Objectives. The aims of this piece of work were to: 1) record the background concentrations of blood chromium (Cr) and cobalt (Co) concentrations in a large group of subjects; 2) to compare blood/serum Cr and Co concentrations with retrieved metal-on-metal (MoM) hip resurfacings; 3) to examine the distribution of Co and Cr in the serum and whole blood of patients with MoM hip arthroplasties; and 4) to further understand the partitioning of metal ions between the serum and whole blood fractions. Methods. A total of 3042 blood samples donated to the local transfusion centre were analysed to record Co and Cr concentrations. Also, 91 hip resurfacing devices from patients who had given pre-revision blood/serum samples for metal ion analysis underwent volumetric wear assessment using a coordinate measuring machine. Linear regression analysis was carried out and receiver operating characteristic curves were constructed to assess the reliability of metal ions to identify abnormally wearing implants. The relationship between serum and whole blood concentrations of Cr and Co in 1048 patients was analysed using Bland-Altman charts. This relationship was further investigated in an in vitro study during which human blood was spiked with trivalent and hexavalent Cr, the serum then separated and the fractions analysed. Results. Only one patient in the transfusion group was found to have a blood Co > 2 µg/l. Blood/Serum Cr and Co concentrations were reliable indicators of abnormal wear. Blood Co appeared to be the most useful clinical test, with a concentration of 4.5 µg/l showing sensitivity and specificity for the detection of abnormal wear of 94% and 95%, respectively. Generated metal ions tended to fill the serum compartment preferentially in vivo and this was replicated in the in vitro study when blood was spiked with trivalent Cr and bivalent Co. Conclusions. Blood/serum metal ion concentrations are reliable indicators of abnormal wear processes. Important differences exist however between elements and the blood fraction under study. Future guidelines must take these differences into account

A retrospective study was conducted to investigate the changes in metal ion levels in a consecutive series of Birmingham Hip Resurfacings (BHRs) at a minimum ten-year follow-up. We reviewed 250 BHRs implanted in 232 patients between 1998 and 2001. Implant survival, clinical outcome (Harris hip score), radiographs and serum chromium (Cr) and cobalt (Co) ion levels were assessed. Of 232 patients, 18 were dead (five bilateral BHRs), 15 lost to follow-up and ten had been revised. The remaining 202 BHRs in 190 patients (136 men and 54 women; mean age at surgery 50.5 years (17 to 76)) were evaluated at a minimum follow-up of ten years (mean 10.8 years (10 to 13.6)). The overall implant survival at 13.2 years was 92.4% (95% confidence interval 90.8 to 94.0). The mean Harris hip score was 97.7 (median 100; 65 to 100). Median and mean ion levels were low for unilateral resurfacings (Cr: median 1.3 µg/l, mean 1.95 µg/l (< 0.5 to 16.2); Co: median 1.0 µg/l, mean 1.62 µg/l (< 0.5 to 17.3)) and bilateral resurfacings (Cr: median 3.2 µg/l, mean 3.46 µg/l (< 0.5 to 10.0); Co: median 2.3 µg/l, mean 2.66 µg/l (< 0.5 to 9.5)). In 80 unilateral BHRs with sequential ion measurements, Cr and Co levels were found to decrease significantly (p < 0.001) from the initial assessment at a median of six years (4 to 8) to the last assessment at a median of 11 years (9 to 13), with a mean reduction of 1.24 µg/l for Cr and 0.88 µg/l for Co. Three female patients had a > 2.5 µg/l increase of Co ions, associated with head sizes ≤ 50 mm, clinical symptoms and osteolysis. Overall, there was no significant difference in change of ion levels between genders (Cr, p = 0.845; Co, p = 0.310) or component sizes (Cr, p = 0.505; Co, p = 0.370). Higher acetabular component inclination angles correlated with greater change in ion levels (Cr, p = 0.013; Co, p = 0.002). Patients with increased ion levels had lower Harris hip scores (p = 0.038). In conclusion, in well-functioning BHRs the metal ion levels decreased significantly at ten years. An increase > 2.5 µg/l was associated with poor function. Cite this article: Bone Joint J 2013;95-B:1332–8

Plasma levels of cobalt and chromium ions and Metal Artefact Reduction Sequence (MARS)-MRI scans were performed on patients with 209 consecutive, unilateral, symptomatic metal-on-metal (MoM) hip arthroplasties. There was wide variation in plasma cobalt and chromium levels, and MARS-MRI scans were positive for adverse reaction to metal debris (ARMD) in 84 hips (40%). There was a significant difference in the median plasma cobalt and chromium levels between those with positive and negative MARS-MRI scans (p < 0.001). Compared with MARS-MRI as the potential reference standard for the diagnosis of ARMD, the sensitivity of metal ion analysis for cobalt or chromium with a cut-off of > 7 µg/l was 57%. The specificity was 65%, positive predictive value was 52% and the negative predictive value was 69% in symptomatic patients. A lowered threshold of > 3.5 µg/l for cobalt and chromium ion levels improved the sensitivity and negative predictive value to 86% and 74% but at the expense of specificity (27%) and positive predictive value (44%). Metal ion analysis is not recommended as a sole indirect screening test in the surveillance of symptomatic patients with a MoM arthroplasty. The investigating clinicians should have a low threshold for obtaining cross-sectional imaging in these patients, even in the presence of low plasma metal ion levels

We present a series of 35 patients (19 men and 16 women) with a mean age of 64 years (36.7 to 75.9), who underwent total hip replacement using the ESKA dual-modular short stem with metal on-polyethylene bearing surfaces. This implant has a modular neck section in addition to the modular head. Of these patients, three presented with increasing post-operative pain due to pseudotumour formation that resulted from corrosion at the modular neck-stem junction. These patients underwent further surgery and aseptic lymphocytic vaculitis associated lesions were demonstrated on histological analysis. Retrieval analysis of two modular necks showed corrosion at the neck-stem taper. Blood cobalt and chromium levels were measured at a mean of nine months (3 to 28) following surgery. These were compared with the levels in seven control patients (three men and four women) with a mean age of 53.4 years (32.1 to 64.1), who had an identical prosthesis and articulation but with a prosthesis that had no modularity at neck-stem junction. The mean blood levels of cobalt in the study group were raised at 50.75 nmol/l (5 to 145) compared with 5.6 nmol/l (2 to 13) in control patients. Corrosion at neck-stem tapers has been identified as an important source of metal ion release and pseudotumour formation requiring revision surgery. Finite element modelling of the dual modular stem demonstrated high stresses at the modular stem-neck junction. Dual modular cobalt-chrome hip prostheses should be used with caution due to these concerns

The issues surrounding raised levels of metal ions in the blood following large head metal-on-metal total hip replacement (THR), such as cobalt and chromium, have been well documented. Despite the national popularity of uncemented metal-on-polyethylene (MoP) THR using a large-diameter femoral head, few papers have reported the levels of metal ions in the blood following this combination. Following an isolated failure of a 44 mm Trident–Accolade uncemented THR associated with severe wear between the femoral head and the trunnion in the presence of markedly elevated levels of cobalt ions in the blood, we investigated the relationship between modular femoral head diameter and the levels of cobalt and chromium ions in the blood following this THR. A total of 69 patients received an uncemented Trident–Accolade MoP THR in 2009. Of these, 43 patients (23 men and 20 women, mean age 67.0 years) were recruited and had levels of cobalt and chromium ions in the blood measured between May and June 2012. The patients were then divided into three groups according to the diameter of the femoral head used: 12 patients in the 28 mm group (controls), 18 patients in the 36 mm group and 13 patients in the 40 mm group. A total of four patients had identical bilateral prostheses in situ at phlebotomy: one each in the 28 mm and 36 mm groups and two in the 40 mm group. There was a significant increase in the mean levels of cobalt ions in the blood in those with a 36 mm diameter femoral head compared with those with a 28 mm diameter head (p = 0.013). The levels of cobalt ions in the blood were raised in those with a 40 mm diameter head but there was no statistically significant difference between this group and the control group (p = 0.152). The levels of chromium ions in the blood were normal in all patients. The clinical significance of this finding is unclear, but we have stopped using femoral heads with a diameter of ≤ 36 mm, and await further larger studies to clarify whether, for instance, this issue particularly affects this combination of components. Cite this article: Bone Joint J 2014;96-B:43–7

Aims. This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant. Methods. A total of 63 patients (65 implants) were treated using either a MoM-coated (n = 29) or TiN-coated (n = 7) hinged TKA (GenuX mobile bearing, MUTARS; Implantcast, Germany) versus the BPKS (Brehm, Germany) hinged TKA (n = 27), in which the weight placed on the MoM hinge is diffused through a polyethylene (PE) inlay, reducing the direct load on the MoM hinge. Serum cobalt and chromium ion concentrations were assessed after minimum follow-up of 12 months, as well as functional outcome and quality of life. Results. No differences in mean age (69 years, 40 to 86), mean age adapted Charlson Comorbidity Index (3.1 (SD 1.4)), mean BMI (29.2 kg/m. 2. (SD 5.8)), or number of other implants were observed between groups. Significant improvements in outcome scores and pain levels were achieved for all groups, and there was no difference in quality of life (12-Item Short-Form Health Survey questionnaire (SF-12)). Mean cobalt and chromium ion levels were significantly higher for the GenuX versus the BPKS hinged TKA (GenuX vs BPKS: cobalt: 16.3 vs 9.4 µg/l; chromium: 9.5 vs 5.2 µg/l). The TiN-coated implants did not appear to confer improvement in the metal ion levels. Metal ion concentrations above 7 µg/l were detected in 81%(29/36) of GenuX patients versus 41% (11/27) in the BPKS group. No GenuX patients had normal levels under 2 µg/l, versus 22% of BPKS patients. No significant reduction in outcome scores was observed regardless of the metal ion levels, whereas higher work-related activity was correlated with higher chromium concentrations. Conclusion. Hinged TKA, using MoM hinges, resulted in critically high cobalt and chromium ion concentrations. The BPKS hinged TKA showed significantly lower metal ion concentrations compared with the GenuX TKA. No benefits were observed using TiN coating. The different weightbearing mechanics might influence the wear of the component materials. Higher workloads and physical activity could influence chromium levels. Cite this article: Bone Joint J 2022;104-B(3):376–385

