Objectives. We investigated the reliability of the cobalt-chromium (CoCr) synovial joint fluid ratio (JFR) in identifying the presence of a severe aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) response and/or suboptimal taper performance (SOTP) following metal-on-metal (MoM) hip arthroplasty. We then examined the possibility that the CoCr JFR may influence the serum partitioning of Co and Cr. Methods. For part A, we included all revision surgeries carried out at our unit with the relevant data, including volumetric wear analysis, joint fluid (JF) Co and Cr concentrations, and ALVAL grade (n = 315). Receiver operating characteristic curves were constructed to assess the reliability of the CoCr JFR in identifying severe ALVAL and/or SOTP. For part B, we included only patients with unilateral prostheses who had given matched serum and whole blood samples for Co and Cr analysis (n = 155). Multiple regression was used to examine the influence of JF concentrations on the serum partitioning of Co and Cr in the blood. Results. A CoCr JFR > 1 showed a specificity of 83% (77% to 88%) and sensitivity of 63% (55% to 70%) for the detection of severe ALVAL and/or SOTP. In patients with CoCr JFRs > 1, the median blood Cr to serum Cr ratio was 0.99, compared with 0.71 in patients with CoCr JFRs < 1 (p < 0.001). Regression analysis demonstrated that the blood Cr to serum Cr value was positively associated with the JF Co concentration (p = 0.011) and inversely related to the JF Cr concentration (p < 0.001). Conclusion. Elevations in CoCr JFRs are associated with adverse biological (severe ALVAL) or tribocorrosive processes (SOTP). Comparison of serum Cr with blood Cr concentrations may be a useful additional clinical tool to help to identify these conditions. Cite this article: D. J. Langton, S. Natu, C. F. Harrington, J. G. Bowsher, A. V. F. Nargol. Is the synovial fluid cobalt-to-chromium ratio related to the serum partitioning of metal debris following metal-on-metal hip arthroplasty? Bone Joint Res 2019;8:146–155. DOI: 10.1302/2046-3758.83.BJR-2018-0049.R1

The long term biological effects of wear products following total hip arthroplasty (THA) are unclear. However, the indications for THA are expanding, with increasingly younger patients undergoing the procedure.

This prospective, randomised study compared two groups of patients undergoing THA after being randomised to receive one of two different bearing surfaces: metal-on-polyethylene (MoP) n = 22 and metal-on-metal (MoM) n = 23. We investigated the relationship between three variables: bearing surface (MoP vs MoM), whole blood levels of chromium (Cr) and cobalt (Co) and chromosomal aberrations in peripheral lymphocyte pre-operatively and at one, two and five years post-surgery.

Our results demonstrated significantly higher mean cobalt and chromium (Co and Cr) blood levels in the MoM group at all follow-up points following surgery (p < 0.01), but there were no significant differences in the chromosomal aberration indices between MoM and MoP at two or five years (two years: p = 0.56, p = 0.08, p = 0.91, p = 0.51 and five years: p = 0.086, p = 0.73, p = 0.06, p = 0.34) for translocations, breaks, loss and gain of chromosomes respectively. Regression analysis showed a strong linear relationship between Cr levels and the total chromosomal aberration indices in the MoM group (R² = 0.90016), but this was not as strong for Co (R² = 0.68991). In the MoP group, the analysis revealed a poor relationship between Cr levels and the total chromosomal aberration indices (R² = 0.23908) but a slightly stronger relationship for Co (R² = 0.64292). Across both groups, Spearman’s correlation detected no overall association between Co and Cr levels and each of the studied chromosomal aberrations. There remains no clear indication which THA bearing couple is the most biocompatible, especially in young active patients. While THA continues to be very successful at alleviating pain and restoring function, the long-term biological implications of the procedure still require further scrutiny.

Cite this article: Bone Joint J 2015;97-B:1183–91.

