Aims. To find out if there is an inverse association between estimated glomerular filtration rate (eGFR) and whole blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasties and renal insufficiency, suggesting that renal insufficiency could cause accumulation of Co and Cr in blood. Methods. Out of 2,520 patients with 3,013 MoM hip arthroplasties, we identified 1,244 patients with whole blood Co, Cr, and creatinine measured within no more than a one-year interval. We analyzed the correlation of blood metal ion levels and eGFR to identify a potential trend of accumulating Co or Cr with decreasing eGFR. Results. Of the 1,244 patients, 112 had normal renal function (eGFR > 90 ml/min/1.73 m. 2. ), 715 had mild renal insufficiency (eGFR 60 to 89), 384 had moderate renal insufficiency (eGFR 30 to 59), 27 had severe renal insufficiency (eGFR 15 to 29), and six had end-stage renal insufficiency (eGFR < 15). Median eGFR was 68 ml/min/1.73 m. 2. (interquartile range (IQR) 56 to 82), median whole blood Co was 3.3 µg/l (IQR 1.1 to 9.9), and median Cr was 2.0 µg/l (IQR 1.2 to 3.6). We did not observe an association between decreased eGFR and increased whole blood Co and Cr concentrations, but instead both increased Co and Cr were associated with higher eGFR, indicating better kidney function. Conclusion. As patients with MoM hip arthroplasties get older, the prevalence of renal insufficiency among them will increase, and orthopaedic surgeons will increasingly have to evaluate whether or not this affects patient follow-up. The USA Food and Drug Administration suggests that closer follow-up may be needed for MoM patients with renal insufficiency. We did not observe accumulation of blood Co or Cr in MoM hip arthroplasty patients with mild to severe renal insufficiency. Cite this article: Bone Joint J 2021;103-B(7):1231–1237

Aims. Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods. A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion. This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties. Cite this article: Bone Joint J 2024;106-B(3 Supple A):51–58

Metal-on-metal hip arthroplasty gained significant favor in the first decade of the millennium. However, the past several years have seen increasing reports of failure, pseudotumor and other adverse reactions. This study presents the results of a single center’s 15-year experience with metal-on-metal total hip arthroplasty as strong evidence that metal-on-metal is going, going, gone

Aims. To determine whether there is any association between glomerular filtration rate (GFR) and blood cobalt (Co) and chromium (Cr) levels in patients with metal-on-metal (MoM) hip arthroplasty. Patients and Methods. We identified 179 patients with a unilateral 36 mm diameter head as part of a stemmed Summit-Pinnacle MoM hip arthroplasty. GFR was calculated using the Modification of Diet in Renal Disease formula. Results. Normal renal function (GFR ≥ 90 ml/min/1.73 m. 2. ) was seen in 74 patients. Mild renal insufficiency (GFR 60 to 89 ml/min/1.73 m. 2. ) was seen in 90 patients and moderate renal insufficiency (GFR 30 to 59 ml/min/1.73 m. 2. ) in 15. There was no statistical difference in Co and Cr levels between patients with normal renal function and those with mild or moderate renal insufficiency. No correlation was seen between creatinine and blood metal ion levels or between GFR and blood metal ion levels. Linear regression analysis did not show any association between Co and Cr levels and GFR. Conclusion. We did not find any association between GFR and blood metal ion levels. Consequently, the accumulation of Co and Cr in blood due to renal insufficiency does not seem to be a major risk in patients with mild or moderate renal insufficiency. Cite this article Bone Joint J 2017;99-B:1147–52

We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial fluid and whole blood taken from a group of 92 patients with failed current-generation metal-on-metal hip replacements. We applied acid oxidative digestion to our trace metal analysis protocol, which found significantly higher levels of metal ion concentrations in blood and synovial fluid than a non-digestive method. Patients were subcategorised by mode of failure as either ‘unexplained pain’ or ‘defined causes’. Using this classification, chromium and cobalt ion levels were present over a wider range in synovial fluid and not as strongly correlated with blood ion levels as previously reported. There was no significant difference between metal ion concentrations and manufacturer of the implant, nor femoral head size below or above 50 mm. There was a moderately positive correlation between metal ion levels and acetabular component inclination angle as measured on three-dimensional CT imaging. Our results suggest that acid digestion of samples of synovial fluid samples is necessary to determine metal ion concentrations accurately so that meaningful comparisons can be made between studies

