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.

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

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

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

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

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

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

There are several component position and design variables that increase the risk of edge loading and high wear in metal-on-metal hip resurfacing (MOM-HR). In this study we combined all of these variables to calculate the ‘contact patch to rim distance’ (CPRD) in patients undergoing revision of their MOM-HR. We then determined whether CPRD was more strongly correlated with component wear and blood metal ion levels, when compared to any other commonly reported clinical variable. This was a retrospective study of 168 consecutively collected MOM-HR retrieval cases. All relevant clinical data was documented, including pre-revision whole blood cobalt and chromium ion levels. Wear of the bearing surfaces was then measured using a roundness-measuring machine. We found four variables to be significantly (p < 0.05) correlated with component wear and blood metal ion levels: (1) cup inclination angle, (2) cup version angle, (3) arc of cover, and (4) CPRD. The correlations between CPRD and both wear and ion levels were significantly stronger than those seen with any other variable (all p < 0.0001). Our study has shown that CPRD is the best predictor of component wear and blood metal ion levels, and may therefore be a useful parameter to help determine those patients who are at risk of high wear and require more frequent clinical surveillance

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

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

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°

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

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

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.

Introduction: The purpose of this retrospective study is to compare long-term whole blood metal ion concentrations (Co, Cr, Ni, Mo) between two different metal-on-metal total hip arthroplasties and a metal-on-polyethylene control group, in relationship with physical activity. Materials and methods: Between 1996 and 2000, different conventional prosthetic designs were implanted at our hospital. For this study, three groups were chosen according to the bearing surfaces used. Patients who had undergone other surgical interventions with implantation of potential sources of Cr/Co were excluded. Patients taking medication or dietary supplements containing Cr/Co were also excluded. In group 1, 17 patients with a 28 mm metal-on-metal bearing, type Metasul (Zimmer), were included. Group 2 comprised 11 patients with a 28 mm metal-on-metal bearing, type M2a (Biomet). The control group consisted of 9 patients with a 28 mm metal-on-polyethylene bearing in combination with a cemented CoCr stem. The three groups were demographically comparable. The postoperative clinical performance was evaluated using the Harris hip score and the Merle-dAubigne score. The activity level was measured using the Baecke questionnaire. Whole blood samples were taken in a standardized way and analysed by high resolution inductively coupled plasma mass spectrometer analysis. Results: At an average follow-up of 4 years, the mean Harris Hip Score was 88.35 in group 1, 82.64 in group 2 and 90.89 in the control group. The mean Baecke Activity Score was 7.32 in group 1, 5.51 in group 2 and 6.49 in the control group. The mean Cr level was 0.27 in group 1, 0.63 in group 2 and 0.19 in the control group. The mean Co level was 0.63 in group 1, 1.06 in group 2 and 0.51 in the control group. The mean Ni level was 1.11 in group 1, 1.10 in group 2 and 1.31 in the control group. The mean Mo level was 0.65 in group 1, 0.77 in group 2 and 0.56 in the control group. Conclusions: At a minimum follow-up of 4 years, no statistically significant differences were seen in clinical outcomes among the three groups. The only statistically significant difference in metal ion concentration among the three groups was observed for the Cr concentration between the M2a group and the metal-on-polyethylene group. There is also a positive correlation between the ion concentrations (Cr and Co) on the one hand and the activity level and Body Mass Index on the other

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.

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.

Orthopaedic cobalt chromium particles and ions can induce indirect DNA damage and chromosome aberrations in human cells on the other side of a cellular barrier in tissue culture. This occurs by intercellular signalling across the barrier. We now show that the threshold for this effect depends on the metal form and the particle composition.

Ionic cobalt and chromium induced single strand breaks at concentrations equivalent to those found in the blood of patients with well functioning metal on metal hip prostheses. However, they only caused double strand breaks if the chromium was present as chromium (VI), and did not induce chromosome aberrations. Nanoparticles of cobalt chromium alloy caused DNA double strand breaks and chromosome aberrations, of which the majority were tetraploidy. Ceramic nanoparticles induced only single strand breaks and/or alkaline labile sites when indirectly exposed to human fibroblasts.

The assessment of reproductive risk from maternal exposure to biomaterials, especially those liberated by orthopaedic implants, is not yet possible with epidemiology. Whilst the barrier model used here differs from the in vivo situation in several respects, it may be useful as a framework to evaluate biomaterial induced damage across physiological barriers.

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.

Background

We have previously described the relationship between wear rates of MOM components and soft tissue necrosis. In this study we investigated the link between wear rates, metal ion concentrations and osteolysis.