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

Introduction. The aim of this study was to analyze the results of our series of female patients treated with <48 mm MOMHR devices at a minimum follow-up of 5 years, to understand which is the most important aspects affecting the results and to define if the metal ions dosage has to be indicated as a routinely follow-up. Methods. This is a retrospective clinical study; the cohort included 198 consecutive MOMHR implanted in 181 female patients (17 bilateral procedures). All operations were performed between 2002 and 2011. All operations were performed by the senior surgeon. Indications to MOMHR included primary or secondary osteoarthritis (OA), rheumatoid arthritis and avascular necrosis. Contraindications included poor proximal femoral bone stock (T-score<−2.5sd in BMD of the femoral neck) or severely distorted hip anatomy. All patients were advised to underwent clinical and radiological review with the operating surgeon at 5 weeks, 3, 6 and 12 months postoperatively and then every subsequent 2 years.182 patients answered to our phone calls; 4 patients died (one of them was operated bilaterally) for causes not related to the study, and in 11 cases the phone number was expired. The minimum follow-up was 5.0 years (mean 7.5, maximum 13.2, sd 0.11). Results. Fourteen devices were revised (7%) in 14 patients: 2 of them were operated bilaterally and the controlateral implant is still fine; thus, the Kaplan-Meier survival rate with revision for any reason as the end point was 92.7% at 13 years (95% confidence interval (CI) 0.9 to 1.0). Revisions data are resumed in table 2. Main OHS was 44 points (4–48, sd 7); no statistical relations were found about any aspect about relation between OHS and metal ions dosage (eg Chi Square Analysis p-value = 0.147>0,05 for Score and CR). Metal ions dosage was performed in only 2 cases before and after the revision (14%); in one case, the Cr dosage was 20 µg/L before and 8 µg/L after surgery; in the other case, the Cr dosage was 100 µg/L before and 10 µg/L after surgery, and the Co dosage was 70 µg/L before and 0.2 µg/L after surgery. Metal ions dosage was performed in 64 cases of the survived implants (35%). Main Cr dosage was 1.50 µg/L (0.09–7.00, sd 1.70) and main Co dosage was 1.30 µg/L (0.09–9.00, sd 1.60), at a main follow-up from surgery of 5.7 years (0.2–11.0, sd 3.1), in 14 different laboratories. No statistical relation were found between clinical outcomes and metal ions increase. Conclusions. MOMHR is a good choice for treating severe hip arthritis also in female patients with <48 mm devices. The results are affected especially by surgical technique and indications. The metal ions dosage has to be performed every year for the first two years and then at a larger follow-up. We believe that additional imaging, such as CT scanning to measure anteversion may better identify the ideal candidate, and specific training with largely experienced surgeons would be mandatory; the metal ions dosage would be used as a monitor of failures

Blood metal ion sampling can help detect poorly functioning metal-on-metal hip arthroplasties (MoMHA's) requiring revision. Little is known about the variation in these levels following bearing exchange. This study aimed to determine the changes that occur in blood and urine metal ion concentrations following MoMHA revision. A single-centre prospective cohort study was undertaken between 2005 and 2012 of patients with failing large-diameter MoMHA's and high blood metal ions requiring revision to non-metal-on-metal articulations. All patients had normal renal function. Whole blood and urine were collected for metal ion analysis preoperatively and regularly following revision. Twenty-three MoMHAs (21 hip resurfacings and 2 total hip arthroplasties; mean age 56.0 years and 65% female) were revised at a mean time of 7.9 years (range 2.0–14.5 years) from primary surgery. All revisions were performed by the senior author using primary total hip implants (12 ceramic-on-polyethylene bearings, 10 oxinium-on-polyethylene bearings, and 1 metal-on-polyethylene bearing implanted). 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%), 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%), 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%), 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%), 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%). Following MoM revision cobalt levels decline rapidly in an exponential pattern with a single rate of decay through the 2 year period, reaching reference levels within the first year. Chromium follows a similar pattern but starts lower and takes longer. Renal response to cobalt returns to reference level within days of revision

Metal-on-metal hip bearings are being implanted into younger patients. The consequence of elevated levels of potentially carcinogenic metal ions is therefore a cause for concern. We have determined the levels of cobalt (Co), chromium (Cr), titanium (Ti) and vanadium (Va) in the urine and whole blood of patients who had had metal-on-metal and metal-on-polyethylene articulations in situ for more than 30 years. We compared these with each other and with the levels for a control group of subjects. We found significantly elevated levels of whole blood Ti, Va and urinary Cr in all arthroplasty groups. The whole blood and urine levels of Co were grossly elevated, by a factor of 50 and 300 times respectively in patients with loose metal-on-metal articulations when compared with the control group. Stable metal-on-metal articulations showed much lower levels. Elevated levels of whole blood or urinary Co may be useful in identifying metal-on-metal articulations which are loose

Introduction: Local problems of metal on metal (MOM) hip arthroplasty such as pseudotumours, neck thinning and osteolysis maybe related to concentrations of cobalt and chromium ions in the synovial fluid. There is little reported on these values. Our aim was to determine the range of metal ion levels in synovial fluid, and to investigate the relationship between these samples and simultaneous blood samples. Methods: Synovial fluid and whole blood samples were taken from 30 consecutive patients at the time of revision surgery for a painful MOM hip. Aspirated fluid was not visibly contaminated with blood. Impants were in situ for a mean period of 31 months. All had normal renal function. Samples were analysed using ICP mass spectrometry and compared with 10 samples from patients without implants. Results: The mean (and range) of synovial fluid metal ion levels were 1965 ug/l (30 to 13618) and 6265 ug/l (11 to 81630) for Cobalt and Chromium respectively. There was a good correlation between synovial and blood levels for both cobalt (R=0.65, p = 0.0001) and chromium (R = 0.59, p = 0.006). Discussion and Conclusion: Metal ions in synovial fluid from MOM hips are generated from wear of the bearing surfaces, the correlation with blood metal ion levels, shown in this study, suggest that blood levels may be used as surrogate marker for hip wear rate. Our range of synovial fluid metal ion levels may be useful for those conducting in vitro studies on the biocompatibility of MOM hips

Metal ion levels are used to track the performance of metal containing bearings in hip replacement patients. Changes in whole blood metal ion levels are indicators of wear rates in these bearings. Normal metal ion levels are variable, and range widely. Changes in these “non-bearing” levels over a period of time may influence the monitoring of these bearings. Methods. As part of a prospective randomised trial of different bearing surfaces, whole blood metal ion levels were monitored. This included four cohorts of patients, namely ceramic-on-ceramic (CoC), ceramic-on-polyethylene (CoP), ceramic-on-ceramic (CoC) and ceramic-on-metal (CoM). Serial whole blood metal ion levels in the non-metal bearings, namely CoC and CoP, were analyzed. Results. There was no consistency in these whole blood metal ion levels. Intra-patient variations in these levels over a period of time could not be due to bearing-produced metal ions as these were all metal free, and thus not the source of any endogenous ions. These intra-patient variations may reflect changes in exogenous exposure to these metal ions, fluctuations in these patient's metabolic functions or production of metal ions from non-bearing prosthetic sources. Conclusion. This finding of variations of “normal” intra-patient whole blood metal ions highlights the importance of determining a patient's average baseline levels, particularly when these are used to determine changes in these levels when part of a protocol to monitor the performance of metal containing hip replacement bearings

Metal on metal (MoM) bearings in hip surgery may result in increased blood levels of metal ions. The nature of the relationship between ion levels and failure is still not fully understood. We compared three cohorts of resurfacing patients, grouped for brand and diameter of femoral component. We measured the blood level of Cobalt and Chromium ions at an average of 4 years postoperatively. The results were grouped as follows: Birmingham Hip Resurfacing ≥50 mm diameter, Durom resurfacing ≥50 mm diameter and Durom resurfacing <50 mm diameter. 120 patients were included in each group. There were significant differences in Cobalt levels between the groups. The median cobalt level for the BHR group was 8 nmol/L higher than the Durom ≥50 mm group (P<0.005). The Durom <50 mm group recorded cobalt levels 8.5 nmol/L higher than the Durom ≥50 mm group (P=0.0004). Revision rates were equal in the Large BHR's and Large Durom HRA (both 3.3%) however the small Durom HRA had a revision rate of 8.3%. Elevated blood ion levels can indicate a failing MoM bearing. When similar ion levels were reported for BHR and small Durom the latter had significantly higher revision rates. The large BHR and large Durom HRA have similar revision rates yet the large Durom HRA had significantly lower metal ion levels. Only one of the patients having revision surgery (n=18) had metal ion levels above the MHRA threshold. This suggests ion levels do not absolutely predict the rate of HRA failure. Given similar revision rates with different ion levels between the large BHR and large Durom hips, mechanisms of failure leading to revision must be isolated from the release of metal ions. Therefore clinical and image based follow up are recommended in addition to ion level monitoring

The combination of a ceramic head articulating against a metal acetabular liner (CoM) has shown reduced metal ion levels compared with a metal-on-metal bearing (MoM) in hip simulator studies. A randomized prospective clinical trial was undertaken using CoM and MoM bearings in an otherwise identical total hip procedure. The initial clinical results were encouraging. This report comprises a further review of metal ion data. Patients received identical components with the exception of the bearing surface material but all were 28mm diameter. All components were supplied by DePuy International Ltd. Patients were assessed pre-operatively, 3m, 12m and > 24m (median 32m). Whole blood samples were collected at regular follow-ups, frozen and analysed in batches using high resolution Inductively Coupled Plasma – Mass Spectrometry (ICP-MS). All recruited patients are included irrespective of outcome. However some patients failed to attend specific follow-ups and some contaminated samples had to be discarded. Statistical significance was analyzed using a non-parametric comparison (Mann-Whitney test). After 3m and 12m implantation there were between 21 and 24 patients available for analysis in both the CoM and MoM cohort and after > 24m point 10 and 9 respectively. There were four outliers (either Cr or Co > 10ug/l) in both the CoM and MoM groups. In common with previous studies (with the exception of two marginal outliers), these were related to component position. They were implanted with either a cup abduction angle of > 55°, an anteversion angle of > 30° or both. Other studies with the same design of component have reported no significant outliers. The median Cr and the Co levels are lower with the CoM bearing compared with the MoM at all measurements points following implantation. The median background (pre-operative) levels for the combined CoM and MoM group were Cr: 0.22ug/l and Co: 0.49ug/l. These were significantly different (p=0.006). In the CoM group, the median 12m Cr and Co values were 0.43ug/l and 0.72ug/l respectively. The comparable values for MoM are 0.68ug/l and 0.83ug/l. Increases in metal ion levels from pre-operative levels are used as the primary ion level outcome in this study because the background level will comprise of the order of 30–50% of the overall value. The increase in Cr for CoM and MoM from pre-op levels to 12m significantly different for Cr (p=0.015). It has a lower significance for combined metal ion levels (p=0.029). This difference in not significant for Co (p=0.195). In agreement with predictions from hip simulator studies, CoM bearings in this study produced lower levels of metal ions than comparable MoM bearings at all time points. However the difference is less than that predicted in the laboratory and is much more pronounced with Cr than with Co