Aims. In metal-on-polyethylene (MoP) total hip arthroplasty (THA), large metal femoral heads have been used to increase stability and reduce the risk of dislocation. The increased size of the femoral head can, however, lead to increased taper corrosion, with the release of metal ions and adverse reactions. The aim of this study was to investigate the relationship between the size of the femoral head and the levels of metal ions in the blood in these patients. Methods. A total of 96 patients were enrolled at two centres and randomized to undergo MoP THA using either a 32 mm metal head or a femoral head of between 36 mm and 44 mm in size, being the largest possible to fit the thinnest available polyethylene insert. The levels of metal ions and patient-reported outcome measures (Oxford Hip Score, University of California, Los Angeles Activity Scale) were recorded at two and five years postoperatively. Results. At five years, the median levels of chromium, cobalt, and titanium were 0.5 μg/l (interquartile range (IQR) 0.50 to 0.62), 0.24 μg/l (IQR 0.18 to 0.30), and 1.16 μg/l (IQR 1.0 to 1.68) for the 32 mm group, and 0.5 μg/l (IQR 0.5 to 0.54), 0.23 μg/l (IQR 0.17 to 0.39), and 1.30 μg/l (IQR 1 to 2.05) for the 36 mm to 44 mm group, with no significant difference between the groups (p = 0.825, p = 1.000, p = 0.558). There were increased levels of metal ions at two years postoperatively in seven patients in the 32 mm group, compared with four in the 36 mm to 44 mm group, and at five years postoperatively in six patients in the 32 mm group, compared with seven in the 36 mm to 44 mm group. There was no significant difference in either the OHS (p = 0.665) or UCLA (p = 0.831) scores between patients with or without an increased level of metal ions. Conclusion. In patients who underwent MoP THA, we found no differences in the levels of metal ions five years postoperatively between those with a femoral head of 32 mm and those with a femoral head of between 36 mm and 44 mm, and no corrosion-related revisions. As taper corrosion can start after five years, there remains a need for longer-term studies investigating the relationship between the size of the femoral head size and corrosion in patients undergoing MoP THA. Cite this article: Bone Joint J 2024;106-B(3 Supple A):31–37

The purpose of this study was to evaluate whether concerns about the release of metal ions in metal-on-metal total hip replacements (THR) should be extended to patients with metal-bearing total disc replacements (TDR). Cobalt and chromium levels in whole blood and serum were measured in ten patients with a single-level TDR after a mean follow-up of 34.5 months (13 to 61) using inductively-coupled plasma mass spectrometry. These metal ion levels were compared with pre-operative control levels in 81 patients and with metal ion levels 12 months after metal-on-metal THR (n = 21) and resurfacing hip replacement (n = 36). Flexion-extension radiographs were used to verify movement of the TDR. Cobalt levels in whole blood and serum were significantly lower in the TDR group than in either the THR (p = 0.007) or the resurfacing group (p < 0.001). Both chromium levels were also significantly lower after TDR versus hip resurfacing (p < 0.001), whereas compared with THR this difference was only significant for serum levels (p = 0.008). All metal ion levels in the THR and resurfacing groups were significantly higher than in the control group (p < 0.001). In the TDR group only cobalt in whole blood appeared to be significantly higher (p < 0.001). The median range of movement of the TDR was 15.5° (10° to 22°). These results suggest that there is minimal cause for concern about high metal ion concentrations after TDR, as the levels appear to be only moderately elevated. However, spinal surgeons using a metal-on-metal TDR should still be aware of concerns expressed in the hip replacement literature about toxicity from elevated metal ion levels, and inform their patients appropriately

ZrN-multilayer coating is clinically well established in total knee arthroplasty [1-3] and has demonstrated significant reduction in polyethylene wear and metal ion release [4,5]. The goal of our study was to analyze the biotribological behaviour of the ZrN-multilayer coating on a polished cobalt-chromium cemented hip stem. CoCr28Mo6 alloy hip stems with ZrN-multilayer coating (CoreHip®AS) were tested versus an un-coated version. In a worst-case-scenario the stems with ceramic heads have been tested in bovine serum in a severe cement interface debonding condition under a cyclic load of 3,875 N for 15 million cycles. After 1, 3, 5, 10 & 15 million cycles the surface texture was analysed by scanning-electron-microscopy (SEM) and energy-dispersive x-ray (EDX). Metal ion concentration of Co,Cr,Mo was measured by inductively coupled plasma mass spectroscopy (ICP-MS) after each test interval. Based on SEM/EDX analysis, it has been demonstrated that the ZrN-multilayer coating keeps his integrity over 15 million cycles of severe stem cemented interface debonding without any exposure of the CoCr28Mo6 substrate. The ZrN-multilayer coated polished cobalt-chromium cemented hip stem has shown a reduction of Co & Cr metal ion release by two orders of a magnitude, even under severe stem debonding and high interface micro-motion conditions. ZrN-multilayer coating on polished cobalt-chromium cemented hip stems might be a suitable option for further minimisation of Co & Cr metal ion release in total hip arthroplasty. Clinical evidence has to be proven during the next years

Systemic metal ion monitoring (Co;Cr) has proven to be a useful screening tool for implant performance to detect failure at an early stage in metal-on-metal hip arthroplasty. Several clinical studies have reported elevated metal ion levels after total knee arthroplasty (TKA), with fairly high levels associated with rotating hinge knees (RHK) and megaprostheses. 1. In a knee simulator study, Kretzer. 2. , demonstrated volumetric wear and corrosion of metallic surfaces. However, prospective in vivo data are scarce, resulting in a lack of knowledge of how levels evolve over time. The goal of this study was to measure serum Co and Cr levels in several types TKA patients prospectively, evaluate the evolution in time and investigate whether elevated levels could be used as an indicator for implant failure. The study was conducted at Ghent University hospital. 130 patients undergoing knee arthroplasty were included in the study, 35 patients were lost due to logistic problems. 95 patients with 124 knee prostheses had received either a TKA (primary or revision) (69 in 55 patients), a unicompartimental knee arthroplasty (7 UKA), a RHK (revision −7 in 6 patients) or a megaprosthesis (malignant bone tumours − 28 in 27 patients). The TKA, UKA and RHK groups were followed prospectively, with serum Co and Cr ions measured preoperatively, at 3,6 and 12 months postoperatively. In patients with a megaprosthesis, metal ions were measured at follow-up (cross-sectional study design). In primary knees, we did not observe an increase in serum metal ion levels at 3, 6 or 12 months. Two patients with a hip arthroplasty had elevated preTKA Co and Cr levels. There was no difference between unilateral and bilateral knee prostheses. In the revision group, elevated pre-revision levels were found in 2 failures for implant loosening. In both cases, ion levels decreased postoperatively. In revisions with a standard TKA, there was no significant increase in metal ions compared to primary knee arthroplasty. RHK were associated with a significant increase in Co levels even at short-term (3–12 months). The megaprosthesis group had the highest metal ion levels and showed a significant increase in Co and Cr with time in patients followed prospectively. With the current data, we could not demonstrate a correlation between metal ion levels, size of the implant or length of time in situ. In primary knee arthroplasty with a standard TKA or UKA, metal ion levels were not elevated till one year postoperatively. This suggests a different mechanism of metal ion release in comparison to metal-on-metal hip arthroplasties. In two cases of revision for implant loosening, pre-revision levels were elevated, possibly associated with component wear, and decreased after revision. With RHK, slightly elevated ion levels were found prospectively. Megaprostheses had significantly elevated Co and Cr levels, due to corrosion of large metallic surfaces and/or wear of components which were not perfectly aligned during difficult reconstruction after tumour resection. Further research is needed to assess the clinical relevance of metal ion levels in knee arthroplasty

A concern of metal on metal hip resurfacing arthroplasty is long term exposure to Cobalt (Co) and Chromium (CR) wear debris from the bearing. This study compares whole blood metal ion levels from patients drawn at one-year following Birmingham Hip Resurfacing (BHR) to levels taken at a minimum 10-year follow-up. A retrospective chart review was conducted to identify all patients who underwent a BHR for osteoarthritis with a minimum 10-year follow-up. Whole blood metal ion levels were drawn at final follow-up in June 2019. These results were compared to values from patients with one-year metal ion levels. Of the 211 patients who received a BHR, 71 patients (54 males and 17 females) had long term metal ion levels assessed (mean follow-up 12.7 +/− 1.4 years). The mean Co and Cr levels for patients with unilateral BHRs (43 males and 13 females) were 3.12 ± 6.31 ug/L and 2.62 ± 2.69 ug/L, respectively, and 2.78 ± 1.02 ug/L and 1.83 ± 0.65 ug/L for patients with bilateral BHRs (11 males and 4 females). Thirty-five patients (27 male and 8 female) had metal-ion levels tested at one-year postoperatively. The mean changes in Co and Cr levels were 2.29 ug/l (p = 0.0919) and 0.57 (p = 0.1612), respectively, at one year compared to long-term. These changes were not statistically significant. This study reveals that whole blood metal ion levels do not change significantly when comparing one-year and ten-year Co and Cr levels. These ion levels appear to reach a steady state at one year. Our results also suggest that regular metal-ion testing as per current Medicines and Healthcare products Regulatory Agency (MHRA) guidelines may be impractical for asymptomatic patients. Metal-ion levels, in and of themselves, may in fact possess little utility in determining the risk of failure and should be paired with radiographic and clinical findings to determine the need for revision