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

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

Large-head metal-on-metal (MoM) total hip replacements (THR) have given rise to concern. Comparative studies of small-head MoM THRs over a longer follow-up period are lacking. Our objective was to compare the incidence of complications such as infection, dislocation, revision, adverse local tissue reactions, mortality and radiological and clinical outcomes in small-head (28 mm) MoM and ceramic-on-polyethylene (CoP) THRs up to 12 years post-operatively. A prospective cohort study included 3341 THRs in 2714 patients. The mean age was 69.1 years (range 24 to 98) and 1848 (55.3%) were performed in women, with a mean follow-up of 115 months (18 to 201). There were 883 MoM and 2458 CoP bearings. Crude incidence rates (cases/1000 person-years) were: infection 1.3 vs 0.8; dislocation 3.3 vs 3.1 and all-cause revision 4.3 vs 2.2, respectively. There was a significantly higher revision rate after ten years (adjusted hazard ratio 9.4; 95% CI 2.6 to 33.6) in the MoM group, and ten of 26 patients presented with an adverse local tissue reaction at revision. No differences in mortality, osteolysis or clinical outcome were seen. In conclusion, we found similar results for small-head MoM and CoP bearings up to ten years post-operatively, but after ten years MoM THRs had a higher risk of all-cause revision. Furthermore, the presence of an adverse response to metal debris seen in the small-head MOM group at revision is a cause for concern. Cite this article: Bone Joint J 2014; 96-B:868–75

A total of 397 hips were randomised to receive Metasul metal-on-metal (MoM), metal-on-conventional polyethylene (MoP) or ceramic-on-polyethylene (CoP) bearings using a cemented triple-tapered polished femoral component (MS-30). There were 129 MoM hips in 123 patients (39 male and 84 female, mean age 63.3 years (40.7 to 72.9)), 137 MoP hips in 127 patients (39 male and 88 female, mean age 62.8 years (24.5 to 72.7)) and 131 CoP hips in 124 patients (51 male and 73 female, mean age 63.9 years (30.6 to 73.8)). All acetabular components were cemented Weber polyethylene components with the appropriate inlay for the MoM articulation. Clinical evaluation was undertaken using the Harris hip score (HHS) and radiological assessments were made at two, five and seven years. The HHS and radiological analysis were available for 341 hips after seven years. The MoM group had the lowest mean HHS (p = 0.124), a higher rate of revision (p < 0.001) and a higher incidence of radiolucent lines in unrevised hips (p < 0.001). In all, 12 revisions had been performed in 12 patients: eight in the MoM group (four for infection, four for aseptic loosening, three in the MoP group (one each of infection, dislocation and pain) and one in the CoP group (infection). Our findings reveal no advantage to the MoM bearing and identified a higher revision rate and a greater incidence of radiolucent lines than with the other articulations. We recommend that patients with a 28 mm Metasul MoM bearing be followed carefully. Cite this article: Bone Joint J 2013;95-B:881–6

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

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity. Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately. Cite this article: Bone Joint J 2016;98-B:14–20

We report a systematic review and meta-analysis of the peer-reviewed literature focusing on metal sensitivity testing in patients undergoing total joint replacement (TJR). Our purpose was to assess the risk of developing metal hypersensitivity post-operatively and its relationship with outcome and to investigate the advantages of performing hypersensitivity testing. We undertook a comprehensive search of the citations quoted in PubMed and EMBASE: 22 articles (comprising 3634 patients) met the inclusion criteria. The frequency of positive tests increased after TJR, especially in patients with implant failure or a metal-on-metal coupling. The probability of developing a metal allergy was higher post-operatively (odds ratio (OR) 1.52 (95% confidence interval (CI) 1.06 to 2.31)), and the risk was further increased when failed implants were compared with stable TJRs (OR 2.76 (95% CI 1.14 to 6.70)). Hypersensitivity testing was not able to discriminate between stable and failed TJRs, as its predictive value was not statistically proven. However, it is generally thought that hypersensitivity testing should be performed in patients with a history of metal allergy and in failed TJRs, especially with metal-on-metal implants and when the cause of the loosening is doubtful

