Aims

Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

Objectives. T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty. Methods. In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry. Results. The percentages of CD4+ T-cell subtypes in PB were not different between groups. The CD4+ T-cells in the SF of MoM hips showed a completely different distribution of phenotypes compared with that found in the PB in the same patients, including significantly decreased CD4+ T-central memory cells (p < 0.05) and increased T-effector memory cells (p < 0.0001) in the SF. Inducible co-stimulator (ICOS) was the only co-stimulatory molecule with different expression on CD4+ CD28+ cells between groups. In PB, ICOS expression was increased in MoM (p < 0.001) and MoP (p < 0.05) cases compared with the controls. In SF, ICOS expression was increased in MoM hips compared with MoP hips (p < 0.05). Conclusions. Increased expression of ICOS on CD4+ T-cells in PB and SF of patients with failed arthroplasties suggests that these cells are activated and involved in generating immune responses. Variations in ICOS expression between MoM and MoP hips may indicate different modes of arthroplasty failure. Cite this article: Professor P. A. Revell. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. Bone Joint Res 2016;5:52–60. doi: 10.1302/2046-3758.52.2000574

Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes. Cite this article: Bone Joint Res 2023;12(12):722–733

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776

Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N), interleukin (IL)-18, and IL-1β in NPCs were upregulated, and the number of propidium iodide (PI)-positive cells was also increased, which was able to be alleviated by pretreatment with melatonin. The protective effect of melatonin on pyroptosis was blunted by both the melatonin receptor antagonist luzindole and the nuclear factor erythroid 2–related factor 2 (Nrf2) inhibitor ML385. In addition, the expression of the transcription factor Nrf2 was up- or downregulated when the melatonin receptor was activated or blocked by melatonin or luzindole, respectively. Conclusion. Melatonin protects NPCs against reactive oxygen species-induced pyroptosis by upregulating the transcription factor Nrf2 via melatonin receptors. Cite this article: Bone Joint Res 2023;12(3):202–211

Aims. Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (. 99m. Tc-UBI. 29-41. -Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods. Methods. 99m. Tc-UBI. 29-41. -Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. Results. Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria. Conclusion. The hybrid tracer . 99m. Tc-UBI. 29-41. -Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies. Cite this article: Bone Joint Res 2023;12(1):72–79

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors. Cite this article: Bone Joint Res 2022;11(8):561–574

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. Methods. 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. Results. Rats receiving intra-articular vancomycin showed the best outcomes among the four treatment groups, with negative bacterial cultures, increased weight gain, increased capacity for weightbearing activities, increased residual bone volume preservation, and reduced inflammatory reactions in the joint tissues, indicating MRSA eradication in the knee. The vancomycin-spacer and/or systemic vancomycin failed to eliminate the MRSA infections following a two-week antibiotic course. Serum vancomycin levels did not reach nephrotoxic levels in any group. Mild renal histopathological changes, without changes in serum creatinine levels, were observed in the intraperitoneal vancomycin group compared with the intra-articular vancomycin group, but no changes in hepatic structure or serum alanine aminotransferase or aspartate aminotransferase levels were observed. No local complications were observed, such as sinus tract or non-healing surgical incisions. Conclusion. Intra-articular vancomycin injection was effective and safe for PJI control following debridement and spacer implantation in a rat model during two-stage revision arthroplasties, with better outcomes than systemic vancomycin administration. Cite this article: Bone Joint Res 2022;11(6):371–385

Aims. This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-α) on osteoblasts in metal wear-induced bone loss. Methods. TNF-α immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-α were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results. Macrophages, lymphocytes, and endothelial cells displayed strong TNF-α immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-α with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-α expression in these cells. Cobalt-treated MM6 cells secreted more TNF-α than control cells, reflecting the role of metal wear products in activating the TNF-α pathway in the myeloid cells. While TNF-α did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-α-induced apoptosis. TNF-α further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1α, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-Lα. In addition, TNF-α decreased pro-collagen I α 1 secretion without diminishing its synthesis. TNF-α also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. Conclusion. The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-α and may be involved in metal wear debris-induced periprosthetic bone loss. Cite this article: Bone Joint Res 2020;9(11):827–839