Introduction. Systemic metal ion monitoring (Co;Cr) has proven to be a useful screening tool for implant performance to detect failure at an early stage in metal-on-metal hip arthroplasty. Several clinical studies have reported elevated metal ion levels after total knee arthroplasty (TKA), with fairly high levels associated with rotating hinge knees (RHK) and megaprostheses. 1. In a knee simulator study, Kretzer. 2. , demonstrated volumetric wear and corrosion of metallic surfaces. However, prospective in vivo data are scarce, resulting in a lack of knowledge of how levels evolve over time. The goal of this study was to measure serum Co and Cr levels in several types TKA patients prospectively, evaluate the evolution in time and investigate whether elevated levels could be used as an indicator for implant failure. Patients and Methods. The study was conducted at Ghent University hospital. 130 patients undergoing knee arthroplasty were included in the study, 35 patients were lost due to logistic problems. 95 patients with 124 knee prostheses had received either a TKA (primary or revision) (69 in 55 patients), a unicompartimental knee arthroplasty (7 UKA), a RHK (revision −7 in 6 patients) or a megaprosthesis (malignant bone tumours − 28 in 27 patients) (Fig 1). The TKA, UKA and RHK groups were followed prospectively, with serum Co and Cr ions measured preoperatively, at 3,6 and 12 months postoperatively. In patients with a megaprosthesis, metal ions were measured at follow-up (cross-sectional study design). Results (Fig 2 and 3). In primary knees, we did not observe an increase in serum metal ion levels at 3, 6 or 12 months. Two patients with a hip arthroplasty had elevated preTKA Co and Cr levels. There was no difference between unilateral and bilateral knee prostheses. In the revision group, elevated pre-revision levels were found in 2 failures for implant loosening. In both cases, ion levels decreased postoperatively. In revisions with a standard TKA, there was no significant increase in metal ions compared to primary knee arthroplasty. RHK were associated with a significant increase in Co levels even at short-term (3–12 months). The megaprosthesis group had the highest metal ion levels and showed a significant increase in Co and Cr with time in patients followed prospectively. With the current data, we could not demonstrate a correlation between metal ion levels, size of the implant or length of time in situ. Discussion. In primary knee arthroplasty with a standard TKA or UKA, metal ion levels were not elevated till one year postoperatively. This suggests a different mechanism of metal ion release in comparison to metal-on-metal hip arthroplasties. In two cases of revision for implant loosening, pre-revision levels were elevated, possibly associated with component wear, and decreased after revision. With RHK, slightly elevated ion levels were found prospectively. Megaprostheses had significantly elevated Co and Cr levels, due to corrosion of large metallic surfaces and/or wear of components which were not perfectly aligned during difficult reconstruction after tumour resection. Further research is needed to assess the clinical relevance of metal ion levels in knee arthroplasty. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Metal-on-metal bearings for total hip replacement (THR) are becoming increasingly popular. Improved wear characteristics mean that these articulations are being inserted into younger patients in the form of THR and resurfacing procedures. This has led to concerns regarding potential carcinogenicity because of the increased exposure to metal ions that the procedure brings. We have studied the serum cobalt and chromium concentrations in patients who had primary, well-fixed Ring metal-on-metal THRs for more than 30 years. The levels of cobalt and chromium were elevated by five and three times, respectively compared with those in our reference groups. Metal-on-metal articulations appear to be the source of metal ions throughout the life of the prosthesis. In three patients who had undergone revision of a previous metal-on-metal THR to a metal-on-polyethylene replacement the levels of metal ions were within the normal range. The elevations of cobalt and chromium ions seen in our study were comparable with those in patients with modern metal-on-metal THRs

Objectives. Alarm over the reported high failure rates for metal-on-metal (MoM) hip implants as well as their potential for locally aggressive Adverse Reactions to Metal Debris (ARMDs) has prompted government agencies, internationally, to recommend the monitoring of patients with MoM hip implants. Some have advised that a blood ion level >7 µg/L indicates potential for ARMDs. We report a systematic review and meta-analysis of the performance of metal ion testing for ARMDs. Methods. We searched MEDLINE and EMBASE to identify articles from which it was possible to reconstruct a 2 × 2 table. Two readers independently reviewed all articles and extracted data using explicit criteria. We computed a summary receiver operating curve using a Bayesian random-effects hierarchical model. Results. Our literature search returned 575 unique articles; only six met inclusion criteria defined a priori. The discriminative capacity of ion tests was homogeneous across studies but that there was substantial cut-point heterogeneity. Our best estimate of the “true” area under curve (AUC) for metal ion testing is 0.615, with a 95% credible interval of 0.480 to 0.735, thus we can state that the probability that metal ion testing is actually clinically useful with an AUC ≥ 0.75 is 1.7%. Conclusion. Metal ion levels are not useful as a screening test for identifying high risk patients because ion testing will either lead to a large burden of false positive patients, or otherwise marginally modify the pre-test probability. With the availability of more accurate non-invasive tests, we did not find any evidence for using blood ion levels to diagnose symptomatic patients. Cite this article: M. Pahuta, J. M. Smolders, J. L. van Susante, J. Peck, P. R. Kim, P. E. Beaule. Blood metal ion levels are not a useful test for adverse reactions to metal debris: a systematic review and meta-analysis. Bone Joint Res 2016;5:379–386. DOI: 10.1302/2046-3758.59.BJR-2016-0027.R1

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

There have been no large comparative studies of the blood levels of metal ions after implantation of commercially available hip resurfacing devices which have taken into account the effects of femoral size and inclination and anteversion of the acetabular component. We present the results in 90 patients with unilateral articular surface replacement (ASR) hip resurfacings (mean time to blood sampling 26 months) and 70 patients with unilateral Birmingham Hip Resurfacing (BHR) implants (mean time 47 months). The whole blood and serum chromium (Cr) and cobalt (Co) concentrations were inversely related to the size of the femoral component in both groups (p < 0.05). Cr and Co were more strongly influenced by the position of the acetabular component in the case of the ASR, with an increase in metal ions observed at inclinations > 45° and anteversion angles of < 10° and > 20°. These levels were only increased in the BHR group when the acetabular component was implanted with an inclination > 55°. A significant relationship was identified between the anteversion of the BHR acetabular component and the levels of Cr and Co (p < 0.05 for Co), with an increase observed at anteversion angles < 10° and > 20°. The median whole blood and serum Cr concentrations of the male ASR patients were significantly lower than those of the BHR men (p < 0.001). This indicates that reduced diametral clearance may equate to a reduction in metal ion concentrations in larger joints with satisfactory orientation of the acetabular component

Aims. We have previously demonstrated raised cobalt and chromium levels in patients with larger diameter femoral heads, following metal-on-polyethylene uncemented total hip arthroplasty. Further data have been collected, to see whether these associations have altered with time and to determine the long-term implications for these patients and our practice. Methods. Patients from our previous study who underwent Trident-Accolade primary total hip arthroplasties using a metal-on-polyethylene bearing in 2009 were reviewed. Patients were invited to have their cobalt and chromium levels retested, and were provided an Oxford Hip Score. Serum ion levels were then compared between groups (28 mm, 36 mm, and 40 mm heads) and over time. Results. Metal ion levels were repeated in 33 patients. When comparing the results of serum metal ion levels over time, regardless of head size, there was a significant increase in both cobalt and chromium levels (p < 0.001). Two patients with larger head sizes had undergone revision arthroplasty with evidence of trunnion damage at surgery. Two patients within the 40 mm subgroup had metal ion levels above the MHRA (Medicines and Healthcare Products Regulatory Agency) threshold for detailed investigation. The increase in cobalt and chromium, when comparing the 36 mm and 40 mm groups with those of the 28 mm group, was not significant (36 mm vs 28 mm; p = 0.092/p = 0.191; 40 mm vs 28 mm; p = 0.200/p = 0.091, respectively). There was no difference, between femoral head sizes, when comparing outcome as measured by the Oxford Hip Score. Conclusion. This study shows an increase in cobalt and chromium levels over time for all modular femoral head sizes in patients with metal-on-polyethylene bearings, with two patients demonstrating ion levels above the MHRA threshold for failure, and a further two patients requiring revision surgery. These results may have clinical implications regarding longer term follow-up of patients and future implant choice, particularly among younger patients. Cite this article: Bone Joint J 2020;102-B(7):832–837

We report serum metal ion level data in patients with unilateral and bilateral hip resurfacing over a ten-year period. In these patients there is an increase in both cobalt and chromium levels above the accepted reference ranges during the first 18 months after operation. Metal ion levels remain elevated, but decline slowly for up to five years. However, the levels then appear to start rising again in some patients up to the ten-year mark. There was no significant difference in cobalt or chromium levels between men and women. These findings appear to differ from much of the current literature. The clinical significance of a raised metal ion level remains under investigation

Purpose. Total shoulder arthroplasty (TSA) has become a successful treatment option for degenerative shoulder disease. With the increasing incidence in primary TSA procedures during the last decades, strategies to improve implant longevity become more relevant. Implant failure is mainly associated with mechanical or biological causes. Chronic inflammation as a response to wear particle exposure is regarded as a main biological mechanism leading to implant failure. Metal ions released by fretting and corrosion at modular taper connections of orthopedic implants can cause cell-mediated hypersensitivity reactions and might lead to aseptic loosening. Modularity is also commonly used in total shoulder replacement. However, little is known about metal ion exposure in patients following TSA. The objective of this study was to determine in-vivo blood metal ion levels in patients after TSA and to compare blood metal ion levels to control subjects without metal implants. Methods. A total of 19 patients with anatomical total shoulder prosthesis (TSA group) and 20 patients with reverse total shoulder prosthesis (RSA group) who underwent unilateral total shoulder replacement at our hospital between March 2011 and December 2014 with no other metal implant or history of environmental metal ion exposure were recruited for analysis of blood metal ion concentrations of cobalt (Co), chromium (Cr) and titanium (Ti) at a mean follow-up period of 2.3 years (0.7–4.3). For comparison of metal ion concentrations blood samples were obtained in a healthy control group of 23 subjects without metal implants. Ethical approval and informed consent of each patient were obtained for this study. Results. Median cobalt ion levels were 0.14µg/l (range 0.03–0.48) in the TSA group, 0.18 µg/l (0.10–0.66) in the RSA group and 0.11µg/l (0.03–0.19) in the control goup. Median chromium ion levels were 0.34µg/l (0.09–1.26) in the TSA group, 0.48µg/l (0.17–2.41) in the RSA group and 0.14µg/l (0.04–0.99) in the control goup. Median titanium ion levels were 0.86µg/l (0.10–1.64) in the TSA group, 1.31µg/l (0.75–4.52) in the RSA group and 0.62µg/l (0.32–2.14) in the control goup. There was a statistically significant difference in chromium and titanium ion concentrations between both study groups and the control group (see figure 1–3). Conclusion. Patients with unilateral total shoulder replacement demonstrated elevated blood metal ion concentrations. Median blood metal ion levels were higher in the RSA group compared to the TSA group, which could be attributable to the modularity of the reverse total shoulder system. However, overall metal ion levels were relatively low compared to those seen in patients with metal-on-metal total hip replacements. The role of local metal ion exposure in the development of aseptic loosening or hypersensitivity reactions associated with total shoulder arthroplasty should be further investigated. For figures/tables, please contact authors directly.

