Metallic contacts in hip replacements are susceptible to wear and corrosion processes which lead to the release of particles and metal ions. Adverse local tissue reactions (ALTRs) and systemic manifestations to solid and soluble debris can be debilitating for the patients. It is believed that particles originating from CoCrMo taper junctions trigger more severe body reactions compared to debris from MoM hip bearings. The body's reaction is highly dependent on particle characteristics, such as size, morphology, composition and aggregation state, which can reflect the specific wear and corrosion conditions at the site of release. Here we proposed to investigate wear and corrosion flakes collected from around CoCrMo tapers at the time of revision. The particles were initially characterised with scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). This revealed the microstructure of the corrosion products, which appeared to be made of smaller metallic aggregates, entrapped in a biological matrix. The in depth characterisation of the particles released from the organo-metallic composite, was performed with transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM), both fitted with EDX. The investigation revealed clusters and individual nanoparticles, as small as 3 nm, which represent the building blocks of the large corrosion flakes, reported and characterised in the past mainly with low resolution microscopy techniques. The majority of the particles consisted of Cr and O, potentially in the form of chromium oxides, with little evidence of Co and Mo. Particles size distribution (PSD) provided by STEM and TEM characterisation showed statistically different results. The STEM technique was able to resolve tiny particles found in close proximity and provided a PSD shift towards the smaller end of the size range. The study is the first to show microscopy evidence of Cr rich nanoparticles (3–60 nm) released in vivo from the modular taper interface, which can have important health implications caused by their increased potential to disseminate and corrode within the body

Introduction. Adverse local tissue reactions (ALTR) can result in devastating soft tissue and osseous destruction, while potentially increasing the risk of concomitant periprosthetic joint infection (PJI). The aims of this study were to evaluate cobalt (Co) and chromium (Cr) levels generated in simulators from metal-on-polyethylene (MoP) and ceramic-on-polyethylene (CoP) constructs, and determine their impact on native tissues and PJI risk through evaluation of human adipose-derived mesenchymal stem cells (AMSCs) and Staphylococcus epidermidis isolates. Methods. Ten hip simulator constructs were assembled with 36-mm high-offset femoral heads, highly cross-linked polyethylene liners, and titanium stems. Five constructs used CoCr femoral heads and five used ceramic. Constructs were submerged in bovine serum (BS) and run for 1,000,000 cycles. Samples of BS were collected and evaluated for CoCr concentration. Various concentrations of CoCr were chosen for further assessment of cytotoxicity and growth impact on AMSCs and S. epidermidis and compared to inert SiO2. Results. After 1,000,000 cycles, mean MoP and CoP Co concentration was 2264 ng/mL and 0.6 ng/mL, respectively (p<0.001). Mean MoP and CoP Cr concentration was 217 ng/mL and 4.3 ng/mL, respectively (p<0.001). Mean MoP Co:Cr ratio was 10. Co nanoparticles were significantly more toxic to human AMSCs than control SiO2 in a dose-response manner (p<0.001). S. epidermidis growth was not significantly impacted by Co concentrations derived from the simulators. Conclusions. MoP constructs built in ideal conditions generated substantial CoCr debris, highlighting a baseline risk with these implants that may be exacerbated by host factors or imperfect surgical technique. Evaluation of impact on AMSCs suggests that debris levels produced under ideal conditions can be cytotoxic. Additionally, these concentrations did not potentiate or inhibit S. epidermidis growth, suggesting elevated PJI rates with ALTR may be related to other factors potentially associated with tissue necrosis. For any tables or figures, please contact the authors directly

Total hip arthroplasties are known to corrode predominantly at the taper junctions between Cobalt Chromium Molybedenum (CoCrMo) and Titanium (Ti) alloy components. We aimed to understand the modes underlying clinically significant tissue reactions to metals from corroded implants by determining: (1) what type of metal is present in the tissues, (2) which cells contain the metal species and (3) how this compares with results from metal-on-metal (MOM) hip resurfacings (HRs). This study involved periprosthetic tissue from patients that had undergone revision surgery due to adverse reactions to metal debris (ARMD) from dual-taper prostheses consisting of Ti-based alloy stems paired with CoCrMo necks. We used Synchrotron micro X-ray Fluorescence Spectroscopy (µXRF) and micro X-ray Absorption Near Edge Spectroscopy (µXANES) for detection of Co, Cr and Ti, and determination of their oxidation state. Synchrotron radiation has shown that the chromium in tissues is Cr. 2. O. 3. when derived from corroded CoCrMo/Ti junctions beside the CrPO. 4. species found when hip implants release CoCrMo nanoparticles from their bearing surfaces (MoM HRs). Presence of Cr. 2. O. 3. was associated with titanium oxide TiO. 2. This may be the outcome of the chemical interaction between the two species. Histological examination showed corrosion products present within viable macrophages and in the extracellular connective tissue, Figure 1. Understanding corrosion at taper junctions and the pathogenesis of the biological response is of significant clinical importance. This is the first study to co-register histology and metal distribution maps and to explore the potential synergy effect of CoCrMo with Ti alloy. This study provides guidance for toxicological studies on wear/corrosion particles, how they stimulate the host response and the cellular mechanisms involved in the pathogenesis of ARMD. For any figures or tables, please contact the authors directly by clicking on ‘Info & Metrics’ above to access author contact details

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.