Introduction. A metal ion study was undertaken in patients who had received an articular surface replacement. The design of these components is optimised in line with lubrication theory and produces low levels of wear in hip joint simulators. Methods. Patients were recruited in four centres. Whole blood samples were analysed for metal ion levels using high resolution ICP-MS (inductively coupled plasma mass spectrophotometry). A total of 75 patients was enrolled into the study and 65 and 47 patients were assessed after 12 and 24 months implantation respectively. Results are included irrespective of clinical outcome. Results. The 12 and 24 month median ion levels were 1.4 μg/l and 1.6 μg/l respectively for chromium and 1.5(μg/l and 1.6 μg/l respectively for cobalt. The pre-operative levels were 0.38(μg/l and 0.34(μg/l for chromium and cobalt respectively. Twenty-seven percent of patients had a pre-operative chromium level that was higher than the 24 month median level. Similarly the value for cobalt was seven percent. However close examination of the data shows that it is skewed by 6 outliers with cobalt or chromium levels greater than 10(μg/l after 24 months implantation. This appears to be related to acetabular component placement. Patients with acetabular components implanted at a high inclination angle (>55deg) are more likely to have elevated metal ion levels compared with a standard angle (<55deg). In the 24 month group two patients (both outliers) have been revised. Furthermore, the high metal ion levels at 24 months could be predicted by intermediate levels after 12 months. Conversely those levels below 10ug/l had already stabilised after 12 months in vivo. Conclusion. Large diameter metal-on-metal bearing with optimised tolerances can produce very low blood metal ion levels. However, in line with other studies, mal-positioning of components may lead to significantly elevated levels of wear and hence blood metal ions

The aim of this study is to investigate whether MoM implants result in more chromosome aberrations and increased blood metal ions postoperatively whe compared to MoP implants. MoM arthroplasties are being inserted in increasing numbers of younger patients due to the increased durability and reduced requirements for revision in these implants. Recent studies have raised many concerns over possible genotoxicity of MoM implants. This is a prospective study of patients who have undergone elective total hip replacement, they were selected and then randomised into two groups. Group A received a MoP implant and group B received a MoM implant. Patients are reviewed pre-operatively (control group), at 3 months, 6 months, 1 year and 2 years post-operatively. On each occasion blood tests are taken to quantify metal ion levels (chromium, cobalt, titanium, nickel and vanadium) using HR-ICPMS method and chromosome aberrations in T lymphocytes using 24 colour fluorescent in situ hydridisation (FISH). 51 patients have been recruited to date, 23 of whom had MoP prosthesis and 28 a MoM. 47 of these had their 1 year follow-up with blood analysis and 38 have had 2 year follow up. There appeared to be a bedding period for both MoM and MoP groups, with an increase in metal ion release. The blood concentration of chromium, cobalt and titanium rise significantly in the MoM group at the 2 year stage. Chromosome aberrations occurred in both groups. Both the MoM and MoP groups showed increase frequency of aneuploidy aberrations and structural damage. The greatest increase in metal ion levels occurred at the 1 to 2 year interval corresponding to significant rise in chromosome aberrations. Preliminary results of this study show that the levels of chromium, cobalt and titanium are significantly higher in the MoM group compared to the MoP group. This corresponds to increases in chromosome aberrations in the groups with increases in structural chromosome damage after two years

Introduction: Despite the satisfactory short-term implant survivorship of MoM hip resurfacing arthroplasty, symptomatic abnormal periprosthetic soft-tissue masses relating to the hip joint, ‘pseudotumours’, are being increasingly reported. These were found be locally destructive, requiring revision surgery in 75% of patients. Asymptomatic pseudotumours have not been previously investigated. Methods: The aims were: (1) to investigate the prevalence of asymptomatic pseudotumours; and (2) to investigate their potential association with the level of metal ions. A total of 160 hips in 123 patients with a mean age 56 years (range 33–73) were evaluated at a mean follow-up of 61 months (range 13–88). Radiographs and OHS were assessed. Patients with a cystic or solid mass detected on the ultrasound/MRI had an aspiration or biopsy performed. Cobalt and chromium levels were analysed using Inductively-Coupled Plasma Spectrometer. Results: Pseudotumours were found in 6 patients (5F: 1M). In 80% of bilateral cases, it was found in both sides. Histological examination showed extensive necrosis and diffuse lymphocyte infiltration. The presence of pseudotumour was associated with higher serum cobalt (9.2 μg/L vs. 1.9μg/L, p< 0.001) and chromium levels (12.0μg/L vs. 2.1μg/L, p< 0.001); higher hip aspirate cobalt (1182 μg/L vs. 86.2μg/L, p=0.003) and chromium levels (883μg/L vs. 114.8μg/L, p=0.006); and with inferior OHS (23 vs. 14 p=0.08). Discussion: The prevalence of asymptomatic pseudotumour (5%) was higher than previously reported for the symptomatic pseudotumours (1%). There was a sixfold elevation of serum and a twelve-fold elevation of hip aspirate levels of cobalt and chromium in patients with pseudotumours. This suggests that pseudotumours may be a biological consequence of the large amount of metal debris generated in vivo. The association between pseudotumour and elevated metal ion levels might theoretically be explained by either systemic hypersensitivity responses to metal ions or local cytotoxic effects due to a high level of metal ions

Background: There is a paucity of published literature with regard to metal ion levels following bilateral hip resurfacings. Method: Recent research has identified femoral component size and acetabular cup anteversion and inclination as important variables involved in metal ion release into the blood. We compared 13 patients with bilateral joints resurfaced using the ASR and 11 patients with bilateral BHRs to those with unilateral joints of similar size and cup inclinations/anteversions. Patients were excluded if the last procedure was within 12 months of blood sampling and if they had other metallic implants. Analysis of standing radiographs to determine cup orientation was carried out using EBRA software. Blood samples were analysed using ICPMS. Results: Median whole blood Cr and Co values were higher in the BHR bilateral group when compared to the unilateral BHR group by a factor of 1.12 and 1.24 respectively. (5.17 vs 4.59 for Cr, 2.40 vs 1.93 for Co). The difference was significant for Co (p=0.030) but not for Cr (p=0.136). For the large ASR joints (53mm), median Cr and Co values were higher in the bilateral group by a factor of 1.5 and 1.85 respectively. (4.55 vs 2.97 (Cr) 2.83 vs 1.53 (Co)). The difference was significant for both Cr (p=0.001) and Co (p=0.022). For the small ASR joints (< 53mm), median Cr Co values were higher in the bilateral group by a factor of 1.95 and 2.30 respectively. (8.29 vs 4.25 (Cr), 6.78 vs 2.94 (Co)) (p=0.019 Co) (p=0.007 Co). Conclusion: Metal ion concentrations are significantly greater in patients with bilateral resurfacings. The Cr Co concentrations observed in our patients with bilateral small ASR joints are double those in the published literature on bilateral 28mm metal on metal(MoM) joints implying that the lubrication achieved by small ASRs is sub optimal

Introduction: Potential problems resulting from metal-on-metal hip wear debris are well known. Previous studies have shown an association between high cup angles and raised metal ion levels, but a link to clinical outcome has yet to be established. We aim to show the relationship between high cup angles, raised metal ion levels and pain following hip resurfacing. Methods: This analysis comprised the first 250 Depuy ASR hip resurfacings performed by a single surgeon (senior author) over a 3 yr period at an independent centre. Patients were followed up, examined and x-rayed at regular intervals. We measured Harris Hip Score (HHS) and pain. The acetabular cup inclination angles were measured from standardised pelvic radiographs. A subgroup of 80 patients had serum and whole blood chromium and cobalt measurements performed. This subgroup comprised patients with a similar sex split, age, activity level, follow-up and cup angle profile to the parent group. Results: HHS improved from 51.6 pre-operatively to 94.6 post-operatively. Males had a significantly higher post-op HHS (97.1) compared with the females (91.0). 2.1% of male patients had pain compared with 8.7% of females. High cup angles were associated with pain in females. This relationship did not occur in males. In patients with cup angles of 48° and above there were no males with pain compared to 15.4% of females. Females under 48° had a HHS of 93.7 compared to 88.0 for those over 48°. When we analysed metal ion levels there was a similar relationship. Patients with cup angles of 48° and above had significantly higher serum and whole blood chromium and cobalt levels compared with lower cup angles. Three patients with cup angles over 50° developed ALVAL (aseptic lymphocyte dominated vasculitis associated lesion) based on histological findings. All were female. Discussion: High cup angles are associated with increased pain and elevated metal ion levels. Women seem to be more intolerant of an higher cup angle than men. This may be a consequence of the smaller prostheses in females. Cups implanted lower than 48° had a better clinical outcome and less metal ion wear. Like other 4th generation designs, the ASR cup is not a complete hemisphere (unlike the BHR) and may be susceptible to edge loading at lower inclination angles than previously thought. We believe the current recommendation of 45° +/−5° is too high based on our findings. We recommend an inclination angle that does not exceed 48°

Comparisons of blood metal ion levels of cobalt and chromium (CoCr) between metal-on-metal total and resurfacing hip arthroplasties are limited. High levels of CoCr may result in long-term adverse biological effects. We compare metal ions levels between total and resurfacing implants. 70 patients (28 males and 42 females) had a total hip arthroplasty using the Birmingham (Smith & Nephew) modular femoral component and a variety of stems, articulating with the Birmingham resurfacing component. The average age was 65.5 (±6.8) years and an average follow-up of 6.0 (±2.2) years. 170 patients (145 male and 25 female had a Birmingham resurfacing arthroplasty with an average age of 54.7 (±9.9) years and an average follow-up of 5.9 (±3.0) years. CoCr levels were measured. Bivariate correlations and independent samples t-tests were applied to determine similarities and differences within and between groups. Average ion levels in total arthroplasty patients were: Co 114.17 (±94.01) nmol/L (range 2–414); and Cr 75.12 (±68.45) nmol/L (range 10–312). Average levels in hip resurfacing arthroplasty were: Co 55.98 (±79.5) nmol/L (range 7–505); and Cr 70.77 (±87.41) nmol/L (range 5–751). Both total and resurfacing groups showed significant correlations (p<0.01) between Co and Cr levels. A significant difference was observed between the total and resurfacing group Co levels (p<0.0001). No significant difference was shown between group Cr levels (p>0.672). The average total hip replacement CoCr levels were higher than the hip resurfacing levels. While the overall activity level may be higher in the resurfacing group, possibly the incidence of stop/start frequency may be higher in the total hip replacement group. Hip resurfacing arthroplasty average CoCr levels are lower than those of total hip replacement patients. Associations between Co and Cr metal ion levels are shown within each group. Co levels differ significantly between groups where Cr does not. Long-term follow-up of CoCr levels are required