Objectives. Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery. Methods. A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs). Results. Failed-repair stump tissue showed cellular accumulation of crumpled and disoriented collagen fibres. Compared with normal tendon, stump tissue had significantly higher gene expression of collagens I and III, matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). The stump TDSCs presented both mesenchymal stem and haematopoietic cell markers with significantly increased expression of CD34, CD44, and CD90 markers. Stump TDSCs exhibited similar migration but a lower proliferation rate, as well as similar osteogenic differentiation but a lower chondrogenic/adipogenic differentiation capability, compared with normal TDSCs. Stump TDSCs also showed increasing levels of SRY-box 2 (Sox2), octamer-binding transcription factor 4 (Oct4), tenomodulin (TNMD), and scleraxis (Scx) protein and gene expression. Conclusion. We found that a failed repair stump had increased cellularity that preserved both mesenchymal and haematopoietic stem cell characteristics, with higher collagen synthesis, MMP, and growth factor gene expression. This study provides evidence that tendon stump tissue has regenerative potential. Cite this article: C-C. Lu, T. Zhang, R. L. Reisdorf, P. C. Amadio, K-N. An, S. L. Moran, A. Gingery, C. Zhao. Biological analysis of flexor tendon repair-failure stump tissue: A potential recycling of tissue for tendon regeneration. Bone Joint Res 2019;8:232–245. DOI: 10.1302/2046-3758.86.BJR-2018-0239.R1

Aims

This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model.

Aims

Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH.

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We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

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This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images.

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We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty.

Cite this article: Bone Joint Res 2023;12(5):309–310.

Despite the vast quantities of published artificial intelligence (AI) algorithms that target trauma and orthopaedic applications, very few progress to inform clinical practice. One key reason for this is the lack of a clear pathway from development to deployment. In order to assist with this process, we have developed the Clinical Practice Integration of Artificial Intelligence (CPI-AI) framework – a five-stage approach to the clinical practice adoption of AI in the setting of trauma and orthopaedics, based on the IDEAL principles (https://www.ideal-collaboration.net/). Adherence to the framework would provide a robust evidence-based mechanism for developing trust in AI applications, where the underlying algorithms are unlikely to be fully understood by clinical teams.

Cite this article: Bone Joint Res 2024;13(9):507–512.

Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

Aims

Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

The use of artificial intelligence (AI) is rapidly growing across many domains, of which the medical field is no exception. AI is an umbrella term defining the practical application of algorithms to generate useful output, without the need of human cognition. Owing to the expanding volume of patient information collected, known as ‘big data’, AI is showing promise as a useful tool in healthcare research and across all aspects of patient care pathways. Practical applications in orthopaedic surgery include: diagnostics, such as fracture recognition and tumour detection; predictive models of clinical and patient-reported outcome measures, such as calculating mortality rates and length of hospital stay; and real-time rehabilitation monitoring and surgical training. However, clinicians should remain cognizant of AI’s limitations, as the development of robust reporting and validation frameworks is of paramount importance to prevent avoidable errors and biases. The aim of this review article is to provide a comprehensive understanding of AI and its subfields, as well as to delineate its existing clinical applications in trauma and orthopaedic surgery. Furthermore, this narrative review expands upon the limitations of AI and future direction.

Cite this article: Bone Joint Res 2023;12(7):447–454.

Aims

Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella.

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This cross-sectional study aimed to investigate the in vivo ankle kinetic alterations in patients with concomitant chronic ankle instability (CAI) and osteochondral lesion of the talus (OLT), which may offer opportunities for clinician intervention in treatment and rehabilitation.

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To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI).

Aims

Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

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Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments.

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This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment.

