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
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-a 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
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
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.