Aims. Surgeons have commonly used modular femoral heads and stems from different manufacturers, although this is not recommended by orthopaedic companies due to the different manufacturing processes. We compared the rate of corrosion and rate of wear at the trunnion/head taper junction in two groups of retrieved hips; those with mixed manufacturers (MM) and those from the same manufacturer (SM). . Materials and Methods. We identified 151 retrieved hips with large-diameter cobalt-chromium heads; 51 of two designs that had been paired with stems from different manufacturers (MM) and 100 of seven designs paired with stems from the same manufacturer (SM). We determined the severity of corrosion with the Goldberg corrosion score and the volume of material loss at the head/stem junction. We used multivariable statistical analysis to determine if there was a significant difference between the two groups. . Results. We found no significant difference in the corrosion scores of the two groups. The median rate of material loss at the head/stem junction for the MM and SM groups were 0.39 mm. 3. /year (0.00 to 4.73) and 0.46 mm. 3. /year (0.00 to 6.71) respectively; this difference was not significant after controlling for confounding factors (p = 0.06). . Conclusion. The use of stems with heads of another manufacturer does not appear to affect the amount of metal lost from the surfaces between these two components at total hip arthroplasty. Other surgical, implant and patient factors should be considered when determining the mechanisms of failure of large diameter metal-on-metal hip arthroplasties. Cite this article: Bone Joint J 2016;98-B:917–24

In this paper, we will consider the current role of metal-on-metal bearings by looking at three subtypes of MoM hip arthroplasty separately: Hip resurfacing, large head (> 36 mm) MoM THA and MoM THA with traditional femoral head sizes.

Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry.

Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 μg/l (0.55 to 2.55) and 1.28 μg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 μg/l (0.42 to 1.75) and 0.378 μg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05).

In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 μg/l (0.18 to 0.54) and 0.199 μg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 μg/l (0.17 to 0.5) and 0.194 μg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 μg/l) as in the controls (0.1934 μg/l), this difference was not statistically significant. (p > 0.05)

The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer.

Large-head metal-on-metal total hip replacement has a failure rate of almost 8% at five years, three times the revision rate of conventional hip replacement. Unexplained pain remains a feature of this type of arthroplasty.

All designs of the femoral component of large-head metal-on-metal total hip replacements share a unique characteristic: a subtended angle of 120° defining the proportion of a sphere that the head represents. Using MRI, we measured the contact area of the iliopsoas tendon on the femoral head in sagittal reconstruction of 20 hips of patients with symptomatic femoroacetabular impingement. We also measured the articular extent of the femoral head on 40 normal hips and ten with cam-type deformities. Finally, we performed virtual hip resurfacing on normal and cam-type hips, avoiding overhang of the metal rim inferomedially.

The articular surface of the femoral head has a subtended angle of 120° anteriorly and posteriorly, but only 100° medially. Virtual surgery in a normally shaped femoral head showed a 20° skirt of metal protruding medially where iliopsoas articulates.

The excessive extent of the large-diameter femoral components may cause iliopsoas impingement independently of the acetabular component. This may be the cause of postoperative pain with these implants.

Blood metal ions have been widely used to investigate metal-on-metal hip replacements, but their ability to discriminate between well-functioning and failed hips is not known. The Medicines and Healthcare products Regulatory Agency (MHRA) has suggested a cut-off level of 7 parts per billion (ppb).

We performed a pair-matched, case-control study to investigate the sensitivity and specificity of blood metal ion levels for diagnosing failure in 176 patients with a unilateral metal-on-metal hip replacement. We recruited 88 cases with a pre-revision, unexplained failed hip and an equal number of matching controls with a well-functioning hip. We investigated the 7 ppb cut-off level for the maximum of cobalt or chromium and determined optimal mathematical cut-off levels from receiver-operating characteristic curves.

The 7 ppb cut-off level for the maximum of cobalt or chromium had a specificity of 89% and sensitivity 52% for detecting a pre-operative unexplained failed metal on metal hip replacement. The optimal cut-off level for the maximum of cobalt or chromium was 4.97 ppb and had sensitivity 63% and specificity 86%.

Blood metal ions had good discriminant ability to separate failed from well-functioning hip replacements. The MHRA cut-off level of 7 ppb provides a specific test but has poor sensitivity.

Aims

To determine the outcomes following revision surgery of metal-on-metal hip arthroplasties (MoMHA) performed for adverse reactions to metal debris (ARMD), and to identify factors predictive of re-revision.