Total knee arthroplasty is a well established treatment for degenerative joint disease with good clinical results. However, complications may occur due to a biological response to polyethylene wear particles, leading to osteolysis and aseptic loosening, as well as local and systemic hypersensitivity reactions triggered by metal ions and particles such as chromium, cobalt and molybdenum. Moreover, there is an increasing demand on the performance of these implants, as this treatment is also performed in heavier, younger and middle-aged adults who have a significant physical activity and higher life expectancy. The purpose of the following study was to compare the wear characteristics and performance of a zirconium nitride (ZrN) coated knee implant, designed for patients with metal ion hypersensitivity, against the clinically established cobalt-chromium (CoCr) version under a high demanding activities wear simulation. Medium size AS Columbus® DD (Aesculap AG, Tuttlingen, Germany) femoral and tibial components with a ZrN surface were tested in comparison with the cobalt-chromium version Columbus® DD. For both groups, ultra-high-molecular weight polyethylene (UHMWPE) gliding surfaces (size T3, high 10 mm) were used. Wear simulation was performed on a load controlled 4 station knee wear simulator (EndoLab GmbH, Thansau, Germany) capable of reproducing loads and movement of daily activities measured in vivo (Bergmann et al, 2014) on 8 patients and normalized to a patient weight of 100 kg (Schwiesau et al, 2014). The load profiles were applied for 5 million cycles in a combination of 40% stairs up, 40% stairs down, 10% level walking, 8% chair raising and 2% deep squatting. Test serum was changed every 0.5 million cycles and all the components were cleaned and analyzed according to ISO 14243-2:2009(E). The gliding surfaces were evaluated for gravimetric wear and wear patterns, femur components analyzed for scratches and the test medium analyzed for metal ion concentration (cobalt, chromium, molybdenum and zirconium) using ICP-MS according to ISO 17294-2. The present study showed a wear rate reduction for the ZrN group (1.01 ± 0.29 mg/million) in comparison with the CoCr group (2.40 ± 1.18 mg/million cycles). The articulation surface of the ZrN coated femurs remained polished after the testing period, whereas the uncoated femurs showed wear scratches. Furthermore, the metal ion release from the ZrN coated implants was reduced orders of magnitude in comparison with the CoCr implants through the entire test. These results demonstrate the efficiency of ZrN coated knee implants to reduce wear as well as to prevent metal ion release in the knee joint

The search for the ideal bearing surfaces to be used in Total Hip Replacement continues. The current “best” materials are felt to be various combinations of metal, ceramics and cross linked polyethylene. This study aims to identify the best combination with the lowest side effect profile. In February 2004 a prospective randomised trial on different bearing surfaces was started. The combinations selected were ceramic on cross linked polyethylene, ceramic on ceramic, metal on metal and ceramic on metal. Institutional ethics clearance was obtained. In all patients uncemented femoral stems are used, and an uncemented porocoated acetabular shell. 28mm Head size was selected. Blood samples have been taken to measure the metal ion concentrations in all patients. These are measured pre operatively, and repeated at intended follow up visits at 3 months, 1, 3, 5 and 10 years post operative using a graphite furnace atomic absorption spectrometer. Between February 2004 and 2006 seventy hips have undergone total hip replacement. There are 85 patients (11 bilateral). 40% are males and 60% female. The average age at operation is 52 years (17 to 72). 46% Hips are left and 54% right. Follow up includes blood samples and the Harris Hip Score. Complications to date have been surgeon related, with three femoral components needing early revision for technical reasons. This has not affected the bearing surfaces. Ten patients have hetero-topic ossification. Cup inclination averages at 48 degrees (32 degrees to 69 degrees). Post operative blood metal ion levels are compared to the patient’s pre-operative level. To date there is no increase in the metal ion levels for the ceramic/cross linked poly ethylene and ceramic/ceramic articulations. The ceramic metal group is providing intermediate raised metal ion levels, and the highest metal ion levels are in the metal on metal articulation group. In the laboratory the ceramic on metal articulation demonstrates the least wear of all the groups studied, with metal on metal second. The high level of metal ions in the latter groups has always been of concern. This study demonstrates a lower blood level of metal ions in the ceramic on metal group. If the in vivo wear rate in this group is as good as the laboratory wear, it becomes a very attractive bearing surface in younger active patients

Wear debris associated with CoCr bearings has been implicated in the development of adverse soft tissue reactions and pseudotumors following THA with large metal heads and following hip resurfacing. Additional concerns have been raised regarding trunion fretting and corrosion. Most recently, the neck-stem junction of some modular femoral stem designs have come under additional scrutiny. We undertook a review of patients who had undergone THA with a proximal modular junction stem design in order to ascertain the state of the junction in early follow up. We examined the records of all patients in our practice who had undergone uncomplicated, unilateral THA with the ARC stem (OmniLife Science, East Taunton, MA, USA) between April 2010 and April 2012. Office records, radiographs and laboratory data were included. Serum or blood cobalt and chromium ion levels were obtained at the one-year post-op visit or later or if the patient had unexpected pain. The test obtained (serum or blood) was dependent on the lab performing the study. In the study period 100 patients met the inclusion criteria and had metal ion levels available for review. No patient required revision for adverse soft tissue reaction or elevated metal ion levels. Cobalt levels fell with the normal lab ranges in the majority of patients with a very small percentage demonstrating levels slightly above the normal range. Chromium levels all fell within the expected normal range. One patient had a neck exchange for mechanical reasons at 8 weeks following primary THA. This patient went on to develop elevated serum cobalt levels and a large hip effusion. The hip was revised at one year to a non-modular stem. A modular proximal stem offers the advantages of addressing variable anatomy and allowing less soft tissue dissection. Some designs have enjoyed success while others have been withdrawn from the market due to fatigue failure, dissociation or metal-associated adverse reactions. Modular junction designs vary greatly which can impact their inherent stability and their ability to resist micro-motion. In this patient group the junction has shown good stability in early follow up as judged by clinical and laboratory data. Cobalt levels were all normal or well below the range considered suspicious for adverse reaction. Chromium levels all fell within the normal range. A case of an exchanged neck with retention of the stem was associated with high cobalt levels. We discuss several junction designs and their characteristics

Introduction:. Whole blood metal ion level and clinical outcomes of ceramic-on-metal bearing were comparable to ceramic-on-ceramic THA in this prospective randomized controlled trial. Methods:. We randomized 150 consecutive THA cases at one institution into two groups: Group I and Group II. Group I, 75 cases, received a THA using ceramic-on-metal couplings and Group II, 75 cases, received ceramic-on-ceramic bearing THA. The implant differed only in the bearing surfaces used. We compared the serum levels of cobalt (Co) and chromium (Cr) and functional outcome scores preoperatively, and at 2, 6, and 12 months postoperatively. Results:. The demographics and preoperative Co and Cr levels were similar between the groups. Femoral head size measured 32 and 36 mm and the proportion of each size was similar in both groups. The mean serum cobalt and chromium levels increased significantly at 2 months in Group I (Co p = 0.02, Cr p = 0.04), but no differences noted between groups at 6 and 12 months (Co p > 0.05, Cr p > 0.05). The mean WOMAC hip scores showed comparable improvements at 12 months with no difference between groups. No ceramic fracture has occurred during follow-up period. Discussion & Conclusion:. CoM bearing THA has showed the metal ion levels and the clinical results comparable to CoC couples except for the relatively high metal ion in running-in period

The search for the ideal bearing surface in Total Hip Replacements continues. The current ‘best’ materials are felt to be combinations of metal, ceramics and cross-linked polyethylene. Laboratory studies suggest that ceramic-on-metal articulations may provide distinct advantages. This study aims to identify the best bearing surface combination with the lowest adverse side effect profile. Between February 2004 and September 2007, 164 hips were replaced in 142 patients. 39% were male and 69% were female. The average age at surgery was 53 years (17-72 years). Follow-up assessment included radiographs, the Harris Hip Score and whole blood samples for metal ion levels. Complications to date included 3 hips which needed femoral revision because of surgery related factors, and 3 cases of sepsis of which 1 settled and 2 needed revision. One hip needed revision of head and liner to a larger bearing size for recurrent dislocations, and is no longer being followed up for blood metal ions. Post-operative whole blood metal ion levels were compared to pre-operative levels to determine the increase or decrease in metal ion levels. There were no changes in those patients with ceramic-on-ceramic and ceramic-on-polyethylene articulations. Moderately raised whole blood metal ion levels were noted at 3 months in the ceramic-on-metal group, while the metal-on-metal group show the greatest increase. This study agrees with laboratory bearing surface wear studies demonstrating lower wear rates in the ceramic-on-metal group compared to the metal-on-metal group. With concerns related to high blood metal ion levels in metal-on-metal articulations, ceramic-on-metal bearing surfaces may well become a bearing surface of choice in the future, but progress needs to be monitored in the longer term

Background: Definitive cup position for the reduction of blood metal ion levels has yet to be established. Methods: Samples for serum metal ion analysis are taken routinely from patients under the care of the two senior authors of this paper. Both are high volume experienced hip resurfacing surgeons, one based in England, the other in Belgium. Metal ion results from two centres from patients with unilateral joints were correlated to size and orientation of femoral and acetabular components, UCLA activity score, age, time post surgery and post operative femoral head/neck ratios. EBRA software was used to assess cup inclination and anteversion on standing radiographs. Cup orientation in vivo was compared to explant analysis of 60 retrieved resurfacing components using a coordinate measuring machine. Results: Three resurfacing devices were studied. There were 620 results in total. Only femoral size and cup inclination/anteversion were found to have any effect on ion levels. In all devices, metal ion levels were inversely related to femoral size (p< 0.05). The device providing the smallest acetabular coverage arc was associated with the highest metal ion levels. Consistent throughout the implants, lowest ion levels were associated with cups with radiological inclination of 40–50° and anteversion 10–20°. Cup inclination angles lower than 40° were associated with posterior edge loading and likely sub-luxation of the femoral component. Conclusion: The greater the coverage angle provided by the acetabular component, the greater the tolerance to suboptimal position. Lowest ion levels were found in well positioned lower clearance devices. Cup inclination/ante-version angles of 45/15+/−5° were associated with low ion levels in all three devices. We do not recommend cups to be placed with inclination angles below 40°

The search for the ideal bearing surfaces to be used in Total Hip Replacement continues. The current “best” materials are felt to be various combinations of metal, ceramics and cross-linked polyethylene. Laboratory studies suggest that ceramic-on-metal articulations may provide distinct advantages. This study aims to identify the best combination with the lowest side effect profile. In February 2004 a prospective randomised trial on different bearing surfaces was started. The combinations selected were ceramic-on-cross-linked polyethylene, ceramic-on-ceramic, metal-on-metal and ceramic-on-metal. Institutional ethics clearance was obtained. In all patients uncemented femoral stems are used, with an uncemented porocoated acetabular shell. A uniform 28mm femoral head size was selected. Blood samples have been taken to measure the metal ion concentrations in all patients. These are measured pre operatively, and repeated at follow up visits at 3 months and 1 year, with further follow up at 3,5 and 10 years post operatively. Whole blood ion levels are measured using a graphite furnace atomic absorption spectrometer. Between February 2004 and April 2006 one hundred and ten hips have undergone total hip replacement. There are 105 patients (5 bilateral). 40% are males and 60% female. The average age at operation is 52 years (17 to 72). 49% hips are left and 51% right. Follow up includes blood samples and the Harris Hip Score. Complications to date have been surgeon related, with three femoral components needing early revision for technical reasons. This has not affected the bearing surfaces. Radiological and clinical assessment shows no difference between the different bearing surface groups. Post operative whole blood metal ion levels are compared to the patient’s pre operative level. To date there is no increase in the metal ion levels for the ceramic-on-cross linked polyethylene and ceramic-on-ceramic articulations. The ceramic-on-metal group is providing moderately raised metal ion levels, and the highest metal ion levels are in the metal-on-metal articulation group. At one year, the ceramic-on-metal group demonstrates a drop to close to pre-operative levels and these are still significantly lower than the metal-on-metal group. This confirms laboratory studies on the ceramic-on-metal articulation, which demonstrate significantly lower wear than comparable metal-on-metal articulations. The high level of metal ions in the latter groups has always been of concern. This study demonstrates a lower blood level of metal ions in the ceramic-on-metal group. If the in vivo wear rate in this group continues to replicate the laboratory wear studies, this articulation becomes a very attractive bearing surface in younger active patients, and may well become a bearing surface of choice in the future

