Aims. The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty. Methods. A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated. Results. Escherichia coli was the most common pathogen in GN-PJI, and meropenem was the most sensitive antibiotic. Serum inflammatory markers, weightbearing activity, and Rissing score were significantly improved by meropenem, especially in the IA and IP + IA groups ( p < 0.05). Meropenem in the IA group eradicated E. coli from soft-tissue, bone, and prosthetic surfaces, with the same effect as in the IP + IA group. Radiological results revealed that IA and IP + IA meropenem were effective at relieving bone damage. Haematoxylin and eosin staining also showed that IA and IP + IA meropenem improved synovial inflammation and bone destruction. No pathological changes in the main organs or abnormal serum markers were observed in any of the meropenem-treated rats. The IA group required the lowest amount of meropenem, followed by the IP and IP + IA groups. Conclusion. IA-only meropenem with a two-week treatment course was effective and safe for PJI control following one-stage revision in a rat model, with less meropenem use. Cite this article: Bone Joint Res 2024;13(10):546–558

Aims. We sought to compare functional outcomes and survival between non-smokers, former smokers, and current smokers who underwent anatomical total shoulder arthroplasty (aTSA) in a large cohort of patients. Methods. A retrospective review of a prospectively collected shoulder arthroplasty database was performed between August 1991 and September 2020 to identify patients who underwent primary aTSA. Patients were excluded for preoperative diagnoses of fracture, infection, or oncological disease. Three cohorts were created based on smoking status: non-smokers, former smokers, and current smokers. Outcome scores (American Shoulder and Elbow Surgeons (ASES), Constant-Murley score, Shoulder Pain and Disability Index (SPADI), Simple Shoulder Test (SST), University of California, Los Angeles activity scale (UCLA)), range of motion (external rotation (ER), forward elevation (FE), internal rotation, abduction), and shoulder strength (ER, FE) evaluated at two- to four-year follow-up were compared between cohorts. Evaluation of revision-free survival was performed using the Kaplan-Meier method to final follow-up. Results. We included 428 primary aTSAs with a mean follow-up of 2.4 years (SD 0.6). Our cohort consisted of 251 non-smokers, 138 former smokers who quit a mean 21 years (SD 14) prior to surgery (25 pack-years (SD 22)), and 39 current smokers (23 pack-years (SD 20)). At two- to four-year follow-up, former smokers had less favourable SPADI, SST, and FE strength compared to non-smokers, and current smokers had less favourable SPADI, SST, ASES score, UCLA score, Constant-Murley score, FE, abduction, and ER strength compared to non-smokers. Non-smokers exhibited higher revision-free survival rates at two, five, eight, and ten years postoperatively compared to former smokers and current smokers, who had similar rates. Conclusion. Our study suggests that smoking has a negative effect on aTSA functional outcomes that may persist even after quitting. Cite this article: Bone Joint J 2024;106-B(11):1263–1272

Aims. The primary aim was to assess change in health-related quality of life (HRQoL) of patients as they waited from six to 12 months for a total hip (THA) or total or partial knee arthroplasty (KA). Secondary aims were to assess change in joint-specific function, mental health, quality of sleep, number living in a state worse than death (WTD), wellbeing, and patient satisfaction with their healthcare. Methods. This prospective study included 142 patients awaiting a THA (mean age 66.7 years (SD 11.4); 71 female) and 214 patients awaiting KA (mean age 69.7 years (SD 8.7); 117 female). Patients completed questionnaires (EuroQol five-dimension health questionnaire (EQ-5D), Oxford Hip and Knee Scores (OHS/OKS), Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Score (HADS), University of California, Los Angeles Activity Scale, wellbeing assessment, and satisfaction with their healthcare) at six and 12 months while awaiting surgery. Results. There was a clinical and statistically significant deterioration in the EQ-5D while awaiting THA (mean change 0.071 (95% confidence interval (CI) 0.018 to 0.124); p = 0.009) and KA (mean change 0.069 (95% CI 0.032 to 0.106); p < 0.001). For patients awaiting a THA, there were deteriorations in OHS (p = 0.003), PSQI (p = 0.008), both HADS depression (p = 0.001) and anxiety (p = 0.002), and an increased prevalence in those in a state WTD (p = 0.010). For those awaiting KA, there were significant deteriorations in OKS (p < 0.001), UCLA (p = 0.001), and HADS depression (p < 0.001) and anxiety (p < 0.001). There were significant decreases in wellbeing (satisfaction with life, feeling life to be worthwhile, and happiness) and increases in anxiety for those awaiting THA or KA (p < 0.001). Those awaiting THA (odds ratio (OR) 0.52 (95% CI 0.31 to 0.89); p = 0.016) and KA (OR 0.46 (95% CI 0.31 to 0.71); p < 0.001) had a significant decrease in satisfaction with their healthcare. Conclusion. As patients waited from six to 12 months for THA or KA, they experienced a clinically significant deterioration in HRQoL. There were also deteriorations in joint-specific function, mental health, wellbeing, and patient satisfaction with healthcare. Cite this article: Bone Joint J 2024;106-B(2):166–173

