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. A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.Aims
Methods
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
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
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). Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.Aims
Methods
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. We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators.Aims
Methods
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. A total of 62 patients with an ASR-HRA were included and monitored yearly postoperatively. At follow-up, serum Co and Cr levels were measured and the HHS and the HOOS were scored. In addition, preoperative patient and implant variables and the need for revision surgery were recorded. We used a linear mixed model to relate the serum Co and Cr levels to different patient-reported outcome measures (PROMs). For the survival analyses we used the Kaplan-Meier and Cox regression model.Aims
Methods
This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model.Aims
Methods
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
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). The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Aims
Methods
To analyze the short-term outcome of two types of total wrist arthroplasty (TWA) in terms of wrist function, migration, and periprosthetic bone behaviour. A total of 40 patients suffering from non-rheumatoid wrist arthritis were enrolled in a randomized controlled trial comparing the ReMotion and Motec TWAs. Patient-rated and functional outcomes, radiological changes, blood metal ion levels, migration measured by model-based radiostereometric analysis (RSA), bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), complications, loosening, and revision rates at two years were compared.Aims
Methods
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
Treatment outcomes for methicillin-resistant Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation.Aims
Methods
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. This retrospective study, conducted at the Sint Maartenskliniek, Nijmegen, the Netherlands, included 88 patients who underwent DAIR within 90 days of revision total hip or total knee arthroplasty between 2012 and 2019. Details of the surgical procedures and PJI were collected. Univariate analysis and a subgroup analysis of the culture-positive group were performed. Kaplan-Meier survivorship curves were constructed.Aims
Methods
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. Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references.Aims
Methods
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. A total of 355 patients (400 hips) were treated with Conserve Plus HRA between November 1996 and November 2000. There were 96 female (27%) and 259 male patients (73%). Their mean age was 48.2 years (SD 10.9). The University of California, Los Angeles (UCLA) hip scores and 12-item Short Form Survey (SF-12) quality of life scores were reported. Survivorship was assessed using Kaplan-Meier analyses.Aims
Methods
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. In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups.Aims
Methods
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 ( A total of 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every six hours during a 24-hour period. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin Aims
Methods
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. A total of 42 patients (43 hips) were revised after HRA at our centre to a variety of devices, including four HRA and 39 total hip arthroplasties (THAs). In addition to perioperative complications, University of California, Los Angeles (UCLA) hip scores and 12-Item Short-Form Health Survey questionnaire (SF-12) quality of life scores were collected at follow-up visits after the primary HRA and after revision surgery.Aims
Methods
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. Osteomyelitis was induced in nine pigs by inoculation of 104 colony-forming units (CFUs) of Aims
Methods
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:
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. Murine peritoneal macrophages were cultured and placed on stainless steel, CoCrMo, and Ti6Al4V discs into a 96-well plate. Cells were activated with interferon gamma and lipopolysaccharide. Macrophages on stainless steel discs produced significantly more nitric oxide (NO) compared to their control counterparts after eight to ten days and remained elevated for the duration of the experiment.Aims
Methods
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. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF.Aims
Methods
The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 ( Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (Objectives
Methods
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. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3.Objectives
Methods
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. We analyzed the bacterial composition of 22 SF samples collected from 11 patients with PJIs (first- and second-stage surgery). The V3 and V4 region of bacteria was assessed by comparing the taxonomic distribution of the 16S rDNA amplicons with microbiome sequencing analysis. We also compared the results of bacterial detection from different methods including 16S metagenomics, traditional cultures, and targeted Sanger sequencing.Objectives
Methods
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. Serum Co and Cr levels were measured prospectively in 24 patients with a modular dual-mobility construct and a ceramic femoral head. Patients with CoCr heads or contralateral THAs with CoCr heads were excluded. The mean age was 63 years (35 to 83), with 13 patients (54%) being female. The mean follow-up was four years (2 to 7). Indications for modular dual-mobility were prosthetic joint infection treated with two-stage exchange and subsequent reimplantation (n = 8), ALTR revision (n = 7), complex primary THA (n = 7), recurrent instability (n = 1), and periprosthetic femoral fracture (n = 1). The mean preoperative Co and Cr in patients revised for an ALTR were 29.7 μg/l (2 to 146) and 21.5 μg/l (1 to 113), respectively.Aims
Patients and Methods
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). A total of 72 patients (mean age 46.6 years (37 to 55); 43 men, 29 women; 91 hips) who underwent cementless primary MoM THA with a 28 mm modular head were included. The mean follow-up duration was 20.3 years (18 to 24). All patients had CT scans at a mean 15.1 years (13 to 19) after the index operation and subsequent follow-up at a mean of 20.2 years (18 to 24). Pseudotumour volume, type of mass, and new-onset pseudotumours were evaluated using CT scanning. Clinical outcomes were assessed by Harris Hip Score (HHS) and the presence of groin pain. Serum metal ion (cobalt (Co) and chromium (Cr)) levels were measured at the latest follow-up.Aims
Patients and Methods
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. 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.Objectives
Methods
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. Between December 2009 and December 2011, 62 patients underwent
MoM THA with a large femoral head (Magnum group) and 57 patients
an MoM THA with a conventional femoral head (conventional group).
