Metal-on-metal joint bearings and hematopoetic malignancy
ABSTRACT Abstract This is a review of the hip arthroplasty era. We concentrate on new metal bearings, surface replacements, and the lessons not learned, and we highlight recent reports on malignancies and joint implants. A low incidence of blood malignancies has been found in bone marrow taken at prosthetic surgery. The incidence is increased after replacement with knee implants that release very low systemic levels of metal ions. A carcinogenic effect of the high levels of metal ions released by large metal-on-metal implants cannot be excluded. Ongoing Swedish implant registry studies going back to 1975 can serve as a basis for evaluation of this risk.
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ABSTRACT: Finite element models are becoming increasingly useful tools to conduct parametric analysis, design optimisation and pre-clinical testing for hip joint replacements. However, the verification of the finite element model is critically important. The purposes of this study were to develop a three-dimensional anatomic finite element model for a modular metal-on-polyethylene total hip replacement for predicting its contact mechanics and to conduct experimental validation for a simple finite element model which was simplified from the anatomic finite element model. An anatomic modular metal-on-polyethylene total hip replacement model (anatomic model) was first developed and then simplified with reasonable accuracy to a simple modular total hip replacement model (simplified model) for validation. The contact areas on the articulating surface of three polyethylene liners of modular metal-on-polyethylene total hip replacement bearings with different clearances were measured experimentally in the Leeds ProSim hip joint simulator under a series of loading conditions and different cup inclination angles. The contact areas predicted from the simplified model were then compared with that measured experimentally under the same conditions. The results showed that the simplification made for the anatomic model did not change the predictions of contact mechanics of the modular metal-on-polyethylene total hip replacement substantially (less than 12% for contact stresses and contact areas). Good agreements of contact areas between the finite element predictions from the simplified model and experimental measurements were obtained, with maximum difference of 14% across all conditions considered. This indicated that the simplification and assumptions made in the anatomic model were reasonable and the finite element predictions from the simplified model were valid.Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine 06/2014; · 1.14 Impact Factor
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ABSTRACT: The area of implant osseointegration is of major importance, given the predicted significant rise in the number of orthopaedic procedures and an increasingly ageing population. Osseointegration is a complex process involving a number of distinct mechanisms affected by the implant bulk properties and surface characteristics. Our understanding and ability to modify these mechanisms through alterations in implant design is continuously expanding. The following review considers the main aspects of material and surface alterations in metal implants, and the extent of their subsequent influence on osseointegration. Clinically, osseointegration results in asymptomatic stable durable fixation of orthopaedic implants. The complexity of achieving this outcome through incorporation and balance of contributory factors is highlighted through a clinical case report.Acta Biomaterialia 06/2014; · 5.68 Impact Factor
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ABSTRACT: There is an increase in the levels of metals in the serum and urine after the implantation of some models of metal-metal hip prosthesis. It has recently been demonstrated that there is an association between these levels and the levels found in hair. The aim of this study is to determine the presence of metals in hair, and to find out whether these change over time or with the removal of the implant. The levels of chromium, cobalt and molybdenum were determined in the hair of 45 patients at 3, 4, 5, and 6 years after a hip surface replacement. The mean age was 57.5 years, and two were female. Further surgery was required to remove the replacement and implant a new model with metal-polyethylene friction in 11 patients, 5 of them due to metallosis and a periarticular cyst. The mean levels of metals in hair were chromium 163.27ppm, cobalt 61.98ppm, and molybdenum 31.36ppm, much higher than the levels found in the general population. A decrease in the levels of chromium (43.8%), molybdenum (51.1%), and cobalt (91.1%) was observed at one year in the patients who had further surgery to remove the prosthesis. High concentrations of metals in the hair are observed in hip replacements with metal-metal friction, which decrease when that implant is removed. The determination of metal ions in hair could be a good marker of the metal poisoning that occurs in these arthroplasty models.Revista Espanola de Cirugia Ortopedica y Traumatologia 03/2014;
Acta Orthopaedica 2012; 83 (6): 553–558 553
Metal-on-metal joint bearings and hematopoetic malignancy
Philippe Wagner1, Håkan Olsson2, Jonas Ranstam1, Otto Robertsson1, Ming Hao Zheng3,
and Lars Lidgren1
Departments of 1Orthopedics and 2Oncology, Clinical Sciences Lund, Lund University, Lund; 3Centre for Orthopaedic Research, University of Western
Australia, Nedlands, Australia.
