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

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

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.

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

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

Aims. The purpose of this study was to compare two different types of metal-on-metal (MoM) bearing for total hip arthroplasty (THA): one with a large femoral head (38 mm to 52 mm) and the other with a conventional femoral head (28 mm or 32 mm). We compared clinical outcome, blood metal ion levels, and the incidence of pseudotumour in the two groups. Patients and Methods. Between December 2009 and December 2011, 62 patients underwent MoM THA with a large femoral head (Magnum group) and 57 patients an MoM THA with a conventional femoral head (conventional group). Clinical outcome was assessed using the Harris Hip score, University of California, Los Angeles (UCLA) activity score and EuroQol-5D (EQ-5D). Blood metal ion levels were measured and MRI scans were analyzed at a minimum of five years postoperatively. Results. No acetabular component was implanted with more than 50° of inclination in either group. The Harris Hip Score, UCLA activity score, and EQ-5D improved postoperatively in both groups; no significant clinical differences were noted between the groups. The blood cobalt ion levels in the conventional group continued to rise postoperatively to five years while reaching a plateau at two years postoperatively in the Magnum group. At five years, the mean cobalt ion level of 1.16 μg/l (. sd. 1.32) in the Magnum group was significantly lower than the 3.77 μg/l (. sd. 9.80) seen in the conventional group (p = 0.0015). The incidence of moderate to severe pseudotumour was 4.7% in the Magnum group and 20.6% in the conventional group. There were no dislocations in the Magnum group and two in the conventional group. One patient in the Magnum group underwent revision for pseudotumour at 4.7 years postoperatively. Conclusion. At five years, a well-positioned large head MoM THA has a significantly lower level of metal ion release and a lower incidence of moderate to severe pseudotumour than a MoM bearing of conventional size. Cite this article: Bone Joint J 2018;100-B:1018–24

Recent studies have demonstrated that implant-specific blood metal ion thresholds exist in unilateral and bilateral metal-on-metal (MoM) hip arthroplasty patients, with these thresholds being most effective for identifying patients at low-risk of adverse reactions to metal debris (ARMD). We investigated whether these new blood metal ion thresholds could effectively identify patients at risk of ARMD in an external cohort of MoM hip arthroplasty patients. We performed a validation study involving 803 MoM hip arthroplasties implanted in 710 patients at three European centres (323=unilateral Birmingham Hip Resurfacing (BHR); 93=bilateral BHR; 294=unilateral Corail-Pinnacle). All patients underwent whole blood metal ion sampling. Patients were divided into those with ARMD (revised for ARMD or ARMD on imaging; n=75), and those without ARMD (n=635). Previously devised implant-specific blood metal ion thresholds (cobalt=2.15μg/l for unilateral BHR; maximum cobalt or chromium=5.5μg/l for bilateral BHR; cobalt=3.57μg/l for unilateral Corail-Pinnacle) were applied to the validation cohort, with receiver operating characteristic curve analysis used to establish the discriminatory characteristics for each respective threshold. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for distinguishing between patients with and without ARMD for each implant-specific threshold were respectively: unilateral BHR=89.4% (95% CI=82.8%-96.0%), 78.9%, 86.7%, 44.1%, 96.9%; bilateral BHR=89.2% (95% CI=81.3%-97.1%), 70.6%, 86.8%, 54.5%, 93.0%; unilateral Corail-Pinnacle=76.9% (95% CI=63.9%-90.0%), 65.0%, 85.4%, 24.5%, 97.1%. The 7μg/l UK MHRA threshold missed significantly more patients with ARMD compared with the implant-specific thresholds (4.9% vs. 2.8%; p=0.0003). This external multi-centre validation study has confirmed that MoM hip arthroplasty patients with blood metal ion levels below newly devised implant-specific thresholds have a low-risk of ARMD. Compared to implant-specific thresholds, the currently proposed fixed MHRA threshold missed more patients with ARMD. We recommend using implant-specific thresholds over fixed thresholds when managing MoM hip arthroplasty patients