Aims. It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs. Methods. The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome. Results. The SF-36 physical component summary mean at baseline was 30.9 (95% CI 29.7 to 32.0). At one month, it was unchanged (30.5; 95% CI 29.5 to 31.5; p = 0.447); it had improved statistically significantly at six months (35.5; 95% CI 34.2 to 36.7; p < 0.001) and at 12 months (37.9; 95% CI 36.4 to 39.3; p < 0.001). The SF-36 mental component summary mean at baseline was 42.5 (95% CI 40.8 to 44.2). At one month, it was unchanged (43.1; 95% CI 41.4 to 44.8; p = 0.458); it had improved statistically significantly at six months (47.1; 95% CI 45.4 to 48.7; p < 0.001) and at 12 months (46.7; 95% CI 45.0 to 48.5; p < 0.001). All mental subscales had improved by the end of the study, but mental health status remained compromised in comparison with the average USA population. Conclusion. BJIs considerably impact HRQoL, particularly mental health. Patients suffering from BJIs reported considerable limitations in their daily and social activities due to psychological problems. Impaired mental health may be explained by the chronic nature of BJIs, and therefore the mental wellbeing of these patients should be monitored closely. Cite this article: Bone Jt Open 2024;5(9):721–728

Aims. The aim of this study was to establish consensus statements on medial patellofemoral ligament (MPFL) reconstruction, anteromedialization tibial tubercle osteotomy, trochleoplasty, and rehabilitation and return to sporting activity in patients with patellar instability, using the modified Delphi process. Methods. This was the second part of a study dealing with these aspects of management in these patients. As in part I, a total of 60 surgeons from 11 countries contributed to the development of consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered unanimous. Results. Of 41 questions and statements on patellar instability, none achieved unanimous consensus, 19 achieved strong consensus, 15 achieved consensus, and seven did not achieve consensus. Conclusion. Most statements reached some degree of consensus, without any achieving unanimous consensus. There was no consensus on the use of anchors in MPFL reconstruction, and the order of fixation of the graft (patella first versus femur first). There was also no consensus on the indications for trochleoplasty or its effect on the viability of the cartilage after elevation of the osteochondral flap. There was also no consensus on postoperative immobilization or weightbearing, or whether paediatric patients should avoid an early return to sport. Cite this article: Bone Joint J 2023;105-B(12):1265–1270

Aims. Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Methods. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot. Results. DC-exo inhibited macrophage autophagy (p = 0.002) and promoted M1 macrophage polarization (p = 0.002). DC-exo at 20 μg/ml induced collagen degradation (p < 0.001) and inflammatory cell infiltration (p = 0.023) in rats. OANCT was elevated in DC (p < 0.001) and in cartilage tissues of OA patients (p < 0.001), and positively correlated with patients’ Kellgren-Lawrence grade (p < 0.001). PIK3R5 was increased in DC-exo-treated cartilage tissues (p < 0.001), and OANCT bound to fat mass and obesity-associated protein (FTO) (p < 0.001). FTO bound to PIK3R5 (p < 0.001) to inhibit the stability of PIK3R5 messenger RNA (mRNA) (p < 0.001) and disrupt the PI3K/AKT/mTOR pathway (p < 0.001). Conclusion. Exosomal OANCT from DC could bind to FTO protein, thereby maintaining the mRNA stability of PIK3R5, further activating the PI3K/AKT/mTOR pathway to exacerbate OA. Cite this article: Bone Joint Res 2022;11(9):652–668