Hip resurfacing arthroplasty (HRA) became a popular procedure in the early 90s because of the improved wear characteristic, preserving nature of the procedure and the optimal stability and range of motion. Concerns raised since 2004 when metal ions were seen in blood and urine of patients with a MoM implant. Design of the prosthesis, acetabular component malpositioning, contact-patch-to-rim distance (CPR) and a reduced joint size all seem to play a role in elevated metal ion concentrations. Little is known about the influence of physical activity (PA) on metal ion concentrations. Implant wear is thought to be a function of use and thus of patient activity levels. Wear of polyethylene acetabular bearings was positively correlated with patient's activity in previous studies. It is hypothesized that daily habitual physical activity of patients with a unilateral resurfacing prosthesis, measured by an activity monitor, is associated with habitual physical activity. A prospective, explorative study was conducted. Only patients with a unilateral hip resurfacing prosthesis and a follow-up of 10 ± 1 years were included. Metal ion concentrations were determined using ICP-MS. Habitual physical activity of subjects was measured in daily living using an acceleration-based activity monitor. Outcome consisted of quantitative and qualitative activity parameters. In total, 16 patients were included. 12 males (75%) and 4 females (25%) with a median age at surgery of 55.5 ± 9.7 years [43.0 – 67.9] and median follow-up of 9.9 ± 1.0 years [9.1 – 10.9]. The median cobalt and chromium ion concentrations were 25 ± 13 and 38 ± 28 nmol/L. A significant relationship, when adjusting for age at surgery, BMI, cup size and cup inclination, between sit-stand transfers (p = .034) and high intensity peaks (p = .001) with cobalt ion concentrations were found (linear regression analysis). This study showed that a high number of sit-stand transfers and a high number of high intensity peaks is significantly correlated with high metal ion concentrations, but results should be interpreted with care. For patients it seems save to engage in activities with low intensity peaks like walking or cycling without triggering critical wear or metal ions being able to achieve important general health benefits and quality of life, although the quality (high intensity peaks) of physical activity and behaviour of patients (sit-stand-transfers) seem to influence metal ion concentrations

Introduction. Dual modular hip prostheses were introduced to optimize the individual and intra-surgical adaptation of the implant design to the native anatomics und biomechanics of the hip. The downside of a modular implant design with an additional modular interface is the potential susceptibility to fretting, crevice corrosion and wear [1–2]. The purpose of this study was to characterize the metal ion release of a modular hip implant system with different modular junctions and material combinations in consideration of the corrosive physiological environment. Methods. One design of a dual modular hip prosthesis (Ti6Al4V, Metha®, Aesculap AG, Germany) with a high offset neck adapter (CoCrMo, CCD-angle of 130°, neutral antetorsion) and a monobloc prosthesis (stem size 4) of the same implant type were used to characterize the metal ion release of modular and non-modular hip implants. Stems were embedded in PMMA with 10° adduction and 9° flexion according to ISO 7206-6 and assembled with ceramic (Biolox® delta) or CoCrMo femoral heads (XL-offset) by three light impacts with a hammer. All implant options were tested in four different test fluids: Ringer's solution, bovine calf serum and iron chloride solution (FeCl3-concentration: 10 g/L and 114 g/L). Cyclic axial sinusoidal compressive load (Fmax = 3800 N, peak load level of walking based on in vivo force measurements [3]) was applied for 10 million cycles using a servohydraulic testing machine (MTS MiniBionix 370). The test frequency was continuously varied between 15 Hz (9900 cycles) followed by 1 Hz (100 cycles). The metal ion concentration (cobalt, chromium and titanium) of the test fluids were analysed using ICP-OES and ICP-MS at intervals of 0, 5·105, 2·106 and 10·106 cycles (measuring sensitivity < 1 µg/L). Results. Due to the additional modular interface between stem and neck adapter the total metal ion release of the modular hip endoprosthesis system increased significantly and is comparable to the coupling of a monobloc stem and a CoCrMo femoral head (Fig. 1). The application of ceramic femoral heads reduced the total cobalt and chromium release in the stem-head taper interface of non-modular and modular stems. In comparison between the four test fluids could be observed that lower pH-values and higher FeCl3-concentrations increased the metal ion release (Fig 2). In contrast, the use of bovine calf serum decreased the metal ion release of modular junctions due to the presence of proteins and other organic components. Discussion. For testing hip implants with proximal femoral modularity according to ISO and ASTM standards, sodium chloride solutions are frequently used to determine the fatigue strength and durability of the stem-neck connection. The present study illustrate that the expansion of standard requirements of biomechanical testing and the use of alternative test fluids is necessary to simulate metal ion release by electro-chemical processes. A promising approach is the use of adapted iron-chloride solutions (10 g/L FeCl3, pH 2) to evaluate the susceptibility of modular hip junctions to fretting, crevice and contact corrosion

In metal-on-polyethylene (MoP) THA large femoral metal heads are designed to increase stability and to reduce dislocation risk. The increased head size could lead to increased taper corrosion with the release of metal ions and adverse reactions. Using blood ion measurements, we aimed to investigate the association between femoral head size and metal-ion release after MoP THA. 96 patients were enrolled at two centers and randomized to receive either a 32-mm metal head or a 36–44 mm metal head (the largest possible fitting the thinnest available polyethylene insert). Blood metal ions and PROMs (OHS, UCLA) were measured at two- and five-year follow-ups. Both 2- and 5-year median chrome, cobalt, and titanium levels were below taper corrosion indicative ion levels. At 5 years, median chrome, cobalt, and titanium levels were 0.5 μg/L (0.50–0.62), 0.24 μg/L (0.18–0.30), and 1.16 μg/L (1.0–1.68) for the 32-mm group, and 0.5 μg/L (0.5–0.54), 0.23 μg/L (0.17–0.39), and 1.30 μg/L (1–2.05) for the 36–44 mm group, with no difference between groups (p=0.825, p=1.000, p=0.558). At 2 years, 7 (32-mm) versus 4 (36–44-mm) patients had elevated ions. At 5 years, 6 (32-mm) versus 7 (36–44-mm) patients had elevated ions. There was no difference in either OHS (p=0.665) or UCLA (p=0.831) between patients with or without elevated blood metal ions. 5 years after the insertion of MoP THAs, we found no differences in the blood metal ion levels between 32 mm heads and 36–44 mm heads and no corrosion-related revisions. As taper corrosion can debut after 5 years, there is still a need for long-term follow-up studies on the association between head size and corrosion in MoP THA

Background. Metal-on-metal hip implants can produce adverse tissue reactions to wear debris. Increased metal ion concentrations in the blood are measured as a proxy to wear and the complications it can trigger. Many studies have examined various factors influencing the metal ion concentrations. This is the first study to investigate the effect of physical activity level, as objectively measured in daily life, on blood ion levels, expecting higher concentrations for higher patient activity. Methods. Thirty-three patients (13F/20M, 55.8 ± 6.2 years at surgery) with a unilateral resurfacing hip prosthesis were included. At last follow-up (6.8 ± 1.5 years) cobalt and chromium concentrations in the blood were determined by inductively coupled plasma mass spectrometry. Physical activity was measured during 4 successive days using a 3D-acceleration-based activity monitor. Data was analysed using validated algorithms, producing quantitative and qualitative parameters. Acetabular cup position was measured radiographically. Correlations were tested with Pearson's r'. Results. Wide ranges in cobalt (10-833nmol/l) and chromium (16-592nmol/l) concentrations were measured. No correlations were found between metal ion concentrations and patient characteristics. The mean time of walking per day of was 5475 ± 2730 seconds (≈ 91 minutes) per day, with 6953 ± 3104 steps made during the day. The cadence, the number of steps per minute, was 99.5 ± 7.4. The subjects performed 41 ± 13 sit-stand transfers per day. The number of peak intensity declines when peaks where more intense. No correlations were found between quantitative or qualitative parameters and metal ion concentrations. Conclusions. Higher metal ion concentrations were not correlated with higher activity levels contrary to original expectations. Based on the results the orthopaedic surgeons is able to reassure his or her patients that physical activity in daily living is presumably safe en does not influence metal ion concentrations. Level of Evidence. 2b. Approval. the ethics committee of the Atrium MC, Heerlen approved this study

The purpose of this randomized controlled trial was to evaluate serum metal ion levels in patients undergoing THA with either a standard or modular dual-mobility bearing. Patients undergoing primary THA for osteoarthritis were randomized to receive either a modular dual-mobility or a standard polyethylene bearing. All patients received the same titanium acetabular and femoral component and a ceramic femoral head. Only patients without a prior history of metal implants in their body were eligible for inclusion, thus isolating serum metal ions to the prosthesis itself. Serum metal ion levels were drawn pre-operatively and at 1 year postoperatively. Power analysis determined that 40 patients (20 in each group) were needed to identify a clinically relevant difference in serum cobalt of 0.35 ng/ml (ppb) at 90% power assuming a pooled standard deviation of 0.31 ppb and alpha=0.05; an additional 30% were enrolled to account for potential dropouts. 53 patients were enrolled, with 22 patients in the modular dual-mobility group and 20 in the standard cohort with data available at one-year. No differences in the serum cobalt (0.17 ppb [range 0.07 to 0.50] vs. 0.19 ppb [range 0.07 to 0.62], p = 0.51) or chromium levels (0.19 ppb [range 0.05 to 0.56] vs. 0.16 ppb [range 0.05 to 0.61], p = 0.23) were identified. At 1 year postoperatively, no differences in serum cobalt or chromium levels were identified with this design of a modular dual mobility bearing when compared to a standard polyethylene bearing