Submitted 12-06-14. Accepted 12-09-27
Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use,
distribution, and reproduction in any medium, provided the source is credited.
Abstract This is a review of the hip arthroplasty era. We con-
centrate on new metal bearings, surface replacements, and the
lessons not learned, and we highlight recent reports on malig-
nancies and joint implants. A low incidence of blood malignan-
cies has been found in bone marrow taken at prosthetic surgery.
The incidence is increased after replacement with knee implants
that release very low systemic levels of metal ions. A carcinogenic
effect of the high levels of metal ions released by large metal-on-
metal implants cannot be excluded. Ongoing Swedish implant
registry studies going back to 1975 can serve as a basis for evalu-
ation of this risk.
After more than 3 decades of limited success with hemiarthro-
plasty, the total hip arthroplasty (THA) era started in the 1950s
in Europe. In 1953, the McKee 32-mm metal head articulating
against a metal cup (MOM) made of cobalt-chromium was
introduced (McKee and Watson-Farrar 1966). The success
with low-friction arthroplasty (LFA) (Charnley 1961) was
a dramatic leap forward, at the start only hampered by deep
infections in up to 10% of the cases. At the beginning of the
1970s, strict aseptic and antiseptic routines combined with
systemic and local antibiotic prophylaxis reduced the risk of
infection to less than 1% (Lidgren 2001, Jämsen et al. 2010).
The initial outcome with the cemented MOM THA was
also promising, but early on it resulted in 2 main failure pat-
terns (Benson et al. 1975). Loosening and migration of the
acetabular cup occurred due to high friction and impact forces.
Secondly, local inflammation around the implant with black-
tinted tissue was observed in early revisions for pain, and it
was believed to be caused by metal wear particles (Evans et
al. 1974). Improved production of the McKee with matched
components led to jamming, and increased the failure rate
even more. Coleman et al. (1973) reported a 15-fold increase
in Cr in urine and an 11-fold increased level of Co in whole
blood (Coleman et al. 1973). In addition, Benson et al. (1975)
showed a high incidence of metal sensitivity in MOM McKee-
Farrar THA compared to metal-to-plastic THA.
In a short-term follow-up of MOM McKee-Farrar THA,
revision had been done in 15% of cases at 4 years (Baldursson
1980). Single long-term studies have, however, also reported
prosthetic survival in up to 75% of cases at 20 years (Brown
et al. 2002). At the end of 1970, the McKee-Farrar MOM con-
cept was abandoned in favor of the LFA concept, which has
had a well-documented excellent long-term outcome (Cal-
laghan et al. 2000, Learmonth et al. 2007).
A partly new idea, the surface replacement (SR), was intro-
duced in 1974 by Wagner in Germany (Wagner 1978). A large
(44 mm or more) 3-mm-thick stainless steel cup was placed on
the preserved femoral head and a thin polyethylene cup (4–6
mm) was inserted in the acetabulum. As early as the 1930s,
the same concept—but as a mold hemiarthroplasty—had been
introduced, first made of glass but later made of stainless
steel (Smith-Petersen 1948). The joint-preserving SR method
quickly became popular, especially in active young patients,
reducing the risk of dislocation. But soon afterwards, new
complications were reported, i.e. cervical neck fractures due
to several factors such as femoral notching and loosening of
the femoral cup secondary to bone necrosis (enhanced by par-
ticles and circulatory disturbances). In addition, the thin poly-
ethylene acetabular cup was deformed and it added to a high
early failure rate (Mogensen et al. 1982). A long-term study
of the original Wagner SR showed that after 22 years, only
11 of 270 patients still had this prosthesis left in situ (Costi et
al. 2010). In 16% of the revisions, loosening was only found
on the femoral side. Until the start of the new millennium, the
SR method had a strong foothold in the USA (Amstutz et al.