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A substantial fraction of patients undergoing knee arthroplasty (KA) or hip arthroplasty (HA) do not achieve an improvement as high as the minimal clinically important difference (MCID), i.e. do not achieve a meaningful improvement. Using three patient-reported outcome measures (PROMs), our aim was: 1) to assess machine learning (ML), the simple pre-surgery PROM score, and logistic-regression (LR)-derived performance in their prediction of whether patients undergoing HA or KA achieve an improvement as high or higher than a calculated MCID; and 2) to test whether ML is able to outperform LR or pre-surgery PROM scores in predictive performance.

Aims

Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

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This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification.

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Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up.

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

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The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

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Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism.

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This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

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The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip.

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The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction.

Aims

Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Aims

Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands.

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Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

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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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This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

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The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold.

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This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI).

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310

Aims. Preoperative diagnosis is important for revision surgery after prosthetic joint infection (PJI). The purpose of our study was to determine whether reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which is used to detect bacterial ribosomal RNA (rRNA) preoperatively, can reveal PJI in low volumes of aspirated fluid. Methods. We acquired joint fluid samples (JFSs) by preoperative aspiration from patients who were suspected of having a PJI and failed arthroplasty; patients with preoperative JFS volumes less than 5 ml were enrolled. RNA-based polymerase chain reaction (PCR) and bacterial culture were performed, and diagnostic efficiency was compared between the two methods.According to established Musculoskeletal Infection Society (MSIS) criteria, 21 of the 33 included patients were diagnosed with PJI. Results. RNA-based PCR exhibited 57.1% sensitivity, 91.7% specificity, 69.7% accuracy, 92.3% positive predictive value, and 55.0% negative predictive value. The corresponding values for culture were 28.6%, 83.3%, 48.5%, 75.0%, and 40.0%, respectively. A significantly higher sensitivity was thus obtained with the PCR method versus the culture method. Conclusion. In situations in which only a small JFS volume can be acquired, RNA-based PCR analysis increases the utility of preoperative puncture for patients who require revision surgery due to suspected PJI. Cite this article:Bone Joint Res. 2020;9(5):219–224

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To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms.

Objectives. All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. Materials and Methods. A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05. Results. Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (. se). 17.6) compared with the all-suture anchors (mean 133.1 N . se. 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm . se. 2.5 versus 12.5 mm . se. 0.3; and 29.6 mm . se. 4.8 versus 17.0 mm . se. 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3). All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage. Conclusion. We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon’s choice of implant, in the context of the clinical scenario. Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82–89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

Aims

We aimed to evaluate the utility of ⁶⁸Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with ^99mTc-methylene bisphosphonates (^99mTc-MDP) bone scan.

Aims

Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release.

Aims

With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI).

Aims

Hip arthroplasty aims to accurately recreate joint biomechanics. Considerable attention has been paid to vertical and horizontal offset, but femoral head centre in the anteroposterior (AP) plane has received little attention. This study investigates the accuracy of restoration of joint centre of rotation in the AP plane.

Objectives. The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. Methods. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Results. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Conclusion. Our review helped to identify factors that can influence serum biomarkers’ level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: A. Saleh, J. George, M. Faour, A. K. Klika, C. A. Higuera. Serum biomarkers in periprosthetic joint infections. Bone Joint Res 2018;7:85–93. DOI: 10.1302/2046-3758.71.BJR-2017-0323

Aims

Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning.

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Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.

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Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing.