Aims. In metal-on-polyethylene (MoP) total hip arthroplasty (THA), large metal femoral heads have been used to increase stability and reduce the risk of dislocation. The increased size of the femoral head can, however, lead to increased taper corrosion, with the release of metal ions and adverse reactions. The aim of this study was to investigate the relationship between the size of the femoral head and the levels of metal ions in the blood in these patients. Methods. A total of 96 patients were enrolled at two centres and randomized to undergo MoP THA using either a 32 mm metal head or a femoral head of between 36 mm and 44 mm in size, being the largest possible to fit the thinnest available polyethylene insert. The levels of metal ions and patient-reported outcome measures (Oxford Hip Score, University of California, Los Angeles Activity Scale) were recorded at two and five years postoperatively. Results. At five years, the median levels of chromium, cobalt, and titanium were 0.5 μg/l (interquartile range (IQR) 0.50 to 0.62), 0.24 μg/l (IQR 0.18 to 0.30), and 1.16 μg/l (IQR 1.0 to 1.68) for the 32 mm group, and 0.5 μg/l (IQR 0.5 to 0.54), 0.23 μg/l (IQR 0.17 to 0.39), and 1.30 μg/l (IQR 1 to 2.05) for the 36 mm to 44 mm group, with no significant difference between the groups (p = 0.825, p = 1.000, p = 0.558). There were increased levels of metal ions at two years postoperatively in seven patients in the 32 mm group, compared with four in the 36 mm to 44 mm group, and at five years postoperatively in six patients in the 32 mm group, compared with seven in the 36 mm to 44 mm group. There was no significant difference in either the OHS (p = 0.665) or UCLA (p = 0.831) scores between patients with or without an increased level of metal ions. Conclusion. In patients who underwent MoP THA, we found no differences in the levels of metal ions five years postoperatively between those with a femoral head of 32 mm and those with a femoral head of between 36 mm and 44 mm, and no corrosion-related revisions. As taper corrosion can start after five years, there remains a need for longer-term studies investigating the relationship between the size of the femoral head size and corrosion in patients undergoing MoP THA. Cite this article: Bone Joint J 2024;106-B(3 Supple A):31–37

Aims. National hip fracture registries audit similar aspects of care but there is variation in the actual data collected; these differences restrict international comparison, benchmarking, and research. The Fragility Fracture Network (FFN) published a revised minimum common dataset (MCD) in 2022 to improve consistency and interoperability. Our aim was to assess compatibility of existing registries with the MCD. Methods. We compared 17 hip fracture registries covering 20 countries (Argentina; Australia and New Zealand; China; Denmark; England, Wales, and Northern Ireland; Germany; Holland; Ireland; Japan; Mexico; Norway; Pakistan; the Philippines; Scotland; South Korea; Spain; and Sweden), setting each of these against the 20 core and 12 optional fields of the MCD. Results. The highest MCD adherence was demonstrated by the most recently established registries. The first-generation registries in Scandinavia collect data for 60% of MCD fields, second-generation registries (UK, other European, and Australia and New Zealand) collect for 75%, and third-generation registries collect data for 85% of MCD fields. Five of the 20 core fields were collected by all 17 registries (age; sex; surgery date/time of operation; surgery type; and death during acute admission). Two fields were collected by most (16/17; 94%) registries (date/time of presentation and American Society of Anesthesiologists grade), and five more by the majority (15/17; 88%) registries (type, side, and pathological nature of fracture; anaesthetic modality; and discharge destination). Three core fields were each collected by only 11/17 (65%) registries: prefracture mobility/activities of daily living; cognition on admission; and bone protection medication prescription. Conclusion. There is moderate but improving compatibility between existing registries and the FFN MCD, and its introduction in 2022 was associated with an improved level of adherence among the most recently established programmes. Greater interoperability could be facilitated by improving consistency of data collection relating to prefracture function, cognition, bone protection, and follow-up duration, and this could improve international collaborative benchmarking, research, and quality improvement. Cite this article: Bone Joint J 2023;105-B(9):1013–1019