Introduction. The biological pathways responsible for adverse reactions to metal debris (ARMD) are unknown. Necrotic and inflammatory changes in response to Co-Cr nanoparticles in periprosthetic tissues may involve both a cytotoxic response and a type IV delayed hypersensitivity response. Our aim was to establish whether differences in biological cascade activation exists in tissues of patients with end-stage OA compared to those with aseptic loosening of a metal on polyethylene (MoP) THR and those with ARMD from metal-on-metal (MoM) THR. Patients & Methods. A microarray experiment (Illumina HT12-v4) was performed to identify the range of differential gene expression between 24 patients across 3 phenotypes: Primary OA (n=8), revision for aseptic loosening of MoP THR (n=8) and ARMD associated with MoM THR (n=8). Results were validated using Taqman Low Density Array (TLDA) selecting the top 36 genes in terms of fold-change (FC)>2 and a significant difference (p<0.05) on ANOVA. Pathways of cellular interaction were explored using Ingenuity IPA software. Results. There is a similar pattern of gene expression between MoP and MoM phenotypes versus primary OA across 33,777 genes. One hundred and thirty significantly differentially expressed genes across 3 phenotypes were identified. Fifteen pathways were associated with differentially expressed genes between MoP and MoM phenotypes. TLDA demonstrated qualitative mirroring of the expression pattern observed in the microarray and consistency in the direction of change for individual genes. Discussion. There were no signature pathways in which multiple genes are differentially expressed such that inferences between the contributions of innate macrophage and adaptive T-cell responses can be made. TIMP3 & MMP12 were consistently identified in 15 pathways that were associated with differential gene expression between MoP and MoM phenotypes. Conclusion. Analyses of the expression of individual genes such as PRG4 (lubricin) have demonstrated patterns that may provide avenues for further research into biomarkers for periprosthetic osteolysis and ARMD

Aims

Cardiac magnetic resonance (CMR) was used to assess whether cardiac function or tissue composition was affected in patients with well-functioning metal-on-metal hip resurfacing arthroplasties (MoMHRA) when compared with a group of controls, and to assess if metal ion levels correlated with any of the functional or structural parameters studied.

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.

Lately, concerns have arisen following the use of large metal-on-metal bearings in hip replacements owing to reports of catastrophic soft-tissue reactions resulting in implant failure and associated complications. This review examines the literature and contemporary presentations on current clinical dilemmas in metal-on-metal hip replacement.

The aim of this study was to establish the natural course of unrevised asymptomatic pseudotumours after metal-on-metal (MoM) hip resurfacing during a six- to 12-month follow-up period. We used repeated metal artefact reduction sequence (MARS)-magnetic resonance imaging (MRI), serum metal ion analysis and clinical examination to study 14 unrevised hips (mean patient age 52.7 years, 46 to 68, 5 female, 7 male) with a pseudotumour and 23 hips (mean patient age 52.8 years, 38 to 69, 7 female, 16 male) without a pseudotumour. The mean post-operative time to the first MARS-MRI scan was 4.3 years (2.2 to 8.3), and mean time between the first and second MARS-MRI scan was eight months (6 to 12). At the second MRI scan, the grade of severity of the pseudotumour had not changed in 35 hips. One new pseudotumour (Anderson C2 score, moderate) was observed, and one pseudotumour was downgraded from C2 (moderate) to C1 (mild). In general, the characteristics of the pseudotumours hardly changed.

Repeated MARS-MRI scans within one year in patients with asymptomatic pseudotumours after MoM hip resurfacing showed little or no variation. In 23 patients without pseudotumour, one new asymptomatic pseudotumour was detected.

This is the first longitudinal study on the natural history of pseudotumours using MARS-MRI scans in hip resurfacing, and mirrors recent results for 28 mm diameter MoM total hip replacement.

Cite this article: Bone Joint J 2013;95-B:1626–31.

We retrospectively analysed concentrations of chromium and cobalt ions in samples of synovial fluid and whole blood taken from a group of 92 patients with failed current-generation metal-on-metal hip replacements. We applied acid oxidative digestion to our trace metal analysis protocol, which found significantly higher levels of metal ion concentrations in blood and synovial fluid than a non-digestive method. Patients were subcategorised by mode of failure as either ‘unexplained pain’ or ‘defined causes’. Using this classification, chromium and cobalt ion levels were present over a wider range in synovial fluid and not as strongly correlated with blood ion levels as previously reported. There was no significant difference between metal ion concentrations and manufacturer of the implant, nor femoral head size below or above 50 mm. There was a moderately positive correlation between metal ion levels and acetabular component inclination angle as measured on three-dimensional CT imaging.

Our results suggest that acid digestion of samples of synovial fluid samples is necessary to determine metal ion concentrations accurately so that meaningful comparisons can be made between studies.