-metal bearing.16 With regard to adverse biological reactions, the malfunctioning joint is a greater threat to the host than the intended wear of the metal-metal articulation.

Although the actual nature of the metallic wear particles and organometallic complexes formed in vivo is still under investigation, recent studies have attempted to utilize more clinically relevant models, for example, by exposing particles to serum prior to use in vitro, employing particles extracted from periprosthetic tissues, or using particle doses similar to those occurring in vivo.12,20,27 While experiments conducted with variable cell types, particles, and analytical methods often lead to conflicting results,15 it consistently appears that, at clinically relevant concentrations, the wear products from CoCr implants are able to modulate cytokine expression in macrophages10,11,15,33 and may have inhibitory effects upon osteoblasts,1 neutrophils,24 and T cells9 but do not induce cytotoxic effects.1,14,33 In contrast to the latter observation from cell culture models is the frequent observation of necrosis in the periprosthetic tissues of metal-metal total hips.2'7,8,19 However, a direct correlation between necrosis and visible metallic particles has not been established and extensive necrosis is also seen in tissues around failed metal-UHMWPE total hips.7

Studies of the levels of cobalt and chromium in the hair, blood, and urine have shown that metallic content in patients with metal-metal total hips are generally higher than in patients with metal-UHMWPE articulations.5 This finding has been repeated in more recent studies of serum and urine metal levels that employed analytical instruments with increased sensitivity and stringent methods to avoid contamination of the samples.17,18 These studies indicated that cobalt ions are rapidly transported from the implant site and mostly eliminated in the urine while chromium tends to be stored in the tissues and eliminated more slowly. While the release of cobalt and chromium ions from metal-metal total hips has been verified, the clinical significance of this finding is still unclear.

Cobalt and chromium wear particles have been shown to induce carcinoma in animal models,13 giving rise to the concern that such alloys could have the same effect if present in sufficient amounts in human tissue for a sufficient length of time. Elevated levels of cobalt and chromium have been found in human tissues surrounding orthopaedic implants and in tissues at remote sites.3 The concern, therefore, is that metal-metal bearings used in total hip arthroplasty may pose a higher risk of malignant degeneration because of an increased exposure to metal particles and ions. Although metal particles and ions have been the prominent concern, there have also been reports of cancer induction with polymethylmethacrylate (bone cement)23 and polyethylene22 in animal models. Overall, the available epidemiological data do not demonstrate an increase in cancer risk following total hip replacement.32 At the same time, it is important to recognize the limitations of the available data with regard to sample size, length of follow-up, and lack of stratification for other co-morbidities.30

The issue of delayed-type hypersensitivity (DTH) to the main elements in metal-metal total hips - cobalt, chromium, and nickel -was addressed in the 1960s and 1970s using skin patch testing. Although this is now recognized as unreliable for the assessment of hypersensitivity to implants, this type of testing has shown that cobalt, chromium, and nickel are associated with contact dermatitis, and as many as 15% of the population is estimated to be sensitive to cobalt and nickel and 8% to chromium. Because there is a higher reported incidence of metal sensitivity in patients with loose components, the association between metal sensitivity and loose implants has fueled a long-standing debate: does hypersensitivity cause loosening or does loosening cause hypersensitivity? Either way, it does appear that a small number of patients with metal-metal total hips develop an adverse local tissue response and present with unexplained pain and chronic effusions that resolve when the metal-metal bearings are exchanged for metal-UHMWPE hips. The histology of abundant lymphocytes and plasma cells is highly suggestive of an immune response. Therefore, caution should be taken in the implantation of a metal-metal bearing in patients with a known sensitivity to metals.

Further investigations of the local and systemic effects related to the wear of the primary articulating surface are needed. It should be emphasized, however, that clinical success is multifactorial. Patient selection, surgical technique, component fixation, and the other aspects of the prosthetic joint will influence the clinical performance of any articulation.

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