We undertook a retrospective cohort study to determine clinical outcomes following the revision of metal-on-metal (MoM) hip replacements for adverse reaction to metal debris (ARMD), and to identify predictors of time to revision and outcomes following revision. Between 1998 and 2012 a total of 64 MoM hips (mean age at revision of 57.8 years; 46 (72%) female; 46 (72%) hip resurfacings and 18 (28%) total hip replacements) were revised for ARMD at one specialist centre. At a mean follow-up of 4.5 years (1.0 to 14.6) from revision for ARMD there were 13 hips (20.3%) with post-operative complications and eight (12.5%) requiring re-revision.

The Kaplan–Meier five-year survival rate for ARMD revision was 87.9% (95% confidence interval 78.9 to 98.0; 19 hips at risk). Excluding re-revisions, the median absolute Oxford hip score (OHS) following ARMD revision using the percentage method (0% best outcome and 100% worst outcome) was 18.8% (interquartile range (IQR) 7.8% to 48.3%), which is equivalent to 39/48 (IQR 24.8/48 to 44.3/48) when using the modified OHS. Histopathological response did not affect time to revision for ARMD (p = 0.334) or the subsequent risk of re-revision (p = 0.879). Similarly, the presence or absence of a contralateral MoM hip bearing did not affect time to revision for ARMD (p = 0.066) or the subsequent risk of re-revision (p = 0.178).

Patients revised to MoM bearings had higher rates of re-revision (five of 16 MoM hips re-revised; p = 0.046), but those not requiring re-revision had good functional results (median absolute OHS 14.6% or 41.0/48). Short-term morbidity following revision for ARMD was comparable with previous reports. Caution should be exercised when choosing bearing surfaces for ARMD revisions.

Cite this article: Bone Joint J 2014;96-B:1600–9.

Metal-on-metal (MOM) bearings for hip arthroplasty are increasing in popularity. Concern remains, however, regarding the potential toxicological effects of the metal ions which these bearings release.

The serum levels of cobalt and chromium in 22 patients who had undergone MOM resurfacing arthroplasty were compared with a matched group of 22 patients who had undergone 28 mm MOM total hip arthroplasty (THA).

At a median of 16 months (7 to 56) after resurfacing arthroplasty, we found the median serum levels of cobalt and chromium to be 38 nmol/l (14 to 44) and 53 nmol/l (23 to 165) respectively. These were significantly greater than the levels after 28 mm MOM THA which were 22 nmol/l (15 to 87, p = 0.021) and 19 nmol/l (2 to 58, p < 0.001) respectively.

Since the upper limit for normal patients without implants is typically 5 nmol/l, both groups had significantly raised levels of metal ions. MOM bearings of large diameter, however, result in a greater systemic exposure of cobalt and chromium ions than bearings of small diameter. This may be of relevance for potential long-term side-effects. It is not known to what extent this difference is due to corrosion of the surfaces of the component or of the wear particles produced.

We carried out a cross-sectional study with analysis of the demographic, clinical and laboratory characteristics of patients with metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacements. Our aim was to evaluate the relationship between metal-on-metal replacements, the levels of cobalt and chromium ions in whole blood and the absolute numbers of circulating lymphocytes. We recruited 164 patients (101 men and 63 women) with hip replacements, 106 with metal-on-metal hips and 58 with non-metal-on-metal hips, aged < 65 years, with a pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders.

Laboratory-defined T-cell lymphopenia was present in13 patients (15%) (CD8⁺ lymphopenia) and 11 patients (13%) (CD3⁺ lymphopenia) with unilateral metal-on-metal hips. There were significant differences in the absolute CD8⁺ lymphocyte subset counts for the metal-on-metal groups compared with each control group (p-values ranging between 0.024 and 0.046). Statistical modelling with analysis of covariance using age, gender, type of hip replacement, smoking and circulating metal ion levels, showed that circulating levels of metal ions, especially cobalt, explained the variation in absolute lymphocyte counts for almost all lymphocyte subsets.

Aims. There are many guidelines that help direct the management of patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken a study to compare the management of patients with MOM hip arthroplasties in different countries. . Methods. Six international tertiary referral orthopaedic centres were invited to participate by organising a multi-disciplinary team (MDT) meeting, consisting of two or more revision hip arthroplasty surgeons and a musculoskeletal radiologist. A full clinical dataset including history, blood tests and imaging for ten patients was sent to each unit, for discussion and treatment planning. Differences in the interpretation of findings, management decisions and rationale for decisions were compared using quantitative and qualitative methods. Results. Overall agreement between the orthopaedic centres and the recommended treatment plans for the ten patients with MOM hip implants was moderate (kappa = 0.6). Full agreement was seen in a third of cases, however split decisions were also seen in a third of cases. Units differed in their interpretation of the significance of the investigation findings and put varying emphasis on serial changes, in the presence of symptoms. Discussion. In conclusion, the management of raised or rising blood metal ions, cystic pseudotumours and peri-acetabular osteolysis led to inconsistency in the agreement between centres. Coordinated international guidance and MDT panel discussions are recommended to improve consensus in decision making. Take home message: A lack of evidence and the subsequent variation in regulator guidance leads to differences in opinions, the clinical impact of which can be reduced through a multi-disciplinary team approach to managing patients with MOM hip implants. Cite this article: Bone Joint J 2016;98-B:179–86