Introduction. The MHRA guidelines for metal on metal (MOM) suggest cobalt and chromium levels of more than 7ppb as potential for soft tissue reaction. However, in some patients soft tissue reaction is seen even in the presence of normal serum metal ions levels. Methods. A prospective review of all patients who had metal-on-metal hip arthroplasty was done. Patients who had both serum metal ion levels and MARS MRI scan were included in this study. Results. There were 574 patients with 319 females and 255 males. 240 patients had both MARS MRI scan and serum metal ions. Fifty nine (24.5%) patients with normal metal ions had metallosis/pseudo tumour on MRI scans, and 17 (7%) patients with increased metal ions had normal MRI scans. Conclusion. This study confirms that there is poor correlation between serum metal ions and soft tissue reaction. Nearly a quarter of patients with normal serum metal ions had evidence of metallosis on MRI scan. Clinicians should be aware of the potential for soft tissue reaction even in the presence of normal metal ions. Hence, consideration should be given to further imaging where appropriate, to ensure early metallosis is picked up and further complications of pseudo tumour prevented

Increased concentrations of metal ions after metal-on-metal resurfacing arthroplasty of the hip remain a concern. Although there has been no proven link to long-term health problems or early prosthetic failure, variables associated with high metal ion concentrations should be identified and, if possible, corrected. Our study provides data on metal ion levels from a series of 76 consecutive patients (76 hips) after resurfacing arthroplasty with the Articular Surface Replacement. Chromium and cobalt ion concentrations in the whole blood of patients with smaller (≤ 51 mm) femoral components were significantly higher than in those with the larger (≥ 53 mm) components (p < 0.01). Ion concentrations in the former group were significantly related to the inclination (p = 0.01) and anteversion (p = 0.01) of the acetabular component. The same relationships were not significant in the patients with larger femoral components (p = 0.61 and p = 0.49, respectively). Accurate positioning of the acetabular component intra-operatively is essential in order to reduce the concentration of metal ions in the blood after hip resurfacing arthroplasty with the Articular Surface Replacement implant

Introduction. Mechanical or corrosive failure of total knee arthroplasties (TKAs) is difficult to diagnose with current laboratory and radiographic analyses. As such, the goal of this study was to determine the mean blood concentration of cobalt, chromium, and titanium in a series of revision TKAs with mechanical implant failure and evaluate whether they facilitated identification of the underlying TKA failure mechanism. Methods. Serum cobalt, chromium, and titanium levels and synovial fluid characteristics were evaluated in 12 patients (13 aseptic revision TKAs) who underwent revision TKA between 2000 and 2020 at a single academic institution for mechanical implant failure or corrosion. Seventy-five percent were re-revisions of previously revised TKAs. Mean time to revision was 6 years. Modular metallic junctions were present in 100%. Twenty-five percent did not have another in situ total joint arthroplasty, and the remaining patients did not have a metal-on-metal articulation that could lead to elevation in serum metal ion levels. Mean follow-up after the revision TKA was 8 months. Results. Mean serum cobalt, chromium, and titanium concentrations were 11 ng/mL, 6 ng/mL, and 3 ng/mL, respectively. Serum metal ion levels facilitated failure mechanism identification in 75%, which included modular junction failure (6 cases), constraint locking mechanism failure (3 cases), corrosion of modular metallic interfaces (2 cases), and implant fracture (1 case). Arthrocentesis was performed in 75%. Mean synovial fluid cell count was 950 cells/mcL. Monocytes were the predominant mean cell type (41%), followed by neutrophils (35%), and lymphocytes (22%). Conclusion. Serum metal ion assessment should be considered when the etiology of painful primary or revision TKAs, particularly those with modular metallic junctions, remains elusive after routine evaluation

Introduction. Metal-metal surface replacement (MoMSRA) continues to be used in young women. Systemic metal ion release and its effects cause concern. Do metal ions crossing the placenta in pregnant women have potential mutagenic effects? The hypothesis is that metal ions pass freely through the placenta and there is no difference in maternal and cord metal levels. Methods. This is a controlled cross-sectional study of women with MoMSRA. (n = 25, 3 bilateral, mean age 32 years, time from implantation to delivery 60 months). The control group consisted of 24 subjects, mean age 31 years, with no metallic implant and not receiving cobalt/chromium supplements. No patient was known to have renal failure. Whole blood specimens were obtained before delivery and before any infusion or transfusion, and cord blood specimens immediately after delivery. Results. Cobalt and chromium were detectable in all specimens in both cohorts. In the control group, the difference between maternal and cord levels was only 5 to 7% indicating free passage. Study group cord cobalt (0.88 mg/L) and chromium levels (0.34 mg/L) were significantly lower than maternal cobalt (1.57 mg/L, p < 0.05) and chromium Levels (1.43 mg/L, p 0.05). However there is a significant difference between the cord cobalt levels in the study (0.88 mg/L) and control (0.41 mg/L, p < 0.05) groups. Discussion and Conclusion. The limitation of this study is that none of the patients in the study had the excessive metal ion levels recorded in recent times in some of the withdrawn resurfacing arthroplasties. The differences between maternal and cord metal ions in the controls indicate that normally the placenta allows an almost free passage of metal ions. Within the range of levels studied, the relative levels of metal ions in the maternal and cord blood in the study group reveal that the placenta exerts a regulatory influence on metal ion transfer

High short-term failure rates have been observed with a number of metal-on-metal (MoM) hip designs. Most patients require follow-up with blood metal ions, whichprovide a surrogate marker of in-vivo bearing wear. Given these results are used in clinical decision making it is important values obtained within and between laboratories are reproducible. To assess the intra-laboratory and inter-laboratory variability of blood metal ion concentrations analysed by four accredited laboratories. Whole blood was taken from two participants in this prospective study. The study specimen was obtained from a 42 year-old female with ceramic-on-ceramic hip arthroplasty failure resulting in unintended metal-on-ceramic wear and excessively high systemic metal ion levels. The control specimen was from a 52 year-old healthy male with no metal exposure. The two specimens were serially diluted to produce a total of 25 samples with different metal ion concentrations in two different anticoagulants each. Thus 50 samples were sent blinded in duplicate (total 100) to four accredited laboratories (A, B, C, D) to independently analyse blood metal ion concentrations. Ten commercially available reference specimens spiked with different amounts of metal ions were also obtained with known blood metal ion concentrations (range for cobalt 0.15µg/l-11.30µg/l and chromium 0.80µg/l to 37.00µg/l) and analysed by the four laboratories. The intra-laboratory coefficients of variation for repeat analysis of identical patient specimens were 7.32% (laboratory A), 4.64% (B), 7.50% (C), and 20.0% (D). The inter-laboratory variability for the analysis of all 25 samples was substantial. For the unmixed study specimen the laboratory results ranged from a cobalt of 263.7µg/l (D) to 525.1µg/l (D) and a chromium of 13.3µg/l (D) to 36.9µg/l (A). For the unmixed control specimen the laboratory results ranged from a cobalt of 0.13µg/l (B) to 0.77µg/l (D) and a chromium of 0.13µg/l (D) to 7.1µg/l (A). For one of the mixed specimens the laboratory results ranged from a cobalt of 12.50µg/l (A) to 20.47µg/l (D) and a chromium of 0.73µg/l (D) to 5.60µg/l (A). Similar inter-laboratory variation was observed for the other mixed samples. The true mean (standard deviation) of the 10 commercial samples was 4.48µg/l (4.20) for cobalt and 8.97µg/l (10.98) for chromium. This was similar to the values obtained by all four laboratories: mean (standard deviation) cobalt ranged from 3.54µg/l (3.17) in laboratory A to 4.35µg/l (4.13) in laboratory D, and chromium ranged from 7.76µg/l (9.50) in laboratory B to 9.55µg/l (9.16) in laboratory A. When testing patient samples, large variations existed both between and within four laboratories accredited to perform analysis of blood metal ion concentrations. However, this was not the case when assessing commercially spiked samples which are regularly used to validate laboratory testing. This is of great clinical concern and could lead clinicians to either recommend unnecessary revision or delay surgery, with both having the potential to adversely affect patient outcomes. It is recommended that laboratories use patient samples to assess the accuracy and reproducibility of the analyses performed. This may also assist in explaining the variations observed in this study

We examined the relationships between the serum levels of chromium and cobalt ions and the inclination angle of the acetabular component and the level of activity in 214 patients implanted with a metal-on-metal resurfacing hip replacement. Each patient had a single resurfacing and no other metal in their body. All serum measurements were performed at a minimum of one year after operation. The inclination of the acetabular component was considered to be steep if the abduction angle was greater than 55°. There were significantly higher levels of metal ions in patients with steeply-inclined components (p = 0.002 for chromium, p = 0.003 for cobalt), but no correlation was found between the level of activity and the concentration of metal ions. A highly significant (p < 0.001) correlation with the arc of cover was found. Arcs of cover of less than 10 mm were correlated with a greater risk of high concentrations of serum metal ions. The arc of coverage was also related to the design of the component and to size as well as to the abduction angle of the acetabular component. Steeply-inclined acetabular components, with abduction angles greater than 55°, combined with a small size of component are likely to give rise to higher serum levels of cobalt and chromium ions. This is probably due to a greater risk of edge-loading

Metal ions generated from joint replacements are a cause for concern. There is no consensus on the best surrogate measure of metal ion exposure. This study investigates whether serum and whole blood concentrations can be used interchangeably to report results of cobalt and chromium ion concentrations. Concentrations of serum and whole blood were analysed in 262 concurrent specimens using high resolution inductively-coupled plasma mass-spectrometry. The agreement was assessed with normalised scatterplots, mean difference and the Bland and Altman limits of agreement. The wide variability seen in the normalised scatterplots, in the Bland and Altman plots and the statistically significant mean differences between serum and whole blood concentrations suggest that they cannot be used interchangeably. A bias was demonstrated for both ions in the Bland-Altman plots. Regression analysis provided a possible conversion factor of 0.71 for cobalt and 0.48 for chromium. However, even when the correction factors were applied, the limits of agreement were greater than ±67% for cobalt and greater than ±85% for chromium, suggesting that serum and whole blood cannot be used interconvertibly. This suggests that serum metal concentrations are not useful as a surrogate measure of systemic metal ion exposure

Introduction. Metal on metal (MoM) bearings have been dealt a severe blow in the past few years. The release of metal ions may have arisen from corrosion, wear, or a combination of the two. Edge loading due to implant malposition is thought to cause a failure of lubrication and to contribute to excessive wear and increased metal ion release [1]. Literature reports aseptic lymphocytic vasculitis-associated lesions (ALVAL) are associated with a variety of failures which occur to some degree in all implanted metal femoral components [2, 3]. Moreover, Willert et al [4] has described ALVAL in non-MoM bearing designs too. This paper has investigated the metal ion release due to total hip replacement (THR), Hip Resurfacing (HR) and total knee replacement (TKR). Methods. Following human ethics approval 200 patients were enrolled in this single surgeon randomised controlled study. The treatment groups were total knee replacement (TKR) (n=100), HR (n=50) and THR (n=50). Serum cobalt (Co) and chromium (Cr) ion levels were taken preoperatively for baseline measurement then at 6 month, 1 year and 2 years postoperatively. Results. A preliminary observation of the data was performed to investigate the release trend of the Metal Ions (Figs 1 & 2). Initially there is a significant difference (p<0.05) between TKR and THR for the 6 month ion levels. At the 1 year time-point there is no difference between the TKR and THR for Cr levels. However, there is a significant difference (p<0.05) between TKR and HR for Cr levels at the 1 year time-point and a highly significant difference (p<0.001) between TKR, THR and HR for Co levels at 1 year. At the 2 year time-point there is no difference (p>0.05) between the TKR and THR for Cr levels. However, there is still a highly significant difference (p<0.001) between TKR, THR and HR for Co levels at 2 years. There was no significant difference detected between THR and HR (p>0.05) for both Co and Cr levels at all time-points. Discussion and Conclusion. All patient metal ion levels were in the safe range. Whilst there are other reported studies comparing the effect of head diameter of MoM bearings on systemic release of metal ions, this is the first paper to compare MoM hip bearings with TKR bearings. There was no difference between the release of Cr levels for the TKR and THR at the 2 year time-point. The trend of metal ion release is similar for all implants. However, THA deviates from HR at the 12 month time-point for Co levels. This paper demonstrates that surgical technique plays an important role in metal ion release and the long term integrity of a MoM bearing

Purpose. There is a postulated association between increased serum metal ions and pseudotumour formation in patients with metal-on-metal hip replacements. The primary aim of this study was to assess the prevalence of pseudotumour in 31 asymptomatic patients with a large femoral head (LFH) metal-on-metal hip implant. This was compared to the prevalence of pseudotumour in 20 matched asymptomatic patients with a hip resurfacing (HRA) and 24 matched asymptomatic patients with a standard metal-on-polyethylene (MOP) total hip. A secondary objective was to assess possible correlation between increased serum metal ions and pseudotumour formation. Method. Ultrasound examination of the three groups was performed at a minimum follow up of two years. Serum metal ions were measured in the metal-on-metal LFH and HRA groups at a minimum of two years. Results. There were 10 (32%) solid or cystic masses in the LFH group with a mean size of 89.3 (8 to 437) cm3. In the HRA group there were five (25%) masses with a mean size of 41.6 (6 to 119) cm3. In the MOP group there was one cystic mass measuring 9.8 cm3. Median serum cobalt and chromium ion levels in the LFH group were 4.50 gL (interquartile range, 2.38 to 7.47) and 2.82 gL (interquartile range, 1.48 to 3.18) compared to 0.83 gL (interquartile range, 0.65 to 1.12) and 1.08 gL (interquartile range, 0.78 to 1.31) in the HRA group. Conclusion. This study demonstrates a significantly higher prevalence of pseudotumours in patients with large head metal-on-metal total hips. The higher levels of metal ions in this group suggest that elevated metal ions may lead to pseudotumour formation

This study evaluates metal ion levels in patients enrolled in a prospective evaluation of hip resurfacing arthroplasty utilizing the Conserve Plus implant (Wright Medical Technology). Serum, urine and erythrocyte metal ion levels were assessed preoperatively and postoperatively. Average levels at three months were 24 nmol/l for cobalt and 40 nmol/l for chromium. These increased to 40 nmol/l for cobalt and 80 nmol/l for chromium at the six-month mark. The clinical significance of increased metal ion levels is yet to be determined. To evaluate the clinical, functional and radiographic outcome of hip resurfacing arthroplasty utilizing the Conserve Plus implant (Wright Medical Technology). Serum, urine and erythrocyte metal ion levels were evaluated both pre and postoperatively. Ion levels for both cobalt and chromium increased from the three-month to the six-month mark postoperatively and were significantly elevated relative to preoperative values. This study helps to establish a baseline for metal ion levels following hip resurfacing arthroplasty. Serum, urine and erythrocyte metal ion levels were assessed preoperatively and postoperatively. All levels were within normal range preoperatively. Average serum levels at three months were 24 nmol/l for cobalt and 40 nmol/l for chromium. These increased to 40 nmol/l for cobalt and 80 nmol/l for chromium at the six-month mark. Average erythrocyte metal ion levels at three months were 0.92 ug/l for cobalt and 1.8 ug/l for chromium. The average erythrocyte levels at six months were 1.3 ug/l for cobalt and 2.0 ug/l for chromium. A prospective multi-center study to evaluate the outcome of hip resurfacing arthroplasty was initiated in July 2003. Each patient was evaluated preoperatively and postoperatively with outcome scores, radiographs as well as serum, urine and erythrocyte metal ion levels. The results of this prospective evaluation show a rise in ion levels from three to six months postoperatively. Further follow-up is necessary to assess future trends with respect to the ion levels as well as the clinical significance. Funding: This study has been sponsored in part by Wright Medical Technology

Introduction: The accepted method of assessing wear following a hip simulator test has been to use a precision balance. As the MoM devices produce significantly less weight loss than hard-on-soft bearings, the measurements of MoM devices are now almost at the detection limit of many balances. There is a need for a method that can be used in conjunction with gravimetric analysis that will provide an accurate assessment of ion concentration levels that will support the gravimetric measurements. Aim: To develop a method to assess wear using metal ion analysis in order to support gravimetric measurements of metal on metal devices. Materials and methods: Hip simulator test: Three pairs of 50 mm diameter as cast CoCr MoM devices were tested in a ProSim hip wear simulator (SimSol Stockport/UK) under physiologically relevant conditions. The lubricant was new born calf serum with 0.2 % sodium azide concentration diluted with de-ionised water for protein concentration of 20 g/l. Stop-start motion was implemented every 100 cycles. Lubricant changed every 125 k cycles. The frequency was 0.5 Hz. Wear was assessed gravimetrically at every 0.5 million cycles (Mc) interval. Ion analysis: Serum was collected from test station and allowed to settle for 12 hours. An aliquot of 20 ml from lubricant was collected. Each sample was centrifuged at 2500 g-force for 10 minutes. A 10 ml aliquot was collected from each sample and was further centrifuged at 2500 g-force for 10 minutes. 1.5 ml aliquot was collected and stored at −20 °C. A high resolution inductively-coupled plasma mass spectrometry instrument (ELEMENT, ThermoFinnigan MAT, Bremen/Germany) was then used for the analysis of metal ions. Results and Discussion: The average cumulative metal ion levels at 0.5, 1 and 1.5 Mc showed similar trends in wear to that of the average cumulative weight loss assessed gravimetrically. There were similar biphasic wear trends in both metal ion levels and gravimetric weight losses. Other studies have also shown similar correlation between volume loss and ion concentration levels. The percentage distribution of Co, Cr and Mo in the metal ion samples are in close agreement with nominal chemical composition of the material tested. Conclusion: This study showed that metal ion measurements can help to confirm gravimetrically measured material loss

There has been much discussion and controversy in the media recently regarding metal toxicity following large head metal on metal (MoM) total hip replacement (THR). Patients have been reported as having hugely elevated levels of metal ions with, at times, devastating systemic, neurolgical and/or orthopaedic sequelae. However, no direct correlation between metal ion level and severity of metallosis has yet been defined. Normative levels of metal ions in well functioning, non Cobalt-Chrome hips have also not been defined to date. The Exeter total hip replacement contains no Cobalt-Chrome (Co-Cr) as it is made entirely from stainless steel. However, small levels of these metals may be present in the modular head of the prosthesis, and their effect on metal ion levels in the well functioning patient has not been investigated. We proposed to define the “normal” levels of metal ions detected by blood test in 20 well functioning patients at a minimum 1 year post primary Exeter total hip replacement, where the patient had had only one joint replaced. Presently, accepted normal levels of blood Chromium are 10–100 nmol/L and plasma Cobalt are 0–20 nmol/L. The UK Modern Humanities Research Association (MHRA) has suggested that levels of either Cobalt or Chromium above 7 ppb (equivalent to 135 nmol/L for Chromium and 120 nmol/L for Cobalt) may be significant. Below this level it is indicated that significant soft tissue reaction and tissue damage is less likely and the risk of implant failure is reduced. Hips were a mixture of cemented and hybrid procedures performed by two experienced orthopaedic consultants. Seventy percent were female, with a mixture of head sizes used. In our cohort, there were no cases where the blood Chromium levels were above the normal range, and in more than 70% of cases, levels were below recordable levels. There were also no cases of elevated plasma Cobalt levels, and in 35% of cases, levels were negligible. We conclude that the implantation with an Exeter total hip replacement does not lead to elevation of blood metal ion levels

Introduction. Higher concentrations of metal ion levels after Metal-on-metal (MoM) THA are a cause for concern. Elevated cobalt (Co) and chromium (Cr) ion levels in the blood indicate metal wear, and may predict secondary soft-tissue damage (adverse reaction to metal debris; ARMD). Although, it is well known that concentrations of metal ion levels are elevated in the short term after MoM, the long-term consequences in ion concentration and risk factors for increased ion levels are not clarified. We sequentially investigated the postoperative Co and Cr ion levels after MoM THA and the relationship between the metal ion levels and several risk factors. Materials and Methods. We reviewed the data on one hundred and eighty six patients of two hundred ninety one MoM THA cases. The one hundred eighty six patients were measured at least three times after a MoM THA surgery over a five year (2005–2010) period in our institution. Serum cobalt and chromium levels were measured by inductor coupled plasma – mass spectrometry at several times in follow-up period, (measured at the preoperative period, the third month, the sixth month, the first year, the second year, and the fourth year after MoM THA). Furthermore, we investigated the correlation between the metal ion levels and various factors which might influence the release of metal ions, such as Body mass index (BMI), renal function, femoral head size, unilateral or bilateral THA, the cup position, and postoperative activity. The renal function was evaluated by measuring estimated glomerular filtration ratio (GFR) at preoperative examination. A postoperative activity was assessed with a pedometer measurement counting number of steps a day. A cup position was evaluated by lateral inclination measured by X-ray or computed tomography. Results. Average serum Co and Cr concentrations in preoperative period were 0.69 and 0.05 mg/ ml, respectively. Postoperative serum Co and Cr ion levels were significantly increased compared with preoperative value throughout the postoperative period. There was no significant correlation with regards to BMI, renal function, femoral head size tothe metal ion level measurement. In bilateral THA cases, Co and Cr ion concentrations were significantly increased compared with unilateral THA cases. In addition, in cases that its cup inclination was more than 50 degrees, Co and Cr ion concentration were significantly increased compared with cases less than 50 degrees in the first year after surgery. There was a trend for higher metal ion levels in the group of patients who walked more than 7000 steps a day, but this did not reach statistical significance. Conclusion. Metal ion concentrations of almost patients were increased after MoM THA surgery. Side effects related to elevation of serum Co or Cr concentration were currently not identified and overall clinical results were good. However, Longer follow-up would be necessary if the patients have overlapping risk factors, because those patients may experience elevation of the level in postoperative late stage

