Objectives. Inflammation of the retrocalcaneal bursa (RB) is a common clinical problem, particularly in professional athletes. RB inflammation is often treated with corticosteroid injections however a number of reports suggest an increased risk of Achilles tendon (AT) rupture. The aim of this cadaveric study was to describe the anatomical connections of the RB and to investigate whether it is possible for fluid to move from the RB into AT tissue. Methods. A total of 20 fresh-frozen AT specimens were used. In ten specimens, ink was injected into the RB. The remaining ten specimens were split into two groups to be injected with radiological contrast medium into the RB either with or without ultrasonography guidance (USG). Results. In specimens injected with ink, diffusion outside the RB was observed with staining of the anterior portion of the AT. In eight contrast-injected specimens (five USG, three non-USG), a similar localised diffusion pattern was observed, with the contrast identified superiorly and anteriorly. In two contrast-injected specimens (non-USG), the diffusion pattern was more extensive. Conclusion. This study confirmed the existence of connections between the RB and the AT, especially rich in the anteroinferior portion of the tendon, which should be considered a weak zone for substances injected into the RB. We hypothesise that this part of the AT might be most vulnerable to rupture after corticosteroid injections. Cite this article: P. A. Pękala, B. M. Henry, J. R. Pękala, K. Piska, K. A. Tomaszewski. The Achilles tendon and the retrocalcaneal bursa: An anatomical and radiological study. Bone Joint Res 2017;6:446–451. DOI:10.1302/2046-3758.67.BJR-2016-0340.R1

Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles. Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure. Bone Joint Res 2016;5:162–168. DOI: 10.1302/2046-3758.55.BJR-2016-0086

Objective. Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery. Methods. This was a single centre, prospective, case-control study. Following enrolment, blood samples were taken pre-operatively, and further samples were collected at day one and day seven post-operatively. One patient in the cemented group developed a deep-vein thrombosis confirmed on ultrasonography and was excluded, leaving 19 patients in this cohort (mean age 67.4, (. sd. 10.62)), and one patient in the uncemented group developed a post-operative wound infection and was excluded, leaving 19 patients (mean age 66.5, (. sd. 7.82)). Results. Both groups had a similar response with regards to the levels of C-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNFα). CD40 levels rose significantly on the cemented group over day one to day seven compared with that of the uncemented group, which occurred over the first 24 hours. The CD14/42a levels demonstrated a statistically significant increase in the cemented group (p < 0.001 first 24 hours and p = 0.02 between days one and seven). . Conclusions. The uncemented and cemented groups demonstrated significant changes in the various parameters measured at various time points but apart from CD14/42a levels, there was no significant difference in the serum markers of inflammation, coagulation and endothelial dysfunction following cemented TKR. Cite this article: Bone Joint Res 2014;3:108–16

Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2

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).

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This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients.

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To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment.

Aims. Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure. Methods. A total of 50 patients undergoing revision hip and knee arthroplasty were enrolled into a prospective study. According to Musculoskeletal Infection Society (MSIS) criteria, 25 patients were classified as infected and 25 as not infected. In all patients, neutrophil CD64 index and percentage of polymorphonuclear neutrophils (PMN%) in synovial fluid, serum CRP, ESR, and serum CD64 index levels were measured preoperatively. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed for each biomarker. Results. Serum CD64 index showed no significant difference between the two groups (p = 0.091). Synovial fluid CD64 index and PMN% discriminated good differentiation between groups of PJI and aseptic failure with AUC of 0.946 (95% confidence interval (CI) 0.842 to 0.990) and 0.938 (95% CI 0.832 to 0.987) separately. The optimal threshold value of synovial CD64 index for the diagnosis of PJI was 0.85, with a sensitivity of 92.00%, a specificity of 96.00%, and diagnostic odds ratio (DOR) of 227.11. Conclusion. The present study demonstrates that CD64 index in synovial fluid could be a promising laboratory marker for screening PJI. The cut-off values of 0.85 for synovial CD64 index has the potential to distinguish aseptic failure from PJI. Cite this article: Bone Joint J 2020;102-B(4):463–469

Objectives. Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co. 2+. ) during wear of MOM hip implants, but the toxic mechanism is not clear. Methods. To evaluate the protective effect of zinc ions (Zn. 2+. ), Balb/3T3 mouse fibroblast cells were pretreated with 50 μM Zn. 2+. for four hours. The cells were then exposed to different concentrations of CoNPs and Co. 2+. for four hours, 24 hours and 48 hours. The cell viabilities, reactive oxygen species (ROS) levels, and inflammatory cytokines were measured. Results. CoNPs and Co. 2+. can induce the increase of ROS and inflammatory cytokines, such as tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, Zn pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co. 2+. , decrease ROS production, and decrease levels of inflammatory cytokines in Balb/3T3 mouse fibroblast cells. Conclusion. These results suggest that Zn pretreatment can provide protection against inflammation and cytotoxicity induced by CoNPs and Co. 2+. in Balb/3T3 cells. Cite this article: Y. Liu, H. Zhu, H. Hong, W. Wang, F. Liu. Can zinc protect cells from the cytotoxic effects of cobalt ions and nanoparticles derived from metal-on-metal joint arthroplasties? Bone Joint Res 2017;6:649–655. DOI: 10.1302/2046-3758.612.BJR-2016-0137.R2

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Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

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This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

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Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps.

Cite this article: Bone Joint Res 2022;11(7):426–438.

Aims

This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods. In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days. Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

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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.

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Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

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The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions’ safety and efficacy.

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To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA).