Aims

Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA.

Cite this article: Bone Joint Res 2021;10(4):285–297.

We evaluated the concentrations of chromium and cobalt ions in blood after metal-on-metal surface replacement arthroplasty using a wrought-forged, high carbon content chromium-cobalt alloy implant in 64 patients. At one year, mean whole blood ion levels were 1.61 μg/L (0.4 to 5.5) for chromium and 0.67 μg/L (0.23 to 2.09) for cobalt. The pre-operative ion levels, component size, female gender and the inclination of the acetabular component were inversely proportional to the values of chromium and/or cobalt ions at one year postoperatively. Other factors, such as age and level of activity, did not correlate with the levels of metal ions. We found that the levels of the ions in the serum were 1.39 and 1.37 times higher for chromium and cobalt respectively than those in the whole blood. The levels of metal ions obtained may be specific to the hip resurfacing implant and reflect its manufacturing process

Aims

Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA.

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: Bone Joint J 2013;95-B:1332–8

There is widespread concern regarding the incidence of adverse soft-tissue reactions after metal-on-metal (MoM) hip replacement. Recent National Joint Registry data have shown clear differences in the rates of failure of different designs of hip resurfacing. Our aim was to update the failure rates related to metal debris for the Articular Surface Replacement (ASR). A total of 505 of these were implanted. Kaplan-Meier analysis showed a failure rate of 25% at six years for the ASR resurfacing and of 48.8% for the ASR total hip replacement (THR). Of 257 patients with a minimum follow-up of two years, 67 (26.1%) had a serum cobalt concentration which was greater than 7 μg/l. Co-ordinate measuring machine analysis of revised components showed that all patients suffering adverse tissue reactions in the resurfacing group had abnormal wear of the bearing surfaces. Six THR patients had relatively low rates of articular wear, but were found to have considerable damage at the trunion-taper interface. Our results suggest that wear at the modular junction is an important factor in the development of adverse tissue reactions after implantation of a large-diameter MoM THR

Aims

As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients.

Aims

The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision.

Cephamandole levels in serum and drain fluid were measured in 32 knee replacement operations to determine the benefit of an intravenous dose of antibiotic at the time of tourniquet deflation. Concentrations of cephamandole in drain fluid were directly proportional to the serum concentration at the time of tourniquet release. A 'tourniquet-release' dose of antibiotic increased drain fluid concentration threefold

Metal-on-metal bearings for total hip replacement (THR) are becoming increasingly popular. Improved wear characteristics mean that these articulations are being inserted into younger patients in the form of THR and resurfacing procedures. This has led to concerns regarding potential carcinogenicity because of the increased exposure to metal ions that the procedure brings. We have studied the serum cobalt and chromium concentrations in patients who had primary, well-fixed Ring metal-on-metal THRs for more than 30 years. The levels of cobalt and chromium were elevated by five and three times, respectively compared with those in our reference groups. Metal-on-metal articulations appear to be the source of metal ions throughout the life of the prosthesis. In three patients who had undergone revision of a previous metal-on-metal THR to a metal-on-polyethylene replacement the levels of metal ions were within the normal range. The elevations of cobalt and chromium ions seen in our study were comparable with those in patients with modern metal-on-metal THRs

We prospectively studied 50 patients with the diagnosis of primary frozen shoulder. The serum lipid levels were measured in 43 of these patients and compared with those in 43 age-matched and sex-matched control subjects. The fasting serum triglyceride and cholesterol levels were significantly elevated in the frozen-shoulder group (cholesterol p < 0.01; triglyceride p < 0.02)

Aims

Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Serum 1.25 dihydroxyvitamin D concentrations were reduced in elderly patients with femoral neck fractures, irrespective of the presence of osteomalacia. This reduction was not attributable to a decrease in vitamin D binding protein. The low rate of bone turnover in these elderly patients might reduce the requirement for vitamin D and protect against the development of osteomalacia. Serum vitamin D metabolite concentration cannot be used as a screening test for osteomalacia in these patients

Aims

Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

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Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

Scoliosis seen in the chicken after pinealectomy resembles adolescent idiopathic scoliosis in man. It has been suggested that in both species, deficiency of the pineal hormone, melatonin, is responsible for this phenomenon. In nine patients with adolescent idiopathic scoliosis and in ten age- and gender-matched controls, the circadian levels of serum melatonin and the excretion of urinary 6-hydroxy-melatonin-sulphate, the principal metabolite of melatonin, were determined. There were no statistically significant differences in the secretion of serum melatonin or the excretion of urinary 6-hydroxy-melatonin-sulphate between the patients and the control group. The hypothesis of melatonin deficiency as a causative factor in the aetiology of adolescent idiopathic scoliosis cannot be supported by our data

Aims

The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.

Aims

We aimed to report the mid- to long-term rates of septic and aseptic failure after two-stage revision surgery for periprosthetic joint infection (PJI) following total hip arthroplasty (THA).

Aims

Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

Concomitant tumour resistance (CTR) is a unique phenomenon in which animals harbouring large primary tumours are resistant to the growth of smaller metastatic tumours by systemic angiogenic suppression. To examine this clinically, in ten patients with osteosarcoma, we investigated the effects of removal of the primary tumour on the development of pulmonary metastases, the systemic angiogenesis-inducing ability and the serum levels of several angiogenesis modulators. We found that removal of the primary tumour significantly elevated systemic angiogenesis-inducing ability in five patients who had post-operative recurrence of the tumour. Post-operative elevation of the angiogenesis-induced ability was suppressed by the addition of an angiogenic inhibitor, endostatin. Also, primary removal of the tumour decreased the serum levels of vascular endothelial growth factor and endostatin. These findings suggest, for the first time, the presence of CTR in patients with osteosarcoma for whom postoperative antiangiogenic therapy may be used to prevent the post-operative progression of micrometastases