The October 2012 Research Roundup. 360. looks at: whether you can escape your genes; oral prophylaxis for DVT; non-responders and the internet; metal-on-metal, mice and damaged livers; sleeping on the job; cartilage contact stress in the normal human hip; and a perfect reason to subscribe to 360

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

We undertook a retrospective cohort study to determine clinical outcomes following the revision of metal-on-metal (MoM) hip replacements for adverse reaction to metal debris (ARMD), and to identify predictors of time to revision and outcomes following revision. Between 1998 and 2012 a total of 64 MoM hips (mean age at revision of 57.8 years; 46 (72%) female; 46 (72%) hip resurfacings and 18 (28%) total hip replacements) were revised for ARMD at one specialist centre. At a mean follow-up of 4.5 years (1.0 to 14.6) from revision for ARMD there were 13 hips (20.3%) with post-operative complications and eight (12.5%) requiring re-revision. . The Kaplan–Meier five-year survival rate for ARMD revision was 87.9% (95% confidence interval 78.9 to 98.0; 19 hips at risk). Excluding re-revisions, the median absolute Oxford hip score (OHS) following ARMD revision using the percentage method (0% best outcome and 100% worst outcome) was 18.8% (interquartile range (IQR) 7.8% to 48.3%), which is equivalent to 39/48 (IQR 24.8/48 to 44.3/48) when using the modified OHS. Histopathological response did not affect time to revision for ARMD (p = 0.334) or the subsequent risk of re-revision (p = 0.879). Similarly, the presence or absence of a contralateral MoM hip bearing did not affect time to revision for ARMD (p = 0.066) or the subsequent risk of re-revision (p = 0.178). . Patients revised to MoM bearings had higher rates of re-revision (five of 16 MoM hips re-revised; p = 0.046), but those not requiring re-revision had good functional results (median absolute OHS 14.6% or 41.0/48). Short-term morbidity following revision for ARMD was comparable with previous reports. Caution should be exercised when choosing bearing surfaces for ARMD revisions. Cite this article: Bone Joint J 2014;96-B:1600–9

The peri-prosthetic tissue response to wear debris is complex and influenced by various factors including the size, area and number of particles. We hypothesised that the ‘biologically active area’ of all metal wear particles may predict the type of peri-prosthetic tissue response. . Peri-prosthetic tissue was sampled from 21 patients undergoing revision of a small diameter metal-on-metal (MoM) total hip arthroplasty (THA) for aseptic loosening. An enzymatic protocol was used for tissue digestion and scanning electron microscope was used to characterise particles. Equivalent circle diameters and particle areas were calculated. Histomorphometric analyses were performed on all tissue specimens. Aspirates of synovial fluid were collected for analysis of the cytokine profile analysis, and compared with a control group of patients undergoing primary THA (n = 11) and revision of a failed ceramic-on-polyethylene arthroplasty (n = 6). . The overall distribution of the size and area of the particles in both lymphocyte and non-lymphocyte-dominated responses were similar; however, the subgroup with lymphocyte-dominated peri-prosthetic tissue responses had a significantly larger total number of particles. . 14 cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, interferon (IFN)-γ, and IFN-gamma-inducible protein 10), chemokines (macrophage inflammatory protein (MIP)-1α and MIP-1ß), and growth factors (granulocyte macrophage colony stimulating factor (GM-CSF) and platelet derived growth factor) were detected at significantly higher levels in patients with metal wear debris compared with the control group. . Significantly higher levels for IL-1ß, IL-5, IL-10 and GM-CSF were found in the subgroup of tissues from failed MoM THAs with a lymphocyte-dominated peri-prosthetic response compared with those without this response. . These results suggest that the ‘biologically active area’ predicts the type of peri-prosthetic tissue response. The cytokines IL-1ß, IL-5, IL-10, and GM-CSF are associated with lymphocyte-dominated tissue responses from failed small-diameter MoM THA. Cite this article: Bone Joint J 2015;97-B:917–23

Objectives. Mechanical wear and corrosion at the head-stem junction of total hip arthroplasties (THAs) (trunnionosis) have been implicated in their early revision, most commonly in metal-on-metal (MOM) hips. We can isolate the role of the head-stem junction as the predominant source of metal release by investigating non-MOM hips; this can help to identify clinically significant volumes of material loss and corrosion from these surfaces. Methods. In this study we examined a series of 94 retrieved metal-on-polyethylene (MOP) hips for evidence of corrosion and material loss at the taper junction using a well published visual grading method and an established roundness-measuring machine protocol. Hips were retrieved from 74 male and 20 female patients with a median age of 57 years (30 to 76) and a median time to revision of 215 months (2 to 324). The reasons for revision were loosening of both the acetabular component and the stem (n = 29), loosening of the acetabular component (n = 58) and infection (n = 7). No adverse tissue reactions were reported by the revision surgeons. Results. Evidence of corrosion was observed in 55% of hips. The median Goldberg taper corrosion score was 2 (1 to 4) and the annual rate of material loss at the taper was 0.084 mm. 3. /year (0 to 0.239). The median trunnion corrosion score was 1 (1 to 3). Conclusions. We have reported a level of trunnionosis for MOP hips with large-diameter heads that were revised for reasons other than trunnionosis, and therefore may be clinically insignificant. Cite this article: H. S. Hothi, D. Kendoff, C. Lausmann, J. Henckel, T. Gehrke, J. Skinner, A. Hart. Clinically insignificant trunnionosis in large-diameter metal-on-polyethylene total hip arthroplasty. Bone Joint Res 2017;6:52–56. DOI: 10.1302/2046-3758.61.BJR-2016-0150.R2

Symptomatic cobalt toxicity from a failed total hip replacement is a rare but devastating complication. It has been reported following revision of fractured ceramic components, as well as in patients with failed metal-on-metal articulations. Potential clinical findings include fatigue, weakness, hypothyroidism, cardiomyopathy, polycythaemia, visual and hearing impairment, cognitive dysfunction, and neuropathy. We report a case of an otherwise healthy 46-year-old patient, who developed progressively worsening symptoms of cobalt toxicity beginning approximately six months following synovectomy and revision of a fractured ceramic-on-ceramic total hip replacement to a metal-on-polyethylene bearing. The whole blood cobalt levels peaked at 6521 µg/l. The patient died from cobalt-induced cardiomyopathy. Implant retrieval analysis confirmed a loss of 28.3 g mass of the cobalt–chromium femoral head as a result of severe abrasive wear by ceramic particles embedded in the revision polyethylene liner. Autopsy findings were consistent with heavy metal-induced cardiomyopathy. We recommend using new ceramics at revision to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components. Cite this article: Bone Joint J 2013;95-B:31–7

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

The February 2013 Hip & Pelvis Roundup. 360 . looks at: amazing alumina; dual mobility; white cells and periprosthetic infection; cartilage and impingement surgery; acetabulum in combination; cementless ceramic prosthesis; metal-on-metal hips; and whether size matters in failure

Hip resurfacing has been proposed as an alternative to traditional total hip arthroplasty in young, active patients. Much has been learned following the introduction of metal-on-metal resurfacing devices in the 1990s. The triad of a well-designed device, implanted accurately, in the correct patient has never been more critical than with these implants. . Following Food and Drug Administration approval in 2006, we studied the safety and effectiveness of one hip resurfacing device (Birmingham Hip Resurfacing) at our hospital in a large, single-surgeon series. We report our early to mid–term results in 1333 cases followed for a mean of 4.3 years (2 to 5.7) using a prospective, observational registry. The mean patient age was 53.1 years (12 to 84); 70% were male and 91% had osteoarthritis. Complications were few, including no dislocations, no femoral component loosening, two femoral neck fractures (0.15%), one socket loosening (0.08%), three deep infections (0.23%), and three cases of metallosis (0.23%). There were no destructive pseudotumours. Overall survivorship at up to 5.7 years was 99.2%. Aseptic survivorship in males under the age of 50 was 100%. We believe this is the largest United States series of a single surgeon using a single resurfacing system. Cite this article: Bone Joint J 2016;98-B (1 Suppl A):10–13

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis

The June 2012 Hip & Pelvis Roundup. 360. looks at: whether metal-on-metal is really such a disaster; resurfacings with unexplained pain; large heads and high ion levels; hip arthroscopy for FAI; the inaccuracy of clinical tests for impingement; arthroscopic lengthening of iliopsoas; the OA hip; the injured hamstring – football’s most common injury; an algorithm for hip fracture surgery; and sparing piriformis at THR

Aims

Head-taper corrosion is a cause of failure in total hip arthroplasty (THA). Recent reports have described an increasing number of V40 taper failures with adverse local tissue reaction (ALTR). However, the real incidence of V40 taper damage and its cause remain unknown. The aim of this study was to evaluate the long-term incidence of ALTR in a consecutive series of THAs using a V40 taper and identify potentially related factors.

Aims

The aim of this study was to estimate the clinical and economic burden of dislocation following primary total hip arthroplasty (THA) in England.

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

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

Aims

Total hip arthroplasty (THA) is a very successful and cost-effective operation, yet debate continues about the optimum fixation philosophy in different age groups. The concept of the 'cementless paradox' and the UK 'Getting it Right First Time' initiative encourage increased use of cemented fixation due to purported lower revision rates, especially in elderly patients, and decreased cost.

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