Introduction: In vitro simulation experiments and in vivo metal ion studies have been used to investigate metal-metal bearing wear. In vitro studies demonstrate an early high wear phase followed by a rapid decline to a significantly lower steady state phase. Clinical metal ion studies have never shown such a significant fall in later years although they reveal early high wear. This study compares in vitro and in vivo wear rates. Methods: In vivo measurements were obtained from daily cobalt excretion in 26 patients with 50 and 54mm resurfacings up to 4 years. Their activity averaged 2Mcyc-per-yr. In vitro measurements were obtained from gravimetric wear rates (Prosim hip simulator) of ten 50 mm diameter resurfacings of the same design. Diluted calf serum was the lubricant. Results: Simulator results, shown in fig 1, are wear per day equivalent. In fig 2 it is seen that during the first year simulator results predict wear that exceeds metal ion output. This can be accounted for by postulating that particulate debris is higher during the early years. Subsequently the plots converge showing that particulate debris release is progressively reduced in comparison to metal ion release. At 3 years the simulator predicts lower wear than that observed in the metal ion study. This can be accounted for by postulating that corrosion of previously shed particles is responsible for the difference. Discussion: From these results it can be stated that during the run-in period, 4/5ths of bearing wear occurs as insoluble particles and the rest is soluble metal ions. This relationship progressively changes through the steady state phase. At around the 3-year stage, even if we assume that most bearing wear releases soluble metal ions, nearly a fifth (2.8/14.4) can only be accounted for through passive corrosion of wear particles

Introduction: Pain and mass lesions around hip resurfacing are reported with increasing frequency. The aetiology is unknown but reaction to metal wear debris and mechanical impingement have both been suggested. We are aware of a group of our patients with significant pain following resurfacing. We sought to correlate metal ion levels with X-ray findings and any local soft tissue reaction around the prosthesis. Methods: Patients with significant groin pain following hip resurfacing were identified from routine clinics. Blood was tested for cobalt and chromium levels using inductively coupled mass spectrometry in all patients. Cup abduction angle and femoral stem version were estimated from plain radiographs. Patients underwent ultrasound scan (USS) of the affected hip joint. Bilateral prostheses were excluded to avoid confounding. Results: 47 unilateral painful hip resurfacings (24 female) were identified. USS was performed in 42 patients and was abnormal in 25 (15 female). Abnormalities ranged from simple joint effusion with or without synovial thickening, through to cystic masses in the posterior joint and solid masses related to the ileopsoas tendon similar to the appearances previously described in pseudotumours. A two sample t-test demonstrated cobalt and chromium ion levels were significantly higher in patients with abnormalities on USS (p=0.038, p=0.05 respectively), patients with normal USS were more likely to have a retroverted femoral component (p=0.01). Discussion: We describe two groups of patients with a painful hip resurfacing: those with raised metal ions and local soft tissue reaction, and those with lower metal ions and no soft tissue reaction. The retroverted stems in the second group could cause an iatrogenic cam-type impingement. Metal ion levels are useful to guide further imaging. Raised levels should prompt investigation for a soft tissue abnormality with either USS or MRI, lower levels suggest investigation should look for mechanical impingement with imaging such as CT

We have studied the relationship between metal ion levels and lymphocyte counts in patients with metal-on-metal hip resurfacings. Peripheral blood samples were analysed for lymphocyte subtypes and whole blood cobalt and chromium ion levels in 68 patients (34 with metal-on-metal hip resurfacings and 34 with standard metal-on-polyethylene total hip replacements). All hip components were radiologically well-fixed and the patients were asymptomatic. Cobalt and chromium levels were significantly elevated in the patients with metal-on-metal hip resurfacings, compared with the patients with standard metal-on-polyethylene designs (p < 0.0001). There was a statistically significant decrease in the level of CD8. +. cells (T-cytotoxic/suppressor) (p = 0.005) in the metal-on-metal hip resurfacing group. A threshold level of blood cobalt and chromium ions was associated with reduced CD8. +. T-cell counts. We have no evidence that our patients suffered as a result of this reduced level of CD8. +. T-cells

Metal-on-metal (MOM) bearings for hip arthroplasty are increasing in popularity. Concern remains, however, regarding the potential toxicological effects of the metal ions which these bearings release. The serum levels of cobalt and chromium in 22 patients who had undergone MOM resurfacing arthroplasty were compared with a matched group of 22 patients who had undergone 28 mm MOM total hip arthroplasty (THA). At a median of 16 months (7 to 56) after resurfacing arthroplasty, we found the median serum levels of cobalt and chromium to be 38 nmol/l (14 to 44) and 53 nmol/l (23 to 165) respectively. These were significantly greater than the levels after 28 mm MOM THA which were 22 nmol/l (15 to 87, p = 0.021) and 19 nmol/l (2 to 58, p < 0.001) respectively. Since the upper limit for normal patients without implants is typically 5 nmol/l, both groups had significantly raised levels of metal ions. MOM bearings of large diameter, however, result in a greater systemic exposure of cobalt and chromium ions than bearings of small diameter. This may be of relevance for potential long-term side-effects. It is not known to what extent this difference is due to corrosion of the surfaces of the component or of the wear particles produced

Introduction. Metal ion and particle release, particularly cobalt, has become an important subject in total hip arthroplasty, as it has shown to induce metal hypersensitivity, adverse local tissue reactions and systemic ion related diseases. The purpose of the following study was compare the ion release barrier function of a zirconium nitride (ZrN) multilayer coated hip stem for cemented use, designed for patients with metal ion hypersensitivity, against its uncoated version in a test configuration simulating the worst case scenario of a severely debonded hip stem. The ZrN multilayer coating is applied on a CoCrMo hip stem and consists of a thin adhesive chromium layer, five alternating intermediate layers out of chromium nitride (CrN) and chromium carbonitride (CrCN) and a final zirconium nitride (ZrN) shielding layer [1]. Methods. Hip stems with a ZrN multilayer coating (CoreHip AS, Aesculap AG, Germany) were tested in comparison with a cobalt-chrome uncoated version (CoreHip, Aesculap AG, Germany). In order to create a worst case scenario, the smallest stem size with the biggest offset in combination with an XL ceramic head (offset +7 mm) was used. The stems were embedded according to the ISO 7206-6 test in a bone cement sheet. Once the bone cement was bonded, the stem was pulled out and a PMMA grain was placed inside the femoral cavity in order to uprise the hip stem above its embedding line and simulate a debonded cemented hip stem with a severe toggling condition. The dynamic test was performed under bovine serum environment with an axial force of 3.875 kN [2] at 11.6 Hz for 15 million cycles. The test was interrupted after 1, 3, 5, 10 and 15 million cycles and the surfaces of the stems were analyzed through scanning electron microscopy (SEM) with energy dispersive X-Ray (EDX). Moreover, the test medium was analyzed for metal ion concentration (cobalt, chromium and molybdenum) using ICP-MS. Results. The SEM/EDX analysis demonstrated that the ZrN multilayer coating kept its integrity, as no trace of the substrate material (CoCrMo) could be detected. Furthermore, the taper of the ZrN group showed less fretting and corrosion than the taper of the CoCrMo stem (Fig.1). Moreover, the ion concentration analysis showed a reduction of up to two orders of magnitude in the release of cobalt, chromium and molybdenum in the ZrN coated stems in comparison with the uncoated version. Discussion. The results showed that, even in a worst case scenario of high micro-motion due to a severe stem debonding within the cement mantle, the hip stems with a ZrN multilayer coating substantially reduce the release of ions from the substrate material. For any figures or tables, please contact the authors directly

Purpose: Metal-on-metal articulations are an increasingly popular choice as an alternate bearing surface in total hip arthroplasty (THA) and Resurfacing implants. One advantage of a metal-on-metal bearing is the use of larger diameter femoral heads with hip simulator data demonstrating reduced wear. We performed a prospective, multicentre, randomized, blinded clinical trial comparing 28mm to 36mm metal-on-metal bearings assessing multiple validated outcome measures and serum, erythrocyte and urine metal ions. Method: Ninety-one patients were randomized to receive a metal-on-polyethylene (34), a 28mm metal-on-metal (25) or a 36mm metal-on-metal (32) insert. All patients received the same acetabular and femoral component. Patients were evaluated pre-operatively, at 6, 12 months and annually thereafter, including an evaluation of serum, erythrocyte and urine cobalt, chromium, and titanium, outcome measures (WOMAC, SF-12, Harris Hip Score) and radiographs. Results: At a minimum two years follow-up there were no differences in WOMAC, SF-12, Harris Hip scores or radiographs. Patients receiving metal liners had significantly (p< 0.001) elevated metal ion measurements compared with the polyethylene control group, however there were no differences between the 28mm and 36mm metal-on-metal bearings (Median serum Co (mg/L): 0.14(poly), 0.77(28mm), 0.73(36mm). Median erythrocyte Co (mg/L): 0.11(poly), 0.42(28mm), 0.42(36mm). Median urine Co(mg/day): 0.44(poly), 4.55(28mm), 5.42(36mm)). (Median serum Cr(mg/L): 0.17(poly), 1.29(28mm), 0.91(36mm). Median erythrocyte Cr(mg/ L): 1.10(poly), 1.10(28mm), 1.20(36mm). Median urine Cr(mg/day): 0.27(poly), 1.92(28mm), 2.02(36mm)). Conclusion: Both cobalt and chromium ion measurements were significantly elevated in the blood and urine of the patients randomized to receive the metal-on-metal bearings at all time intervals. There were no differences seen between the 28mm and 36mm metal-on-metal bearings, keeping all other variables identical. The larger diameter bearing therefore provides the potential clinical advantages of improved range of motion and stability, while providing a similar metal ion profile. While reduced wear is seen with larger diameter metal-on-metal bearings in-vitro, we could not demonstrate a reduction in blood or urine metal ion levels in-vivo