A randomised prospective study of four bearing surfaces in hip replacements is being conducted. The primary objective is to identify the best long term bearing surf ace clinically and radiographically, and metal ion levels have been measured in all cases. Patients have been randomised to the four bearing surfaces viz. Ceramic-on-XLinked Polyethelene, Ceramic-on-Ceramic, Metal-on-Metal and Ceramic-on-Metal. Pre-operative blood samples and follow-up blood samples for metal ion analysis using ICP-MS method have been taken in all patients. As at February 2008 187 patients have been recruited, and metal ion levels at one year are available in 52 patients. Metal ion levels are not increased with Ceramic-on-XLPE or Ceramic-on-Ceramic bearings. At one year follow-up the metal ion levels in Ceramic-on–Metal bearings is half that of Metal-on-Metal bearings using mean levels, and one third using median levels. Of note is that chromium levels in Ceramic-on-Metal bearings is the least elevated. Due to the laboratory evidence that ceramic-on-metal bearings have the best surf ace wear characteristics with no head stripe wear on a ceramic head, and the laboratory and clinic al evidence of lower metal ion levels, Ceramic-on-Metal hip replacements could be one of the bearing surfaces of the future

Objectives. We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL). Patients and Methods. We examined the influence of the ALVAL grade on synovial fluid Co and Cr concentrations following adjustment for patient and device variables, including volumetric wear rates. Initially restricting the analysis to include only patients with one MoM hip resurfacing device, we performed multiple regression analyses of prospectively collected data. We then repeated the same statistical approach using results from a larger cohort with different MoM designs, including total hip arthroplasties. Results. In the resurfacing cohort (n = 76), the statistical modelling indicated that the presence of severe ALVAL and a large fluid collection were associated with greater joint fluid Co concentrations after adjustment for volumetric wear rates (p = 0.005). These findings were replicated in the mixed implant group (n = 178), where the presence of severe ALVAL and a large fluid collection were significantly associated with greater fluid Co concentrations (p < 0.001). Conclusion. The development of severe ALVAL is associated with elevations in metal ion concentrations far beyond those expected from the volumetric loss from the prosthetic surfaces. This finding may aid the understanding of the sequence of events leading to soft-tissue reactions following MoM hip arthroplasties. Cite this article: D. J. Langton, R. P. Sidaginamale, T. J. Joyce, J. G. Bowsher, J. P. Holland, D. Deehan, A. V. F. Nargol, S. Natu. Aseptic lymphocyte-dominated vasculitis-associated lesions are related to changes in metal ion handling in the joint capsules of metal-on-metal hip arthroplasties. Bone Joint Res 2018;7:388–396. DOI: 10.1302/2046-3758.76.BJR-2018-0037

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

Introduction. Modern metal-on-metal bearing resurfacings have been in use for nearly two decades. Local and systemic metal ion exposure continues to cause concern. We could not find a prospective metal ion study in such patients with a 10-year follow-up. This is the first ten year prospective study of metal ion levels in blood and their release in urine following hybrid fixed metal-on-metal surface arthroplasty. Methods. Twenty six patients were included in an ongoing longitudinal metal ion study of patients with unilateral metal-on-metal hip resurfacings. Three of them were excluded due to subsequent contralateral resurfacing and one has relocated abroad. Cobalt and chromium levels were assessed in 12 hour urine collections before and periodically after operation (5 days to 10 years) using high resolution plasma mass spectrometry. Mean age at operation was 53 years and mean BMI 27.9. Results. Hip function questionnaires at the 10-year review showed that the patients have well-functioning pain-free resurfacings (mean Oxford hip score 14.3). Metal ion results show median cobalt and chromium release at 10 years were 8.3 μg/24 hr and 4.35 μg/24 hr respectively. A statistically significant early peak 6 months to 1 year after operation is followed by a steady decrease over the following seven years although the reductions are not statistically significant. Discussion and Conclusion. Elevated systemic metal ion exposure continues to cause concern in patients treated with metal-metal arthroplasties. Our results show that metal release in these bearings shows a reducing trend after an initial peak. The unknown significance of persistent metal ion elevation underlines the need for continued long-term monitoring

We describe the findings at six years in an ongoing prospective clinicoradiological and metal ion study in a cohort of 26 consecutive male patients with unilateral Birmingham Hip Resurfacing arthroplasties with one of two femoral head sizes (50 mm and 54 mm). Their mean age was 52.9 years (29 to 67). We have previously shown an early increase in the 24-hour urinary excretion of metal ions, reaching a peak at six months (cobalt) and one year (chromium) after operation. Subsequently there is a decreasing trend in excretion of both cobalt and chromium. The levels of cobalt and chromium in whole blood also show a significant increase at one year, followed by a decreasing trend until the sixth year

Introduction: The increasing use of metal-metal bearings in hip arthroplasty raises concerns of elevated systemic metal levels. Lubrication theory and in-vitro studies suggest that larger diameter bearings generate less wear. Does this hold true in real life?. Methods: This is a cross-sectional study of 181 patients with either a Birmingham Hip Resurfacing or a 28mm Metasul THR. Whole blood levels (at 1year) and urinary metal ion output in the early (1 to 3) years and medium term (4 to 6years) in patients with these bearings were compared. None of the patients had other metal devices or compromised renal function. Both devices used a high-carbon cobalt-chrome bearing with no post-casting heat treatment. Cementless porous-ingrowth titanium cups and cemented polished tapered stainless steel stems or cementless porous-ingrowth titanium alloy stems were used in THRs. Results: Whole blood metal levels at 1-year and daily output of metal ions in the early years and medium term (figure 1) in both bearings were in the same range and without a significant difference. Discussion: Metal ion monitoring is the best way to estimate bearing wear in vivo and the best measure of device safety in the long term. Total wear over a given time period is best estimated from timed metal ion excretion rates. Blood levels represent a balance between the release of metal from the device and its renal clearance. An earlier study (Clarke et al JBJS(Br) 2003) suggests that smaller bearings generate less wear. In that study bearings with different metallurgy and wear properties were grouped together, a potential confounding factor. The present study does not suffer from that error and our findings do not support the view that a larger bearing diameter leads to either an increase or decrease in metal ion generation

Introduction. The advantages of metal on metal (MOM) hip replacement are decreased wear rate, preservation of bone stock, anatomical restoration and enhanced stability. Large amounts of metal wear particles and metal ions are released which may induce adverse reactions including local soft tissue toxicity, hypersensitivity reactions, bone loss and risk of carcinogenesis. Aseptic loosening can be the result of a peri prosthetic osteolysis generated as a result of a biological response to particulate wear debris. Our aim in this study was to determine whether a steeply inclined acetabular component would give rise to a higher concentration of metal ions. Patients and methods. Between April 2003 and June 2006, 22 patients had MOM hip replacement for osteoarthritis by a single Surgeon. There were 12 male and 10 female patients. The average age at the time of surgery was 56 years (Range: 44–69 years). We divided the 22 patients into 2 groups, one group (A) of 11 patients with the acetabular inclination angle more than 50 degrees and the other group (B) of 11 patients with the angle less than 50 degrees. The inclination of the acetabular cup was measured using a standard AP radiograph of the pelvis. The patients had metal ion levels (blood chromium and serum cobalt) measured at an average follow up of 3.2 years (Range 2.4 to 5 years). Results. Mean blood chromium level in the group A (146 nM/L) was significantly higher (p=0.005) than in Group B (92 nM/L). Mean serum cobalt level in the group A (245 nM/L) was significantly higher (p=0.002) than in Group B (110 nM/L). Discussion. The early to mid term published results of MOM hip replacements have been encouraging. There are, however, a number of concerns about the MOM bearing. Although its wear rate is low, it still releases metal ions into the body particularly cobalt and chromium since most metal on metal bearings are made of a cobalt chromium alloy. The long-term consequences of increased levels of these ions in the body are not known. High concentrations of Co and Cr are toxic and are known to interfere with a number of biological functions. There also have been recent reports of soft tissue reactions with MOM hip replacement. In the light of these concerns, it is important to examine factors which may influence the release of metal ions after MOM hip replacement. It has been reported in the recent literature that the position of the acetabular component will influence the bearing wear inturn leading to the release of metal ions after MOM hip replacement. Our findings indicate that steeply inclined acetabular components with an inclination angle greater than 50 degrees gives rise to higher concentration of metal ions

A randomised prospective study of 4 bearing surfaces in hip replacements is being conducted. The primary objective is to identify the best long term bearing surface clinically and radiographically, and metal ion levels have been measured in all cases. Patieents have been randomised to the 4 bearing surfaces viz. Ceramic on XLinked Poly, Ceramic on Ceramic, Metal on Metal and Ceramic on Metal. Pre operative blood samples and follow up blood samples for metal ion analysis using the ICPMS method have been taken in all patients. As at February 2008 187 patients have been recruited, and metal ion levels at 1 year are available in 52 patients. Metal ion levels are not increased with Ceramic on XLinked Poly or Ceramic on Ceramic bearings. At 1 year follow up the metal ion levels in Ceramic on Metal bearings is half that of Metal on Metal bearings using the mean levels, and one third using the madian levels. Of note is that the chromium levels in Ceramic on Metal bearings is the least elevated. Due to laboratory evidence that Ceramic on Metal bearings have the best surface wear characteristics with no head stripe wear, and laboratory and clinical evidence of lower metal ion blood levels, Ceramic on Metal hip replacements could be a bearing surface of the future