Clinical outcome was assessed using the Harris Hip score, University
of California, Los Angeles (UCLA) activity score and EuroQol-5D
(EQ-5D). Blood metal ion levels were measured and MRI scans were
analyzed at a minimum of five years postoperatively.Aims
Patients and Methods
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). We examined the influence of the ALVAL grade on synovial fluid Co and Cr concentrations following adjustment for patient and device variables, including volumetric wear rates. Initially restricting the analysis to include only patients with one MoM hip resurfacing device, we performed multiple regression analyses of prospectively collected data. We then repeated the same statistical approach using results from a larger cohort with different MoM designs, including total hip arthroplasties.Objectives
Patients and Methods
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. 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.Aims
Patients and Methods
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. A hospital case-control study (n = 149/146) examined the association
between tobacco smoke exposure and Perthes’ disease, adjusting for
area-level socioeconomic deprivation. Tobacco smoke exposure was
assessed by parental questionnaire of smoking habits during pregnancy,
and by quantitative assay of current exposure using the urinary
cotinine-creatinine ratio, which is a widely used and validated
measure of tobacco smoke exposure.Aims
Patients and Methods
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. We used multiple logistic regression to determine what variables
differed between the patients who had high and low cobalt (CoS)
and chromium (CrS) serum ion concentrations within a cohort of patients
with low (<
10 mm) CPR distances. A total of 56 patients treated
with unilateral hip resurfacing arthroplasty (HRA) had CoS and CrS
ion studies performed more than one year after surgery. The mean
age of the patients at the time of surgery was 51.7 years (29 to
70), with 38 women (68%) and 18 men (32%).Aims
Patients and Methods
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
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. In this study, a coordinate measuring machine (CMM) was used to measure the wear on five failed cementless Biomet Magnum/ReCap/ Taperloc large head MoM THAs, along with one Biomet ReCap resurfacing joint. Surface roughness measurements were also taken. The reason for revision of these implants was pain and/or adverse reaction to metal debris (ARMD) and/or elevated blood metal ion levels.Objectives
Methods
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
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 pilot study, 16 patients with primary THA were recruited (eight MoM, eight MoP). DCE-MRI of the hip was performed at 1.5 Tesla (T). For each patient, Ktrans was computed voxel-by-voxel in all tissue lateral to the bladder. The mean Ktrans for all voxels was then calculated. These values were compared with respect to implant type and gender, and further correlated with clinical parameters.Objectives
Methods
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:
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
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:
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:
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 44.8o (28o to
63o), 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:
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:
The issues surrounding raised levels of metal
ions in the blood following large head metal-on-metal total hip replacement
(THR), such as cobalt and chromium, have been well documented. Despite
the national popularity of uncemented metal-on-polyethylene (MoP)
THR using a large-diameter femoral head, few papers have reported
the levels of metal ions in the blood following this combination.
Following an isolated failure of a 44 mm Trident–Accolade uncemented
THR associated with severe wear between the femoral head and the
trunnion in the presence of markedly elevated levels of cobalt ions
in the blood, we investigated the relationship between modular femoral head
diameter and the levels of cobalt and chromium ions in the blood
following this THR. A total of 69 patients received an uncemented Trident–Accolade
MoP THR in 2009. Of these, 43 patients (23 men and 20 women, mean
age 67.0 years) were recruited and had levels of cobalt and chromium
ions in the blood measured between May and June 2012. The patients
were then divided into three groups according to the diameter of
the femoral head used: 12 patients in the 28 mm group (controls),
18 patients in the 36 mm group and 13 patients in the 40 mm group.
