A Potential Concern in Total Joint Arthroplasty: Systemic Dissemination of Wear Debris

This issue of The Journal contains an important article by Urban et al., which discusses the dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients who have had a total hip or knee replacement and focuses on the systemic effects rather than the local effects of a total joint arthroplasty12. In a 1993 issue of The Journal, an editorial that I coauthored proclaimed that the problem in total joint arthroplasty was aseptic loosening5. Indeed, osteolysis and aseptic loosening are the most frequently recognized complications of total joint arthroplasty13. Much is known about the mechanical production of wear debris stimulating a biological response leading to osteolysis and, in many cases, to loosening of the implant. In situ degradation of implants commonly occurs. The most prevalent form of such degradation is wear, but there also can be corrosion of the metallic components of the implant as well as a synergistic combination of wear and corrosion7. Debris is most commonly produced as a result of three primary forms of wear: adhesive, abrasive, and fatigue (also known as delamination)2. Such debris is produced at various sites, including the articular surface, modular implant junctions, and various interfaces such as implant-bone, implant-cement, and cement-bone interfaces. Numerous studies have demonstrated that various particulate materials, including polyethylene, metal, and cement, can become phagocytosed by macrophages and stimulate the release of soluble proinflammatory mediators known as cytokines. These cytokines include interleukin-1 and tumor necrosis factor-α and are released adjacent to the bone, which may contribute to bone resorption through the activation of osteoclasts. In addition, studies have shown that polyethylene4 as well as particulate metal debris1 may directly suppress osteoblast function. Therefore, not only may there be a direct effect in terms of increased bone resorption but there also may be decreased bone formation resulting in osteolysis. Wear debris is frequently phagocytosed by the macrophages within the synovial membrane surrounding the total joint prosthesis. However, the debris may overwhelm the synovial macrophages, resulting in migration of the debris into periprosthetic tissue, where it may become phagocytosed by macrophages and enter the lymphatic system10. In addition, as pointed out in the article by Urban et al., such debris has been found in the fixed macrophages or Kupffer cells lining the hepatic sinusoids, which suggests the possibility of hematogenous dissemination as well. Urban et al. correctly point out that the local effects of wear debris resulting in osteolysis and aseptic loosening are well understood; they undertook their study to investigate the prevalence and histopathological characteristics of disseminated debris in the liver, spleen, and abdominal para-aortic lymph nodes12. The authors studied postmortem specimens from twenty-nine patients and biopsy specimens from two living patients with failed prostheses. The postmortem investigations included twenty-one patients who had had a primary total joint arthroplasty (eleven had had a total hip arthroplasty, and ten had had a total knee arthroplasty). The other eight had had a revision hip arthroplasty for loosening of one or more of the components. Urban et al. found that metallic wear particles were more prevalent in patients who had had a failed hip arthroplasty than in those who had had a primary hip or knee replacement12. Interestingly, they determined that the principal source of wear debris was the nonbearing surfaces of the implant. Metallic wear particles and polyethylene particles were detected in the para-aortic lymph nodes in the majority of patients with implants. In 38 percent (eleven) of the twenty-nine patients, metallic particles were found to have been further disseminated to the liver and spleen, and polyethylene particles were found in the liver or the spleen in 14 percent (four) of the twenty-nine patients. The majority of disseminated wear particles were less than one micrometer in size. Urban et al. concluded that the systemic distribution of metal and polyethylene was a common finding, not only in patients who had had a previously failed implant but also in those who had had a primary total hip or knee arthroplasty12. They found an increased amount of debris in patients who had had a previously failed implant. In the majority of patients, the concentration of wear debris was relatively low and without apparent pathological importance. It is clear not only that the production of wear debris from total joint implants has important ramifications with regard to osteolysis and aseptic loosening but also that there is a potential systemic impact of such particulate matter. Indeed, a major goal of implant design and development is to minimize the production of such debris. In addition to implant design factors, patient factors such as activity level may have a notable effect on the production of debris. Furthermore, certain advances may actually pose additional unforeseen problems. Experience with hydroxyapatite-coated polyethylene acetabular components has shown that the hydroxyapatite may become dislodged from the surface of the implant and result in third-body wear producing debris, which could cause osteolysis and implant failure9. In addition, ultra-high molecular weight polyethylene has been identified as the most common source of debris6,8,11, and there has been renewed interest in alternative bearing surfaces. It has been shown, however, that the use of so-called metal-on-metal articulations results in an increased serum concentration of cobalt3, the clinical importance of which is yet to be determined. It is clear that the implications of modifying a design feature must be carefully assessed to ensure that an untoward effect does not occur. Furthermore, many of these effects, which ultimately may result in osteolysis and loosening, may take many, many years to occur, and the long-term follow-up of patients with such design modifications is essential. Studies involving the local and systemic effects of debris will influence the design of implants, thereby allowing us to lessen the mechanical production of such debris. In addition, future efforts with pharmacological interventions may help us to modulate the biological effects of this debris as well. More study is necessary regarding not only the local effects of wear debris but also its systemic dissemination. Furthermore, issues such as the risk of malignancy are being explored, but no direct association has been identified to date. The study by Urban et al. underscores the necessity of minimizing the production of particulate debris and the need to consider revision of the implant in patients in whom large amounts of debris may be generated. In addition, we need to continue the long-term study of disseminated, mechanically produced debris to determine if there are direct biological effects that may have clinical importance beyond the rare case, described by these authors, of a patient with mechanical failure of an implant and compromised hepatic function in whom granulomas formed in the liver, spleen, and abdominal lymph nodes. The study by Urban et al. further emphasizes the need for long-term clinical and radiographic follow-up of all patients who have had a total joint arthroplasty, even if the patient is asymptomatic.