554 Acta Orthopaedica 2012; 83 (6): 553–558
Metal on metal
It was expected that when the MOM THA concept was revis-
ited by Weber in Switzerland in the 1980s (Weber 1996, Ran-
delli et al. 2012)—and followed in the 1990s by the Birming-
ham MOM SR in the UK (Carrothers et al. 2010)—that some
of the earlier observations and experience of outcome during
the previous 70 years had been taken into consideration. The
new cobalt-chromium MOM joint bearings were tested tribo-
logically by wear-simulator testing and were claimed to over-
come the high friction and wear seen earlier with the McKee-
Farrar MOM THA. The risk of femoral neck fracture and loos-
ening were expected to diminish with surgical training using a
more gentle technique and better instrumentation.
The initial early success reported by Daniel et al. already
in 2004 resulted in a number of “generic” MOM SR pros-
theses being quickly released by competing companies; these
were based on a predicative 510 K process, starting from the
BHR approval in May 2006 (http://www.fda.gov/downloads/
ocuments/ucm080189.pdf). At the same time, several MOM
THAs made of cobalt-chromium were reintroduced with the
same claim that the new high-precision production methods
should give less friction than the LFA. In the USA in 2009,
approximately one third of the hip joint procedures were large
MOM articulations (Bozic et al. 2010).
Based on the data available today, it is possible to con-
clude that, except for there being less dislocation with a larger
head, none of the claims have come true. For some of the new
implants with minimal clearance between the larger metal
components, this has resulted (as before) in jamming from
local polar edge contact, with wear and increased blood metal
ion levels if perfect positioning is not achieved (De Haan et
al. 2008, Langton et al. 2008, Hart et al. 2009). There have
been no clinical studies verifying the importance of lubrica-
tion and optimal clearance between the bearing surfaces for
new implant designs.
There is still an increased risk of early revision, of 1.5–3%,
for femoral neck fractures with MOM SR (Steffen et al. 2009).
Isolated femoral complications could be expected to increase
further with time from age-related fragility, accelerated stress
shielding, and particle reaction—especially in women with a
small neck-to-head ratio.
Metal wear and particle release is a major issue with the
new larger bearings, despite the improved tribology verified
on the bench. Shedding of large amounts of particles may
occur, leading to painful local inflammation and reoperation
(Smith et al. 2012). About one trillion small nanoparticles
are released in a year in a MOM bearing, which is 14,000
times more particles than with an LFA articulation (Daniel
et al. 2012). Recent studies have shown that in patients with
well-functioning implants, the average serum levels of Co and
Cr are 1–2 μg/L. Levels of up to 387 μg/L for Co and 179
μg/L for Cr have, however, been found. Very high levels in the
fluid surrounding a MOM THA have been measured: up to
400 mg/L of Cr and up to 22 mg/L of Co (Sampson and Hart
2012, Srinivasan et al. 2011). In a MOM THA with a modular
morse-taper head-neck junction, with metal-on-metal contacts
and possible corrosion, the particle release may be even higher
(Meyskens and Yang 2011).
Large aggregations of lymphocytes, so-called pseudotu-
mors, in asymptomatic patients studied with ultrasound have
been reported in as many as one third of them operated with
a MOM THA (Williams et al. 2011, Wynn-Jones et al. 2011).
Technical aspects of performing MRI after hip arthroplasty
were reviewed recently (Hayter et al. 2012). In a recent reg-
istry study from the UK, a clinical failure rate up to 6% in
females was found at 5 years for MOM THA (Smith et al.
