Aims. The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures. Methods. A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively. Results. Compared with the control group, the ERAS group had a shorter operating time, hospital stay, preoperative waiting time, postoperative discharge time, less intraoperative blood loss, and higher albumin and haemoglobin on the first postoperative day. The time to removal of the urinary catheter/drainage tube was shortened, and the drainage volume was also significantly reduced in the ERAS group. There was no significant difference in the visual analogue scale (VAS) scores on postoperative return to the ward, but the ERAS group had lower scores on the first, second, and third postoperative days. There were no significant differences in the incidence of complications, other than 10% more nausea and vomiting in the control group. The limb function scores at one-year follow-up were similar between the two groups, but time to radiological fracture union and time to return to physical work and sports were significantly reduced in the ERAS group. Conclusion. The implementation of a series of perioperative nursing measures based on the concept of ERAS in PLWH with limb fracture can significantly reduce the operating time and intraoperative blood loss, reduce the occurrence of postoperative pain and complications, and accelerate the improvement of the functional status of the affected limb in the early stage, which is worthy of applying in more medical institutions. Cite this article: Bone Joint Res 2024;13(11):647–658

Objectives. The National Hip Fracture Database (NHFD) publishes hospital-level risk-adjusted mortality rates following hip fracture surgery in England, Wales and Northern Ireland. The performance of the risk model used by the NHFD was compared with the widely-used Nottingham Hip Fracture Score. Methods. Data from 94 hospitals on patients aged 60 to 110 who had hip fracture surgery between May 2013 and July 2013 were analysed. Data were linked to the Office for National Statistics (ONS) death register to calculate the 30-day mortality rate. Risk of death was predicted for each patient using the NHFD and Nottingham models in a development dataset using logistic regression to define the models’ coefficients. This was followed by testing the performance of these refined models in a second validation dataset. Results. The 30-day mortality rate was 5.36% in the validation dataset (n = 3861), slightly lower than the 6.40% in the development dataset (n = 4044). The NHFD and Nottingham models showed a slightly lower discrimination in the validation dataset compared with the development dataset, but both still displayed moderate discriminative power (c-statistic for NHFD = 0.71, 95% confidence interval (CI) 0.67 to 0.74; Nottingham model = 0.70, 95% CI 0.68 to 0.75). Both models defined similar ranges of predicted mortality risk (1% to 18%) in assessment of calibration. Conclusions. Both models have limitations in predicting mortality for individual patients after hip fracture surgery, but the NHFD risk adjustment model performed as well as the widely-used Nottingham prognostic tool and is therefore a reasonable alternative for risk adjustment in the United Kingdom hip fracture population. Cite this article: Bone Joint Res 2017;6:550–556

Aims. We performed a systematic review of the literature to determine whether earlier surgical repair of acute rotator cuff tear (ARCT) leads to superior post-operative clinical outcomes. Methods. The MEDLINE, Embase, CINAHL, Web of Science, Cochrane Libraries, controlled-trials.com and clinicaltrials.gov databases were searched using the terms: ‘rotator cuff’, or ‘supraspinatus’, or ‘infraspinatus’, or ‘teres minor’, or ‘subscapularis’ AND ‘surgery’ or ‘repair’. This gave a total of 15 833 articles. After deletion of duplicates and the review of abstracts and full texts by two independent assessors, 15 studies reporting time to surgery for ARCT repair were included. Studies were grouped based on time to surgery < 3 months (group A, seven studies), or > 3 months (group B, eight studies). Weighted means were calculated and compared using Student’s t-test. . Results. Group B had a significantly higher pre-operative Constant score (CS) (p < 0.001), range of movement in external rotation (p = 0.003) and abduction (p < 0.001) compared with group A. Both groups showed clinical improvement with surgical repair; group A had a significantly improved Constant score, University of California, Los Angeles (UCLA) shoulder score, abduction and elevation post-operatively (all p < 0.001). Group B had significantly improved Constant score (p < 0.001) and external rotation (p < 0.001) post-operatively. The mean Constant score improved by 33.5 for group A and by 27.5 for group B. Conclusion. These findings should be interpreted with caution due to limitations and bias inherent to case-series. We suggest a trend that earlier time to surgery may be linked to better Constant score, and active range of movement in abduction and elevation. Additional prospective studies are required

Aims. 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. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422

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

Cite this article: Bone Joint Res 2023;12(6):372–374.

Aims. To determine the major risk factors for unplanned reoperations (UROs) following corrective surgery for adult spinal deformity (ASD) and their interactions, using machine learning-based prediction algorithms and game theory. Methods. Patients who underwent surgery for ASD, with a minimum of two-year follow-up, were retrospectively reviewed. In total, 210 patients were included and randomly allocated into training (70% of the sample size) and test (the remaining 30%) sets to develop the machine learning algorithm. Risk factors were included in the analysis, along with clinical characteristics and parameters acquired through diagnostic radiology. Results. Overall, 152 patients without and 58 with a history of surgical revision following surgery for ASD were observed; the mean age was 68.9 years (SD 8.7) and 66.9 years (SD 6.6), respectively. On implementing a random forest model, the classification of URO events resulted in a balanced accuracy of 86.8%. Among machine learning-extracted risk factors, URO, proximal junction failure (PJF), and postoperative distance from the posterosuperior corner of C7 and the vertical axis from the centroid of C2 (SVA) were significant upon Kaplan-Meier survival analysis. Conclusion. The major risk factors for URO following surgery for ASD, i.e. postoperative SVA and PJF, and their interactions were identified using a machine learning algorithm and game theory. Clinical benefits will depend on patient risk profiles. Cite this article: Bone Joint Res 2023;12(4):245–255

Cite this article: Bone Joint Res 2022;11(12):890–892.

Aims. The use of 3D printing has become increasingly popular and has been widely used in orthopaedic surgery. There has been a trend towards an increasing number of publications in this field, but existing literature incorporates limited high-quality studies, and there is a lack of reports on outcomes. The aim of this study was to perform a scoping review with Level I evidence on the application and effectiveness of 3D printing. Methods. A literature search was performed in PubMed, Embase, and Web of Science databases. The keywords used for the search criteria were ((3d print*) OR (rapid prototyp*) OR (additive manufactur*)) AND (orthopaedic). The inclusion criteria were: 1) use of 3D printing in orthopaedics, 2) randomized controlled trials, and 3) studies with participants/patients. Risk of bias was assessed with Cochrane Collaboration Tool and PEDro Score. Pooled analysis was performed. Results. Overall, 21 studies were included in our study with a pooled total of 932 participants. Pooled analysis showed that operating time (p < 0.001), blood loss (p < 0.001), fluoroscopy times (p < 0.001), bone union time (p < 0.001), pain (p = 0.040), accuracy (p < 0.001), and functional scores (p < 0.001) were significantly improved with 3D printing compared to the control group. There were no significant differences in complications. Conclusion. 3D printing is a rapidly developing field in orthopaedics. Our findings show that 3D printing is advantageous in terms of operating time, blood loss, fluoroscopy times, bone union time, pain, accuracy, and function. The use of 3D printing did not increase the risk of complications. Cite this article: Bone Joint Res 2021;10(12):807–819

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells. Cite this article: Bone Joint Res 2020;9(12):857–869

Aims. This study explores the reported rate of surgical site infection (SSI) after hip fracture surgery in published studies concerning patients treated in the UK. Methods. Studies were included if they reported on SSI after any type of surgical treatment for hip fracture. Each study required a minimum of 30 days follow-up and 100 patients. Meta-analysis was undertaken using a random effects model. Heterogeneity was expressed using the I. 2. statistic. Risk of bias was assessed using a modified Newcastle-Ottawa Scale (NOS) system. Results. There were 20 studies reporting data from 88,615 patients. Most were retrospective cohort studies from single centres. The pooled incidence was 2.1% (95% confidence interval (CI) 1.54% to 2.62%) across ‘all types’ of hip fracture surgery. When analyzed by operation type, the SSI incidences were: hemiarthroplasty 2.87% (95% CI 1.99% to 3.75%) and sliding hip screw 1.35% (95% CI 0.78% to 1.93%). There was considerable variation in definition of infection used, as well as considerable risk of bias, particularly as few studies actively screened participants for SSI. Conclusion. Synthesis of published estimates of infection yield a rate higher than that seen in national surveillance procedures. Biases noted in all studies would trend towards an underestimate, largely due to inadequate follow-up

Aims. A systematic literature review focusing on how long before surgery concurrent viral or bacterial infections (respiratory and urinary infections) should be treated in hip fracture patients, and if there is evidence for delaying this surgery. Methods. A total of 11 databases were examined using the COre, Standard, Ideal (COSI) protocol. Bibliographic searches (no chronological or linguistic restriction) were conducted using, among other methods, the Patient, Intervention, Comparison, Outcome (PICO) template. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for flow diagram and checklist. Final reading of the complete texts was conducted in English, French, and Spanish. Classification of papers was completed within five levels of evidence (LE). Results. There were a total of 621 hits (526 COre; 95 Standard, Ideal) for screening identification, and 107 records were screened. Overall 67 full-text articles were assessed for eligibility, and 21 articles were included for the study question. A total of 46 full-text articles were excluded with reasons. No studies could be included in quantitative synthesis (meta-analyses), and there were many confounding variables including surgeons’ experience, prosthesis models used, and surgical technique. Conclusion. Patients with hip fracture and with a viral infection in the upper respiratory tract or without major clinical symptoms should be operated on as soon as possible (LE: I-III). There is no evidence that patients with coronavirus disease 2019 (COVID-19) should be treated differently. In relation to pneumonia, its prevention is a major issue. Antibiotics should be administered if surgery is delayed by > 72 hours or if bacterial infection is present in the lower respiratory tract (LE: III-V). In patients with hip fracture and urinary tract infection (UTI), delaying surgery may provoke further complications (LE: I). However, diabetic or immunocompromised patients may benefit from immediate antibiotic treatment. Cite this article: Bone Joint Res 2020;9(12):884–893

Objectives. The PROximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial has recently demonstrated that surgery is non-superior to non-operative treatment in the management of displaced proximal humeral fractures. The objective of this study was to assess current surgical practice in the context of the PROFHER trial in terms of patient demographics, injury characteristics and the nature of the surgical treatment. Methods. A total of ten consecutive patients undergoing surgery for the treatment of a proximal humeral fracture from each of 11 United Kingdom hospitals were retrospectively identified over a 15 month period between January 2014 and March 2015. Data gathered for the 110 patients included patient demographics, injury characteristics, mode of surgical fixation, the grade of operating surgeon and the cost of the surgical implants. Results. A majority of the patients were female (66%, 73 of 110). The mean patient age was 62 years (range 18 to 89). A majority of patients met the inclusion criteria for the PROFHER trial (75%, 83 of 110). Plate fixation was the most common mode of surgery (68%, 75 patients), followed by intramedullary fixation (12%, 13 patients), reverse shoulder arthroplasty (10%, 11 patients) and hemiarthroplasty (7%, eight patients). The consultant was either the primary operating surgeon or supervising the operating surgeon in a large majority of cases (91%, 100 patients). Implant costs for plate fixation were significantly less than both hemiarthroplasty (p < 0.05) and reverse shoulder arthroplasty (p < 0.0001). Implant costs for intramedullary fixation were significantly less than plate fixation (p < 0.01), hemiarthroplasty (p < 0.0001) and reverse shoulder arthroplasty (p < 0.0001). Conclusions. Our study has shown that the majority of a representative sample of patients currently undergoing surgical treatment for a proximal humeral fracture in these United Kingdom centres met the inclusion criteria for the PROFHER trial and that a proportion of these patients may, therefore, have been effectively managed non-operatively. Cite this article: Mr B. J. F. Dean. A review of current surgical practice in the operative treatment of proximal humeral fractures: Does the PROFHER trial demonstrate a need for change? Bone Joint Res 2016;5:178–184. DOI: 10.1302/2046-3758.55.2000596

Research into COVID-19 has been rapid in response to the dynamic global situation, which has resulted in heterogeneity of methodology and the communication of information. Adherence to reporting standards would improve the quality of evidence presented in future studies, and may ensure that findings could be interpreted in the context of the wider literature. The COVID-19 pandemic remains a dynamic situation, requiring continued assessment of the disease incidence and monitoring for the emergence of viral variants and their transmissibility, virulence, and susceptibility to vaccine-induced immunity. More work is needed to assess the long-term impact of COVID-19 infection on patients who sustain a hip fracture. The International Multicentre Project Auditing COVID-19 in Trauma & Orthopaedics (IMPACT) formed the largest multicentre collaborative audit conducted in orthopaedics in order to provide an emergency response to a global pandemic, but this was in the context of many vital established audit services being disrupted at an early stage, and it is crucial that these resources are protected during future health crises. Rapid data-sharing between regions should be developed, with wider adoption of the revised 2022 Fragility Fracture Network Minimum Common Data Set for Hip Fracture Audit, and a pragmatic approach to information governance processes in order to facilitate cooperation and meta-audit. This editorial aims to: 1) identify issues related to COVID-19 that require further research; 2) suggest reporting standards for studies of COVID-19 and other communicable diseases; 3) consider the requirement of new risk scores for hip fracture patients; and 4) present the lessons learned from IMPACT in order to inform future collaborative studies.

Cite this article: Bone Joint Res 2022;11(6):342–345.

This protocol describes a pragmatic multicentre randomised controlled trial (RCT) to assess the clinical and cost effectiveness of arthroscopic and open surgery in the management of rotator cuff tears. This trial began in 2007 and was modified in 2010, with the removal of a non-operative arm due to high rates of early crossover to surgery. . Cite this article: Bone Joint Res 2014;3:155–60

Objectives. The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery. Methods. A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included. Results. The literature search resulted in 823 manuscripts of which 64 manuscripts met the final inclusion criteria. The included manuscripts consisted of four randomised controlled trials (level I), eight cohort studies (level III) and 49 case-series (level IV). No clinical studies were found for ten DBM products, and most DBM products were only used in combination with other grafting materials. DBM products were most extensively investigated in spinal surgery, showing limited level I evidence that supports the use Grafton DBM (Osteotech, Eatontown, New Jersey) as a bone graft extender in posterolateral lumbar fusion surgery. DBM products are not thoroughly investigated in trauma surgery, showing mainly level IV evidence that supports the use of Allomatrix (Wright Medical, London, United Kingdom), DBX (DePuy Synthes, Zuchwil, Switzerland), Grafton DBM, or OrthoBlast (Citagenix Laval, Canada) as bone graft extenders. Conclusions. The clinical level of evidence that supports the use of DBM in trauma and orthopaedic surgery is limited and consists mainly of poor quality and retrospective case-series. More prospective, randomised controlled trials are needed to understand the clinical effect and impact of DBM in trauma and orthopaedic surgery. Cite this article: J. van der Stok, K. A. Hartholt, D. A. L. Schoenmakers, J. J. C. Arts. The available evidence on demineralised bone matrix in trauma and orthopaedic surgery: A systemati c review. Bone Joint Res 2017;6:423–432. DOI: 10.1302/2046-3758.67.BJR-2017-0027.R1

Objectives. The Manchester–Oxford Foot Questionnaire (MOXFQ) is a validated 16-item, patient-reported outcome measure for evaluating outcomes of foot or ankle surgery. The original development of the instrument identified three domains. This present study examined whether the three domains could legitimately be summed to provide a single summary index score. . Methods. The MOXFQ and Short-Form (SF)-36 were administered to 671 patients before surgery of the foot or ankle. Data from the three domains of the MOXFQ (pain, walking/standing and social interaction) were subjected to higher order factor analysis. Reliability and validity of the summary index score was assessed. Results. The mean age of the participants was 52.8 years (. sd. 15.68; 18 to 89). Higher order principle components factor analysis produced one factor, accounting for 74.7% of the variance. The newly derived single index score was found to be internally reliable (α = 0.93) and valid, achieving at least moderate correlations (r ≥ 0.5, p < 0.001) with related (pain/function) domains of the SF-36. Conclusions. Analyses indicated that data from the MOXFQ can be presented in summary form. The MOXFQ summary index score (MOXFQ-Index) provides an overall indication of the outcomes of foot and ankle surgery. Furthermore, the single index reduces the number of statistical comparisons, and hence the role of chance, when exploring MOXFQ data

Objectives

To explore whether orthopaedic surgeons have adopted the Proximal Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial results routinely into clinical practice.

Objectives. Indocyanine green (ICG) fluorescence angiography is an emerging technique that can provide detailed anatomical information during surgery. The purpose of this study is to determine whether ICG fluorescence angiography can be used to evaluate the blood flow of the rotator cuff tendon in the clinical setting. Methods. Twenty-six patients were evaluated from October 2016 to December 2017. The participants were categorized into three groups based on their diagnoses: the rotator cuff tear group; normal rotator cuff group; and adhesive capsulitis group. After establishing a posterior standard viewing portal, intravenous administration of ICG at 0.2 mg/kg body weight was performed, and fluorescence images were recorded. The time from injection of the drug to the beginning of enhancement of the observed area was measured. The hypovascular area in the rotator cuff was evaluated, and the ratio of the hypovascular area to the anterolateral area of the rotator cuff tendon was calculated (hypovascular area ratio). Results. ICG fluorescence angiography allowed for visualization of blood flow in the rotator cuff in all groups. The adhesive capsulitis group showed significantly earlier enhancement than the other groups. Furthermore, the adhesive capsulitis group had a significantly smaller hypovascular area ratio than the other groups. Conclusion. ICG fluorescence angiography allowed for evaluation of real-time blood flow of the rotator cuff in arthroscopic shoulder surgery. The techniques of ICG fluorescence angiography are simple and easy to observe, observer reliability is high, and it has utility for evaluating blood flow during surgery. Cite this article: N. Doi, T. Izaki, S. Miyake, T. Shibata, T. Ishimatsu, Y. Shibata, T. Yamamoto. Intraoperative evaluation of blood flow for soft tissues in orthopaedic surgery using indocyanine green fluorescence angiography: A pilot study. Bone Joint Res 2019;8:118–125. DOI: 10.1302/2046-3758.83.BJR-2018-0151.R1

The aim of this study was to review the role of clinical trial networks in orthopaedic surgery. A total of two electronic databases (MEDLINE and EMBASE) were searched from inception to September 2013 with no language restrictions. Articles related to randomised controlled trials (RCTs), research networks and orthopaedic research, were identified and reviewed. The usefulness of trainee-led research collaborations is reported and our knowledge of current clinical trial infrastructure further supplements the review. Searching yielded 818 titles and abstracts, of which 12 were suitable for this review. Results are summarised and presented narratively under the following headings: 1) identifying clinically relevant research questions; 2) education and training; 3) conduct of multicentre RCTs and 4) dissemination and adoption of trial results. This review confirms growing international awareness of the important role research networks play in supporting trials in orthopaedic surgery. Multidisciplinary collaboration and adequate investment in trial infrastructure are crucial for successful delivery of RCTs. Cite this article: Bone Joint Res 2014;3:169–74

Objectives. The period of post-operative treatment before surgical wounds are completely closed remains a key window, during which one can apply new technologies that can minimise complications. One such technology is the use of negative pressure wound therapy to manage and accelerate healing of the closed incisional wound (incisional NPWT). . Methods. We undertook a literature review of this emerging indication to identify evidence within orthopaedic surgery and other surgical disciplines. Literature that supports our current understanding of the mechanisms of action was also reviewed in detail. . Results. A total of 33 publications were identified, including nine clinical study reports from orthopaedic surgery; four from cardiothoracic surgery and 12 from studies in abdominal, plastic and vascular disciplines. Most papers (26 of 33) had been published within the past three years. Thus far two randomised controlled trials – one in orthopaedic and one in cardiothoracic surgery – show evidence of reduced incidence of wound healing complications after between three and five days of post-operative NPWT of two- and four-fold, respectively. Investigations show that reduction in haematoma and seroma, accelerated wound healing and increased clearance of oedema are significant mechanisms of action. . Conclusions. There is a rapidly emerging literature on the effect of NPWT on the closed incision. Initiated and confirmed first with a randomised controlled trial in orthopaedic trauma surgery, studies in abdominal, plastic and vascular surgery with high rates of complications have been reported recently. The evidence from single-use NPWT devices is accumulating. There are no large randomised studies yet in reconstructive joint replacement. Cite this article: Bone Joint Res 2013;2:276–84

High-quality randomised controlled trials (RCTs) evaluating surgical therapies are fundamental to the delivery of evidence-based orthopaedics. Orthopaedic clinical trials have unique challenges; however, when these challenges are overcome, evidence from trials can be definitive in its impact on surgical practice. In this review, we highlight several issues that pose potential challenges to orthopaedic investigators aiming to perform surgical randomised controlled trials. We begin with a discussion on trial design issues, including the ethics of sham surgery, the importance of sample size, the need for patient-important outcomes, and overcoming expertise bias. We then explore features surrounding the execution of surgical randomised trials, including ethics review boards, the importance of organisational frameworks, and obtaining adequate funding. Cite this article: Bone Joint Res 2014;3:161–8

Objectives. We performed a systematic review of the literature to determine the safety and efficacy of bone morphogenetic protein (BMP) compared with bone graft when used specifically for revision spinal fusion surgery secondary to pseudarthrosis. Methods. The MEDLINE, EMBASE and Cochrane Library databases were searched using defined search terms. The primary outcome measure was spinal fusion, assessed as success or failure in accordance with radiograph, MRI or CT scan review at 24-month follow-up. The secondary outcome measure was time to fusion. Results. A total of six studies (three prospective and three retrospective) reporting on the use of BMP2 met the inclusion criteria (203 patients). Of these, four provided a comparison of BMP2 and bone graft whereas the other two solely investigated the use of BMP2. The primary outcome was seen in 92.3% (108/117) of patients following surgery with BMP2. Although none of the studies showed superiority of BMP2 to bone graft for fusion, its use was associated with a statistically quicker time to achieving fusion. BMP2 did not appear to increase the risk of complication. Conclusion. The use of BMP2 is both safe and effective within the revision setting, ideally in cases where bone graft is unavailable or undesirable. Further research is required to define its optimum role. Cite this article: Mr P. Bodalia. Effectiveness and safety of recombinant human bone morphogenetic protein-2 for adults with lumbar spine pseudarthrosis following spinal fusion surgery: A systematic review. Bone Joint Res 2016;5:145–152. DOI: 10.1302/2046-3758.54.2000418

Objectives . The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics. . Methods . Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively. . Results. Significant structural differences existed between torn and control groups. Differences were identifiable early in the disease spectrum, and increased with increasing tear size. Neither SCI nor SAD surgery altered the structural properties of partially torn tendons seven weeks after treatment. . Conclusions . These findings may suggest the need for early clinical intervention strategies for torn rotator cuff tendons in order to prevent further degeneration of the tissue as tear size increases. Further work is required to establish the long-term abilities of SCI and SAD to prevent, and even reverse, such degeneration. Cite this article: Bone Joint Res 2014;3:252–61

Objectives. The aim of this study was to determine whether there is any significant difference in temporal measurements of pain, function and rates of re-tear for arthroscopic rotator cuff repair (RCR) patients compared with those patients undergoing open RCR. Methods. This study compared questionnaire- and clinical examination-based outcomes over two years or longer for two series of patients who met the inclusion criteria: 200 open RCR and 200 arthroscopic RCR patients. All surgery was performed by a single surgeon. . Results. Most pain measurements were similar for both groups. However, the arthroscopic RCR group reported less night pain severity at six months, less extreme pain and greater satisfaction with their overall shoulder condition than the open RCR group. The arthroscopic RCR patients also had earlier recovery of strength and range of motion, achieving near maximal recovery by six months post-operatively whereas the open RCR patients took longer to reach the same recovery level. The median operative times were 40 minutes (20 to 90) for arthroscopic RCR and 60 minutes (35 to 120) for open RCR. Arthroscopic RCR had a 29% re-tear rate compared with 52% for the open RCR group (p < 0.001). . Conclusions. Arthroscopic RCR involved less extreme pain than open RCR, earlier functional recovery, a shorter operative time and better repair integrity

Aims. Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery. Methods. Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites. Results. We initially identified 4,402 clinical trials, 27 of which were eligible for inclusion and analysis, including nine shoulder surgery trials, eight knee surgery trials, two ankle surgery trials, two hand surgery trials, and six peripheral nerve graft trials. Nine of the trials were completed. We identified only one product that will be commercially available for use in knee surgery with significant mechanical load resistance. Peracetic acid and gamma irradiation were frequently used for sterilization. Conclusion. Despite the demand for decellularized tissue, few decellularized tissue products are currently commercially available, particularly for the knee joint. To be viable in orthopaedic surgery, decellularized tissue must exhibit biocompatibility and mechanical strength, and these requirements are challenging for the clinical application of decellularized tissue. However, the variety of available decellularized products has recently increased. Therefore, decellularized grafts may become a promising option in orthopaedic surgery. Cite this article: Bone Joint Res 2023;12(3):179–188

Aims. Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians’ health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations. Methods. The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 μm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures. Results. Diathermy (electrocautery) and oscillating bone saw use had a high aerosol yield (> 100 particles detected per s) consistent with high exposure to aerosol in the respirable range (< 5 µm) for the lead surgeon. Pulsed lavage, reaming, osteotome use, and jig application/removal were medium aerosol yield (10 to 100 particles s. -1. ). However, pulsed lavage aerosol was largely attributed to the saline jet, osteotome use was always brief, and jig application/removal had a large variability in the associated aerosol yield. Suctioning (with/without saline irrigation) had a low aerosol yield (< 10 particles s. -1. ). Most surprisingly, other high-speed procedures, such as drilling and screwing, had low aerosol yields. Conclusion. This work suggests that additional precautions should be recommended for diathermy and bone sawing, such as enhanced personal protective equipment or the use of suction devices to reduce exposure. Cite this article: Bone Joint Res 2023;12(10):636–643

Aims. 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. Methods. A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry. Results. We found that PA28γ knockdown in chondrocytes can effectively improve anabolism and catabolism and inhibit inflammation, apoptosis, and ER stress. Moreover, PA28γ knockdown affected the phosphorylation of IRE1α and the expression of TRAF2, thereby affecting the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signalling pathways, and finally affecting the inflammatory response of chondrocytes. In addition, we found that PA28γ knockdown can promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting ER stress in chondrocytes. The use of Stattic (an inhibitor of STAT3 phosphorylation) enhanced ER stress. In vivo, we found that PA28γ knockdown effectively reduced cartilage destruction in a mouse model of OA induced by the DMM surgery. Conclusion. PA28γ knockdown in chondrocytes can inhibit anabolic and catabolic dysregulation, inflammatory response, and apoptosis in OA. Moreover, PA28γ knockdown in chondrocytes can inhibit ER stress by promoting STAT3 phosphorylation. Cite this article: Bone Joint Res 2024;13(11):659–672

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

Aims. To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope. Methods. Based on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system. Results. Surgical DMM with or without stereomicroscope led to decrease in the mean of weightbearing percentages (-20.64% vs -21.44%, p = 0.792) and paw withdrawal response thresholds (-21.35% vs -24.65%, p = 0.327) of the hind limbs. However, the coefficient of variation (CV) of weight-bearing percentages and paw withdrawal response thresholds in naked-eye group were significantly greater than that in the microscope group (19.82% vs 6.94%, p < 0.001; 21.85% vs 9.86%, p < 0.001). The gait analysis showed a similar pattern. Cartilage degeneration was observed in both DMM-surgery groups, evidenced by increased OARSI scores (summed score: 11.23 vs 11.43, p = 0.842), but the microscope group showed less variation in OARSI score than the naked-eye group (CV: 21.03% vs 32.44%; p = 0.032). Conclusion. Although surgical DMM aided by stereomicroscope is technically difficult, it produces a relatively more homogeneous OA model in terms of the discrete degree of pain behaviours and histopathological grading when compared with surgical DMM without stereomicroscope. Cite this article: Bone Joint Res 2022;11(8):518–527

Aims. Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation. Methods. This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR. Results. From 2009 to 2018, the short-term re-rupture rate for Achilles tendon surgeries was 2.14%. Risk factors included male sex, younger age, and the presence of Achilles tendinopathy. Conclusion. This large-scale, big-data study reaffirmed known risk factors for short-term Achilles tendon re-rupture, specifically identifying male sex and younger age. Moreover, this study discovered that a prior history of Achilles tendinopathy emerges as an independent risk factor for re-rupture, even following initial operative fixation. Cite this article: Bone Joint Res 2024;13(7):315–320

Aims. Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. Results. In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. Conclusion. Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA. Cite this article: Bone Joint Res 2023;12(2):121–132

Aims. Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis. Methods. Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression. Results. Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. Conclusion. Taken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA. Cite this article: Bone Joint Res 2023;12(1):33–45

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

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. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273

Aims. This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm. 3. ). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm. 2. . Conclusion. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):590–597

Aims. Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Methods. Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically. Results. Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR. Conclusion. HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR. Cite this article: Bone Joint Res 2023;12(8):455–466

Aims. Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. Methods. In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results. The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion. Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA. Cite this article: Bone Joint Res 2024;13(3):110–123

Aims. The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD. Methods. A comprehensive literature search was conducted to identify eligible studies reporting postoperative outcomes in IBD patients undergoing joint arthroplasty. The primary outcomes included postoperative complications, while the secondary outcomes included unplanned readmission, length of stay (LOS), joint reoperation/implant revision, and cost of care. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model when heterogeneity was substantial. Results. Eight retrospective studies involving 29,738 patients with IBD were included. Compared with non-IBD controls, patients with IBD were significantly more likely to have overall complications (OR 2.11 (95% CI 1.67 to 2.66), p < 0.001), medical complications (OR 2.15 (95% CI 1.73 to 2.68), p < 0.001), surgical complications (OR 1.43 (95% CI 1.21 to 1.70), p < 0.001), and 90-day readmissions (OR 1.42 (95% CI 1.23 to 1.65), p < 0.001). The presence of IBD was positively associated with the development of venous thromboembolism (OR 1.60 (95% CI 1.30 to 1.97), p < 0.001) and postoperative infection (OR 1.95 (95% CI 1.51 to 2.51), p < 0.001). In addition, patients with IBD tended to experience longer LOS and higher costs of care. Conclusion. The findings suggest that IBD is associated with an increased risk of postoperative complications and readmission after joint arthroplasty, resulting in longer hospital stay and greater financial burden. Surgeons should inform their patients of the possibility of adverse outcomes prior to surgery and make appropriate risk adjustments to minimize potential complications. Cite this article: Bone Joint Res 2023;12(6):362–371

Aims. The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results. PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion. This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations. Cite this article: Bone Joint Res 2023;12(10):644–653

Aims. Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals. Methods. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify English studies, including ≥ 18-year-old participants, without evidence of hip or spine pathology or a history of previous surgery or interventional treatment, documenting lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). From a total of 2,543 articles retrieved after the initial database search, 61 articles were eventually selected for data extraction. Results. When all ethnicities were combined the mean values for LL, SS, PT, and PI were: 47.4° (SD 11.0°), 35.8° (SD 7.8°), 14.0° (SD 7.2°), and 48.8° (SD 10°), respectively. LL, SS, and PT had statistically significant (p < 0.001) changes per decade at: −1.5° (SD 0.3°), −1.3° (SD 0.3°), and 1.4° (SD 0.1°). Asian populations had the largest age-dependent change in LL, SS, and PT compared to any other ethnicity per decade at: −1.3° (SD 0.3°) to −0.5° (SD 1.3°), –1.2° (SD 0.2°) to −0.3° (SD 0.3°), and 1.7° (SD 0.2°) versus 1.1° (SD 0.1°), respectively. Conclusion. Ageing alters the orientation between the spine and pelvis, causing LL, SS, and PT to modify their orientations in a compensatory mechanism to maintain sagittal alignment for balance when standing. Asian populations have the largest degree of age-dependent change to their spinopelvic parameters compared to any other ethnicity, likely due to their lower PI. Cite this article: Bone Joint Res 2023;12(4):231–244

Aims. 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. Methods. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve. Results. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians’ experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs. Cite this article: Bone Joint Res 2024;13(9):497–506

Aims. A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. Methods. A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing. Results. The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups. Conclusion. This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion. Cite this article: Bone Joint Res 2022;11(8):585–593

Aims. Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. Methods. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. Results. The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). Conclusion. Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group — that is, osteoclast suppression — may contribute to the reduction of the postoperative revision rate after THA. Cite this article: Bone Joint Res 2022;11(12):873–880

Aims. 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. Methods. We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model. Results. A total of 45 of 398 (11.3%) eligible patients were taking an oral bisphosphonate at the time of knee surgery, with a mean age of 75.8 years (SD 6.2) in bisphosphonate users and 75.7 years (SD 6.8) in non-users. The mean joint space narrowing rate was 0.04 mm/year (SD 0.11) in bisphosphonate users and 0.12 mm/year (SD 0.25) in non-users (p < 0.001). In the multivariate model, age (standardized coefficient = 0.0867, p = 0.016) and the use of a bisphosphonate (standardized coefficient = −0.182, p < 0.001) were associated with the joint space narrowing rate. After successfully matching 43 bisphosphonate users and 86 non-users, the joint narrowing rate was smaller in bisphosphonate users (p < 0.001). Conclusion. The use of bisphosphonates is associated with decreased joint degeneration in non-arthritic hips after knee arthroplasty. Bisphosphonates slow joint degeneration, thus maintaining the thickness of joint cartilage in the normal joint or during the early phase of osteoarthritis. Cite this article: Bone Joint Res 2022;11(11):826–834

Aims. To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods. Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 10. 6. ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results. In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion. ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786

Aims. 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. Methods. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. Results. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Conclusion. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022;11(10):700–714