A total of four patients had identical bilateral prostheses in situ
at phlebotomy: one each in the 28 mm and 36 mm groups and two in
the 40 mm group. There was a significant increase in the mean levels of cobalt
ions in the blood in those with a 36 mm diameter femoral head compared
with those with a 28 mm diameter head (p = 0.013). The levels of
cobalt ions in the blood were raised in those with a 40 mm diameter
head but there was no statistically significant difference between
this group and the control group (p = 0.152). The levels of chromium
ions in the blood were normal in all patients. The clinical significance of this finding is unclear, but we
have stopped using femoral heads with a diameter of ≤ 36 mm, and
await further larger studies to clarify whether, for instance, this
issue particularly affects this combination of components. Cite this article:
A retrospective study was conducted to investigate
the changes in metal ion levels in a consecutive series of Birmingham
Hip Resurfacings (BHRs) at a minimum ten-year follow-up. We reviewed
250 BHRs implanted in 232 patients between 1998 and 2001. Implant
survival, clinical outcome (Harris hip score), radiographs and serum chromium
(Cr) and cobalt (Co) ion levels were assessed. Of 232 patients, 18 were dead (five bilateral BHRs), 15 lost
to follow-up and ten had been revised. The remaining 202 BHRs in
190 patients (136 men and 54 women; mean age at surgery 50.5 years
(17 to 76)) were evaluated at a minimum follow-up of ten years (mean
10.8 years (10 to 13.6)). The overall implant survival at 13.2 years
was 92.4% (95% confidence interval 90.8 to 94.0). The mean Harris
hip score was 97.7 (median 100; 65 to 100). Median and mean ion
levels were low for unilateral resurfacings (Cr: median 1.3 µg/l,
mean
1.95 µg/l (<
0.5 to 16.2); Co: median 1.0 µg/l, mean 1.62 µg/l
(<
0.5 to 17.3)) and bilateral resurfacings (Cr: median 3.2 µg/l,
mean 3.46 µg/l (<
0.5 to 10.0); Co: median 2.3 µg/l, mean 2.66
µg/l (<
0.5 to 9.5)). In 80 unilateral BHRs with sequential ion
measurements, Cr and Co levels were found to decrease significantly
(p <
0.001) from the initial assessment at a median of six years
(4 to 8) to the last assessment at a median of 11 years (9 to 13),
with a mean reduction of 1.24 µg/l for Cr and 0.88 µg/l for Co.
Three female patients had a >
2.5 µg/l increase of Co ions, associated with
head sizes ≤ 50 mm, clinical symptoms and osteolysis. Overall, there
was no significant difference in change of ion levels between genders
(Cr, p = 0.845; Co, p = 0.310) or component sizes (Cr, p = 0.505;
Co, p = 0.370). Higher acetabular component inclination angles correlated
with greater change in ion levels (Cr, p = 0.013; Co, p = 0.002).
Patients with increased ion levels had lower Harris hip scores (p
= 0.038). In conclusion, in well-functioning BHRs the metal ion levels
decreased significantly at ten years. An increase >
2.5 µg/l was
associated with poor function. Cite this article:
The aims of this study were to evaluate the incidence
of local argyria in patients with silver-coated megaprostheses and
to identify a possible association between argyria and elevated
levels of silver both locally and in the blood. Between 2004 and
2011, 32 megaprostheses with silver coatings were implanted in 20
female and 12 male patients following revision arthroplasty for
infection or resection of a malignant tumour, and the levels of
silver locally in drains and seromas and in the blood were determined.
The mean age of the patients was 46 years (10 to 81); one patient
died in the immediate post-operative period and was excluded. Seven patients (23%) developed local argyria after a median of
25.7 months (interquartile range 2 to 44.5). Patients with and without
local argyria had comparable levels of silver in the blood and aspiration
fluids. The length of the implant did not influence the development
of local argyria. Patients with clinical evidence of local argyria
had no neurological symptoms and no evidence of renal or hepatic
failure. Thus, we conclude that the short-term surveillance of blood
silver levels in these patients is not required. Cite this article:
The aims of this piece of work were to: 1) record the background
concentrations of blood chromium (Cr) and cobalt (Co) concentrations
in a large group of subjects; 2) to compare blood/serum Cr and Co
concentrations with retrieved metal-on-metal (MoM) hip resurfacings;
3) to examine the distribution of Co and Cr in the serum and whole
blood of patients with MoM hip arthroplasties; and 4) to further
understand the partitioning of metal ions between the serum and
whole blood fractions. A total of 3042 blood samples donated to the local transfusion
centre were analysed to record Co and Cr concentrations. Also, 91
hip resurfacing devices from patients who had given pre-revision
blood/serum samples for metal ion analysis underwent volumetric
wear assessment using a coordinate measuring machine. Linear regression analysis
was carried out and receiver operating characteristic curves were
constructed to assess the reliability of metal ions to identify
abnormally wearing implants. The relationship between serum and
whole blood concentrations of Cr and Co in 1048 patients was analysed
using Bland-Altman charts. This relationship was further investigated
in an Objectives
Methods
The Articular Surface Replacement (ASR) hip resurfacing arthroplasty has a failure rate of 12.0% at five years, compared with 4.3% for the Birmingham Hip Resurfacing (BHR). We analysed 66 ASR and 64 BHR explanted metal-on-metal hip replacements with the aim of understanding their mechanisms of failure. We measured the linear wear rates of the acetabular and femoral components and analysed the clinical cause of failure, pre-revision blood metal ion levels and orientation of the acetabular component. There was no significant difference in metal ion levels (chromium, p = 0.82; cobalt, p = 0.40) or head wear rate (p = 0.14) between the two groups. The ASR had a significantly increased rate of wear of the acetabular component (p = 0.03) and a significantly increased occurrence of edge loading (p <
0.005), which can be attributed to differences in design between the ASR and BHR. The effects of differences in design on the
In 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.