Bone related adverse events including failure of implant osseo-integration, periprosthetic fracture, femoral neck narrowing, and unexplained pain occur more frequently following metal-on-metal hip resurfacing (MoMHR) versus total hip arthroplasty (THA). The exact mechanism for the adverse effects is still unclear and may be due to the direct effect on bone cells of metal ions released from the prostheses. The aim of the present study was to determine the effect of clinically relevant combinations of metal ions on osteoblast cell survival and function. To assess cell proliferation and alkaline phosphatase (ALP) activity of osteoblasts, human osteoblast cells (SaOS-2), were cultured in 96-well plates for 24-hours and then treated with metal ions. Cell proliferation was measured at day 3 and day 7 using MTS assay, whilst ALP activity was assessed at day 3 by measuring pNPP substrate hydrolysis by the cell lysate. Mineralisation ability of the cells was assessed in 24-well plates cultured until day 21 and staining the calcium deposits using Alizarin red. All cultures were treated with the IC50 concentration of Co(II) (135μM) and an equivalent Cr(III) concentration (1Co(II):1Cr(III)). After 3 days, Co(II) at an IC50 concentration decreased osteoblast proliferation as expected, but no further decrease in proliferation was observed with the 1Co(II):1Cr(III) combination treatment. However, after 7 days, a further significant decrease (P<0.05) in proliferation was observed with the combination treatment compared to Co(II) IC50. A similar significant decrease (P<0.01) was observed for ALP activity at day 3 with 1Co(II):1Cr(III) compared to Co(II) alone. For mineralization, a significant reduction (P<0.0001) was observed for Co(II) IC50 concentration, however no further reduction was seen with the 1Co(II):1Cr(III) combination treatment. The observed decrease in cell proliferation and ALP activity with combination treatments suggest an additive detrimental effect compared to single ions alone. The mineralisation ability did not show any additive effect due to cell toxicity of chronic exposure to IC50 concentrations calculated from 3 day proliferation cultures. The results suggest that presence of both cobalt and chromium ions in the periprosthetic environment have more severe detrimental effect on osteoblasts than single ions alone and extend our understanding of the periprosthetic bone health

Total knee arthroplasty is a well-established treatment for degenerative joint disease, on the other hand metal ion release of cobalt or chromium and particle formation can trigger intolerance reactions. Biotribological examinations can help to assess the metal ion release in different settings. The purpose of this study was the evaluation of inter-laboratory differences in the metal ion concentration analysis. Samples were generated in a 3+1 station knee wear simulator (EndoLab GmbH, Thansau, Germany) with a medium size Columbus Knee System with or without AS multilayer coating. The wear simulation was performed under highly demanding activity (HDA) profile and samples were taken after 0.5, 5.0, 5.5. and 8.0 million cycles. The samples were blinded and sent to three different laboratories and the content of chromium, cobalt, molybdenum, nickel, and zirconium was assessed by inductively coupled plasma mass spectrometry (ICP-MS). The AS multilayer coating clearly reduced the release of chromium, cobalt and molybdenum. Mean levels were: Chromium 9329.78µg/l ± 985.44 vs 503.75µg/l ± 54.19, cobalt 10419.00µg/l ± 15.517.53 vs 2.60µg/l ± 1.35, molybdenum 2496.33µg/l ± 102.62 vs 2.46µg/l ± 2.31. Interestingly we found especially for nickel and zirconium big inter-laboratory differences in the metal assessment. There were up to 10-fold higher values in comparison of one laboratory to another. The data demonstrate that results of metal ion assessment should be evaluated by interlaboratory comparison and should be critically interpreted

Introduction. Little is known about variations in blood metal ions following bearing exchange for poorly functioning metal-on-metal hip replacements (MoMHRs). This study aimed to determine the changes that occur in blood and urine metal ion concentrations following MoMHR revision. Methods. Between 2005–2012, a single-centre prospective cohort study was undertaken of patients with large-diameter MoMHRs and high blood metal ions requiring revision. Whole blood and urine were collected both pre-revision and post-revision for metal ion analysis. Results. Twenty-three MoMHRs (21 hip resurfacings and 2 total hip replacements) were revised at a mean time of 7.9 years from primary surgery (mean age 56.0 years; 65% female). All revisions were performed using primary total hip implants and non-metal-on-metal bearings. Mean (range) metal ion concentrations pre-revision were: blood cobalt 13.9µg/l (1.32–74.7µg/l), blood chromium 8.9µg/l (1.29–57.3µg/l), urine cobalt 104.6µg/24 hours (4.35–747.3µg/24 hours), urine chromium 33.2µg/24 hours (4.39–235.4µg/24 hours). After revision the mean metal ion concentrations (percentage of pre-revision values) were: blood cobalt at 2 days=10.7µg/l (77%), 4 days=8.4µg/l (61%), 6 days=7.7µg/l (55%), 2 months=3.4µg/l (24%), 1 year=1.0µg/l (7%), 2 years=0.42µg/l (3%); blood chromium at 2 days=8.7µg/l (98%), 4 days=6.5µg/l (73%), 6 days=5.5µg/l (62%), 2 months=2.2µg/l (25%), 1 year=1.5µg/l (16%), 2 years=0.97µg/l (11%); urine cobalt at 2 days=31.9µg/24 hours (30%), 4 days=22.5µg/24 hours (22%), 6 days=21.5µg/24 hours (21%), 2 months=6.1µg/24 hours (6%), 1 year=0.99µg/24 hours (1%), 2 years=0.61µg/24 hours (1%); urine chromium at 2 days=34.4µg/24 hours (103%), 4 days=19.2µg/24 hours (58%), 6 days=15.8µg/24 hours (48%), 2 months=9.3µg/24 hours (28%), 1 year=2.8µg/24 hours (8%), 2 years=1.9µg/24 hours (6%). Discussion. The most dramatic reductions in systemic metal ion concentrations in MoMHR patients occur early following bearing exchange, with little variation after one-year. Conclusions. Blood and urine metal ion sampling performed as early as two-months following MoMHR revision is sufficient to determine the success of bearing exchange

It has been suggested that metal ion levels are indicative of in vivo bearing performance of metal-on-metal hip replacements. A cobalt or Chromium level of 7μg/L or higher is proposed to be indicative of a bearing malfunction and the need for clinical intervention. Component design, size, acetabular orientation, patient gender and activity level have been suggested as factors leading to accelerated wear and elevated metal ions. The contact patch to rim (CPR) distance is a calculation that describes the distance from the point where a theoretical joint reaction force intersects the cup to the acetabular rim for a patient in standing position, dependent on the coverage, size, and orientation of the acetabular component. It has been suggested that CPR distance determines the hip joint susceptibility to edge loading, and the risk for increased wear and high ion levels (Langton et al JBJS Br 91: 2009). This study examined the effects of patient activity, gender, and CPR distance on serum metal ion concentrations in a series of patients treated with one type of metal on metal hip resurfacing arthroplasty (MMHRA) performed by one surgeon. 182 patients (73 females and 109 males)with a unilateral Conserve Plus (WMT, TN USA) MMHRA and had who had provided blood for metal ion analysis data from December 2000 to June 2011 were retrospectively studied. Only measurements made more than 12 months after surgery were included in order to exclude hips that had yet to reach steady-state wear. For patients with multiple draws, the most recent qualifying draw was used. Activity level was assessed by the UCLA activity score. The mean age was 51.5 years (20.0 to 77.5 years). The mean follow-up time for the last blood draw was 70 months (range, 12 to 165). Serum cobalt (CoS) and chromium (CrS) levels were analyzed using inductively coupled plasma mass spectrometry in a specialized trace element lab. Using acetabular abduction and anteversion measured by EBRA, component size, and reported coverage angle of the acetabular component, the CPR distance was calculated as previously described. Multiple logistic regression was performed to identify significant relationships between high metal ion levels (7 μg/L or greater) and gender, activity and CPR distance. The median CoS level for the entire cohort was 1.13 μg/L (range, 0.15 to 175.30), and the median CrS level was 1.49 μg/L (range, 0.06 to 88.70). The average CPR distance was 13.8 mm (range, 3.2 to 22.1). There was a significant association between low CPR values and CoS and CrS. There was a 37-fold increase in the risk of CoS >7μg/L (p=0.005) and 11-fold increase in the risk of CrS > 7μg/L (p=0.003) when CPR distance was 10 mm or less. No associations were shown for gender and UCLA activity scores. CPR distance was found to be a reliable predictor of ion levels > 7μg/L and appears to be a useful indicator to evaluate the multi-factorial process of edge-loading and wear. Patients with a low CPR distance should be monitored for increased metal ion levels

Aims. We investigated whether blood metal ion levels could effectively identify patients with bilateral Birmingham Hip Resurfacing (BHR) implants who have adverse reactions to metal debris (ARMD). Patients and Methods. Metal ion levels in whole blood were measured in 185 patients with bilateral BHRs. Patients were divided into those with ARMD who either had undergone a revision for ARMD or had ARMD on imaging (n = 30), and those without ARMD (n = 155). Receiver operating characteristic analysis was used to determine the optimal thresholds of blood metal ion levels for identifying patients with ARMD. Results. The maximum level of cobalt or chromium ions in the blood was the parameter which produced the highest area under the curve (91.0%). The optimal threshold for distinguishing between patients with and without ARMD was 5.5 µg/l (83.3% sensitivity, 88.4% specificity, 58.1% positive and 96.5% negative predictive values). Similar results were obtained in a subgroup of 111 patients who all underwent cross-sectional imaging. Between 3.2% and 4.3% of patients with ARMD were missed if United Kingdom (7 µg/l) and United States (10 µg/l) authority thresholds were used respectively, compared with 2.7% if our implant specific threshold was used, though these differences did not reach statistical significance (p ≥ 0.248). Conclusion. Patients with bilateral BHRs who have blood metal ion levels below our implant specific threshold were at low-risk of having ARMD. Cite this article: Bone Joint J 2016;98-B:1455–62