Aims. The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371

Aims. The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid. Methods. Between October 2017 and September 2019, we collected synovial fluid samples from patients scheduled to undergo revision surgery for painful total knee arthroplasty (TKA). The International Consensus Meeting criteria were used to classify 33 PJIs and 92 aseptic joints. LC-MS assay was performed to measure alpha-defensin in synovial fluid of all included patients. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) were calculated to define the test diagnostic accuracy. Results. The AUC was 0.99 (95% confidence interval (CI) 0.98 to 1.00). Receiver operating characteristic (ROC) analysis showed that the optimal cut-off value of synovial fluid alpha-defensin was 1.0 μg/l. The sensitivity of alpha-defensin was 100% (95% CI 96 to 100), the specificity was 97% (95% CI 90 to 98), the positive predictive value was 89.2% (95% CI 82 to 94), and negative predictive value was 100% (95% CI 96 to 100). ROC analysis demonstrated an AUC of 0.99 (95% CI 0.98 to 1.0). Conclusion. The present study confirms the utility of alpha-defensin in the synovial fluid in patients with painful TKA to select cases of PJI. Since LC-MS is still a time-consuming technology and is available in highly specialized laboratories, further translational research studies are needed to take this evidence into routine procedures and promote a new diagnostic approach. Cite this article: Bone Joint J 2022;104-B(9):1047–1051

Aims. The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma. Cite this article: Bone Joint Res 2024;13(5):214–225

Aims. There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO. 4. ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO. 4. applied locally to treat ODAI. Methods. A total of 30 operations with ceftriaxone-loaded CaSO. 4. had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results. A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion. Our study highlights new clinical data of locally administered ceftriaxone with CaSO. 4. as carrier material. The near-constant release of ceftriaxone from CaSO. 4. observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842

We carried out metal artefact-reduction MRI, three-dimensional CT measurement of the position of the component and inductively-coupled plasma mass spectrometry analysis of cobalt and chromium levels in whole blood on 26 patients with unexplained pain following metal-on-metal resurfacing arthroplasty. MRI showed periprosthetic lesions around 16 hips, with 14 collections of fluid and two soft-tissue masses. The lesions were seen in both men and women and in symptomatic and asymptomatic hips. Using three-dimensional CT, the median inclination of the acetabular component was found to be 55° and its positioning was outside the Lewinnek safe zone in 13 of 16 cases. Using inductively-coupled plasma mass spectrometry, the levels of blood metal ions tended to be higher in painful compared with well-functioning metal-on-metal hips. These three clinically useful investigations can help to determine the cause of failure of the implant, predict the need for future revision and aid the choice of revision prostheses

Objectives. Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature. Methods. In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay. Results. The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. Conclusions. This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers. Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296–306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A. 2. , nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome

Aims

This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).

Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 μg/l (0.55 to 2.55) and 1.28 μg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 μg/l (0.42 to 1.75) and 0.378 μg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 μg/l (0.18 to 0.54) and 0.199 μg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 μg/l (0.17 to 0.5) and 0.194 μg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 μg/l) as in the controls (0.1934 μg/l), this difference was not statistically significant. (p > 0.05). The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer

Aims

Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

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.

Aims. Vancomycin is commonly added to acrylic bone cement during revision arthroplasty surgery. Proprietary cement preparations containing vancomycin are available, but are significantly more expensive. We investigated whether the elution of antibiotic from ‘home-made’ cement containing vancomycin was comparable with more expensive commercially available vancomycin impregnated cement. Materials and Methods. A total of 18 cement discs containing either proprietary CopalG+V; or ‘home-made’ CopalR+G with vancomycin added by hand, were made. Each disc contained the same amount of antibiotic (0.5 g gentamycin, 2 g vancomycin) and was immersed in ammonium acetate buffer in a sealed container. Fluid from each container was sampled at eight time points over a two-week period. The concentrations of gentamicin and vancomycin in the fluid were analysed using high performance liquid chromatography mass spectrometry. Results. The highest peak concentrations of antibiotic were observed from the ‘home-made’ cements containing vancomycin, added as in the operating theatre. The overall elution of antibiotic was, fivefold (vancomycin) and twofold (gentamicin) greater from the ‘home-made’ mix compared with the commercially mixed cement. The use of a vacuum during mixing had no significant effect on antibiotic elution in any of the samples. Conclusion. These findings suggest that the addition of 2 g vancomycin powder to gentamicin-impregnated bone cement by hand significantly increases the elution of both antibiotics compared with commercially prepared cements containing vancomycin. We found no significant advantages of using expensive commercially produced vancomycin-impregnated cement and recommend the addition of vancomycin powder by hand in the operating theatre. Cite this article: Bone Joint J 2017;99-B:73–7

Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Aims

To analyze the short-term outcome of two types of total wrist arthroplasty (TWA) in terms of wrist function, migration, and periprosthetic bone behaviour.

Aims

Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model.