Introduction: Metal-on-metal arthroplasties are being used for their increased durability and reduced requirement for revision. Previous data reports that metal-on-metal bearing surfaces release three times more cobolt and chromium ions than metal-on-polyethelene hip replacements. Data also suggests that these metal ions can cause DNA damage. Method: A prospective study of patients (aged 60–80), meeting exclusion criteria were selected and randomised to metal-on-metal or metal-on-polyethylene articulation. Patients were reviewed preoperatively (control model) and at 3 months, 6 months and one year postoperatively. On each occasion blood tests were taken to quantify metal ion levels (chromium, cobalt, nickel, vanadium and titanium) and chromosome aberrations in T lymphocytes using 24 colour fluorescent in situ hybridization (FISH). Results: The number of chromosome aberrations increased with time; in particular there was a statistically significant increase in aneuploidy after one year, there was also an increase in chromosome translocations. There was a similar increase in blood concentration of metal ions over this same time period which proved significant. Higher levels of metal ions were seen in the metal-on-metal group when compared with the metal-on-polyethylene. Conclusion: This study has highlighted the effects of metal ions on chromosome replication in particular causing aneuploidy aberrations. This provides evidence of the short-term effects of metal-on-metal arthroplasty but further research needs to be undertaken to assess long-term risk and also the risk associated to other cell lines

INTRODUCTION. Metallic ion release may be related to bearing surface wear and thus serve as an indicator of in-vivo performance of metal on metal (MOM) articulations. OBJECTIVES. Compare large head MOM hip components with modular MOM and metal on polyethylene (MOP) to determine their relative effects on serum metal ion levels. METHODS. A prospective controlled trial to compare clinical, radiographic, and serum metal ion concentration (Co and Cr) results between the Large Head ASR XL System (MOM-1), the Ultamet Advanced Modularity System (MOM-2), and the Pinnacle Acetabular Cup System with polyethylene liner (MOP). We enrolled 151 consecutive patients (MOM-1 = 97, MOM-2 = 22, MOP = 32). Radiographs, clinical scores (Harris Hip and WOMAC), and serum ion level assessments (in Parts Per Billion - PPB) were performed pre-operatively and post-operatively (6, 12, and 24 months for all patients and 60 months for MOM-1). At 60 months, we compared WOMAC, Harris Hip scores and serum ion levels (Co and Cr) from MOM-1 (revisions excluded) to 24 month scores from MOM-2 and MOP. After revision, serum ion levels were measured at 1, 3, 6, and 12 months. RESULTS. In MOM-1, 11 patients had significantly elevated ion levels at all postoperative periods (Co AVG 130.35 PPB and Cr AVG 61.46 PPB) after 2 years. Excluding outliers and revised patients, average serum ion levels in the 86 remaining MOP-1 patients at 24 and 60 months were statistically higher than MOP and MOM-2 patients. However, this difference was not clinically relevant (no symptoms, no revisions, Co and Cr AVG below 5 PPB). Table 1. Nine hips (9.3%) in 8 MOM-1 patients required revision and serum ion levels decreased rapidly post-up, but have still not returned to baseline after 1 year. Serum ion levels were not significantly different between MOM-2 and MOP groups at any time. Clinical scores improved after surgery in all groups and continued to improve in MOM-2 and MOP patients after 2 years, but decreased slightly in the MOM-1 patients at 2 and 5 years. Average cup inclination angle did not differ significantly between the groups: MOM-1 50.2, MOM-2 47.8, and MOP 51.7. CONCLUSIONS. We are presenting 5 years of prospectively collected data comparing ion levels among 2 MOM and 1 MOP group, as well as post revision ion levels at 1 year. Average serum ion levels were elevated at all post-operative periods in the MOM-1 group, but this was attributable to significantly elevated levels in a subset of outliers that ultimately required revision. Excluding these outliers, there is a statistically significant but clinically irrelevant difference in post-operative ion levels between MOM-1 vs. MOM-2 and MOP. There was no radiographic evidence of component malposition or aseptic loosening in any group. MOM-2 and MOP performed comparatively across all variables. We present an algorithm to diagnose and manage patients with MOM THA (Yable 2.) and offer evidence that metal ion levels do decrease after revision. Table 3

Introduction. Large diameter metal-on-metal hip arthroplasty (LDMMTHA) provides benefits of reduced dislocation rates and low wear. The use of modular systems allows better restoration of hip biomechanics. There have been reports of modular LDMMTHAs with tapered sleeves generating excessively high metal ions, due to possible mismatch between the titanium stem and the cobalt-chrome sleeve and the dual Morse tapers involved. We evaluated metal ion levels in LDMMTHA patients with and without a cobalt-chrome (CoCr) tapered sleeve. Methods. A cross-sectional series of 91 patients with proximal porous titanium alloy stem LDMMTHA with identical design CoCr bearings, attending a 1 to 2-year review were assessed with routine clinical and radiographic examinations, hip scores and metal ion analysis. Of these 65 had a single Morse taper between monoblock CoCr heads and the stems. Twentysix had a tapered cobalt-chrome sleeve in addition, with the resultant dual taper. Mean bearing diameter was 46 mm in both groups and mean age was 58 years in the monoblocks and 66 years in the tapered sleeve group. Results. Mean Oxford Hip score is worse in the tapered group (14.7) than in the monoblocks (12.6). All patients had well-functioning hips clinically and radiologically. Median blood cobalt and chromium are higher in the tapered sleeve (2.3μg/L and 1.8 μg/L) compared to the monoblocks (1.8 μg/L and 1.1 μg/L). Urine cobalt and chromium levels in the tapered sleeve (13.8 μg/24 hr and 5.3 μg/24 hr) also are higher than those in the monoblocks (12.2 μg/24 hr and 4.5 μg/24 hr respectively). Discussion and Conclusion. The limitation of this study is that it is a cross-sectional study. The results indicate that the use of a tapered sleeve in total hip arthroplasty does lead elevation of cobalt and chromium levels and the difference is statistically significant. However these levels are not as high as the levels reported with some other hip systems which have been withdrawn and the clinical significance of the elevated levels in the present study is unknown

Introduction:. The clinical significance of serum metal ion levels alone in patients with stemmed MoM hip arthroplasty remains uncertain. This study aims to measure the metal ion levels in patients with unilateral and bilateral hip arthroplasty to see whether or not the patients with bilateral hips have higher metal ions. Patients and Methods. All the patients with bilateral MoM hip arthroplasty were identified from the research database. These patients were then matched with those in a similar age group who had a unilateral hip arthroplasty, but same University of California Los Angeles (UCLA) activity score. The UCLA activity scores along with other hip scores have been previously gathered for all the patients. Both sets of patients then had measurement of serum cobalt and chromium levels. The results were analyzed and compared. Results:. There were a total of 53 patients with bilateral hips and 53 matched patients with unilateral hips. The average serum Cobalt and Chromium levels were 34 nmol/L (range <10–76) and 23 nmol/L (range <10–104) respectively in the bilateral group; and 14 nmol/L (range <10–45) and 21 nmol/L (range <10–57) in the unilateral group. Given that the MHRA (UK) threshold levels deemed clinically significant are 120 nmol/L and 135 nmol/L for Cobalt and Chromium respectively; the results obtained here are not clinically significant. Conclusions:. One would normally expect, with mathematical reasoning, a patient with bilateral hip arthroplasty to have higher serum metal ion levels than a patient with unilateral arthroplasty. However, this study goes to show that it is not the case

Metal-on-metal (MOM) bearings after total hip arthroplasty are known to elevate the serum concentrations of metal ions, raising concerns about the long-term effects. One potential modifier of ion release is the bearing diameter used. Resurfacing MOM bearings have a large surface area available for corrosion compared to the typical bearing size of 28 mm in total hip replacement (THR) but may benefit from improved lubrication and reduced production of corrodible wear debris. The net effect of these two variables on metal ion release is unknown. In this study, we compared the level of ion release in patients after large bearing MOM hip resurfacing arthroplasty with patient after small bearing MOM THR. We measured the serum cobalt and chromium levels from 22 patients with large bearing diameter MOM hip resurfacing arthroplasty (Cormet 2000 and Birmingham Hip Resurfacing) and compared them to the serum cobalt and chromium levels of 22 patients with small bearing diameter (28 mm) MOM THR (Ultima). Patients were prospectively matched for activity level, body mass and date after surgery at blood sampling. All were at least 6 months after surgery. We found the median cobalt and chromium levels after hip resurfacing arthroplasty to be 7.6 times normal (median 38 nmol/L, range 14 to 144 nmol/L) and 10.5 times normal (median 53 nmol/L, range 25 to 165 nmol/ L) respectively. This is compared to 4.4 times normal (median 22 nmol/L, range 15 to 87 nmol/L) for cobalt and 3.8 times normal (median 19 nmol/L, range 2 to 58 nmol/L) for chromium after 28 mm MOM THR (p=0.0021 and p< 0.0001). Conclusion: Large diameter MOM bearings result in greater release of cobalt and chromium ions than do small diameter MOM bearings. This may be of relevance when the potential effects of long-term exposure to elevated these metal ions is considered

Background. Modularity in total hip replacement(THR) enables precise recreation of native hip biomechanics. However, there have been concerns about raised metal ion levels with increased number of interfaces. We present the 3 year results of ML taper with Kinectiv technology(MLKT), a modular neck uncemented stem. This system has modular neck options, but has only one [0] head in various diameters. Methods. 97 hips in 97 patients with a MLKT stem and Continuum socket were included in this prospective study. Harris hip score, Oxford hip scores (HHS and OHS) and yearly blood Cobalt(Co), Chromium(Cr) and Titanium(Ti) were recorded. The primary end point was revision for any reason. Paired t- test was used to assess improvement in functional scores. Results. The mean age was 62.1±8.7 years. The mean follow-up was 3.75±0.67years. The mean HHS improved from 45.8±5.1 to 92.6±3.1(p<0.001) and the mean OHS improved form 17.59±4.71 to 43.1±2.2(p<0.001). One hip was revised for deep infection at 2.6 years. The mean Co, Cr and Ti levels at 3 years were 18.45,19.62 and 36.47 nmol/l respectively. The survivorship of the cohort at a minimum follow-up of 3 years was 98.7%. Conclusion. Our study suggests that despite the presence of an additional interface between the neck and the stem, the MLKT stem does not result in increased metal ion levels or higher failure rate. This is a prospective and consecutive series of patients with complete radiological and functional follow-up. The MLKT stem has good functional results with no concerns about raised metal ion levels in the short term

