The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries. This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors

Shoulder injury related to vaccine administration (SIRVA) is a prolonged episode of shoulder dysfunction that commences within 24 to 48 hours of a vaccination. Symptoms include a combination of shoulder pain, stiffness, and weakness. There has been a recent rapid increase in reported cases of SIRVA within the literature, particularly in adults, and is likely related to the mass vaccination programmes associated with COVID-19 and influenza. The pathophysiology is not certain, but placement of the vaccination in the subdeltoid bursa or other pericapsular tissue has been suggested to result in an inflammatory capsular process. It has been hypothesized that this is associated with a vaccine injection site that is “too high” and predisposes to the development of SIRVA. Nerve conduction studies are routinely normal, but further imaging can reveal deep-deltoid collections, rotator cuff tendinopathy and tears, or subacromial subdeltoid bursitis. However, all of these are common findings within a general asymptomatic population. Medicolegal claims in the UK, based on an incorrect injection site, are unlikely to meet the legal threshold to determine liability. Cite this article: Bone Joint J 2023;105-B(8):839–842

Aims. 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. Methods. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426

Eleven patients with arthrogryposis multiplex congenita neurologica have been reviewed. Distinct patterns of deformity and muscle activity were identified which have been correlated with specific levels of segmental neurological motor deficit without sensory loss. The clinical picture was consistent with localised lesions of the anterior horn cell cell columns. This finding agreed with the recorded pathological lesions. Orthopaedic treatment should take account of the paralytic nature of the deformities.

Cite this article: Bone Joint Res 2022;11(8):514–517.

Aims. Children with spinal dysraphism can develop various musculoskeletal deformities, necessitating a range of orthopaedic interventions, causing significant morbidity, and making considerable demands on resources. This systematic review aimed to identify what outcome measures have been reported in the literature for children with spinal dysraphism who undergo orthopaedic interventions involving the lower limbs. Methods. A PROSPERO-registered systematic literature review was performed following PRISMA guidelines. All relevant studies published until January 2023 were identified. Individual outcomes and outcome measurement tools were extracted verbatim. The measurement tools were assessed for reliability and validity, and all outcomes were grouped according to the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT) filters. Results. From 91 eligible studies, 27 individual outcomes were identified, including those related to clinical assessment (n = 12), mobility (n = 4), adverse events (n = 6), investigations (n = 4), and miscellaneous (n = 1). Ten outcome measurement tools were identified, of which Hoffer’s Functional Ambulation Scale was the most commonly used. Several studies used unvalidated measurement tools originally developed for other conditions, and 26 studies developed new measurement tools. On the OMERACT filter, most outcomes reported pathophysiology and/or the impact on life. There were only six patient- or parent-reported outcomes, and none assessed the quality of life. Conclusion. The outcomes that were reported were heterogenous, lack validation and failed to incorporate patient or family perceptions. Until outcomes can be reported unequivocally, research in this area will remain limited. Our findings should guide the development of a core outcome set, which will allow consistency in the reporting of outcomes for this condition. Cite this article: Bone Joint J 2024;106-B(3):277–285

Aims. 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. Methods. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy. Cite this article: Bone Joint Res 2022;11(12):862–872

Aims. The increase in prescription opioid misuse and dependence is now a public health crisis in the UK. It is recognized as a whole-person problem that involves both the medical and the psychosocial needs of patients. Analyzing aspects of pathophysiology, emotional health, and social wellbeing associated with persistent opioid use after injury may inform safe and effective alleviation of pain while minimizing risk of misuse or dependence. Our objectives were to investigate patient factors associated with opioid use two to four weeks and six to nine months after an upper limb fracture. Methods. A total of 734 patients recovering from an isolated upper limb fracture were recruited in this study. Opioid prescription was documented retrospectively for the period preceding the injury, and prospectively at the two- to four-week post-injury visit and six- to nine-month post-injury visit. Bivariate and multivariate analysis sought factors associated with opioid prescription from demographics, injury-specific data, Patient Reported Outcome Measurement Instrumentation System (PROMIS), Depression computer adaptive test (CAT), PROMIS Anxiety CAT, PROMIS Instrumental Support CAT, the Pain Catastrophizing Scale (PCS), the Pain Self-efficacy Questionnaire (PSEQ-2), Tampa Scale for Kinesiophobia (TSK-11), and measures that investigate levels of social support. Results. A new prescription of opioids two to four weeks after injury was independently associated with less social support (odds ratio (OR) 0.26, p < 0.001), less instrumental support (OR 0.91, p < 0.001), and greater symptoms of anxiety (OR 1.1, p < 0.001). A new prescription of opioids six to nine months after injury was independently associated with less instrumental support (OR 0.9, p < 0.001) and greater symptoms of anxiety (OR 1.1, p < 0.001). Conclusion. This study demonstrates that potentially modifiable psychosocial factors are associated with increased acute and chronic opioid prescriptions following upper limb fracture. Surgeons prescribing opioids for upper limb fractures should be made aware of the screening and management of emotional and social health. Cite this article: Bone Jt Open 2021;2(2):119–124