We investigated whether the indentation of bone cement spacers used in revision of infected joint arthroplasty with a MacDonald dissector increased the elution of antibiotic in vitro. A total of 24 cement discs containing either 0.17 g (0.88% w/w), 0.25 g (1.41% w/w), or 0.33 g (1.75% w/w) gentamicin of constant size were made. Of these, 12 were indented with the dissector. Each disc was immersed in ammonium acetate buffer in a sealed container, and fluid from each container was sampled at zero, one, three, six, 24, 48 and 72 hours and at one, and two weeks. The concentration of gentamicin in the fluid was analysed using high performance liquid chromatography mass spectrometry. . The fluid sampled at 72 hours from the indented discs containing 0.17 g gentamicin (0.88% w/w) contained a mean of 113 mcg/ml (90.12 to 143.5) compared with 44.5 mcg/ml (44.02 to 44.90) in the fluid sampled from the plain discs (p = 0.012). In discs containing 0.33 g gentamicin (1.75% w/w), the concentration eluted from the indented discs at 72 hours was a mean of 316 mcg/ml (223 to 421) compared with a mean of 118 mcg/ml (100 to 140) from the plain discs (p < 0.001). . At two weeks, these significant differences persisted. At nine weeks the indented discs eluted a greater concentration for all gentamicin doses, but the difference was only significant for the discs containing 0.17 g (0.88% w/w, p = 0.006). However if the area under the curve is taken as a measure of the total antibiotic eluted, the indented discs eluted more gentamicin than the plain discs for the 0.17 g (0.88% w/w, p = 0.031), the 0.25 g (1.41% w/w, p < 0.001) and the 0.33 g (1.75% w/w, p < 0.001) discs. . When preparing antibiotic spacers for use in staged revision arthroplasty surgery we recommend indenting the spacer with a MacDonald dissector to increase the elution of antibiotic. Cite this article: Bone Joint J 2015;97-B:1519–24

Aims

Debridement, antibiotics, and implant retention (DAIR) is a widely accepted form of surgical treatment for patients with an early periprosthetic joint infection (PJI) after primary arthroplasty. The outcome of DAIR after revision arthroplasty, however, has not been reported. The aim of this study was to report the success rate of DAIR after revision arthroplasty with a follow-up of two years.

Aims

Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.

We have investigated the effect of joint tamponade and of traction in extension on the oxygen and carbon dioxide tensions in the femoral head of the immature goat, using mass spectrometry. Tamponade of 75 mmHg caused the oxygen tension in the femoral head to drop from 48 +/- 4 mmHg to 29 +/- 3 mmHg. Traction in extension further decreased the oxygen tension. Both these changes were highly significant. The partial pressure of carbon dioxide increased, but to a lesser extent and only effusion together with traction gave a statistically significant effect. Our study showed that joint effusion can produce hypoxia in the bone as a result of impaired blood flow to the femoral head. The application of traction increases this haemodynamic effect

The purpose of this study was to evaluate whether concerns about the release of metal ions in metal-on-metal total hip replacements (THR) should be extended to patients with metal-bearing total disc replacements (TDR). Cobalt and chromium levels in whole blood and serum were measured in ten patients with a single-level TDR after a mean follow-up of 34.5 months (13 to 61) using inductively-coupled plasma mass spectrometry. These metal ion levels were compared with pre-operative control levels in 81 patients and with metal ion levels 12 months after metal-on-metal THR (n = 21) and resurfacing hip replacement (n = 36). Flexion-extension radiographs were used to verify movement of the TDR. Cobalt levels in whole blood and serum were significantly lower in the TDR group than in either the THR (p = 0.007) or the resurfacing group (p < 0.001). Both chromium levels were also significantly lower after TDR versus hip resurfacing (p < 0.001), whereas compared with THR this difference was only significant for serum levels (p = 0.008). All metal ion levels in the THR and resurfacing groups were significantly higher than in the control group (p < 0.001). In the TDR group only cobalt in whole blood appeared to be significantly higher (p < 0.001). The median range of movement of the TDR was 15.5° (10° to 22°). These results suggest that there is minimal cause for concern about high metal ion concentrations after TDR, as the levels appear to be only moderately elevated. However, spinal surgeons using a metal-on-metal TDR should still be aware of concerns expressed in the hip replacement literature about toxicity from elevated metal ion levels, and inform their patients appropriately

Aims

Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes.

Aims

Adverse local tissue reactions associated with abnormal wear considerably slowed down the general use of metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), now limited to a few specialized centres. In this study, we provide the clinical results of 400 consecutive MoM HRAs implanted more than 20 years ago in one such centre.

Aims

This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys.

Aims

The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF.

Aims

Flucloxacillin is commonly administered intravenously for perioperative antimicrobial prophylaxis, while oral administration is typical for prophylaxis following smaller traumatic wounds. We assessed the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT > MIC) for methicillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model.

Aims

Hip resurfacing arthroplasty (HRA) is typically indicated for young and active patients. Due to the longevity of arthroplasty, these patients are likely to undergo revision surgery during their lifetime. There is a paucity of information on the long-term outcome of revision surgeries performed after failed HRA. The aim of our study was to provide survivorship data as well as clinical scores after HRA revisions.