Objectives. Taper junctions between modular hip arthroplasty femoral heads and stems fail by wear or corrosion which can be caused by relative motion at their interface. Increasing the assembly force can reduce relative motion and corrosion but may also damage surrounding tissues. The purpose of this study was to determine the effects of increasing the impaction energy and the stiffness of the impactor tool on the stability of the taper junction and on the forces transmitted through the patient’s surrounding tissues. Methods. A commercially available impaction tool was modified to assemble components in the laboratory using impactor tips with varying stiffness at different applied energy levels. Springs were mounted below the modular components to represent the patient. The pull-off force of the head from the stem was measured to assess stability, and the displacement of the springs was measured to assess the force transmitted to the patient’s tissues. Results. The pull-off force of the head increased as the stiffness of the impactor tip increased but without increasing the force transmitted through the springs (patient). Increasing the impaction energy increased the pull-off force but also increased the force transmitted through the springs. Conclusions. To limit wear and corrosion, manufacturers should maximize the stiffness of the impactor tool but without damaging the surface of the head. This strategy will maximize the stability of the head on the stem for a given applied energy, without influencing the force transmitted through the patient’s tissues. Current impactor designs already appear to approach this limit. Increasing the applied energy (which is dependent on the mass of the hammer and square of the contact speed) increases the stability of the modular connection but proportionally increases the force transmitted through the patient’s tissues, as well as to the surface of the head, and should be restricted to safe levels. Cite this article: A. Krull, M. M. Morlock, N. E. Bishop. Maximizing the fixation strength of modular components by impaction without tissue damage. Bone Joint Res 2018;7:196–204. DOI: 10.1302/2046-3758.72.BJR-2017-0078.R2

Objectives. The aim of this study was to investigate the structural integrity of torn and non-torn human acetabular labral tissue. Methods. A total of 47 human labral specimens were obtained from a biobank. These included 22 torn specimens and 25 control specimens from patients undergoing total hip arthroplasty with macroscopically normal labra. The specimens underwent dynamic shear analysis using a rheometer to measure storage modulus, as an indicator of structural integrity. Results. There was a significant difference in the storage modulus between torn (mean modulus = 2144.08 Pa) and non-torn (3178.1 Pa) labra (p = 0.0001). Conclusion. The acetabular labrum of young patients with a tear has significantly reduced structural integrity compared with a non-torn labrum in older patients with end-stage osteoarthritis. This study contributes to the understanding of the biomechanics of labral tears, and the observation of reduced structural integrity in torn labra may explain why some repairs fail. Our data demonstrate that labral tears probably have a relatively narrow phenotype, presenting a basis for further investigations that will provide quantifiable data to support their classification and a means to develop a standardized surgical technique for their repair. This study also demonstrates the value of novel biomechanical testing methods in investigating pathological tissues of orthopaedic interest. Cite this article: A. K. Woods, J. Broomfield, P. Monk, F. Vollrath, S. Glyn-Jones. Dynamic shear analysis: a novel method to determine mechanical integrity of normal and torn human acetabular labra: Implications for prediction of outcome of repair. Bone Joint Res 2018;7:440–446. DOI: 10.1302/2046-3758.77.BJR-2017-0282.R2

Aims

We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants.

Aims

To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities.

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. Methods. 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. Results. The mean wear rate of the articulating surfaces of the heads and acetabular components of all six joints tested was found to be 6.1 mm. 3. /year (4.1 to 7.6). The mean wear rate of the femoral head tapers of the five THAs was 0.054 mm. 3. /year (0.021 to 0.128) with a mean maximum wear depth of 5.7 µm (4.3 to 8.5). Conclusion. Although the taper wear was relatively low, the wear from the articulating surfaces was sufficient to provide concern and was potentially large enough to have been the cause of failure of these joints. The authors believe that patients implanted with the ReCap system, whether the resurfacing prosthesis or the THA, should be closely monitored. Cite this article: S. C. Scholes, B. J. Hunt, V. M. Richardson, D. J. Langton, E. Smith, T. J. Joyce. Explant analysis of the Biomet Magnum/ReCap metal-on-metal hip joint. Bone Joint Res 2017;6:113–122. DOI: 10.1302/2046-3758.62.BJR-2016-0130.R2

Aims

The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone.

Objectives. To assess the effectiveness of a modified tibial tubercle osteotomy as a treatment for arthroscopically diagnosed chondromalacia patellae. Methods. A total of 47 consecutive patients (51 knees) with arthroscopically proven chondromalacia, who had failed conservative management, underwent a modified Fulkerson tibial tubercle osteotomy. The mean age was 34.4 years (19.6 to 52.2). Pre-operatively, none of the patients exhibited signs of patellar maltracking or instability in association with their anterior knee pain. The minimum follow-up for the study was five years (mean 72.6 months (62 to 118)), with only one patient lost to follow-up. Results. A total of 50 knees were reviewed. At final follow-up, the Kujala knee score improved from 39.2 (12 to 63) pre-operatively to 57.7 (16 to 89) post-operatively (p < 0.001). The visual analogue pain score improved from 7.8 (4 to 10) pre-operatively to 5.0 (0 to 10) post-operatively. Overall patient satisfaction with good or excellent results was 72%. Patients with the lowest pre-operative Kujala score benefitted the most. Older patients benefited less than younger ones. The outcome was independent of the grade of chondromalacia. Six patients required screw removal. There were no major complications. Conclusions. We conclude that this modification of the Fulkerson procedure is a safe and useful operation to treat anterior knee pain in well aligned patellofemoral joints due to chondromalacia patellae in adults, when conservative measures have failed

Aims

Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model.

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy.

Cite this article: Bone Joint Res 2021;10(6):340–347.

Aims

The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants.

Objectives. We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling. Materials and Methods. Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically. Results. At 16 weeks post-operatively, histological scores amongst treatment groups were not statistically different (TMPG: overall 12.7, cartilage 8.6, bone 4.1; TM: overall 14.2, cartilage 9.5, bone 4.9; ED: overall 13.6, cartilage 9.1, bone 4.5). Metal scaffolds were incorporated into the surrounding bone, both in TM and TMPG. The sGAG yield was lower in the neo-cartilage regions compared with the articular cartilage (AC) controls (TMPG 20.8/AC 39.5, TM 25.6/AC 33.3, ED 32.2/AC 40.2 µg sGAG/1 mg respectively), with statistical significance being achieved for the TMPG group (p < 0.05). Hypercellularity of the neo-cartilage was found in TM and ED, as the dsDNA content was significantly higher (p < 0.05) compared with contralateral AC controls (TM 126.7/AC 71.1, ED 99.3/AC 62.8 ng dsDNA/1 mg). The highest type II collagen content was found in neo-cartilage after TM compared with TMPG and ED (TM 60%/TMPG 40%/ED 39%). Inter-treatment differences were not significant. Conclusions. TM is a highly suitable material for the reconstitution of osseous defects. TM enables excellent bony ingrowth and fast integration. However, combined with autologous periosteum, such a biocomposite failed to promote satisfactory neo-cartilage formation. Cite this article: E. H. Mrosek, H-W. Chung, J. S. Fitzsimmons, S. W. O’Driscoll, G. G. Reinholz, J. C. Schagemann. Porous tantalum biocomposites for osteochondral defect repair: A follow-up study in a sheep model. Bone Joint J 2016;5:403–411. DOI: 10.1302/2046-3758.59.BJR-2016-0070.R1

Objectives. Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain. Methods. We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells. Results. We showed that both N- and C-terminal PTHrP peptides at 100 nM decreased reactive oxygen species production and forkhead box protein O activation following hydrogen peroxide (H. 2. O. 2. )-induced oxidation, which was related to decreased lipid oxidative damage and caspase-3 activation in these cells. This was associated with their ability to restore the deleterious effects of H. 2. O. 2. on cell growth and alkaline phosphatase activity, as well as on the expression of various osteoblast differentiation genes. The addition of Rp-cyclic 3′,5′-hydrogen phosphorothioate adenosine triethylammonium salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2 inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal PTHrP. Conclusion. These findings indicate that the antioxidant properties of PTHrP act through its N- and C-terminal domains and provide novel insights into the osteogenic action of PTHrP. Cite this article: S. Portal-Núñez, J. A. Ardura, D. Lozano, I. Martínez de Toda, M. De la Fuente, G. Herrero-Beaumont, R. Largo, P. Esbrit. Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic cells through its N-terminal and osteostatin domains. Bone Joint Res 2018;7:58–68. DOI: 10.1302/2046-3758.71.BJR-2016-0242.R2

Aims

Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur.