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. . The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. . The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. . This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties. Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications. Cite this article: Bone Joint J 2016;98-B:6–13

Evaluating musculoskeletal conditions of the lower limb and understanding the pathophysiology of complex bone kinematics is challenging. Static images do not take into account the dynamic component of relative bone motion and muscle activation. Fluoroscopy and dynamic MRI have important limitations. Dynamic CT (4D-CT) is an emerging alternative that combines high spatial and temporal resolution, with an increased availability in clinical practice. 4D-CT allows simultaneous visualization of bone morphology and joint kinematics. This unique combination makes it an ideal tool to evaluate functional disorders of the musculoskeletal system. In the lower limb, 4D-CT has been used to diagnose femoroacetabular impingement, patellofemoral, ankle and subtalar joint instability, or reduced range of motion. 4D-CT has also been used to demonstrate the effect of surgery, mainly on patellar instability. 4D-CT will need further research and validation before it can be widely used in clinical practice. We believe, however, it is here to stay, and will become a reference in the diagnosis of lower limb conditions and the evaluation of treatment options. Cite this article: Bone Joint J 2021;103-B(5):822–827

Aims. Patient engagement in adaptive health behaviours and interactions with their healthcare ecosystem can be measured using self-reported instruments, such as the Patient Activation Measure (PAM-13) and the Effective Consumer Scale (ECS-17). Few studies have investigated the influence of patient engagement on limitations (patient-reported outcome measures (PROMs)) and patient-reported experience measures (PREMs). First, we assessed whether patient engagement (PAM-13, ECS-17) within two to four weeks of an upper limb fracture was associated with limitations (the Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH), and Patient-Reported Outcome Measurement Information System Upper Extremity Physical Function computer adaptive test (PROMIS UE PF) scores) measured six to nine months after fracture, accounting for demographic, clinical, and psychosocial factors. Secondly, we assessed the association between patient engagement and experience (numerical rating scale for satisfaction with care (NRS-C) and satisfaction with services (NRS-S) six to nine months after fracture. Methods. A total of 744 adults with an isolated fracture of the proximal humerus, elbow, or distal radius completed PROMs. Due to multicollinearity of patient engagement and psychosocial variables, we generated a single variable combining measures of engagement and psychosocial factors using factor analysis. We then performed multivariable analysis with p < 0.10 on bivariate analysis. Results. Patient engagement and psychosocial factors combined to form a single factor (factor 1) accounting for 20% (QuickDASH, semi-partial R. 2. = 0.20) and 14% (PROMIS UE PF, semi-partial R. 2. = 0.14) of the variation in limitations six to nine months after fracture. Factor 1 also accounted for 17% (NRS-C, semi-partial R. 2. = 0.17) of variation in satisfaction with care, and 21% (NRS-S, semi-partial R. 2. = 0.21) of variation in satisfaction with services. Demographic factors (age, sex, work status) and measures of greater pathophysiology (type of fracture, high-energy injury, post-surgical complications), accounted for much less variation. Conclusion. Patients who actively manage their health and demonstrate effective emotional and social functioning share a common underlying trait. They have fewer limitations and greater satisfaction with care during recovery from upper limb fractures. Future efforts should focus on evaluating initiatives that optimize patient engagement, such as patient education, coaching, and a communication strategy for healthcare professionals. Cite this article: Bone Joint J 2020;102-B(1):42–47

Objectives. Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. Methods. Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint. Results. Microarray analysis showed that there were 14 miRNAs at day five and 17 miRNAs at day 11, with a greater than twofold change in the DM group compared with the control group. Among these types of miRNA, five were selected based on a comparative and extended literature review. Real-time PCR analysis revealed that five types of miRNA (miR-140-3p, miR-140-5p, miR-181a-1-3p, miR-210-3p, and miR-222-3p) were differentially expressed with changing patterns of expression during fracture healing in diabetic rats compared with controls. Conclusions. Our findings provide information to further understand the pathology of impaired fracture healing in a diabetic rat model. These results may allow the potential development of molecular therapy using miRNA for the treatment of impaired fracture healing in patients with DM. Cite this article: S. Takahara, S. Y. Lee, T. Iwakura, K. Oe, T. Fukui, E. Okumachi, T. Waki, M. Arakura, Y. Sakai, K. Nishida, R. Kuroda, T. Niikura. Altered expression of microRNA during fracture healing in diabetic rats. Bone Joint Res 2018;7:139–147. DOI: 10.1302/2046-3758.72.BJR-2017-0082.R1

Objectives. Legg–Calvé–Perthes’ disease (LCP) is an idiopathic osteonecrosis of the femoral head that is most common in children between four and eight years old. The factors that lead to the onset of LCP are still unclear; however, it is believed that interruption of the blood supply to the developing epiphysis is an important factor in the development of the condition. Methods. Finite element analysis modelling of the blood supply to the juvenile epiphysis was investigated to understand under which circumstances the blood vessels supplying the femoral epiphysis could become obstructed. The identification of these conditions is likely to be important in understanding the biomechanics of LCP. Results. The results support the hypothesis that vascular obstruction to the epiphysis may arise when there is delayed ossification and when articular cartilage has reduced stiffness under compression. Conclusion. The findings support the theory of vascular occlusion as being important in the pathophysiology of Perthes disease. Cite this article: M. Pinheiro, C. A. Dobson, D. Perry, M. J. Fagan. New insights into the biomechanics of Legg-Calvé-Perthes’ disease: The Role of Epiphyseal Skeletal Immaturity in Vascular Obstruction. Bone Joint Res 2018;7:148–156. DOI: 10.1302/2046-3758.72.BJR-2017-0191.R1

In this study, we describe a morphological classification for greater tuberosity fractures of the proximal humerus. We divided these fractures into three types: avulsion, split and depression. We retrospectively reviewed all shoulder radiographs showing isolated greater tuberosity fractures in a Level I trauma centre between July 2007 and July 2012. We identified 199 cases where records and radiographs were reviewed and included 79 men and 120 women with a mean age of 58 years (23 to 96). The morphological classification was applied to the first 139 cases by three reviewers on two occasions using the Kappa statistic and compared with the AO and Neer classifications. The inter- and intra-observer reliability of the morphological classification was 0.73 to 0.77 and 0.69 to 0.86, respectively. This was superior to the Neer (0.31 to 0.35/0.54 to 0.63) and AO (0.30 to 0.32/0.59 to 0.65) classifications. The distribution of avulsion, split and depression type fractures was 39%, 41%, and 20%, respectively. This classification of greater tuberosity fractures is more reliable than the Neer or AO classifications. These distinct fracture morphologies are likely to have implications in terms of pathophysiology and surgical technique. Cite this article: Bone Joint J 2014;96-B:646–51

Aims

CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

This paper describes how we came to understand the pathophysiology of Volkmann’s ischaemic contracture with references to relevant papers in this Journal, and the investigation and management of acute compartment syndrome is briefly discussed

Cite this article: Bone Joint Res 2023;12(3):199–201.

Aims

Paediatric triplane fractures and adult trimalleolar ankle fractures both arise from a supination external rotation injury. By relating the experience of adult to paediatric fractures, clarification has been sought on the sequence of injury, ligament involvement, and fracture pattern of triplane fractures. This study explores the similarities between triplane and trimalleolar fractures for each stage of the Lauge-Hansen classification, with the aim of aiding reduction and fixation techniques.

Aims

The aim of this study is to evaluate the surgical treatment with the best healing rate for patients with proximal femoral unicameral bone cysts (UBCs) after initial surgery, and to determine which procedure has the lowest adverse event burden during follow-up.

Heterotopic ossification following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (< four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indometacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indometacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities

Aims

The study aimed to assess the clinical outcomes of arthroscopic debridement and partial excision in patients with traumatic central tears of the triangular fibrocartilage complex (TFCC), and to identify prognostic factors associated with unfavourable clinical outcomes.

Aims

Dupuytren’s contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis.

Aims

Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

Aims

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.

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine. Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2

The August 2024 Children’s orthopaedics Roundup³⁶⁰ looks at: Antibiotic prophylaxis and infection rates in paediatric supracondylar humerus fractures; Clinical consensus recommendations for the non-surgical treatment of children with Perthes’ disease in the UK; Health-related quality of life in idiopathic toe walkers: a multicentre prospective cross-sectional study; Children with spinal dysraphism: a systematic review of reported outcomes; No delay in age of crawling, standing, or walking with Pavlik harness treatment: a prospective cohort study; No value found with routine early postoperative radiographs after implant removal in paediatric patients; What do we know about the natural history of spastic hip dysplasia and pain in total-involvement cerebral palsy?; Evaluating the efficacy and safety of preoperative gallows traction for hip open reduction in infants

The June 2024 Children’s orthopaedics Roundup³⁶⁰ looks at: Proximal femoral unicameral bone cysts: is ESIN the answer?; Hybrid-mesh casts in the conservative management of paediatric supracondylar humeral fractures: a randomized controlled trial; Rate and risk factors for contralateral slippage in adolescents treated for slipped capital femoral epiphysis; CRP predicts the need to escalate care after initial debridement for musculoskeletal infection; Genu valgum in paediatric patients presenting with patellofemoral instability; Nusinersen therapy changed the natural course of spinal muscular atrophy type 1: what about spine and hip?; The necessity of ulnar nerve exploration and translocation in open reduction of medial humeral epicondyle fractures in children.

The June 2023 Shoulder & Elbow Roundup³⁶⁰ looks at: Proximal humerus fractures: what does the literature say now?; Infection risk of steroid injections and subsequent reverse shoulder arthroplasty; Surgical versus non-surgical management of humeral shaft fractures; Core outcome set needed for elbow arthroplasty; Minimally invasive approaches to locating radial nerve in the posterior humeral approach; Predictors of bone loss in anterior glenohumeral instability; Does the addition of motor control or strengthening exercises improve rotator cuff-related shoulder pain?; Terminology and diagnostic criteria used in patients with subacromial pain syndrome.

Aims

We assessed the long-term outcomes of a large cohort of patients who have undergone a periacetabular osteotomy (PAO), and sought to validate a patient satisfaction questionnaire for use in a PAO cohort.

Orthopaedic surgery is in an exciting transitional period as modern surgical interventions, implants and scientific developments are providing new therapeutic options. As advances in basic science and technology improve our understanding of the pathology and repair of musculoskeletal tissue, traditional operations may be replaced by newer, less invasive procedures which are more appropriately targeted at the underlying pathophysiology. However, evidence-based practice will remain a basic requirement of care. Orthopaedic surgeons can and should remain at the forefront of the development of novel therapeutic interventions and their application. Progression of the potential of bench research into an improved array of orthopaedic treatments in an effective yet safe manner will require the development of a subgroup of specialists with extended training in research to play an important role in bridging the gap between laboratory science and clinical practice. International regulations regarding the introduction of new biological treatments will place an additional burden on the mechanisms of this translational process, and orthopaedic surgeons who are trained in science, surgery and the regulatory environment will be essential. Training and supporting individuals with these skills requires special consideration and discussion by the orthopaedic community. In this paper we review some traditional approaches to the integration of orthopaedic science and surgery, the therapeutic potential of current regenerative biomedical science for cartilage repair and ways in which we may develop surgeons with the skills required to translate scientific discovery into effective and properly assessed orthopaedic treatments

Aims

Contemporary outcomes of primary total hip arthroplasties (THAs) with highly cross-linked polyethylene (HXLPE) liners in patients with inflammatory arthritis have not been well studied. This study examined the implant survivorship, complications, radiological results, and clinical outcomes of THA in patients with inflammatory arthritis.

Aims

Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance.

Aims

A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach.

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.

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.

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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Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

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Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK.

The April 2023 Foot & Ankle Roundup³⁶⁰ looks at: Outcomes following a two-stage revision total ankle arthroplasty for periprosthetic joint infection; Temporary bridge plate fixation and joint motion after an unstable Lisfranc injury; Outcomes of fusion in type II os naviculare; Total ankle arthroplasty versus arthrodesis for end-stage ankle osteoarthritis; Normal saline for plantar fasciitis: placebo or therapeutic?; Distraction arthroplasty for ankle osteoarthritis: does it work?; Let there be movement: ankle arthroplasty after previous fusion; Morbidity and mortality after diabetic Charcot foot arthropathy.

Aims

After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA.

Aims

The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome.

Aims

Pelvic discontinuity is a rare but increasingly common complication of total hip arthroplasty (THA). This single-centre study evaluated the performance of custom-made triflange acetabular components in acetabular reconstruction with pelvic discontinuity by determining: 1) revision and overall implant survival rates; 2) discontinuity healing rate; and 3) Harris Hip Score (HHS).

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Aims

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

Aims

Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

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.

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.

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This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.

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Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

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The rationale for exacting restoration of skeletal anatomy after unstable ankle fracture is to improve outcomes by reducing complications from malunion; however, current definitions of malunion lack confirmatory clinical evidence.

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity. Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately. Cite this article: Bone Joint J 2016;98-B:14–20

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The aim of this retrospective study was to evaluate the rate of conversion to surgical release after a steroid injection in patients with a trigger finger, and to analyze which patient- and trigger finger-related factors affect the outcome of an injection.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

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.

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

The aim of this study was to estimate time to arthroplasty among patients with hip and knee osteoarthritis (OA), and to identify factors at enrolment to first-line intervention that are prognostic for progression to surgery.

Objectives. Although many clinical and experimental investigations have shed light on muscle atrophy and intramuscular accumulation of fat after rotator cuff disruption, none have reported on their onset in the absence of muscle retraction. Methods. In 30 rabbits, we detached one supraspinatus (SSP) tendon and repaired it immediately, thus preventing muscle retraction. The animals were killed in groups of 10 at one, two and six weeks. Both shoulders of 15 non-operated rabbits served as controls. We measured the weight and volume of SSP muscles and quantified the cross-sectional area of intramuscular fat (i-fat) histologically. Results. There was significant loss of muscle weight and volume after one week (p = 0.004 and 0.003, respectively), and two weeks (both p < 0.001) in the experimental group; which recovered to control values after six weeks. I-fat accumulated one week after immediate repair, greater than in the control group and statistically significant at the mid-part of the muscle (mean 2.7% vs 1.5%, p = 0.008). I-fat continued to accumulate up to six weeks at all sites of the SSP muscle (all 3, p < 0.001). More fat accumulated closer to the musculotendinous junction than at the mid-part after two and six weeks (p = 0.012 and 0.019, respectively). Conclusion. Muscle atrophy and i-fat accumulation occur early after SSP tendon tear and immediate repair. While early repair benefitted muscle recovery, it did not prevent fat accumulation. SSP muscle retraction was not essential to the muscle alterations. The divergent evolution of muscle and fat points to different pathophysiologies. Cite this article: Bone Joint Res 2014;3:117–22

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The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice.

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Cervical radiculopathy is a significant cause of pain and morbidity. For patients with severe and poorly controlled symptoms who may not be candidates for surgical management, treatment with transforaminal epidural steroid injections (CTFESI) has gained widespread acceptance. However, a paucity of high-quality evidence supporting their use balanced against perceived high risks of the procedure potentially undermines the confidence of clinicians who use the technique. We undertook a systematic review of the available literature regarding CTFESI to assess the clinical efficacy and complication rates of the procedure.

There has been a marked increase in the number of hip arthroscopies performed over the past 16 years, primarily in the management of femoroacetabular impingement (FAI). Insights into the pathoanatomy of FAI, and high-level evidence supporting the clinical effectiveness of arthroscopy in the management of FAI, have fuelled this trend. Arthroscopic management of labral tears with repair may have superior results compared with debridement, and there is now emerging evidence to support reconstructive options where repair is not possible. In situations where an interportal capsulotomy is performed to facilitate access, data now support closure of the capsule in selective cases where there is an increased risk of postoperative instability. Preoperative planning is an integral component of bony corrective surgery in FAI, and this has evolved to include computer-planned resection. However, the benefit of this remains controversial. Hip instability is now widely accepted, and diagnostic criteria and treatment are becoming increasingly refined. Instability can also be present with FAI or develop as a result of FAI treatment. In this annotation, we outline major current controversies relating to decision-making in hip arthroscopy for FAI.

Cite this article: Bone Joint J 2022;104-B(5):532–540.

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Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Osteonecrosis of the femoral head usually affects young individuals and is responsible for up to 12% of total hip arthroplasties. The underlying pathophysiology of the death of the bone cells remains uncertain. We have investigated nitric oxide mediated apoptosis as a potential mechanism and found that steroid- and alcohol-induced osteonecrosis is accompanied by widespread apoptosis of osteoblasts and osteocytes. Certain drugs or their metabolites may have a direct cytotoxic effect on cancellous bone of the femoral head leading to apoptosis rather than purely necrosis

It is not uncommon to observe bone cement in the pelvis on radiographs after total hip replacement, a finding which is generally considered to be benign. This paper reviews some catastrophic late complications from intrapelvic methylmethacrylate. We also describe a case of progressive, unbearable dyspareunia beginning three years after total hip replacement. A possible explanation of the pathophysiology is suggested. Recommendations for prevention, diagnosis, and treatment of these late complications are offered

It has been suggested that transient osteoporosis or the bone marrow oedema syndrome (BMOS) may be the initial phase of osteonecrosis of the femoral head (ONFH) and that there may be a common pathophysiology. In this study, we have assessed the MR images of 200 consecutive patients with ONFH in respect of the BMO pattern in order to test this hypothesis. This pattern was not observed in the early stage of ONFH. The initial abnormal finding detected on the MR images was an abnormal band of intensity at the junction between the necrotic area and the normal bone. Structural damage of the head seems to result in the appearance of the BMO pattern and the development of pain in ONFH. There was no finding to support the existence of a continuum between BMOS and ONFH

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Circular RNA (circRNA) S-phase cyclin A-associated protein in the endoplasmic reticulum (ER) (circSCAPER, ID: hsa_circ_0104595) has been found to be highly expressed in osteoarthritis (OA) patients and has been associated with the severity of OA. Hence, the role and mechanisms underlying circSCAPER in OA were investigated in this study.

Clinical assessment of equinus in children before and after operation was made over a twenty-year period (1958-1978), and three groups were defined. Forty-three muscles (Group I) had abnormal shortening without spasticity and the deformity progressed steadily despite immediate improvement after operation; this was considered to be the result of a lack of muscle growth during bone growth. Forty-one muscles (Group II) had both shortening and spasticity with an imbalance which might be unchanged after operation, or reversed or improved. Fourteen muscles (Group III) had spasticity only and progression was unpredictable and could not be defined. Improvement in gait was regularly observed in Group I in the early years after operation. In Groups II and III the results were variable. These results did not depend on surgical technique but on differences in pathophysiology

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Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations.

Previous studies on the anatomy of the lumbar spine have not clarified the precise relationship of the origin of the lumbar roots to their corresponding discs or their angulation to the dural sac. We studied 33 cadavers (25 formalin-preserved and eight fresh-frozen) and their radiographs to determine these details. All cadavers showed a gradual decrease in the angle of the nerve root from L1 to S1. The origin of the root was found to be below the corresponding disc for the L1 to L4 roots. In the formalin-preserved cadavers 8% of the L5 roots originated above, 64% below and 28% at the L4/L5 disc. In the fresh cadavers the values were 12.5%, 62.5% and 25%, respectively. For the S1 root 76% originated above and 24% at the L5-S1 disc in the formalin-preserved cadavers and 75% and 25%, respectively, in the fresh cadavers. A herniated disc usually compresses the root before division of the root sleeve. Thus, compression of the thecal sac before the origin of the root sleeve is common for L1 to L5 whereas compression at the root sleeve is common for S1. Our findings are of value in understanding the pathophysiology of prolapse of the disc and in preventing complications during surgery

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This study addressed two questions: first, does surgical correction of an idiopathic scoliosis increase the volume of the rib cage, and second, is it possible to evaluate the change in lung function after corrective surgery for adolescent idiopathic scoliosis (AIS) using biplanar radiographs of the ribcage with 3D reconstruction?

Diurnal changes in the loads acting on the spine affect the water content and height of the intervertebral discs. We have reviewed the effects of these changes on spinal mechanics, and their possible clinical significance. Cadaveric lumbar spines subjected to periods of creep loading show a disc height change similar to the physiological change. As a result intervertebral discs bulge more, become stiffer in compression and more flexible in bending. Disc tissue becomes more elastic as its water content falls, and its affinity for water increases. Disc prolapse becomes more difficult. The neural arch and associated ligaments resist an increasing proportion of the compressive and bending stresses acting on the spine. Observations on living people show that these changes are not fully compensated for by modified muscle activity. We conclude that different spinal structures are more heavily loaded at different times of the day. Therefore, the time of onset of symptoms and signs, and any diurnal variation in their severity, may help us understand more about the pathophysiology of low back pain and sciatica

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This study assessed the impact of COVID-19 on hip and distal femur fracture patient outcomes across three successive UK lockdown periods over one year.

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

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Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy.

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

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We studied the outcomes of hip and knee arthroplasties in a high-volume arthroplasty centre to determine if patients with morbid obesity (BMI ≥ 40 kg/m²) had unacceptably worse outcomes as compared to those with BMI < 40 kg/m².

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

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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The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones.

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Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

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The primary aim was to determine the influence of COVID-19 on 30-day mortality following hip fracture. Secondary aims were to determine predictors of COVID-19 status on presentation and later in the admission; the rate of hospital acquired COVID-19; and the predictive value of negative swabs on admission.

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To analyze the potential role of synovial fluid peptidase activity as a measure of disease burden and predictive biomarker of progression in knee osteoarthritis (KOA).

Evidence suggests that the alleviation of pain is enhancedby a strong patient-clinician relationship and attending to a patient’s social and mental health. There is a limited role for medication, opioids in particular.

Orthopaedic surgeons can use comprehensive biopsychosocial strategies to help people recover and can work with colleagues who have the appropriate expertise in order to maximize pain alleviation with optimal opioid stewardship.

Preparing patients for elective surgery and caring for them after unplanned injury or surgery can benefit from planned and practiced strategies based in communication science.

Cite this article: Bone Joint J 2020;102-B(9):1122–1127.

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The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA).

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

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The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

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Perthes’ disease is a condition which leads to necrosis of the femoral head. It is most commonly reported in children aged four to nine years, with recent statistics suggesting it affects around five per 100,000 children in the UK. Current treatment for the condition aims to maintain the best possible environment for the disease process to run its natural course. Management typically includes physiotherapy with or without surgical intervention. Physiotherapy intervention often will include strengthening/stretching programmes, exercise/activity advice, and, in some centres, will include intervention, such as hydrotherapy. There is significant variation in care with no consensus on which treatment option is best. The importance of work in this area has been demonstrated by the British Society for Children’s Orthopaedic Surgery through the James Lind Alliance’s prioritization of work to determine/identify surgical versus non-surgical management of Perthes’ disease. It was identified as the fourth-highest priority for paediatric lower limb surgery research in 2018.

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Within the UK, around 70,000 patients suffer neck of femur (NOF) fractures annually. Patients presenting with this injury are often frail, leading to increased morbidity and a 30-day mortality rate of 6.1%. COVID-19 infection has a broad spectrum of clinical presentations with the elderly, and those with pre-existing comorbidities are at a higher risk of severe respiratory compromise and death. Further increased risk has been observed in the postoperative period. The aim of this study was to assess the impact of COVID-19 infection on the complication and mortality rates of NOF fracture patients.