2012b). The authors reported less revisions with smaller
MOM THA articulations, but the rates were still significantly
higher than for the metal-on-plastic LFA.
There are significant differences between metal-on-metal
concepts, and it might be unfair to lump them together. Excel-
lent results have been reported with the Pinnacle MOM pros-
thesis, for example, with 98% survival at 7 years (Kindsfater
et al. 2012).
That the ASR MOM SR with a less hemispherical cup
design is a clear outlier was first reported in Australia (De
Steiger et al. 2011), but during the last 2 years several other
MOM hip prostheses with large joint bearings have been with-
drawn. There has been company-initiated post-marketing sur-
veillance, with patients being informed, and also largely in
cooperation with the orthopedic profession. Very recently, the
problems have also been taken up by a few regulatory bodies.
The lack of international coordination and the need for an
independent alert system has been emphasized in 3 succes-
sive articles (Langton et al. 2008, Cohen 2011, Heneghan et
Malignancy and metal ion release
A recent concern has been whether the large amount of
cobalt and chromium nanoparticles released could cause
The most relevant systems and organs that might be affected
in the medium term (the first 10–20 years) are the hematopoi-
etic system, the urogenital system, and the skin. In the long
term (20–40 years), the solid organs might be affected (Little
By cross-checking of hospital data with national cancer
databases, it would be possible to obtain information on
increased risk. This has been done with some consistent
results on hematopoietic tumors, but with less convincing
data on other tumors except prostate cancer and melanoma
(Lewold et al. 1996, Lidgren 2008, Wagner et al. 2011). Often,
rheumatoid arthritis (with a higher risk of tumor development)
is not differentiated from OA; with information taken from
hospital systems, this raises some concern about the reliability
of the data from the studies already published. A recent short-
Acta Orthopaedica 2012; 83 (6): 553–558 555
term study (Smith et al. 2012a) using the NHS joint register
and hospital data from England and Wales found no overall
increase in solid and hematopoetic cancer, and also no differ-
ences comparing LFA with MOM SR and MOM THA. The
median observation time was only 2.8 years, and there was no
differentiation between RA and OA.
The specific increase in hematopoetic tumors has recently
been verified in a long-term follow-up in a joint replacement
registry for patients who received knee prostheses for RA
but—never before reported—for OA (Wagner et al. 2011). The
release of metal in a metal-to-polyethylene knee joint (TKA)
could be expected to be higher than for an LFA because of a
bearing contact area that is 10 times greater. The wear patterns
in the knee joint are well described, and result in larger plastic
particles than those produced in prosthetic hips (Blunn et al.
1992, 1997, Goodman and Lidgren 1992). Co-Cr levels have
been reported to be comparable to those with well-functioning
MOM THA with a small head, and to be only slightly elevated
than those for LFA (Luetzner et al. 2007, Garrett et al. 2010).
Several studies have, however, shown higher levels in hinged
or semiconstrained TKA (Liu et al. 1998) and loose TKA
(Sunderman et al. 1989, Liu et al. 1998).
Several authors have reported an increase in melanoma
after joint prosthetic surgery (Nyren et al. 1995, Onega et al.
2006, Visuri et al. 2006, Wagner et al. 2011). It is reasonable
to suspect that this is caused by higher long-term exposure to
chromium released from the implant. Hexavalent chromium
especially has a profound effect on melanocytes at low levels
(Meyskens and Yang 2011). In future, the use of X-ray syn-
chronization radiation methods may allow measurement of
chromium in single cells (Bohic et al. 2008). This should be
studied in more detail in MOM joints that shed a large amount
of smaller particles. It might be time to start discussing
whether actively giving advice on sun protection to patients
with large MOM bearings and high serum levels of chromium
is indicated. Development of novel UV-activated chromium-
protective chelators was suggested for melanoma prevention
not related to joint implants before the MOM era (Yiakouvaki
et al. 2006).
Regarding the urogential tract, our earlier findings of a
slight increase in prostatic cancer (Wagner et al. 2011) have
recently come into focus after unexpected findings of epithe-
lial precancer in the bladders of MOM THA patients; this was
reported at the British Hip Society meeting in 2012 (Maclean
et al., unpublished observations). An additional study with
longer follow-up, reported at the same BHS meeting, found,
however, that there was no increase in urogenital malignancies
(Kumar et al., unpublished observations). Thus, these findings
must be verified statistically and confirmed epidemiologically
before any association between an implant and urogenital
malignancy can be considered.
Joint disease and tumor
It is well known that inflammation influences tumor develop-
ment. This is evident in a number of inflammatory musculosk-
eletal conditions such as RA, Sjögren’s syndrome, and SLE.
An increased risk has been seen for lymphatic tumors espe-
cially (Solomon et al. 2012). Interestingly, anti-inflammatory
steroid treatment in RA reduces the risk of developing lym-
phoma (Hellgren et al. 2010). It has been postulated that it is
the severity of inflammation and duration of the rheumatoid
arthritis that contributes to the increased risk of lymphoma
(Askling et al. 2009). The risk of hematological cancer is
higher in younger RA patients (Chen et al. 2011).
There is also evidence that patients with seronegative arthri-
tis have an increased risk of developing myelodysplastic
malignancies (MDS) (Chandran et al. 1996). In smaller patient
series, blood malignancies (i.e leukemia and lymphoma) have
been diagnosed in patients who have developed osteonecrosis
(Kozuch et al. 2000). The immunological and thrombogenic
malignant cascade that results in impaired circulation and
therefore osteonecrosis is only partially understood.
The question is therefore whether osteoarthritis could also
initiate and drive hematopoietic malignancies irrespective of
the implant intervention. At replacement surgery, in advanced
cases we often find inflammation and large subchondral cysts
filled with fluid and hypertrophic synovial tissue.
As part of bone bank routines, between 1994 and 2005 a
Dutch group investigated 852 donor femoral heads for malig-
nancies, using histology. They found unexpectedly that 14
(1.6%) had malignant cells indicative of low-grade B cell lym-
phoma (Zwitser et al. 2009). At a follow-up after an average of
7 (1–12) years, 2 of the donors had developed active disease
and 3 more were being followed up by an oncologist because
of suspected disease. None of the recipients who accidently
received a low-grade lymphoma bone transplant had devel-
oped an MDS malignancy.
In a recent large study of 6,161 osteoarthritic femoral heads
donated for transplantation in Perth, Australia, 19 patients had
an unexpected neoplasm in the femoral head, 9 of which had
systemic disease on further investigation; all of them were
hematologic malignancies. Thus, 1 verified malignancy in
770 femoral heads was found. This is much lower than in the
Dutch study, but in addition 45 femoral heads had a nodular
lymphocyte infiltration and plasmocytosis was found in 10
femoral heads (Mackie et al. 2011). This is similar to the find-
ings by Palmer et al. (1999), with 3 malignancies in 1,146
It was suggested in the paper my Mackie et al. (2011) that
routine histology of the removed bone should be carried out
in all joint replacements, and that this would be a cost-effec-
tive routine for screening for blood malignancies. The ethical
implications of how to handle the finding of malignancy in a
donor have not been discussed in the literature.
Lymphoid aggregation is accidently found in bone marrow
at post-mortem studies, and increases with age. The distinc-
tion between benign reactive aggregates and well-differenti-
ated lymphoma may be difficult, and it is also unclear whether
556 Acta Orthopaedica 2012; 83 (6): 553–558
and how a tumor transition in OA takes place, probably driven
The findings in the Australian, Dutch, and UK studies were
similar regarding lymphoma, myelodysplasia, and myelopro-
liferative lymphoid aggregations. It is important that one third
of the indolent local blood malignancies found in the Dutch
study over an observation period of less than 10 years devel-
oped an overt systemic blood disease.