Background: Blood metal ion levels have been shown to correlate with wear of retrieved components. Increased articular wear is associated with early failure. It is not clear what the management of patients with raised metal ions who remain asymptomatic should be. Methods: A prospective study of the DePuy ASR resurfacing device was commenced in 2004 at our independent centre. Blood and serum metal ion analysis is carried out routinely. We assessed the clinical outcome of all patients with cobalt (Co) concentrations > 5μg/L (n=25). We consider this value to be a clear indicator of a poorly performing bearing surface. Patients who remained asymptomatic were brought back for repeat ions testing and clinical assessment. A parallel study was carried out to examine the relationship between the wear depth of retrieved explants (assessed using a coordinate measuring) and blood ion levels. Results: Increases in chromium(Cr) and Co levels from the second blood sample correlated with the first sample (p< 0.05). The four patients with the highest Cr Co levels went on to suffer spontaneous femoral neck fractures between 3 and 4 years post op (pseudotumours in two of these cases). Of the remaining 25, 5 were revised for worsening pain (large effusions and areas of tissue necrosis were seen at revision) and 10 were under investigation for new onset of pain. Wear depths correlated well with blood ion concentrations (p< 0.05) substantiating the results of another centre. Conclusion: 60% of patients with raised metal ion levels went on to develop complications within two years of the blood test. This suggests patients may only have temporary tolerances to excessive concentrations of metal wear debris. One novel association appears to be spontaneous delayed femoral fracture. Results suggest increased ion concentrations associated with small joint size/sub optimal cup orientation will continue to rise and these patients should be followed up closely

Introduction: Spinal arthrodesis with stainless steel implants is a common procedure to correct scoliosis however, the long-term consequences of retained implants is unclear. Raised serum metal ion levels have been widely published in arthroplasty literature with concern over possible toxic adverse effects associated with chronic exposure. We investigated serum metal ion levels in patients who had undergone instrumented spinal arthrodesis for scoliosis correction. Methods: The study included patients who underwent posterior spinal arthrodesis using ISOLA instrumentation for scoliosis between 1998 and 2002. The minimal period of follow up was 3 years. Clinical information was available from a comprehensive Scoliosis Database, Department of Orthopaedic Surgery, Women’s and Children’ Hospital, Adelaide (WCH). Patients having post-operative complications, spinal instrumentation removed, revision surgery or additional in situ metal implants were excluded. Participants completed a questionnaire to evaluate exogenous chromium exposure. Blood samples were collected and processed by the WCH Core Laboratory. Serum levels of chromium, molybdenum, iron and ferritin were measured by Sydney South West Pathology Service. Participants with serum chromium levels outside the normal reference range underwent further analysis to evaluate chromium levels in erythrocyte haemolysate preparations (to assess the valency of abnormal chromium levels detected). Comparisons were made with two control groups; the first being individuals with scoliosis who had not undergone operative intervention and the other, “normal” unaffected volunteers. All control group participants underwent serum and erythrocyte analysis (as above). Ethics approval was obtained from the WCH Research Ethics Committee. Results: Thirty patients (26 females and 4 males) who underwent instrumented scoliosis surgery, 10 non instrumented scoliosis patients and 10 unaffected volunteers were included in the study. Mean age of the operative group at surgery was 13.8 years (11.1–16.9) with a mean length of time from surgery of 5.8 years (3.5–8.2). In the study group, raised serum chromium levels were demonstrated in 11/30 (36.6%) of patients. Five of the 11 patients with raised chromium levels also had low levels of serum iron and/or ferritin. Erythrocyte levels of chromium were undetectable in all of the 11 (100%) patients. There did not appear to be an exogenous source of chromium exposure in any of these patients. In the non-operative control group with scoliosis, none had elevated serum chromium, iron or ferritin levels. 2/10 (20%) had high molybdenum levels. In the unaffected control group, 1/10 (10%) had raised serum chromium and molybdenum levels. Three control patients had low levels of serum iron and/or ferritin. All control participants, but one, had undetectable erythrocyte chromium levels. There was a significant difference in serum chromium levels between the study and control groups (p=0.01) with the group of patients who underwent instrumented scoliosis surgery having a greater proportion with high chromium and lower proportion with normal chromium. Discussion: Raised serum chromium levels were detected in patients after instrumented spinal arthrodesis for scoliosis correction. This new finding in young patients has relatively unknown health implications but potential genotoxic and carcinogenic sequelae; this is especially concerning with most scoliosis patients being female and with their reproductive years ahead. These findings should prompt further research in this area, particularly to similarly investigate other spinal implant systems and assess the long term implications of raised chromium levels

We investigated the role of ion release in the assessment of fixation of the implant after total knee replacement and hypothesised that ion monitoring could be a useful parameter in the diagnosis of prosthetic loosening. We enrolled 59 patients with unilateral procedures and measured their serum aluminium, titanium, chromium and cobalt ion levels, blinded to the clinical and radiological outcome which was considered to be the reference standard. The cut-off levels for detection of the ions were obtained by measuring the levels in 41 healthy blood donors who had no implants. Based on the clinical and radiological evaluation the patients were divided into two groups with either stable (n = 24) or loosened (n = 35) implants. A significant increase in the mean level of Cr ions was seen in the group with failed implants (p = 0.001). The diagnostic accuracy was 71% providing strong evidence of failure when the level of Cr ions exceeded the cut-off value. The possibility of distinguishing loosening from other causes of failure was demonstrated by the higher diagnostic accuracy of 83%, when considering only patients with failure attributable to loosening. Measurement of the serum level of Cr ions may be of value for detecting failure due to loosening when the diagnosis is in doubt. The other metal ions studies did not have any diagnostic value

Instrumented spinal arthrodesis is a common procedure to correct scoliosis. The long-term consequences of these retained implants is unclear. Concern of possible toxic effects of raised metal ion levels have been reported in arthroplasty literature. We investigated serum metal ion levels in patients having instrumented spinal arthrodesis for scoliosis correction. The study included patients who underwent posterior spinal arthrodesis using Isola stainless steel instrumentation for scoliosis between 1998 and 2002. Patients having post-operative complications, instrumentation removed, revision surgery or additional in situ metal implants were excluded. Participants completed a questionnaire to evaluate exogenous chromium exposure. Serum levels of chromium, molybdenum, iron and ferritin were measured in venous blood samples. Participants with elevated serum chromium levels underwent further erythrocyte chromium analysis. Comparisons were made with two control groups;. “non-instrumented” individuals with scoliosis and. “normal” unaffected volunteers. All control group participants underwent serum and erythrocyte analysis (as above). Thirty “instrumented” patients (Group 1, 26 females and 4 males), 10 “non instrumented” patients with scoliosis (Group 2) and 10 unaffected volunteers (Group 3) were included in the study. Mean age at surgery was 13.8 years (range 6.6 to 13.2), mean time from surgery 5.7 years (range 3.4 to 8.1). Elevated serum chromium levels were demonstrated in 11/30 (37%) Group 1 participants. In the control groups, elevated serum chromium levels were demonstrated in 0/10 (0%) in Group 2 and 2/10 (20 %) in Group 3. There was a statistically significant (p=0.001) elevation in serum chromium levels between scoliosis participants with retained spinal implants, and those without. There was no significant correlation found between Groups 1, 2 and 3 for serum molybdenum, iron and ferritin levels. Erythrocyte chromium measurements from all participants (n=31, 100%) were considered within the normal range. At a multivariant level, the results of a stepwise censored regression (n=50) indicated the significant predictors of serum chromium to be spinal implants (p=0.001), gender (male versus female, p=0.04) and iron grading (low, normal or high, p=0.05). Time since surgery was found not to have a significant correlation with chromium levels (p=0.147). Raised serum chromium levels were detected in 37% of patients after instrumented spinal arthrodesis for scoliosis correction. This new finding has relatively unknown health implications but potential genotoxic, dysmorphic and carcinogenic sequelae; this is especially concerning with most scoliosis patients being adolescent females with their reproductive years ahead

Introduction: Systemic metal ion elevation continues to cause concern with metal-on-metal (MM) bearings, particularly in young people, in view of their expected long life-time usage. Reducing bearing clearance is claimed to be a means of reducing metal ion release. Methods: 26 consecutive male patients (mean age 55 years, mean BMI 26) who fulfilled the inclusion criteria and received a 50mm bearing (diametral clearance 100 μm) were included. Clinico-radiographic review and urine and blood specimens were obtained before and periodically after the procedure. Two hips were excluded during follow-up, (one revision and another contralateral hip arthroplasty). Results were compared with a similar design bearing, 50 or 54 mm diameter and conventional clearance. Results: At the four-year stage all patients had excellent hip function. However three patients had progressive acetabular radiolucent lines. Cobalt and chromium in both cohorts at all follow-up levels were significantly higher than the preoperative levels. Compared to the conventional clearance (CC) group, the pre-operative urine chromium and 6M to 48M urine cobalt and chromium were significantly lower in the LC group (p < 0.005). Blood metal levels were lower in the LC group at 1-year follow-up but showed a converging trend thereafter. At 4-year follow-up, the differences are considerably less, with no significant difference in blood cobalt (figure). Discussion: Under ideal conditions, closely matched components (lower clearance) would lead to a thicker fluid film and less wear. However a larger clearance than ideal is needed to allow for asphericities, surface roughness, deformation and the evolution of in vivo lubricant. Peri-acetabular radiolucent lines cause concern. Attempts to reduce systemic metal exposure should not adversely affect other bearing characteristics such as friction. The search for a bearing which would generate low wear without producing a detrimental effect on other bearing attributes, such as friction, should continue

We performed a prospective, randomised, blinded clinical trial comparing metal versus polyethylene bearing surfaces in patients receiving a THA. Forty-one patients were randomised to receive a metal (twenty-three) or a polyethylene (eighteen) insert with identical femoral and acetabular components. The metal bearing was a 28mm low carbon on high carbon couple. Patients were evaluated pre-operatively, at three, six, twelve months and annually thereafter, including an evaluation of erythrocyte and urine cobalt, chromium, and titanium, outcome measures (WOMAC, SF-12, Harris Hip Score) and radiographs. No patients were lost to follow-up. At an average 7.2 (range 6.1 – 7.8) years follow-up there were no differences in any outcome measures or radiographic findings. Patients receiving metal liners had significantly elevated metal ion measurements. At most recent follow-up, compared to the polyethylene control group, patients receiving a metal on metal bearing had erythrocyte cobalt levels were eleven times elevated (median 1.4 μg/L (metal) vs 0.12 μg/L (poly), p< .001). Urine cobalt levels were thirty-nine times elevated (median 11.4 μg/L/day (metal) vs 0.29 μg/day (poly), p< .001) and urine chromium levels were twenty-eight times elevated (median 4.75 μg/day (metal) vs 0.17 μg/day (poly), p< .001). Additionally the metal ion levels reached an early steady state level and did not decrease over time. (Erythrocyte Co (μg/L): 1.29 (6 mos), 1.20 (1 yr), 1.0 (2 yr), 1.10 (3 yr), 1.35 (4 yr), 1.40 (5 yr)). Both cobalt and chromium ion measurements were significantly elevated in the blood and urine of the patients randomised to receive the metal on metal THA at all time intervals. Contrary to previous reports, in 34% of patients with a metal liner, metal ion (erythrocyte cobalt) elevation was still increasing at latest follow-up, and in the overall metal on metal patient cohort, metal ion median levels were not decreasing over time. As in polyethylene wear data, metal ion results are not necessarily generalizable, but are bearing design specific