Objectives

Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI.

Aims

CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.

Objectives

The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.

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.

Aims

Modular dual-mobility constructs reduce the risk of dislocation after revision total hip arthroplasty (THA). However, questions about metal ions from the cobalt-chromium (CoCr) liner persist, and are particularly germane to patients being revised for adverse local tissue reactions (ALTR) to metal. We determined the early- to mid-term serum Co and Cr levels after modular dual-mobility components were used in revision and complex primary THAs, and specifically included patients revised for ALTR.

Objectives

Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study.

Aims

The present study investigated the five-year interval changes in pseudotumours and measured serum metal ions at long-term follow-up of a previous report of 28 mm diameter metal-on-metal (MoM) total hip arthroplasty (THA).

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.

Objectives

We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL).

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.

Aims

It is well established that there is a strong association between Perthes’ disease and worsening socioeconomic deprivation. It has been suggested that the primary determinant driving this association is exposure to tobacco smoke. This study aimed to examine this hypothesis.

Aims

A contact patch to rim (CPR) distance of < 10 mm has been associated with edge-loading and excessive wear. However, not all arthroplasties with a low CPR distance show problems with wear. Therefore, CPR distance may not be the only variable affecting the post-operative metal ion concentrations.

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.

Objectives

Hips with metal-on-metal total hip arthroplasty (MoM THA) have a high rate of adverse local tissue reactions (ALTR), often associated with hypersensitivity reactions. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures tissue perfusion with the parameter Ktrans (volume transfer constant of contrast agent). Our purpose was 1) to evaluate the feasibility of DCE-MRI in patients with THA and 2) to compare DCE-MRI in patients with MoM bearings with metal-on-polyethylene (MoP) bearings, hypothesising that the perfusion index Ktrans in hips with MoM THA is higher than in hips with MoP THA.

In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients.

We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.

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.

The recent resurgence in the use of metal-on-metal bearings has led to fresh concerns over metal wear and elevated systemic levels of metal ions.

In order to establish if bearing diameter influences the release of metal ions, we compared the whole blood levels of cobalt and chromium (at one year) and the urinary cobalt and chromium output (at one to three and four to six years) following either a 50 mm or 54 mm Birmingham hip resurfacing or a 28 mm Metasul total hip replacement. The whole blood concentrations and daily output of cobalt and chromium in these time periods for both bearings were in the same range and without significant difference.

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.

Adverse reaction to wear and corrosion debris is a cause for concern in total hip arthroplasty (THA). Modular junctions are a potential source of such wear products and are associated with secondary pseudotumour formation.

We present a consecutive series of 17 patients treated at our unit for this complication following metal-on-highly cross-linked polyethylene (MoP) THA. We emphasise the risk of misdiagnosis as infection, and present the aggregate laboratory results and pathological findings in this series.

The clinical presentation was pain, swelling or instability. Solid, cystic and mixed soft-tissue lesions were noted on imaging and confirmed intra-operatively. Corrosion at the head–neck junction was noted in all cases. No bacteria were isolated on multiple pre- and intra-operative samples yet the mean erythrocyte sedimentation rate was 49 (9 to 100) and C-reactive protein 32 (0.6 to 106) and stromal polymorphonuclear cell counts were noted in nine cases.

Adverse soft–tissue reactions can occur in MoP THA owing to corrosion products released from the head–neck junction. The diagnosis should be carefully considered when investigating pain after THA. This may avoid the misdiagnosis of periprosthetic infection with an unidentified organism and mitigate the unnecessary management of these cases with complete single- or two-stage exchange.

Cite this article: Bone Joint J 2015;97-B:1024–1030.

Ceramic-on-metal (CoM) is a relatively new bearing combination for total hip arthroplasty (THA) with few reported outcomes. A total of 287 CoM THAs were carried out in 271 patients (mean age 55.6 years (20 to 77), 150 THAs in female patients, 137 in male) under the care of a single surgeon between October 2007 and October 2009. With the issues surrounding metal-on-metal bearings the decision was taken to review these patients between March and November 2011, at a mean follow-up of 34 months (23 to 45) and to record pain, outcome scores, radiological analysis and blood ion levels. The mean Oxford Hip Score was 19.2 (12 to 53), 254 patients with 268 hips (95%) had mild/very mild/no pain, the mean angle of inclination of the acetabular component was 44.8^o (28^o to 63^o), 82 stems (29%) had evidence of radiolucent lines of > 1 mm in at least one Gruen zone and the median levels of cobalt and chromium ions in the blood were 0.83 μg/L (0.24 μg/L to 27.56 μg/L) and 0.78 μg/L (0.21 μg/L to 8.84 μg/L), respectively. The five-year survival rate is 96.9% (95% confidence interval 94.7% to 99%).

Due to the presence of radiolucent lines and the higher than expected levels of metal ions in the blood, we would not recommend the use of CoM THA without further long-term follow-up. We plan to monitor all these patients regularly.

Cite this article: Bone Joint J 2015;97-B:300–5.