Patient-reported outcome measures (PROMs) are being used increasingly in total knee arthroplasty (TKA). We conducted a systematic review aimed at identifying psychometrically sound PROMs by appraising their measurement properties. Studies concerning the development and/or evaluation of the measurement properties of PROMs used in a TKA population were systematically retrieved via PubMed, Web of Science, Embase, and Scopus. Ratings for methodological quality and measurement properties were conducted according to updated COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. Of the 155 articles on 34 instruments included, nine PROMs met the minimum requirements for psychometric validation and can be recommended to use as measures of TKA outcome: Oxford Knee Score (OKS); OKS–Activity and Participation Questionnaire (OKS-APQ); 12-item short form Knee Injury and Osteoarthritis Outcome (KOOS-12); KOOS Physical function Short form (KOOS-PS); Western Ontario and McMaster Universities Arthritis Index-Total Knee Replacement function short form (WOMAC-TKR); Lower Extremity Functional Scale (LEFS); Forgotten Joint Score (FJS); Patient’s Knee Implant Performance (PKIP); and University of California Los Angeles (UCLA) activity score. The pain and function subscales in WOMAC, as well as the pain, function, and quality of life subscales in KOOS, were validated psychometrically as standalone subscales instead of as whole instruments. However, none of the included PROMs have been validated for all measurement properties. Thus, further studies are still warranted to evaluate those PROMs. Use of the other 25 scales and subscales should be tempered until further studies validate their measurement properties.

Cite this article: Bone Joint Res 2021;10(3):203–217.

Objectives. Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. Methods. To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. Results. eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. Conclusion. Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression. Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186–193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2

Aims

The aim of this study was to systematically compare the safety and accuracy of robot-assisted (RA) technique with conventional freehand with/without fluoroscopy-assisted (CT) pedicle screw insertion for spine disease.

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To determine whether half-threaded screw holes in a new titanium locking plate design can substantially decrease the notch effects of the threads and increase the plate fatigue life.

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Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones.

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In wound irrigation, 1 mM ethylenediaminetetraacetic acid (EDTA) is more efficacious than normal saline (NS) in removing bacteria from a contaminated wound. However, the optimal EDTA concentration remains unknown for different animal wound models.

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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.

Objectives. Third-body wear is believed to be one trigger for adverse results with metal-on-metal (MOM) bearings. Impingement and subluxation may release metal particles from MOM replacements. We therefore challenged MOM bearings with relevant debris types of cobalt–chrome alloy (CoCr), titanium alloy (Ti6Al4V) and polymethylmethacrylate bone cement (PMMA). Methods. Cement flakes (PMMA), CoCr and Ti6Al4V particles (size range 5 µm to 400 µm) were run in a MOM wear simulation. Debris allotments (5 mg) were inserted at ten intervals during the five million cycle (5 Mc) test. . Results. In a clean test phase (0 Mc to 0.8 Mc), lubricants retained their yellow colour. Addition of metal particles at 0.8 Mc turned lubricants black within the first hour of the test and remained so for the duration, while PMMA particles did not change the colour of the lubricant. Rates of wear with PMMA, CoCr and Ti6Al4V debris averaged 0.3 mm. 3. /Mc, 4.1Â mm. 3. /Mc and 6.4 mm. 3. /Mc, respectively. . Conclusions. Metal particles turned simulator lubricants black with rates of wear of MOM bearings an order of magnitude higher than with control PMMA particles. This appeared to model the findings of black, periarticular joint tissues and high CoCr wear in failed MOM replacements. The amount of wear debris produced during a 500 000-cycle interval of gait was 30 to 50 times greater than the weight of triggering particle allotment, indicating that MOM bearings were extremely sensitive to third-body wear. Cite this article: Bone Joint Res 2015;4:29–37