Arthroplasty registries are important for the surveillance of joint replacements and the evaluation of outcome. Independent validation of registry data ensures high quality. The ability for orthopaedic implant retrieval centres to validate registry data is not known. We analysed data from the National Joint Registry for England, Wales and Northern Ireland (NJR) for primary metal-on-metal hip arthroplasties performed between 2003 and 2013. Records were linked to the London Implant Retrieval Centre (RC) for validation. A total of 67 045 procedures on the NJR and 782 revised pairs of components from the RC were included. We were able to link 476 procedures (60.9%) recorded with the RC to the NJR successfully. However, 306 procedures (39.1%) could not be linked. The outcome recorded by the NJR (as either revised, unrevised or death) for a primary procedure was incorrect in 79 linked cases (16.6%). The rate of registry-retrieval linkage and correct assignment of outcome code improved over time. The rates of error for component reference numbers on the NJR were as follows: femoral head category number 14/229 (5.0%); femoral head batch number 13/232 (5.3%); acetabular component category number 2/293 (0.7%) and acetabular component batch number 24/347 (6.5%). . Registry-retrieval linkage provided a novel means for the validation of data, particularly for component fields. This study suggests that NJR reports may underestimate rates of revision for many types of metal-on-metal hip replacement. This is topical given the increasing scope for NJR data. We recommend a system for continuous independent evaluation of the quality and validity of NJR data. Cite this article: Bone Joint J 2015;97-B:10–18

The biological significance of cobalt-chromium wear particles from metal-on-metal hip replacements may be different to the effects of the constituent metal ions in solution. Bacteria may be able to discriminate between particulate and ionic forms of these metals because of a transmembrane nickel/cobalt-permease. It is not known whether wear particles are bacteriocidal. We compared the doubling time of coagulase negative staphylococcus, Staphylococcus aureus and methicillin resistant S. aureus when cultured in either wear particles from a metal-on-metal hip simulator, wear particles from a metal-on-polyethylene hip simulator, metal ions in solution or a control. Doubling time halved in metal-on-metal (p = 0.003) and metal-on-polyethylene (p = 0.131) particulate debris compared with the control. Bacterial nickel/cobalt-transporters allow metal ions but not wear particles to cross bacterial membranes. This may be useful for testing the biological characteristics of different wear debris. This experiment also shows that metal-on-metal hip wear debris is not bacteriocidal

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. . The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. . The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. . This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties. Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications. Cite this article: Bone Joint J 2016;98-B:6–13

This study compared component wear rates and pre-revision blood metal ions levels in two groups of failed metal-on-metal hip arthroplasties: hip resurfacing and modular total hip replacement (THR). There was no significant difference in the median rate of linear wear between the groups for both acetabular (p = 0.4633) and femoral (p = 0.0872) components. There was also no significant difference in the median linear wear rates when failed hip resurfacing and modular THR hips of the same type (ASR and Birmingham hip resurfacing (BHR)) were compared. Unlike other studies of well-functioning hips, there was no significant difference in pre-revision blood metal ion levels between hip resurfacing and modular THR. Edge loading was common in both groups, but more common in the resurfacing group (67%) than in the modular group (57%). However, this was not significant (p = 0.3479). We attribute this difference to retention of the neck in resurfacing of the hip, leading to impingement-type edge loading. This was supported by visual evidence of impingement on the femur. These findings show that failed metal-on-metal hip resurfacing and modular THRs have similar component wear rates and are both associated with raised pre-revision blood levels of metal ions

Aims

The first aim of this study was to evaluate whether preoperative renal function is associated with postoperative changes in whole blood levels of metal ions in patients who have undergone a Birmingham Hip Resurfacing (BHR) arthroplasty with a metal-on-metal bearing. The second aim was to evaluate whether exposure to increased cobalt (Co) and chromium (Cr) levels for ten years adversely affected renal function.