Despite a large body of literature the optimal choice of bearing surface for total hip arthoplasty (THA) remains controversial. To avoid the brittleness and squeaking noted with ceramic-on-ceramic and the metal ion release associated with metal-on-metal (MOM) articulations, a novel hybrid coupling of ceramic-on-metal (COM) has been introduced. The purpose of this study was to compare changes in serum metal ion levels and the functional performance of COM and MOM bearing combinations. Eighty-six patients (86 hips) undergoing THA between April 2009 and October 2010 were randomized to COM or MOM bearing couplings. All received identical uncemented acetabular shells and femoral components from two experienced surgeons using the same operative technique. Demographic and peri-operative data were recorded. Serum cobalt and chromium levels, renal function and disease specific outcome scores (Oxford Hip, Harris Hip, UCLA activity) were assessed at baseline, 6 and 12 months post-operatively. Patients and outcome assessors remained blinded. Mean age of the total cohort was 62.5 years. Randomization successfully matched groups for age, Body Mass Index, baseline serum Cobalt and Chromium levels, and pre-operative functional performance scores. One-year data is currently available for 25 of 44 COM and 26 of 42 MOM patients. No significant difference in serum cobalt (P value = 0.81) and chromium (P value = 0.66) levels between groups was noted. Improvements in outcome scores (Oxford Hip, Harris Hip, UCLA activity) were equivalent (P values 0.16 – 0.46). At 1-year, COM and MOM hip arthroplasty articulations appear equivalent in terms of function and serum metal ion levels. Data collection out to 5-years post-surgery continues

Purpose: A ceramic head coupled to a metal liner is a proposed new alternate bearing in THA. The authors participated in an FDA approved multicentre prospective, randomized, blinded clinical trial comparing ceramic-on-metal (CoM) to metal-on-metal (MoM) in patients receiving a THA. Method: 390 patients received the same acetabular component and metal insert. 194 patients received a delta ceramic head (CoM) and 196 received a metal head (MoM). Metal ions were evaluated in 72 patients (36-CoM, 36-MoM). Harris Hip scores, radiographs, and metal ion levels (cobalt, chromium and titanium in serum, erythrocytes and urine) were evaluated pre-operatively and at three, 12 and 24 months. Results: No patients were lost to follow-up. There were no differences between groups’ baseline demographics and clinical scores. At two years there were no differences in Harris Hip scores, radiographs, adverse events or postoperative complications. Both groups had overall very low median metal ion profiles with no statistically significant differences. 24 month MoM vs CoM; Serum cobalt ( g/L), mean: 1.2(+/−0.5) vs 1.1(+/−0.3), median: 0.66(range: 0.2–5.6) vs 1.0 (range: 0.3–2.7); Serum chromium ( g/L), mean: 1.1(+/−0.5) vs 1.4(+/−0.4), median: 0.86(range: 0.3–6.9) vs 1.2(range: 0.3–4.9). Urine cobalt and urine chromium ( g/day) demonstrated similar trends to serum ion levels. Conclusion: While CoM is a new bearing surface in North America and not currently FDA or HPB approved, it has been in clinical use globally since 2006. Results of this non-inferiority RCT demonstrated no clinical outcome, metal ion, radiographic or adverse event differences between CoM and MoM cohorts

As a result of the increased popularity of metal-on-metal bearings for total hip arthroplasty, concerns have been expressed about patient exposure to increased serum metal ion levels. We therefore performed a retrospective review of patients with metal-on-metal, uncemented Ring total hip replacements with a minimum follow up of thirty years. After allowing for prosthesis revision and patient mortality, 6 hips in 5 patients were reviewed and serum ion levels measured. Similar cohorts of patients with other combinations of bearings were compared with an age-matched osteoarthritic control group. Serum cobalt and chromium levels in the metal-on-metal hip arthroplasty group were significantly higher than in all other groups and approximately five and three times greater respectively than in the group with no implants. Unlike the stainless steel-on-plastic group, the cobalt/chrome-on-plastic group showed significantly raised serum cobalt levels compared with the control group. It is of interest that patients who have had their metal-on-metal hip replacements revised to metal-on-plastic, have metal ion levels that are not statistically different to those of the osteoarthritic control group. Though we acknowledge the small numbers of patients studied, no identifiable harmful effects were found. We conclude that serum metal ions remain elevated throughout the life of the metal-on-metal articulation. Metal bearing hip arthroplasty is being used in ever younger patients and together with increased life expectancy we are exposing our patients to potentially harmful levels of metal ions throughout the life of the implant

Serum and blood cobalt (Co) and chromium (Cr) ion levels are used to monitor patients at risk for adverse reaction to metal debris (ARMD) following metal-on-metal (MoM) total hip arthroplasty (THA). However, these levels often do not correlate with the degree of local soft-tissue reaction and damage observed at the time of revision. The purpose of this study was to analyze synovial fluid metal ion concentrations in patients with a failed THA in the setting of an ARMD and determine if these levels can be more predictive of soft-tissue destruction than serum or whole blood levels. Synovial, blood and serum samples were prospectively collected from patients undergoing revision THA with ARMD (n=29) and those undergoing aseptic revision without ARMD (n=29). There was no difference in mean age (P=0.50), BMI (P=0.18), sex distribution (P=0.18), serum creatinine (P=0.74), or time to revision THA (P=0.13) between the cohorts. In the AMRD cohort, the components included MoM THA (n=18), hip resurfacing (n=5), dual-modular taper THA (n=4) and MoM and dual-modular taper THA (n=2). At the time of revision THA, 26 (90%) patients in the metal reaction cohort had gross evidence of metallosis in the soft-tissues, the remaining 3 (10%) had evidence of corrosion of the dual taper neck or MoM bearing. In the non ARMD cohort the bearing surfaces included metal-on-polyethylene (n=19) and ceramic-on-polyethylene (n=10). The indications for revision included isolated acetabular loosening (n=11), isolated femoral component loosening (n=11), polyethylene wear (n=5), recurrent dislocation (n=1) and combined femoral and acetabular component loosening (n=1). None had a clinical diagnosis or gross evidence of taper corrosion. Pre-revision, 21 (72%) patients in the metal reaction group had periarticular fluid collections or a mass on MRI. Mean cyst size was 202.9±71.6 cm3 and masses were grouped into Type I (cyst wall <3 mm, n=10), Type II (cyst wall ≥3 mm, n=8) and Type III (mainly solid, n=3). At the time of revision THA, the mean Co levels were elevated in patients with ARMD compared to those without in synovial fluid (1,833 ppb vs. 12.3 ppb, P=0.008), whole blood (22.6 ppb vs 0.5 ppb, P=0.005)) and serum (19.6 vs. 0.6, P=0.001). Likewise, mean Cr levels were significantly elevated in patients with an ARMD compared to those undergoing revision without in synovial fluid (3,128 ppb vs. 10.3 ppb, P=0.01), whole blood (8.9 ppb vs. 0.5 ppb, P=0.009) and serum (14.1 ppb vs. 0.5 ppb, P=0.005). The synovial fluid Co levels were the most accurate test for detecting pseudotumor (AUC 0.951) and adverse local tissue reaction (AUC 0.826). At a synovial fluid Cr level of 110 ppb, the synovial fluid metal ion analysis was 94% sensitive and 86% specific for pseudotumor formation. In this prospective study, synovial fluid analysis of metal ion levels was more accurate in predicting the presence and extent of pseudo-tumor or ALTR compared to blood or serum analysis. The addition of synovial aspiration with metal ion analysis may provide another helpful data point when risk stratifying these patients for need for revision THA

Introduction. Wear and corrosion of metal-on-metal (MM) bearings releases (a) soluble metal ions which collect locally and pass into the systemic circulation and (b) insoluble particles which undergo local deposition and lymphoreticular dissemination. Debris-related failures from osteolysis, metallosis and pseudotumours warrants revision of these MM bearing devices to non-MM bearing arthroplasties with the expectation that both the systemic and local effects will be reversed with time since the source of metal ion release is removed. The purpose of the present study is to determine (a) whether metal ion levels in blood and urine decrease after revision of a MM bearing arthroplasty to a non-MM bearing device and (b) the rate at which this decrease is effected. Methods. Blood and urine levels of cobalt and chromium ions are studied prospectively over two years in 15 patients whose MM resurfacings were revised to cross-linked polyethylene containing total hip replacements (THRs). Specimen collection was started before and periodically after the revision at 2, 4 and 6 days and 2 months, 6, 12 and 24 months after operation. None of the patients had other MM devices or compromised renal function. Results. Pre-revision mean urine-cobalt was 676 nmol/day (range 84 to 1691 nmol/day) and urine-chromium 348 nmol/day (range 68 to 804 nmol/day). As anticipated these are higher than the expected levels in patients with well-functioning metal-on-metal bearings. Post-revision metal levels decrease in a biphasic manner. Over the first week there is a rapid decline to 235 nmol/day cobalt and 217 nmol/day chromium followed by a period of slow decrease over the next 24 months to 10 nmol/day cobalt and 44 nmol/day chromium. Blood cobalt also shows a similar biphasic decrease from a preoperative level of 151 nmol/L to 79 nmol/L during the first week and further reduction to 13 nmol/L over the following 2 years and with blood chromium the reduction is from 103 nmol/L preoperative to 64 in the first week and on to 14 nmol/L at 2 years. Discussion and Conclusion. A limitation of the study is the small cohort of 15 patients with a wide range of pre-revision blood and urine levels. However the same biphasic trend as seen in the group is evidenced in each individual patient which gives us confidence that the trend will not be different in much larger groups of patients. The early steep reduction following revision supports the reported short half-life of cobalt. The later protracted trend is explainable through progressive corrosion from deposited particles. This trend is also not sustained indefinitely and tends to approach control levels at 2 years

Purpose of the study: Tribology studies of total hip arthroplasty (THA) have demonstrated that large diameter head in metal-on-metal bearings produce fewer wear particles than small diameter heads. The other advantages of this option are better stability, less dislocation, and optimal joint range of motion. The purpose of this work was to compare blood levels of chromium, cobalt and titanium six months and one year after implantation of different models of large diameter metal-on-metal THA. Material and methods: We conducted a retrospective comparative and randomised study including 110 patients who had been implanted with a larger diameter head THA/Zimmer? Smith and Nephez, Biomet or Depuy. The metal ion concentrations (Cr, Co, Ti) were measured in whole blood by an independent laboratory using high-resolution mass spectrometry (HR-ICP-MS). Blood samples were drawn preoperatively and postoperatively at six months and one year. Results: At six months, the concentrations of metal ions in whole blood expressed as mean (range) for Cr (μg/L) Co (μg/L) and Ti (μg/L) were, respectively: Zimmer 1.3 (0.4/2.8) 1.7 (0.9/6.8) 2.5 (0.6/6.7); Smith and Nephew 2.0 (0.7/4.2) 2.1 (0.5/6.6) 1.1 (0.5/4.1); Biomet 1.2 (0.4/2.2) 0.9 (0.3/3.4) 1.4 (0.8/2.4); Depuy 1.7 (0.5/3.2) 1.9 (0.3/4.2) 1.3 (0.5/3.9). There was a significant difference between groups for Cr (p=0.006), Co (p=0.047) and Ti (p< 0.001). The Biomet implants presented the lowest concentrations for Cr and Co; the Zimmer implants gave the highest levels of Ti. Discussion and Conclusion: Several implant-related factors affect blood concentrations of metal ions: contact surfaces leading to “active” abrasion but also wear in other parts of the implant giving rise to “passive” corrosion. Bearing wear is related to the diameter of the head, its roughness, its spherical shape, joint clearance, the manufacturing technique (forging, casting) and its carbon content. The Biomet head corresponds to a better compromise for these different factors. Passive corrosion can result from an exposed metal surface or from metal to metal contact. This explains the high level of Ti ions found for all implants tested since titanium is not present in the bearings

This is a longitudinal study of the daily urinary output and the concentrations in whole blood of cobalt and chromium in patients with metal-on-metal resurfacings over a period of four years. Twelve-hour urine collections and whole blood specimens were collected before and periodically after a Birmingham hip resurfacing in 26 patients. All ion analyses were carried out using a high-resolution inductively-coupled plasma mass spectrometer. Clinical and radiological assessment, hip function scoring and activity level assessment revealed excellent hip function. There was a significant early increase in urinary metal output, reaching a peak at six months for cobalt and one year for chromium post-operatively. There was thereafter a steady decrease in the median urinary output of cobalt over the following three years, although the differences are not statistically significant. The mean whole blood levels of cobalt and chromium also showed a significant increase between the pre-operative and one-year post-operative periods. The blood levels then decreased to a lower level at four years, compared with the one-year levels. This late reduction was statistically significant for chromium but not for cobalt. The effects of systemic metal ion exposure in patients with metal-on-metal resurfacing arthroplasties continue to be a matter of concern. The levels in this study provide a baseline against which the in vivo wear performance of newer bearings can be compared

Summary. Five year migration results of 49 large-head metal-metal (MoM) total hip arthroplasties show good implant stability and no association between implant migration and metal-ions levels, stem and cup position, or femoral bone mineral density. Introduction. The failure mechanism of metal-metal (MoM) total hip arthroplasty has been related to metal wear-debris and pseudotumor, but it is unknown whether implant fixation is affected by metal wear-debris. Patients and Methods. In July-August 2012 41 patients (10 women) at a mean age of 47 (23–63) years with a total of 49 MoM hip arthroplasties (ReCap Shell/M2a-Magnum head/Bi-Metric stem; Biomet Inc.) participated in a 5–7 year follow-up with blood tests (chrome and cobalt serum ions), questionnaires (Oxford Hip Score (OHS) and Harris Hip Score (HHS), measurement of cup and stem position and periprosthetic BMD. Further the patients had been followed with stereo-radiographs post-operative and at 1, 2 and 5 years for analysis of implant migration (Model-Based RSA 3.32). Results. 4 patients (6 hips) had elevated metal-ion levels (>7ug/l). The mean cup inclination was 45°(sd 6), the mean cup anteversion was 17°(sd7), and the mean stem anteversion was 19°(sd7). The difference between genders was statistically insignificant (p>0.09). At 5 years follow-up total translation (TT) for the stems (n=39 hips) was a mean 0.79mm (sd 0.53) and total rotation (TR) was a mean 1.99° (sd 1.53). Between 1–2 years there was no significant difference in mean TT (p=0.49)for the stems and between 2–5 years TT was mean 0.13 mm (sd 0.35) which was significant (p=0.03) but clinically very small and within the precision limits of the method. We found no significant migration along the 3 separate axes. There was no significant association between stem migration and metal ion levels >7ug/l (p=0.55), female gender (p=0.86), stem anteversion > 25° (p=0.29), T-scores < −1 (p=0.23), total OHS < 40 (p=0.19) or total HHS < 90 (p=0.68). Between 1–5 years there was no significant change in neither subsidence (p=0.14) nor in version (p=0.91) of the stems. At 5 years TT for the cups (n=36) was mean 1.21 mm (sd 0.74) and TR was mean 2.63° (sd 1.71). Between 1–2 years cup migration along the z-axis was mean 0.29 (sd 0.73) (p=0.03), which was also within precision limits of the method. There was a positive association between total OHS below 40 (n=4) and cup migration (p=0.04), but no association between cup migration and metal ion levels >7ug/l (p=0.80), female gender (p=0.74), cup inclination > 50° (p=0.93), cup anteversion > 25° (p=0.88) or HHS < 90 (p=0.93). Proximal cup migration at 5 years was mean 0.46 mm (sd 0.47), which was similar to the cup migration at 1 year (p=0.91) and 2 years (p=0.80) follow-up. No patients were revised before the final 5–7 year follow-up. Patient satisfaction was high (94%). Conclusion. All cups and stems were well-fixed between 1–5 years. We found no statistical significant correlation between implant migration and other factors that have been associated with failure of MoM hip arthroplasty such as elevated metal ion levels, component position, and female gender. Cup migration was higher in patients with a total OHS below 40. In conclusion, metal wear-debris does not seem to influence fixation of hip components in large-head MoM articulations at mid-term follow-up

Summary. Management of metal on metal hip replacements can be accomplished with a simple algorithm including easily available metal ion levels and hip MRI with metal artifact reducing software. After revision serum metal ion levels can be expected to fall rapidly. Introduction. Metallic ion release may be related to bearing surface wear and thus serves as an indicator of the in-vivo performance of metal on metal articulations. The purpose of this prospective, controlled study was to compare new large head metal on metal hip components with established modular metal on metal and metal on polyethylene and to determine their effects on serum metal levels before and after revision. Patients & Methods. We performed a multi-surgeon, prospective, controlled trial to compare clinical, radiographic, and metal ion concentration in serum (cobalt and chrome) results across multiple devices including the Large Head ASR XL System (MoM-1), the Ultamet Advanced Modularity System (MoM-2), and as the control the Pinacle Acetabular Cup System with polyethylene liner (MoP). One hundred and fifty-one consecutive patients undergoing THA were enrolled in the study: MoM-1 n=97; MoM-2 n=22; MoP n=32. Clinical, radiographic, and venous blood assessments were performed pre-operatively, and post-operatively at 6 months, 1 year and 2 years, and after revision (1,3,6,12 months). All serum ion concentrations are reported in nmol/L. We are following metal ion levels after revision and have developed an algorithm to diagnose and manage patients with MoM THA. Results. MoM-1 patients had significantly increased average cobalt and chromium levels. Clinical scores improved after surgery in all groups and continued to improve in MoM-2 and MoP patients after 2 years but decreased slightly in the MoM-1 patients at 2 years. Average cup inclination angle did not differ significantly between the groups: MoM-1 50.2, MoM-2 47.8, and MoP 51.7. In the MoM-1 group 11 patients (11%) had significantly elevated ion levels (MoM-1 Outliers). Nine hips (9.3%) in 8 MoM-1 outlier patients required revision. Metal ion levels were not significantly different between MoM-2 and MoP groups. Metal ion levels after revision in the MoM-1 group decreased rapidly but at one year post-operatively have still not returned to an equivalent baseline comparable to the MoM-2 and MoP groups. All revisions were in the MoM-1 group. Chromium levels decreased more slowly than Cobalt levels. Discussion. To our knowledge this is the only data in the literature prospectively comparing ion levels among groups and reporting post revision ion levels. Average serum ion levels were elevated at all post-operative samples in the MoM-1 group but this was due to significantly elevated levels in a subset of outliers who required revision. Excluding the outliers there is not a significant difference in post-operative ion levels between the groups. There was no radiographic evidence of component malposition or aseptic loosening in any of the groups. Control groups (MoM-2, MoP) performed comparatively across all variables. We present an algorithm to diagnose and manage patients with metal on metal THA and offer evidence that metal ion levels do decrease after revision but still remain abnormally elevated at one-year post revision compared to the control group. A significant portion of MoM-1 performs comparatively to the controls in terms of ions

The aim of this study is to investigate whether Metal-on-Metal (MoM) implants result in more chromosome aberrations and increased blood metal ions post-operatively when compared to Metal-on-Polyethylene (MoP) implants. Metal-on-metal arthroplasties are being inserted in increasing numbers of younger patients due to the increased durability and reduced requirement for revision in these implants. Recent studies have raised many concerns over possible genotoxicity of MoM implants. This is a prospective study of patients who have undergone elective total hip replacement, they were selected and then randomised into two groups. Group A received a MoP implant and group B received a MoM implant. Patients are reviewed pre-operatively (control group), at 3 months, 6 months, 1 year and 2 years post-operatively. On each occasion blood tests are taken to quantify metal ion levels (chromium, cobalt, titanium, nickel and vanadium) using HR-ICPMS method and chromosome aberrations in T lymphocytes using 24 colour fluorescent in situ hybridisation (FISH). 53 patients have been recruited to date. 24 of whom had MoP prosthesis and 29 a MoM. 37 of these have had their one year follow-up with blood analysis and 14 have had 2 year follow up. Cobalt and chromium concentration increased during the first 6 months in both MoM and MoP groups, in the MoM group the chromium levels were twice that of MoP group and 12x that of the preoperative samples. Chromosome aberrations occurred in both groups. At 6 months both the MoM and MoP groups showed increase frequency of aneuploidy aberrations with further increases after one year. Structural damage in the form of translocations occurred in the MoM group after one year, but not in the MoP group, by two years there was a profound increase in translocations Preliminary results of this study show that the levels of chromium and cobalt are significantly higher in the MoM group compared to the MoP group. This corresponds to increases in chromosome aberrations in the groups with increases in structural chromosome damage after two years

Bearing diameter and acetabular component orientation have been shown to be important variables effecting blood metal ion levels following hip resurfacing arthroplasty. So far no studies on bilateral hip resurfacings have taken into account these variables. We examined the serum ion results of patients under the care of two experienced hip resurfacing surgeons who carry out ion analysis as part of routine post operative care. Surgeon 1: Patients were implanted exclusively with a “third generation” resurfacing device. Surgeon 2: Patients were implanted with the same “third generation” device and also a low clearance “fourth generation” resurfacing device. Only ion results from patients who were 12 months post surgery were included. Bilateral patients were matched to unilateral patients according to the surgeon performing the operation; the resurfacing system implanted and cup inclination and anteversion angles. The ion data from each bilateral group was tested against the corresponding unilateral groups using the Mann Whitney U test for non parametric data. Significance was drawn at p<0.05. Surgeon 1: There were 310 patients with unilateral joints and 50 with bilateral joints. There were no significant differences with regard to time to follow up, activity levels, joint sizes or cup orientations. Serum chromium (Cr) and cobalt (Co) concentrations were significantly greater in the bilateral group (p<0.001). Median ion levels were greater in the bilateral group by a factor of >2 in the smallest joint sizes and <2 in the largest joints. Surgeon 2: There were 11 patients with bilateral third generation resurfacing joints and 50 with unilateral joints of the same design. The same relationship as described above was identified. There was a notable difference in the fourth generation implant group (n=13 bilateral, n=100 unilateral). Median ion levels for patients receiving bilateral joints of sizes <47mm were ten times greater than in the corresponding unilateral group. Bearing diameter and component design are critical factors in determining metal ion levels following bilateral hip resurfacings. Surgeons must consider the potential implications of gross increases in metal ion levels prior to performing bilateral hip resurfacings in smaller patients