Objectives. Metal-on-metal (MoM) hip resurfacing was introduced into clinical practice because it was perceived to be a better alternative to conventional total hip replacement for young and active patients. However, an increasing number of reports of complications have arisen focusing on design and orientation of the components, the generation of metallic wear particles and serum levels of metallic ions. The procedure introduced a combination of two elements: large-dimension components and hard abrasive particles of metal wear. The objective of our study was to investigate the theory that microseparation of the articular surfaces draws in a high volume of bursal fluid and its contents into the articulation, and at relocation under load would generate high pressures of fluid ejection, resulting in an abrasive water jet. Methods. This theoretical concept using MoM resurfacing components (head diameter 55 mm) was modelled mathematically and confirmed experimentally using a material-testing machine that pushed the head into the cup at a rate of 1000 mm/min until fully engaged. Results. The mathematical model showed the pattern but not the force of fluid ejection, the highest pressures were expected when the separation of the components was only a fraction of one millimetre. The experimental work confirmed the results; with the mean peak ejection pressure of 43 763 N/m. 2. equivalent to 306 mmHg or 5 psi. Conclusions. The mechanical effect of the high-pressure abrasive water jet is the likely cause of the spectrum of complications reported with metal-on-metal resurfacing. Investigating serum levels of metallic elements may not be the best method for assessing the local mechanical effects of the abrasive water jet

Aims

The aims of this study were to determine if an increasing serum cobalt (Co) and/or chromium (Cr) concentration is correlated with a decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), and to evaluate the ten-year revision rate and show if sex, inclination angle, and Co level influenced the revision rate.

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression. . These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement. Cite this article: Bone Joint J 2014; 96-B:1172–7

We conducted a retrospective study to assess the prevalence of adverse reactions to metal debris (ARMD) in patients operated on at our institution with metal-on-metal (MoM) total hip replacements with 36 mm heads using a Pinnacle acetabular shell. A total of 326 patients (150 males, 175 hips; 176 females, 203 hips) with a mean age of 62.7 years (28 to 85) and mean follow-up of 7.5 years (0.1 to 10.8) participating in our in-depth modern MoM follow-up programme were included in the study, which involved recording whole blood cobalt and chromium ion measurements, Oxford hip scores (OHS) and plain radiographs of the hip and targeted cross-sectional imaging. Elevated blood metal ion levels (> 5 parts per billion) were seen in 32 (16.1%) of the 199 patients who underwent unilateral replacement. At 23 months after the start of our modern MoM follow-up programme, 29 new cases of ARMD had been revealed. Hence, the nine-year survival of this cohort declined from 96% (95% CI 95 to 98) with the old surveillance routine to 86% (95% CI 82 to 90) following the new protocol. Although ARMD may not be as common in 36 mm MoM THRs as in those with larger heads, these results support the Medicines and Healthcare Products Regulatory Agency guidelines on regular reviews and further investigations, and emphasise the need for specific a follow-up programme for patients with MoM THRs. Cite this article: Bone Joint J 2014; 96-B:1610–17

A total of 219 hips in 192 patients aged between 18 and 65 years were randomised to 28-mm metal-on-metal uncemented total hip replacements (THRs, 107 hips) or hybrid hip resurfacing (HR, 112 hips). At a mean follow-up of eight years (6.6 to 9.3) there was no significant difference between the THR and HR groups regarding rate of revision (4.0% (4 of 99) vs 5.8% (6 of 104), p = 0.569) or re-operation rates without revision (5.1% (5 of 99) vs 2.9% (3 of 104), p = 0.428). In the THR group one recurrent dislocation, two late deep infections and one peri-prosthetic fracture required revision, whereas in the HR group five patients underwent revision for femoral head loosening and one for adverse reaction to metal debris. The mean University of California, Los Angeles activity scores were significantly higher in HR (7.5 (. sd. 1.7) vs 6.9 (. sd. 1.7), p = 0.035), but similar mean Western Ontario and McMaster Universities Osteoarthritis Index scores were obtained (5.8 (. sd. 9.5) in HR vs 5.1 (. sd. 8.9) in THR, p = 0.615) at the last follow-up. Osteolysis was found in 30 of 81 THR patients (37.4%), mostly in the proximal femur, compared with two of 83 HR patients (2.4%) (p < 0.001). At five years the mean metal ion levels were < 2.5 μg/l for cobalt and chromium in both groups; only titanium was significantly higher in the HR group (p = 0.001). Although revision rates and functional scores were similar in both groups at mid-term, long-term survival analysis is necessary to determine whether one procedure is more advantageous than the other. Cite this article: Bone Joint J 2013;95-B:1464–73

Metal artefact reduction (MAR) MRI is now widely considered to be the standard for imaging metal-on-metal (MoM) hip implants. The Medicines and Healthcare Products Regulatory Agency (MHRA) has recommended cross-sectional imaging for all patients with symptomatic MoM bearings. This paper describes the natural history of MoM disease in a 28 mm MoM total hip replacement (THR) using MAR MRI. Inclusion criteria were patients with MoM THRs who had not been revised and had at least two serial MAR MRI scans. All examinations were reported by an experienced observer and classified as A (normal), B (infection) or C1–C3 (mild, moderate, severe MoM-related abnormalities). Between 2002 and 2011 a total of 239 MRIs were performed on 80 patients (two to four scans per THR); 63 initial MRIs (61%) were normal. On subsequent MRIs, six initially normal scans (9.5%) showed progression to a disease state; 15 (15%) of 103 THRs with sequential scans demonstrated worsening disease on subsequent imaging. Most patients with a MoM THR who do not undergo early revision have normal MRI scans. Late progression (from normal to abnormal, or from mild to more severe MoM disease) is not common and takes place over several years. Cite this article: Bone Joint J 2013;95-B:1035–9

The popularity of cementless total hip replacement (THR) has surpassed cemented THR in England and Wales. This retrospective cohort study records survival time to revision following primary cementless THR with the most common combination (accounting for almost a third of all cementless THRs), and explores risk factors independently associated with failure, using data from the National Joint Registry for England and Wales. Patients with osteoarthritis who had a DePuy Corail/Pinnacle THR implanted between the establishment of the registry in 2003 and 31 December 2010 were included within analyses. There were 35 386 procedures. Cox proportional hazard models were used to analyse the extent to which the risk of revision was related to patient, surgeon and implant covariates. The overall rate of revision at five years was 2.4% (99% confidence interval 2.02 to 2.79). In the final adjusted model, we found that the risk of revision was significantly higher in patients receiving metal-on-metal (MoM: hazard ratio (HR) 1.93, p < 0.001) and ceramic-on-ceramic bearings (CoC: HR 1.55, p = 0.003) compared with the best performing bearing (metal-on-polyethylene). The risk of revision was also greater for smaller femoral stems (sizes 8 to 10: HR 1.82, p < 0.001) compared with mid-range sizes. In a secondary analysis of only patients where body mass index (BMI) data were available (n = 17 166), BMI ≥ 30 kg/m. 2. significantly increased the risk of revision (HR 1.55, p = 0.002). The influence of the bearing on the risk of revision remained significant (MoM: HR 2.19, p < 0.001; CoC: HR 2.09, p = 0.001). The risk of revision was independent of age, gender, head size and offset, shell, liner and stem type, and surgeon characteristics. We found significant differences in failure between bearing surfaces and femoral stem size after adjustment for a range of covariates in a large cohort of single-brand cementless THRs. In this study of procedures performed since 2003, hard bearings had significantly higher rates of revision, but we found no evidence that head size had an effect. Patient characteristics, such as BMI and American Society of Anesthesiologists grade, also influence the survival of cementless components. Cite this article: Bone Joint J 2013;95-B:747–57

Peri-articular soft-tissue masses or ‘pseudotumours’ can occur after large-diameter metal-on-metal (MoM) resurfacing of the hip and conventional total hip replacement (THR). Our aim was to assess the incidence of pseudotumour formation and to identify risk factors for their formation in a prospective cohort study. A total of 119 patients who underwent 120 MoM THRs with large-diameter femoral heads between January 2005 and November 2007 were included in the study. Outcome scores, serum metal ion levels, radiographs and CT scans were obtained. Patients with symptoms or an identified pseudotumour were offered MRI and an ultrasound-guided biopsy. There were 108 patients (109 hips) eligible for evaluation by CT scan at a mean follow-up of 3.6 years (2.5 to 4.5); 42 patients (39%) were diagnosed with a pseudotumour. The hips of 13 patients (12%) were revised to a polyethylene acetabular component with small-diameter metal head. Patients with elevated serum metal ion levels had a four times increased risk of developing a pseudotumour. This study shows a substantially higher incidence of pseudotumour formation and subsequent revisions in patients with MoM THRs than previously reported. Because most revision cases were identified only after an intensive screening protocol, we recommend close monitoring of patients with MoM THR