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

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

Introduction. Many worldwide regulatory authorities recommend regular surveillance of metal-on-metal hip arthroplasty patients given high failure rates. However concerns have been raised about whether such regular surveillance, which includes asymptomatic patients, is evidence-based and cost-effective. We determined: (1) the cost of implementing the 2015 MHRA surveillance in “at-risk” Birmingham Hip Resurfacing (BHR) patients, and (2) how many asymptomatic hips with adverse reactions to metal debris (ARMD) would have been missed if patients were not recalled. Methods. All BHR patients subject to the 2015 MHRA recall (all females, and males with head sizes 46mm or below, regardless of symptoms) at one specialist centre were invited for review (707 hips). All patients were investigated (Oxford Hip Score, radiographs, blood metal ions, and targeted cross-sectional imaging) and managed accordingly. Surveillance costs were calculated using finance department data, as was the number needed to treat (NNT) to avoid missing one case of asymptomatic ARMD. Results. The overall institutional surveillance cost to investigate all patients once was £105,922 (range £148 to £258 per patient). The most expensive aspects of surveillance were radiographs (£39,598), advanced nurse practitioner assistance (£23,618), cross-sectional imaging (£14,828), and blood metal ions (£14,825). 31 hips had imaging evidence of ARMD (12 revised, with 19 under surveillance). Seven hips were asymptomatic, however all revisions were symptomatic. The NNT to avoid missing one case of asymptomatic ARMD (on imaging and/or requiring revision) was 101 patients, equating to a screening cost of £18,041 to avoid one case of asymptomatic ARMD. Conclusions. Implementing MHRA surveillance for “at-risk” BHR patients was extremely costly, both financially and logistically. As the risk of asymptomatic ARMD was low, our data suggests the 2015 MHRA surveillance is not cost-effective. We therefore have concerns about the increasingly intensive surveillance recommended in the 2017 MHRA guidance for all metal-on-metal hip arthroplasty patients

Aims. Dual mobility (DM) implants have been shown to reduce the dislocation rate after total hip arthroplasty (THA), but there remain concerns about the use of cobalt chrome liners inserted into titanium shells. The aim of this study was to assess the clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) at mid-term follow-up in young, active patients receiving a modular DM THA. Methods. This was a prospective study involving patients aged < 65 years, with a BMI of < 35 kg/m. 2. , and University of California, Los Angeles activity score of > 6 who underwent primary THA with a modular cobalt chrome acetabular liner, highly cross-linked polyethylene mobile bearing, and a cementless titanium femoral stem. Patient-reported outcome measures, whole blood metal ion levels (μg/l), and periprosthetic femoral BMD were measured at baseline and at one, two, and five years postoperatively. The results two years postoperatively for this cohort have been previously reported. Results. A total of 43 patients were enrolled. At minimum follow-up of five years, 23 (53.4%) returned for clinical and radiological review, 25 (58.1%) had metal ion analysis performed, 19 (44.2%) underwent dual energy x-ray absorptiometry scans, and 25 (58%) completed a pain-drawing questionnaire. The mean modified Harris Hip Scores improved significantly from 54.8 (SD 19) preoperatively to 93.08 (SD 10.5) five years postoperatively (p < 0.001). One patient was revised for aseptic acetabular loosening. The mean cobalt levels increased from 0.065 μg/l (SD 0.03) to 0.08 (SD 0.05) and the mean titanium levels increased from 0.35 (SD 0.13) to 0.78 (SD 0.29). The femoral BMD ratio decreased in Gruen Zone 1 (91.9%) at five years postoperatively compared with the baseline scores at six weeks potoperatively. The femoral BMD ratio was maintained in Gruen zones 2 to 7. Conclusion. The use of a modular DM component and a cementless, tapered femoral stem shows excellent mid-term survivorship with minimal concerns for corrosion and metal ion release in a cohort of young, active patients undergoing primary THA. Cite this article: Bone Joint J 2021;103-B(7 Supple B):73–77