Does a joint implant drive malignancy in blood?
One remaining concern is whether a specific joint implant
will accelerate and/or start tumor development over a longer
period of time.
As mentioned, it has been clearly shown that it is possible
to have an indolent local malignancy in the bone marrow
adjacent to an osteoarthritic joint. In cases of resection of the
joint, i.e. on total joint replacement and if the tumor is only
located adjacent to the joint, this might prevent tumor devel-
opment. Whether or not this will have any influence on the
MOM SR concept is unclear, and it is unlikely considering the
generalized nature of MDS and lymphoma. All the published
long-term studies on small MOM bearings and hematological
malignancies have been on total joint replacements where the
proximal and distal parts of the joint have been resected, i.e.
McKee-Farrar THA. Due to the vast amount of large MOM
bearings inserted in the USA and the UK, this should be ana-
lyzed continuously and needs to be followed in the long term.
Pooling and aggregation of the available ongoing MOM reg-
istry data from several countries is possible, but complicated
because of data-protection laws. However, cross-checking of
joint registries with the national cancer registries is warranted.
As an extension of our and others’ earlier published stud-
ies (Lewold et al. 1996, Lidgren 2008, Mackie et al. 2011,
Wagner et al. 2011), we compared the incidence of hema-
tological malignancies taken from the national cancer data-
base in Sweden, bone biopsy tumor findings from the large
Australian Hip OA cohort, and data from OA patients in the
prospective national knee prosthetic register cohort in Sweden
(going back to 1975 and covering all clinics). The aim was
therefore to determine whether there has been—in addition to
the baseline level of malignancies seen in bone marrow at pri-
mary prosthetic replacement—a long-term increase in blood
malignancies related to joint implants releasing low levels of
metal particles. This could give some indication of the follow-
up necessary for MOM bearings releasing several orders of
magnitude higher levels of metal ions.
Assuming that the disease duration of hematological malig-
nancies was equal in the Australian and Swedish knee cohorts,
an approximate annual incidence of 31/105 could be calcu-
lated using the prevalence of indolent blood malignancies
in femoral heads taken from the large Australian study (De
Steiger et al. 2011). This is almost the same incidence as was
observed using data from the Swedish study (Wagner et al.
2011) in the 10 years prior to knee replacement: 34/105. After
surgery, the Swedish incidence of blood malignancies was
137/105 (unpublished data). The corresponding incidence in
the general population of Sweden, had it had the same sex-,
age-, and calendar-year distribution, would have been 81/105
before the operation and 122/105 afterwards. Part of this
increase in incidence may have been due to changes in the
cohort’s distribution of age, sex, and calendar year.
Furthermore, the low preoperative incidence level may have
been affected by the fact that the preoperation cohort was a
selected population, as it is likely that it included healthier
individuals than in the general population, with respect to
hematological malignancies. Consequently, the most severe
cases were automatically excluded. In addition, patients with
multiple diseases and in poor condition because of comorbidi-
ties may have been prevented from having surgery, thereby
excluding them from the preoperative knee cohort.
However, irrespective of whether the increase was caused
by other confounding factors such as frequent radiation expo-
sure and virus infection, or indeed metal exposure, these data
can be seen as a baseline reference for an extended follow-up
of large MOM bearings.
The blood malignancies diagnosed in the bone marrow at
prosthetic replacement could not fully explain the low but
clear increase found after long-term knee replacement. We
therefore propose that the pre-existing condition of lymphoid
aggregates in OA may be further activated by metal ions after
implantation. Depending on the stage of the condition, the
combination of OA pathology in bone marrow and the reac-
tion to metal ions after implantation can contribute to the
development of the blood malignancies.
We are grateful to the Swedish Association of Local Authorities and Regions,
the Faculty of Medicine, Lund University, Stiftelsen för Bistånd åt Rörelse-
hindrade i Skåne, and Region Skåne for financial support.
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