Aims. Current levels of hip fracture morbidity contribute greatly to the overall burden on health and social care services. Given the anticipated ageing of the population over the coming decade, there is potential for this burden to increase further, although the exact scale of impact has not been identified in contemporary literature. We therefore set out to predict the future incidence of hip fracture and help inform appropriate service provision to maintain an adequate standard of care. Methods. Historical data from the Scottish Hip Fracture Audit (2017 to 2021) were used to identify monthly incidence rates. Established time series forecasting techniques (Exponential Smoothing and Autoregressive Integrated Moving Average) were then used to predict the annual number of hip fractures from 2022 to 2029, including adjustment for predicted changes in national population demographics. Predicted differences in service-level outcomes (length of stay and discharge destination) were analyzed, including the associated financial cost of any changes. Results. Between 2017 and 2021, the number of annual hip fractures increased from 6,675 to 7,797 (15%), with a rise in incidence from 313 to 350 per 100,000 (11%) for the at-risk population. By 2029, a combined average projection forecast the annual number of hip fractures at 10,311, with an incidence rate of 463 per 100,000, representing a 32% increase from 2021. Based upon these projections, assuming discharge rates remain constant, the total overall length of hospital stay following hip fracture in Scotland will increase by 60,699 days per annum, incurring an additional cost of at least £25 million per year. Approximately five more acute hip fracture beds may be required per hospital to accommodate this increased activity. Conclusion. Projection modelling demonstrates that hip fracture burden and incidence will increase substantially by 2029, driven by an ageing population, with substantial implications for health and social care services. Cite this article: Bone Joint J 2024;106-B(1):62–68

Aims. In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD. Results. A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion. DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD. Cite this article: Bone Joint Res 2024;13(5):247–260

Aims. This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant. Methods. A total of 63 patients (65 implants) were treated using either a MoM-coated (n = 29) or TiN-coated (n = 7) hinged TKA (GenuX mobile bearing, MUTARS; Implantcast, Germany) versus the BPKS (Brehm, Germany) hinged TKA (n = 27), in which the weight placed on the MoM hinge is diffused through a polyethylene (PE) inlay, reducing the direct load on the MoM hinge. Serum cobalt and chromium ion concentrations were assessed after minimum follow-up of 12 months, as well as functional outcome and quality of life. Results. No differences in mean age (69 years, 40 to 86), mean age adapted Charlson Comorbidity Index (3.1 (SD 1.4)), mean BMI (29.2 kg/m. 2. (SD 5.8)), or number of other implants were observed between groups. Significant improvements in outcome scores and pain levels were achieved for all groups, and there was no difference in quality of life (12-Item Short-Form Health Survey questionnaire (SF-12)). Mean cobalt and chromium ion levels were significantly higher for the GenuX versus the BPKS hinged TKA (GenuX vs BPKS: cobalt: 16.3 vs 9.4 µg/l; chromium: 9.5 vs 5.2 µg/l). The TiN-coated implants did not appear to confer improvement in the metal ion levels. Metal ion concentrations above 7 µg/l were detected in 81%(29/36) of GenuX patients versus 41% (11/27) in the BPKS group. No GenuX patients had normal levels under 2 µg/l, versus 22% of BPKS patients. No significant reduction in outcome scores was observed regardless of the metal ion levels, whereas higher work-related activity was correlated with higher chromium concentrations. Conclusion. Hinged TKA, using MoM hinges, resulted in critically high cobalt and chromium ion concentrations. The BPKS hinged TKA showed significantly lower metal ion concentrations compared with the GenuX TKA. No benefits were observed using TiN coating. The different weightbearing mechanics might influence the wear of the component materials. Higher workloads and physical activity could influence chromium levels. Cite this article: Bone Joint J 2022;104-B(3):376–385

Aims. To describe outcome reporting variation and trends in non-pharmacological randomized clinical trials (RCTs) of distal tibia and/or ankle fractures. Methods. Five electronic databases and three clinical trial registries were searched (January 2000 to February 2022). Trials including patients with distal tibia and/or ankle fractures without concomitant injuries were included. One reviewer conducted all searches, screened titles and abstracts, assessed eligibility, and completed data extraction; a random 10% subset were independently assessed and extracted by a second reviewer at each stage. All extracted outcomes were mapped to a modified version of the International Classification of Functioning, Disability and Health framework. The quality of outcome reporting (reproducibility) was assessed. Results. Overall, 105 trials (n = 16 to 669 participants) from 27 countries were included. Trials compared surgical interventions (n = 62), post-surgical management options (n = 17), rehabilitative interventions (n = 14), surgical versus non-surgical interventions (n = 6), and pre-surgical management strategies (n = 5). In total, 888 outcome assessments were reported across seven domains: 263 assessed body structure or function (85.7% of trials), 136 activities (68.6% of trials), 34 participation (23.8% of trials), 159 health-related quality of life (61.9% of trials), 247 processes of care (80% of trials), 21 patient experiences (15.2% of trials), and 28 economic impact (8.6% of trials). From these, 337 discrete outcomes were described. Outcome reporting was inconsistent across trials. The quality of reporting varied widely (reproducibility ranged 4.8% patient experience to 100% complications). Conclusion. Substantial heterogeneity in outcome selection, assessment methods, and reporting quality were described. Despite the large number of outcomes, few are reported across multiple trials. Most outcomes are clinically focused, with little attention to the long-term consequences important to patients. Poor reporting quality reduces confidence in data quality, inhibiting data synthesis by which to inform care decisions. Outcome reporting guidance and standardization, which captures the outcomes that matter to multiple stakeholders, are urgently required. Cite this article: Bone Jt Open 2022;3(10):832–840

Aims. There has been limited literature regarding outcomes of acetabular rim syndrome (ARS) with persistent acetabular os in the setting of acetabular dysplasia. The purpose of this study was to characterize a cohort of adolescent and young adult patients with ARS with persistent os and compare their radiological and clinical outcomes to patients with acetabular dysplasia without an os. Methods. We reviewed a prospective database of patients undergoing periacetabular osteotomy (PAO) for symptomatic acetabular dysplasia between January 1999 and December 2021 to identify hips with preoperative os acetabuli, defined as a closed triradiate cartilage but persistence of a superolateral os acetabulum. A total of 14 hips in 12 patients with persistent os acetabuli (ARS cohort) were compared to 50 randomly selected ‘control’ hips without persistent os acetabuli. Preoperative and postoperative radiographs were measured for markers of dysplasia: lateral centre-edge angle, anterior centre-edge angle, acetabular inclination, and migration index. Union of the os was determined in patients with ≥ six months’ follow-up. Patient-reported outcome measures (PROMs) included the University of California, Los Angeles (UCLA) activity score and modified Harris Hip Score (mHHS, maximum score 80) completed at one year postoperatively. Results. There was no significant difference between the ARS and control cohorts with regard to sex distribution (p = 0.270), age at surgery (p = 0.186), or BMI (p = 0.442). Preoperatively, the ARS cohort had more severe dysplasia, including lower lateral centre-edge angle (-9.3° (SD 12.5°) vs 7.6° (SD 10.7°); p < 0.001) and greater acetabular inclination (33.9° (SD 8.2°) vs 21.8° (SD 8.7°); p < 0.001). Postoperatively, 6/13 (46%) hips with ≥ six months of radiological follow up demonstrated union of the os. There was no difference between the ARS and control cohorts at one year in UCLA score (9.1 (SD 1.5) vs 8.2 (SD 1.9); p = 0.167) or mHHS (73.4 (SD 9.5) vs 69.9 (SD 8.8); p = 0.312). Conclusion. ARS with persistent acetabular os may occur in more severe dysplasia. Union occurs in 50% cases following corrective PAO. Cite this article: Bone Joint J 2024;106-B(12):1393–1398

Aims. The direct anterior (DA) approach has been associated with rapid patient recovery after total hip arthroplasty (THA) but may be associated with more frequent femoral complications including implant loosening. The objective of this study was to determine whether the addition of a collar to the femoral stem affects implant migration, patient activity, and patient function following primary THA using the DA approach. Methods. Patients were randomized to either a collared (n = 23) or collarless (n = 26) cementless femoral stem implanted using the DA approach. Canal fill ratio (CFR) was measured on the first postoperative radiographs. Patients underwent a supine radiostereometric analysis (RSA) exam postoperatively on the day of surgery and at two, four, six, 12, 26, and 52 weeks postoperatively. Patient-reported outcome measures (Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, the 12-item Short Form Health Survey Mental and Physical Score, and University of California, Los Angeles (UCLA) Activity Score) were measured preoperatively and at each post-surgery clinic visit. Activity and function were also measured as the weekly average step count recorded by an activity tracker, and an instrumented timed up-and-go (TUG) test in clinic, respectively. Results. Comparing the RSA between the day of surgery baseline exam to two weeks postoperatively, subsidence was significantly lower (mean difference 2.23 mm (SD 0.71), p = 0.023) with collared stems, though these patients had a greater CFR (p = 0.048). There was no difference (p = 0.426) in subsidence between stems from a two-week baseline through to one year postoperatively. There were no clinically relevant differences in PROMs; and there was no difference in the change in activity (p = 0.078) or the change in functional capacity (p = 0.664) between the collared stem group and the collarless stem group at any timepoint. Conclusion. Presence of a collar on the femoral stem resulted in reduced subsidence during the first two postoperative weeks following primary THA using the DA approach. However, the clinical implications are unclear, and larger studies examining patient activity and outcomes are required. Cite this article: Bone Joint J 2020;102-B(12):1654–1661

Aims. Deprivation underpins many societal and health inequalities. COVID-19 has exacerbated these disparities, with access to planned care falling greatest in the most deprived areas of the UK during 2020. This study aimed to identify the impact of deprivation on patients on growing waiting lists for planned care. Methods. Questionnaires were sent to orthopaedic waiting list patients at the start of the UK’s first COVID-19 lockdown to capture key quantitative and qualitative aspects of patients’ health. A total of 888 respondents were divided into quintiles, with sampling stratified based on the Index of Multiple Deprivation (IMD); level 1 represented the ‘most deprived’ cohort and level 5 the ‘least deprived’. Results. The least deprived cohort were older (mean 65.95 years (SD 13.33)) than the most deprived (mean 59.48 years (SD 13.85)). Mean symptom duration was lower in the least deprived areas (68.59 months (SD 112.26)) compared to the most deprived (85.85 months (SD 122.50)). Mean pain visual analogue scores (VAS) were poorer in the most compared to the least deprived cohort (7.11 (SD 2.01) vs 5.99 (SD 2.57)), with mean mood scores also poorer (6.06 (SD 2.65) vs 4.71 (SD 2.78)). The most deprived areas exhibited lower mean quality of life (QoL) scores than the least (0.37 (SD 0.30) vs 0.53 (SD 0.31)). QoL findings correlated with health VAS and Generalized Anxiety Disorder 2-item (GAD2) scores, with the most deprived areas experiencing poorer health (health VAS 50.82 (SD 26.42) vs 57.29 (SD 24.19); GAD2: 2.94 (SD 2.35) vs 1.88 (SD 2.07)). Least-deprived patients had the highest self-reported activity levels and lowest sedentary cohort, with the converse true for patients from the most deprived areas. Conclusion. The most deprived patients experience poorer physical and mental health, with this most adversely impacted by lengthy waiting list delays. Interventions to address inequalities should focus on prioritizing the most deprived. Cite this article: Bone Jt Open 2022;3(10):777–785

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722

Aims. This study investigates head-neck taper corrosion with varying head size in a novel hip simulator instrumented to measure corrosion related electrical activity under torsional loads. Methods. In all, six 28 mm and six 36 mm titanium stem-cobalt chrome head pairs with polyethylene sockets were tested in a novel instrumented hip simulator. Samples were tested using simulated gait data with incremental increasing loads to determine corrosion onset load and electrochemical activity. Half of each head size group were then cycled with simulated gait and the other half with gait compression only. Damage was measured by area and maximum linear wear depth. Results. Overall, 36 mm heads had lower corrosion onset load (p = 0.009) and change in open circuit potential (OCP) during simulated gait with (p = 0.006) and without joint movement (p = 0.004). Discontinuing gait’s joint movement decreased corrosion currents (p = 0.042); however, wear testing showed no significant effect of joint movement on taper damage. In addition, 36 mm heads had greater corrosion area (p = 0.050), but no significant difference was found for maximum linear wear depth (p = 0.155). Conclusion. Larger heads are more susceptible to taper corrosion; however, not due to frictional torque as hypothesized. An alternative hypothesis of taper flexural rigidity differential is proposed. Further studies are necessary to investigate the clinical significance and underlying mechanism of this finding. Cite this article: Bone Jt Open 2021;2(11):1004–1016

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

Aims. The aim of this study is to develop a core set of outcome domains that should be considered and reported in all future trials of childhood limb fractures. Methods. A four-phase study was conducted to agree a set of core outcome domains. Identification of candidate outcome domains were identified through systematic review of trials, and outcome domains relevant to families were identified through semi-structured interviews with 20 families (parent-child pairing or group). Outcome domains were prioritized using an international three-round Delphi survey with 205 panellists and then condensed into a core outcome set through a consensus workshop with 30 stakeholders. Results. The systematic review and interviews identified 85 outcome domains as relevant to professionals or families. The Delphi survey prioritized 30 upper and 29 lower limb outcome domains at first round, an additional 17 upper and 18 lower limb outcomes at second round, and four additional outcomes for upper and lower limb at the third round as important domains. At the consensus workshop, the core outcome domains were agreed as: 1) pain and discomfort; 2) return to physical and recreational activities; 3) emotional and psychosocial wellbeing; 4) complications from the injury and treatment; 5) rturn to baseline activities daily living; 6) participation in learning; 7) appearance and deformity; and 8) time to union. In addition, 9a) recovery of mobility and 9b) recovery of manual dexterity was recommended as a core outcome for lower and upper limb fractures, respectively. Conclusion. This set of core outcome domains is recommended as a minimum set of outcomes to be reported in all trials. It is not an exhaustive set and further work is required to identify what outcome tools should be used to measure each of these outcomes. Adoption of this outcome set will improve the consistency of research for these children that can be combined for more meaningful meta-analyses and policy development. Cite this article: Bone Joint J 2021;103-B(12):1821–1830

Aims. To examine the long-term outcome of arthrodesis of the hip undertaken in a paediatric population in treating painful arthritis of the hip. In our patient population, most of whom live rurally in hilly terrain and have limited healthcare access and resources, hip arthrodesis has been an important surgical option for the monoarticular painful hip in a child. Methods. A follow-up investigation was undertaken on a cohort of 28 children previously reported at a mean of 4.8 years. The present study looked at 26 patients who had an arthrodesis of the hip as a child at a mean follow-up of 20 years (15 to 29). Results. The mean Harris Hip Score (HHS) increased from 39.60 (SD 11.06) preoperatively to 81.02 (SD 8.86; p = 0.041) at final review. At latest follow-up, the HHS was found to be excellent in four patients (15%), good in 11 (42%), and fair in 11 (42%). A total of 16 patients (62%) reported mild low back pain, five (19%) had moderate pain, and five (19%) patients had no back pain. Mild ipsilateral knee pain was reported by 19 (73%), moderate pain by one (4%), and no pain by six (23%) patients. Mild contralateral hip pain was reported by ten patients (38%), and no pain by 16 (62%). The 36-Item Short Form Health Survey scores were very good in four patients (15%), good in 18 (70%), and poor in four (15%), with a mean score of 70.92 (SD 12.65). Of 13 female patients who had given birth, 12 did so with uncomplicated vaginal delivery. All patients had to modify their posture for toileting, putting on lower body clothes, foot care, and putting on shoes. Conclusion. Our results show that with hip arthrodesis, most patients have relatively good function at long-term follow-up, although some pain is experienced in adjacent joints, and modification in some activities of daily living is common. Cite this article: Bone Joint J 2022;104-B(9):1089–1094