Introduction. Uncertainties in the management of patients with MOM hip implants continue to be a problem for all surgeons. Guidelines vary and do not fully define or quantify thresholds. We aimed to assess the differences in decision-making amongst an international community of six specialist orthopaedic institutions. Methods. Five international tertiary referral orthopaedic units (one UK, two USA, and two European) were invited to participate. Each unit organised an MDT panel consisting of 2 or more hip surgeons and a musculoskeletal radiologist. All units discussed the same 10 patients. A full clinical dataset was provided including blood test and all imaging. Differences in the interpretation of findings, management decision and rationale for decisions were compared between institutions. Results. Asymptomatic patients with metal ions below 7ppb and intra-articular synovitis were collectively treated with monitoring and repeat ion measurement. Symptomatic patients with similar findings were recommended revision surgery by all units. Raised metal ions and a cystic pseudotumour on imaging that is palpable clinically was also consistently recommended revision surgery. Moderate symptoms (OHS 30), 2B pseudotumour, and moderate metal ions (cobalt 5.5ppb) were seen as an indication for revision in 5 units, however the reverse is seen if the patient had several co-morbidities. Further to this, rising blood metal ions (6 to 7.5ppb) was recommended surgery by 4 units, and watchful waiting in 2 units. Rising blood metal ion levels (6ppb to 10ppb) and a small fluid collection on MRI in asymptomatic patients was recommended clinical review and repeat metal ions by 3 units, repeat MRI by 1 unit and revision for suboptimal implant position by the remaining 2 units. Conclusion. Moderate symptoms, blood metal ions and cystic pseudotumours led to inconsistent agreement between institutions. Coordinated international guidance and MDT panel discussions are recommended to improve consensus in decision-making

Introduction. We investigated whether blood metal ions could effectively identify bilateral metal-on-metal hip patients at risk of adverse reactions to metal debris (ARMD). Patients and methods. This single-centre, prospective study involved 235 patients (185 bilateral Birmingham Hip Resurfacings (BHRs) and 50 bilateral Corail-Pinnacles) undergoing whole blood metal ion sampling (mean time=6.8 years from latest implant to sampling). Patients were divided into ARMD (revised or ARMD on imaging; n=40) and non-ARMD groups (n=195). Metal ion parameters (cobalt; chromium; maximum cobalt or chromium; cobalt-chromium ratio) were compared between groups. Optimal metal ion thresholds for identifying ARMD patients were determined using receiver operating characteristic (ROC) analysis, which compares the performance of different tests using the area under the curve (AUC) (higher AUC=more discriminatory). Results. All ion parameters were significantly higher (p<0.0001) in ARMD patients versus non-ARMD patients. Maximum cobalt or chromium produced the highest AUC for BHRs (91.0%) and Corail-Pinnacles (71.8%). For BHRs, maximum cobalt or chromium AUC was significantly greater than cobalt-chromium ratio AUC (p=0.019) but not compared to cobalt (p=0.574) or chromium (p=0.721). For Corail-Pinnacles, AUCs for all ion parameters were not significantly different (p>0.160). Optimal ion thresholds for identifying ARMD varied between implants (maximum cobalt or chromium: BHR=5.52µg/l; Corail-Pinnacle=4.04µg/l). Thresholds had good sensitivities (83.3%–90.0%) and specificities (65.0%–88.4%), high negative predictive values (96.3%–96.5%) and lower positive predictive values (39.1%–58.1%). Fixed USA (10µg/l) and UK (7µg/l) authority thresholds missed more hips with ARMD (11–14 hips missed; 4.7–6.0%) compared to Implant Specific Thresholds (6 hips missed; 2.6%). Discussion. Bilateral BHR and Corail-Pinnacle patients with blood metal ions below Implant Specific Thresholds were at low-risk of ARMD. These thresholds could rationalise follow-up resources in asymptomatic patients. Conclusion. Implant Specific Thresholds are preferable to fixed authority thresholds given that Implant Specific Thresholds were more effective for identifying patients at risk of ARMD requiring further investigation

Circulating cobalt and chromium from metal-on-metal implants cause rare but fatal autopsy-diagnosed cardiotoxicity. Concern exists that milder cardiotoxicity may be common and under-recognized. Unacceptably high failure rates of metal-on-metal hip implants have prompted regulatory authorities to issue worldwide safety alerts. Despite this, approximately 1 million patients continue to live with metal-on-metal implants, putting them at risk of systemic toxicity. Although blood cobalt and chromium levels are easily measured and track local toxicity, no non-invasive tests for organ deposition exist. We recently demonstrated the utilisation of a T2* protocol (cardiovascular MRI) to detect cobalt and chromium deposition within the liver of a patient with elevated blood cobalt levels (confirmed by liver biopsy tissue analysis and X-ray fluorescence spectroscopy). We sought to detect and constrain the correlation between blood metal ions and a comprehensive panel of established markers of early cardiotoxicity. In addition we applied T2* protocols with the aim of detecting cardiac metal deposition. 90 patients were recruited through RNOH clinics into this prospective single centre blinded study. Patients were divided into 3 age and gender-matched groups according to type of implant and blood metal ion levels as follows: [Group A] Non-metal bearing hip implants; [Group B] Metal-on-metal implants, low blood metal ion levels (<7ppb); and [Group C] Metal-on-metal implants, high blood levels (>7ppb). All underwent detailed cardiovascular phenotyping using cardiac MRI (with T2*, T1 and ECV mapping, in addition to LV size and ejection fraction), advanced echocardiography (LV size and ejection fraction), and cardiac blood biomarker (Troponin and BNP) sampling in the same sitting at the Heart Hospital London. Primary outcomes were pre-specified. See study flow diagram – figure 1. (The study was registered with . clinicaltrials.gov. : NCT02331264). Blood cobalt levels were significantly different between groups (0.17ppb (range 0·10–0·47, SD 0·08) vs. 2·47 (0·72–6·9, SD 1·81) vs. 30·0 (7·54–118.0, SD 29·1) respectively for groups A, B and C). No significant between-group differences were found for LV size, ejection fraction (CMR or echocardiography), LA size, T1, T2*, ECV, BNP or troponin, with all results within normal ranges. There was no relationship between blood cobalt levels and either left ventricular ejection fraction or T2* (r=-0·022 and r=-0·108 respectively). Although small, the study was sufficiently powered to detect, as a minimum, a difference in ejection fraction of 4.8% (Cohen's d effect size 0·8). Using best available technologies, exposure of patients with metal-on-metal hip implants to high (but not extreme) blood cobalt and chromium levels has no detectable effect on the heart. We believe these findings will offer reassurance to one million patients worldwide living with a metal-on-metal hip implant and will support clinicians caring for such patients. For any figures or tables, please contact the authors directly by clicking on ‘Info & Metrics’ above to access author contact details

Aims. The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components. Patients and Methods. A total of 39 patients were recruited, with clinical follow-up of up to two years. Outcome was assessed using the Harris Hip Score (HHS, the 12-Item Short-Form Health Survey (SF-12), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and a visual analogue scale (VAS) for pain. Blood concentrations of cobalt (Co), chromium (Cr), and serum cytokines were measured. Subpopulations of leucocytes were analyzed by flow cytometry. Results. The clinical performance was good. Blood Co levels (ref 1.0 µg/l) were mildly elevated in seven patients at three months, and two patients at two years’ follow-up. The preoperative Cr levels were normal except for one patient with a detectable Cr (1.2 µg/l). Cr levels were detectable in three patients at three months, two patients at one year, and three patients at two years’ follow-up. No patients had symptoms suggestive of failure. Although flow cytometry showed constant circulating leucocyte profiles, there was a significant reduction of serum interleukin (IL)-4, IL-5, and interferon gamma (IFNγ) postoperatively compared with the preoperative levels (p < 0.05). Conclusion. These results suggest that THA using modular dual-mobility components is safe. This allows an opportunity to use a large femoral head and a thick polyethylene bearing surface, which is especially useful in revision procedures or high-risk situations when added stability is required. Cite this article: Bone Joint J 2019;101-B:1035–1041

Aims. Modular dual mobility (DM) prostheses in which a cobalt-chromium liner is inserted into a titanium acetabular shell (vs a monoblock acetabular component) have the advantage of allowing supplementary screw fixation, but the potential for corrosion between the liner and acetabulum has raised concerns. While DM prostheses have shown improved stability in patients deemed ‘high-risk’ for dislocation undergoing total hip arthroplasty (THA), their performance in young, active patients has not been reported. This study’s purpose was to assess clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) in young, active patients receiving a modular DM acetabulum and recently introduced titanium, proximally coated, tapered femoral stem design. Patients and Methods. This was a prospective study of patients between 18 and 65 years of age, with a body mass index (BMI) < 35 kg/m. 2. and University of California at Los Angeles (UCLA) activity score > 6, who received a modular cobalt-chromium acetabular liner, highly crosslinked polyethylene mobile bearing, and cementless titanium femoral stem for their primary THA. Patients with a history of renal disease and metal hardware elsewhere in the body were excluded. A total of 43 patients (30 male, 13 female; mean age 52.6 years (. sd. 6.5)) were enrolled. All patients had a minimum of two years’ clinical follow-up. Patient-reported outcome measures, whole blood metal ion levels (ug/l), and periprosthetic femoral BMD were measured at baseline, as well as at one and two years postoperatively. Power analysis indicated 40 patients necessary to demonstrate a five-fold increase in cobalt levels from baseline (alpha = 0.05, beta = 0.80). A mixed model with repeated measures was used for statistical analysis. Results. Mean Harris Hip Scores improved from 54.1 (. sd. 20.5) to 91.2 (. sd. 10.8) at two years postoperatively (p < 0.001). All patients had radiologically well-fixed components, no patients experienced any instability, and no patients required any further intervention. Mean cobalt levels increased from 0.065 ug/l (. sd. 0.03) preoperatively to 0.30 ug/l (. sd. 0.51) at one year postoperatively (p = 0.01) but decreased at two years postoperatively to 0.16 ug/l (. sd. 0.23; p = 0.2). Four patients (9.3%) had a cobalt level outside the reference range (0.03 ug/l to 0.29 ug/l) at two years postoperatively, with values from 0.32 ug/l to 0.94 ug/l. The mean femoral BMD ratio was maintained in Gruen zones 2 to 7 at both one and two years postoperatively using this stem design. At two years postoperatively, mean BMD in the medial calcar was 101.5% of the baseline value. Conclusion. Use of a modular DM prosthesis and cementless, tapered femoral stem has shown encouraging results in young, active patients undergoing primary THA. Elevation in mean cobalt levels and the presence of four patients outside the reference range at two years postoperatively demonstrates the necessity of continued surveillance in this cohort. Cite this article: Bone Joint J 2019;101-B:365–371

The Articular Surface Replacement (ASR) hip resurfacing arthroplasty has a failure rate of 12.0% at five years, compared with 4.3% for the Birmingham Hip Resurfacing (BHR). We analysed 66 ASR and 64 BHR explanted metal-on-metal hip replacements with the aim of understanding their mechanisms of failure. We measured the linear wear rates of the acetabular and femoral components and analysed the clinical cause of failure, pre-revision blood metal ion levels and orientation of the acetabular component. There was no significant difference in metal ion levels (chromium, p = 0.82; cobalt, p = 0.40) or head wear rate (p = 0.14) between the two groups. The ASR had a significantly increased rate of wear of the acetabular component (p = 0.03) and a significantly increased occurrence of edge loading (p < 0.005), which can be attributed to differences in design between the ASR and BHR. The effects of differences in design on the in vivo wear rates are discussed: these may provide an explanation as to why the ASR is more sensitive to suboptimal positioning than the BHR

Objectives. The high revision rates of the DePuy Articular Surface Replacement (ASR) and the DePuy ASR XL (the total hip arthroplasty (THA) version) have led to questions over the viability of metal-on-metal (MoM) hip joints. Some designs of MoM hip joint do, however, have reasonable mid-term performance when implanted in appropriate patients. Investigations into the reasons for implant failure are important to offer help with the choice of implants and direction for future implant designs. One way to assess the performance of explanted hip prostheses is to measure the wear (in terms of material loss) on the joint surfaces. Methods. In this study, a coordinate measuring machine (CMM) was used to measure the wear on five failed cementless Biomet Magnum/ReCap/ Taperloc large head MoM THAs, along with one Biomet ReCap resurfacing joint. Surface roughness measurements were also taken. The reason for revision of these implants was pain and/or adverse reaction to metal debris (ARMD) and/or elevated blood metal ion levels. Results. The mean wear rate of the articulating surfaces of the heads and acetabular components of all six joints tested was found to be 6.1 mm. 3. /year (4.1 to 7.6). The mean wear rate of the femoral head tapers of the five THAs was 0.054 mm. 3. /year (0.021 to 0.128) with a mean maximum wear depth of 5.7 µm (4.3 to 8.5). Conclusion. Although the taper wear was relatively low, the wear from the articulating surfaces was sufficient to provide concern and was potentially large enough to have been the cause of failure of these joints. The authors believe that patients implanted with the ReCap system, whether the resurfacing prosthesis or the THA, should be closely monitored. Cite this article: S. C. Scholes, B. J. Hunt, V. M. Richardson, D. J. Langton, E. Smith, T. J. Joyce. Explant analysis of the Biomet Magnum/ReCap metal-on-metal hip joint. Bone Joint Res 2017;6:113–122. DOI: 10.1302/2046-3758.62.BJR-2016-0130.R2

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