Fractures of the proximal femur are one of the greatest challenges facing the medical community, constituting a heavy socioeconomic burden worldwide. The National Hip Fracture Audit currently provides a framework for service evaluation. This evaluation is based upon the assessment of process rather than assessment of patient-centred outcome and therefore it fails to provide meaningful data regarding the clinical effectiveness of treatments. This study aims to capture data from the cohort of patients who present with a fracture of the proximal femur at a single United Kingdom Major Trauma Centre. Patient-centred outcomes will be recorded and provide a baseline cohort within which to test the clinical effectiveness of experimental interventions

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The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients.

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Many biomechanical studies have shown that the weakest biomechanical point of a rotator cuff repair is the suture-tendon interface at the medial row. We developed a novel double rip-stop (DRS) technique to enhance the strength at the medial row for rotator cuff repair. The objective of this study was to evaluate the biomechanical properties of the DRS technique with the conventional suture-bridge (SB) technique and to evaluate the biomechanical performance of the DRS technique with medial row knots.

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This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI.

Aims

To investigate the effect of polyethylene manufacturing characteristics and irradiation dose on the survival of cemented and reverse hybrid total hip arthroplasties (THAs).

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data.

Cite this article: Bone Joint Res 2020;9(11):798–807.

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Evaluate if treating an unstable femoral neck fracture with a locking plate and spring-loaded telescoping screw system would improve construct stability compared to gold standard treatment methods.

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Femoroacetabular impingement (FAI) describes abnormal bony contact of the proximal femur against the acetabulum. The term was first coined in 1999; however what is often overlooked is that descriptions of the morphology have existed in the literature for centuries. The aim of this paper is to delineate its origins and provide further clarity on FAI to shape future research.

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This study explores the reported rate of surgical site infection (SSI) after hip fracture surgery in published studies concerning patients treated in the UK.

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The optimum clearance between the bearing surfaces of hip arthroplasties is unknown. Theoretically, to minimize wear, it is understood that clearances must be low enough to maintain optimal contact pressure and fluid film lubrication, while being large enough to allow lubricant recovery and reduce contact patch size. This study aimed to identify the relationship between diametrical clearance and volumetric wear, through the analysis of retrieved components.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated.

Cite this article: Bone Joint Res 2020;9(8):524–530.

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For cementless implants, stability is initially attained by an interference fit into the bone and osteo-integration may be encouraged by coating the implant with bioactive substances. Blood based autologous glue provides an easy, cost-effective way of obtaining high concentrations of growth factors for tissue healing and regeneration with the intention of spraying it onto the implant surface during surgery. The aim of this study was to incorporate nucleated cells from autologous bone marrow (BM) aspirate into gels made from the patient’s own blood, and to investigate the effects of incorporating three different concentrations of platelet rich plasma (PRP) on the proliferation and viability of the cells in the gel.

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The diversity of femoral morphology renders femoral component sizing in total hip arthroplasty (THA) challenging. We aimed to determine whether femoral morphology and femoral component filling influence early clinical and radiological outcomes following THA using fully hydroxyapatite (HA)-coated femoral components.

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Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses.

Aims

Tibial plateau fractures (TPFs) are complex injuries around the knee caused by high- or low-energy trauma. In the present study, we aimed to define the distribution and frequency of TPF lines using a 3D mapping technique and analyze the rationalization of divisions employed by frequently used classifications.

Objectives

This study investigated the biomechanical performance of decellularized porcine superflexor tendon (pSFT) grafts of varying diameters when utilized in conjunction with contemporary ACL graft fixation systems. This aimed to produce a range of ‘off-the-shelf’ products with predictable mechanical performance, depending on the individual requirements of the patient.

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.

Aims

Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown.

Aims

Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells.