Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168

Aims. The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids. Methods. Intact right cadaveric shoulders from donors aged between 50 and 65 years were assigned to a ceramic group (n = 8, four male cadavers) and a metal group (n = 9, four male cadavers). A dedicated shoulder wear simulator was used to simulate daily activity by replicating the relevant joint motion and loading profiles. During testing, the joint was kept lubricated with diluted calf serum at room temperature. Each test of wear was performed for 500,000 cycles at 1.2 Hz. At intervals of 125,000 cycles, micro-CT scans of each glenoid were taken to characterize and quantify glenoid wear by calculating the change in the thickness of its articular cartilage. Results. At the completion of the wear test, the total thickness of the cartilage had significantly decreased in both the ceramic and metal groups, by 27% (p = 0.019) and 29% (p = 0.008), respectively. However, the differences between the two were not significant (p = 0.606) and the patterns of wear in the specimens were unpredictable. No significant correlation was found between cartilage wear and various factors, including age, sex, the size of the humeral head, joint mismatch, the thickness of the native cartilage, and the surface roughness (all p > 0.05). Conclusion. Although ceramic has better tribological properties than metal, we did not find evidence that its use in hemiarthroplasty of the shoulder in patients with healthy cartilage is a better alternative than conventional metal humeral heads. Cite this article: Bone Joint J 2024;106-B(11):1273–1283

Aims. The Cartiva synthetic cartilage implant (SCI) entered mainstream use in the management of first metatarsophalangeal joint (MTPJ) arthritis following the positive results of large trials in 2016. Limited information is available on the longer-term outcomes of this implant within the literature, particularly when independent from the originator. This single-centre cohort study investigates the efficacy of the Cartiva SCI at up to five years. Methods. First MTPJ arthritis was radiologically graded according to the Hattrup and Johnson (HJ) classification. Preoperative and sequential postoperative patient-reported outcome measures (PROMs) were evaluated using the Manchester-Oxford Foot Questionnaire (MOXFQ), and the activities of daily living (ADL) sub-section of the Foot and Ankle Ability Measure (FAAM). Results. Patients were followed up for a mean of 66 months (SD 7.1). Of an initial 66 cases, 16 did not return PROM questionnaires. A total of six failures were noted, with survival of 82%. Overall, significant improvement in both objective scores (MOXFQ and FAAM ADL) was maintained versus preoperatively: 18.2 versus 58.0 (p > 0.001) and 86.2 versus 41.1 (p > 0.001), respectively. The improvement was noted to be less pronounced in males. Subjective scores had deteriorated since early follow-up, with an interval decrease in patient satisfaction from 89% to 68%. Furthermore, a subset of cases demonstrated clinically important interval deterioration in objective scores. However, no specific patient factors were found to be associated with outcomes following analysis. Conclusion. This study represents the longest-term independent follow-up in the literature. It shows reassuring mid-term efficacy of the Cartiva SCI with better-than-expected survival. However, deterioration in scores for a subset of patients and lower satisfaction may predict ongoing failure in this group of patients. Additionally, males were noted to have a lower degree of improvement in scores than females. As such, ongoing observation of the SCI to assess durability and survivability, and identify predictive factors, is key to improving patient selection. Cite this article: Bone Jt Open 2024;5(9):799–805

Aims. A review of the literature on elbow replacement found no consistency in the clinical outcome measures which are used to assess the effectiveness of interventions. The aim of this study was to define core outcome domains for elbow replacement. Methods. A real-time Delphi survey was conducted over four weeks using outcomes from a scoping review of 362 studies on elbow replacement published between January 1990 and February 2021. A total of 583 outcome descriptors were rationalized to 139 unique outcomes. The survey consisted of 139 outcomes divided into 18 domains. The readability and clarity of the survey was determined by an advisory group including a patient representative. Participants were able to view aggregated responses from other participants in real time and to revisit their responses as many times as they wished during the study period. Participants were able to propose additional items for inclusion. A Patient and Public Inclusion and Engagement (PPIE) panel considered the consensus findings. Results. A total of 45 respondents completed the survey. Nine core mandatory domains were identified: ‘return to work or normal daily role’; delivery of care was measured in the domains ‘patient satisfaction with the outcome of surgery’ and ‘would the patient have the same operation again’; ‘pain’; ‘revision’; ‘elbow function’; ‘independence in activities of daily living’; ‘health-related quality of life’; and ‘adverse events’. ‘Elbow range of motion’ was identified as important by consensus but was felt to be less relevant by the PPIE panel. The PPIE panel unanimously stated that pain should be used as the primary outcome domain. Conclusion. This study defined core domains for the clinical outcomes of elbow replacement obtained by consensus from patients, carers, and healthcare professionals. Pain may be used as the primary outcome in future studies, where appropriate. Further work is required to define the instruments that should be used. Cite this article: Bone Joint J 2024;106-B(11):xxx–xxx

Aims. Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients’ decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research. Methods. Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached. Results. Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants’ symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care. Conclusion. Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands. Cite this article: Bone Jt Open 2024;5(7):543–549

Aims. The aim of this study was to develop a core outcome set of what to measure in all future clinical research on hand fractures and joint injuries in adults. Methods. Phase 1 consisted of steps to identify potential outcome domains through systematic review of published studies, and exploration of the patient perspective through qualitative research, consisting of 25 semi-structured interviews and five focus groups. Phase 2 involved key stakeholder groups (patients, hand surgeons, and hand therapists) prioritizing the outcome domains via a three-round international Delphi survey, with a final consensus meeting to agree the final core outcome set. Results. The systematic review of 160 studies identified 74 outcome domains based on the World Health Organization International Classification of Functioning, Disability, and Health. Overall, 35 domains were generated through thematic analysis of the patient interviews and focus groups. The domains from these elements were synthesised to develop 37 outcome domains as the basis of the Delphi survey, with a further four generated from participant suggestions in Round 1. The Delphi survey identified 20 outcome domains as ‘very important’ for the core outcome set. At the consensus meeting, 27 participants from key stakeholder groups selected seven outcomes for the core outcome set: pain/discomfort with activity, pain/discomfort with rest, fine hand use/dexterity, self-hygiene/personal care, return to usual work/job, range of motion, and patient satisfaction with outcome/result. Conclusion. This set of core outcome domains is recommended as a minimum to be reported in all clinical research on hand fractures and joint injuries in adults. While this establishes what to measure, future work will focus on determining how best to measure these outcomes. By adopting this patient-centred core outcome set, consistency and comparability of studies will be improved, aiding meta-analysis and strengthening the evidence base for management of these common and impactful injuries. Cite this article: Bone Jt Open 2023;4(2):87–95

Aims. The aim of this study was to compare the preinjury functional scores with the postinjury preoperative score and postoperative outcome scores following anterior cruciate ligament (ACL) reconstruction surgery (ACLR). Methods. We performed a prospective study on patients who underwent primary ACLR by a single surgeon at a single centre between October 2010 and January 2018. Preoperative preinjury scores were collected at time of first assessment after the index injury. Preoperative (pre- and post-injury), one-year, and two-year postoperative functional outcomes were assessed by using the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score, and Tegner Activity Scale. Results. We enrolled 308 males and 263 females of mean age 27 years (19 to 46). The mean preinjury and preoperative post-injury Lysholm Knee Scores were 94 (73 to 100) and 63 (25 to 85), respectively, while the respective mean scores at one and two years postoperatively were 84 (71 to 100) and 89 (71 to 100; p < 0.001). The mean Tegner preinjury and preoperative post-injury scores were 7 (3 to 9) and 3 (0 to 6), respectively, while the respective mean scores at one and two years postoperatively were 6 (1 to 8) and 6 (1 to 9) (p < 0.001). The mean KOOS scores at preinjury versus two years postoperatively were: symptoms (96 vs 84); pain (94 vs 87); activities of daily living (97 vs 91), sports and recreation function (84 vs 71), and quality of life (82 vs 69), respectively (p < 0.001). Conclusion. Functional scores improved following ACLR surgery at two years in comparison to preoperative post-injury scores. However, at two-year follow-up, the majority of patients failed to achieve their preinjury scores. The evaluation of ACLR outcomes needs to consider the preinjury scores rather than the immediate preoperative score that is usually collected. Cite this article: Bone Jt Open 2023;4(1):46–52

Aims. Periprosthetic proximal femoral fractures (PFFs) are a major complication after total hip arthroplasty (THA). Health status after PFF is not specifically investigated. The aim of this study is to evaluate the health status pattern over two years after sustaining a PFF. Methods. A cohort of patients with PFF after THA was derived from the Brabant Injury Outcomes Surveillance (BIOS) study. The BIOS study, a prospective, observational, multicentre follow-up cohort study, was conducted to obtain data by questionnaires pre-injury and at one week, and one, three, six, 12, and 24 months after trauma. Primary outcome measures were the EuroQol five-dimension three-level questionnaire (EQ-5D-3L), the Health Utility Index 2 (HUI2), and the Health Utility Index 3 (HUI3). Secondary outcome measures were general measurements such as duration of hospital stay and mortality. Results. A total of 70 patients with a PFF were included. EQ-5D utility scores were significantly lower on all timepoints except at six months’ follow-up compared to pre-injury. EuroQol visual analogue scale (EQ-VAS) scores at one month's follow-up were significantly lower compared to pre-injury. The percentage of reported problems at two years was higher for all dimensions except anxiety/depression when compared to pre-injury. The mean EQ-5D utility score was 0.26 higher in males compared to females (95% confidence interval (CI) 0.01 to 0.42; p = 0.003). The mean EQ-VAS score for males was 8.9 points higher when compared to females over all timepoints (95% CI 1.2 to 16.7; p = 0.027). Mortality was 10% after two years’ follow-up. Conclusion. PFF patients are a frail population with substantial functional impairment at baseline. Post-injury, they have a significant and clinically relevant lower health status two years after trauma when compared to pre-injury. Health status improves the most between one and three months after injury. Two years after PFF, more patients experience problems in mobility, self-care, usual activities, and pain/discomfort than pre-injury. Cite this article: Bone Joint J 2024;106-B(5):442–449

Aims. The primary outcome was investigating differences in wear, as measured by femoral head penetration, between cross-linked vitamin E-diffused polyethylene (vE-PE) and cross-linked polyethylene (XLPE) acetabular component liners and between 32 and 36 mm head sizes at the ten-year follow-up. Secondary outcomes included acetabular component migration and patient-reported outcome measures (PROMs) such as the EuroQol five-dimension questionnaire, 36-Item Short-Form Health Survey, Harris Hip Score, and University of California, Los Angeles Activity Scale (UCLA). Methods. A single-blinded, multi-arm, 2 × 2 factorial randomized controlled trial was undertaken. Patients were recruited between May 2009 and April 2011. Radiostereometric analyses (RSAs) were performed from baseline to ten years. Of the 220 eligible patients, 116 underwent randomization, and 82 remained at the ten-year follow-up. Eligible patients were randomized into one of four interventions: vE-PE acetabular liner with either 32 or 36 mm femoral head, and XLPE acetabular liner with either 32 or 36 mm femoral head. Parameters were otherwise identical except for acetabular liner material and femoral head size. Results. A total of 116 patients participated, of whom 77 were male. The median ages of the vE-PE 32 mm and 36 mm groups were 65 (interquartile range (IQR) 57 to 67) and 63 years (IQR 56 to 66), respectively, and of the XLPE 32 mm and 36 mm groups were 64 (IQR 58 to 66) and 61 years (IQR 54 to 66), respectively. Mean total head penetration was significantly lower into vE-PE acetabular liner groups than into XLPE acetabular liner groups (-0.219 mm (95% confidence interval -0.348 to -0.090); p = 0.001). There were no differences in wear according to head size, acetabular component migration, or PROMs, except for UCLA. There were no cases of aseptic loosening or failures requiring revision at long-term follow-up. Conclusion. Significantly lower wear was observed in vE-PE acetabular liners than in XLPE acetabular liners. No difference in wear was observed between different head size or PROMs except for the UCLA at ten years. Cite this article: Bone Joint J 2023;105-B(10):1052–1059

Aims. The prevalence of osteoarthritis (OA) associated with instability of the shoulder ranges between 4% and 60%. Articular cartilage is, however, routinely assessed in these patients using radiographs or scans (2D or 3D), with little opportunity to record early signs of cartilage damage. The aim of this study was to assess the prevalence and localization of chondral lesions and synovial damage in patients undergoing arthroscopic surgery for instablility of the shoulder, in order to classify them and to identify risk factors for the development of glenohumeral OA. Methods. A total of 140 shoulders in 140 patients with a mean age of 28.5 years (15 to 55), who underwent arthroscopic treatment for recurrent glenohumeral instability, were included. The prevalence and distribution of chondral lesions and synovial damage were analyzed and graded into stages according to the division of the humeral head and glenoid into quadrants. The following factors that might affect the prevalence and severity of chondral damage were recorded: sex, dominance, age, age at the time of the first dislocation, number of dislocations, time between the first dislocation and surgery, preoperative sporting activity, Beighton score, type of instability, and joint laxity. Results. A total of 133 patients (95%) had synovial or chondral lesions. At the time of surgery, shoulders were graded as having mild, moderate, and severe OA in 55 (39.2%), 72 (51.4%), and six (4.2%) patients, respectively. A Hill-Sachs lesion and fibrillation affecting the anteroinferior glenoid cartilage were the most common findings. There was a significant positive correlation between the the severity of the development of glenohumeral OA and the patient’s age, their age at the time of the first dislocation, and the number of dislocations (p = 0.004, p = 0.011, and p = 0.031, respectively). Conclusion. Synovial inflammation and chondral damage associated with instability of the shoulder are more prevalent than previously reported. The classification using quadrants gives surgeons more information about the chondral damage, and could explain the pattern of development of glenohumeral OA after stabilization of the shoulder. As the number of dislocations showed a positive correlation with the development of OA, this might be an argument for early stabilization. Cite this article: Bone Joint J 2024;106-B(10):1125–1132

Aims. Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability. Methods. A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia. Results. GIK treatment resulted in a significant protection of skeletal muscle with increased viability (GIK 22.07% (SD 15.48%)) compared to saline control (control 3.14% (SD 3.29%)) (p = 0.005). Additionally, GIK led to a statistically significant reduction in gene expression markers of cell death (CASP3, p < 0.001) and inflammation (NOS2, p < 0.001; IGF1, p = 0.007; IL-1β, p = 0.002; TNFα, p = 0.012), and a significant reduction in serum creatine kinase (p = 0.004) and creatinine (p < 0.001). GIK led to a significant reduction in IR-related pain (p = 0.030). Conclusion. Systemic GIK infusion during and after limb ischaemia protects murine skeletal muscle from cell death, kidneys from reperfusion metabolites, and reduces pain by reducing post-ischaemic inflammation. Cite this article: Bone Joint Res 2023;12(3):212–218

Aims. The aim of this study was to assess the clinical and radiological results of patients who were revised using a custom-made triflange acetabular component (CTAC) for component loosening and pelvic discontinuity (PD) after previous total hip arthroplasty (THA). Methods. Data were extracted from a single centre prospective database of patients with PD who were treated with a CTAC. Patients were included if they had a follow-up of two years. The Hip Disability and Osteoarthritis Outcome Score (HOOS), modified Oxford Hip Score (mOHS), EurQol EuroQoL five-dimension three-level (EQ-5D-3L) utility, and Numeric Rating Scale (NRS), including visual analogue score (VAS) for pain, were gathered at baseline, and at one- and two-year follow-up. Reasons for revision, and radiological and clinical complications were registered. Trends over time are described and tested for significance and clinical relevance. Results. A total of 18 females with 22 CTACs who had a mean age of 73.5 years (SD 7.7) were included. A significant improvement was found in HOOS (p < 0.0001), mOHS (p < 0.0001), EQ-5D-3L utility (p = 0.003), EQ-5D-3L NRS (p = 0.013), VAS pain rest (p = 0.008), and VAS pain activity (p < 0.0001) between baseline and final follow-up. Minimal clinically important improvement in mOHS and the HOOS Physical Function Short Form (HOOS-PS) was observed in 16 patients (73%) and 14 patients (64%), respectively. Definite healing of the PD was observed in 19 hips (86%). Complications included six cases with broken screws (27%), four cases (18%) with bony fractures, and one case (4.5%) with sciatic nerve paresthesia. One patient with concurrent bilateral PD had revision surgery due to recurrent dislocations. No revision surgery was performed for screw failure or implant breakage. Conclusion. CTAC in patients with THA acetabular loosening and PD can result in stable constructs and significant improvement in functioning and health-related quality of life at two years' follow-up. Further follow-up is necessary to determine the mid- to long-term outcome. Cite this article: Bone Jt Open 2023;4(2):53–61

Aims. Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods. A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results. The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion. In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue. Cite this article: Bone Joint Res 2024;13(7):332–341

Aims. Femoroacetabular impingement (FAI) patients report exacerbation of hip pain in deep flexion. However, the exact impingement location in deep flexion is unknown. The aim was to investigate impingement-free maximal flexion, impingement location, and if cam deformity causes hip impingement in flexion in FAI patients. Methods. A retrospective study involving 24 patients (37 hips) with FAI and femoral retroversion (femoral version (FV) < 5° per Murphy method) was performed. All patients were symptomatic (mean age 28 years (SD 9)) and had anterior hip/groin pain and a positive anterior impingement test. Cam- and pincer-type subgroups were analyzed. Patients were compared to an asymptomatic control group (26 hips). All patients underwent pelvic CT scans to generate personalized CT-based 3D models and validated software for patient-specific impingement simulation (equidistant method). Results. Mean impingement-free flexion of patients with mixed-type FAI (110° (SD 8°)) and patients with pincer-type FAI (112° (SD 8°)) was significantly (p < 0.001) lower compared to the control group (125° (SD 13°)). The frequency of extra-articular subspine impingement was significantly (p < 0.001) increased in patients with pincer-type FAI (57%) compared to cam-type FAI (22%) in 125° flexion. Bony impingement in maximal flexion was located anterior-inferior at femoral four and five o’clock position in patients with cam-type FAI (63% (10 of 16 hips) and 37% (6 of 10 hips)), and did not involve the cam deformity. The cam deformity did not cause impingement in maximal flexion. Conclusion. Femoral impingement in maximal flexion was located anterior-inferior distal to the cam deformity. This differs to previous studies, a finding which could be important for FAI patients in order to avoid exacerbation of hip pain in deep flexion (e.g. during squats) and for hip arthroscopy (hip-preservation surgery) for planning of bone resection. Hip impingement in flexion has implications for daily activities (e.g. putting on shoes), sports, and sex. Cite this article: Bone Joint Res 2023;12(1):22–32

Aims. The aim was to assess whether robotic-assisted total knee arthroplasty (rTKA) had greater knee-specific outcomes, improved fulfilment of expectations, health-related quality of life (HRQoL), and patient satisfaction when compared with manual TKA (mTKA). Methods. A randomized controlled trial was undertaken (May 2019 to December 2021), and patients were allocated to either mTKA or rTKA. A total of 100 patients were randomized, 50 to each group, of whom 43 rTKA and 38 mTKA patients were available for review at 12 months following surgery. There were no statistically significant preoperative differences between the groups. The minimal clinically important difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was defined as 7.5 points. Results. There were no clinically or statistically significant differences between the knee-specific measures (WOMAC, Oxford Knee Score (OKS), Forgotten Joint Score (FJS)) or HRQoL measures (EuroQol five-dimension questionnaire (EQ-5D) and EuroQol visual analogue scale (EQ-VAS)) at 12 months between the groups. However, the rTKA group had significantly (p = 0.029) greater improvements in the WOMAC pain component (mean difference 9.7, 95% confidence interval (CI) 1.0 to 18.4) over the postoperative period (two, six, and 12 months), which was clinically meaningful. This was not observed for function (p = 0.248) or total (p = 0.147) WOMAC scores. The rTKA group was significantly (p = 0.039) more likely to have expectation of ‘Relief of daytime pain in the joint’ when compared with the mTKA group. There were no other significant differences in expectations met between the groups. There was no significant difference in patient satisfaction with their knee (p = 0.464), return to work (p = 0.464), activities (p = 0.293), or pain (p = 0.701). Conclusion. Patients undergoing rTKA had a clinically meaningful greater improvement in their knee pain over the first 12 months, and were more likely to have fulfilment of their expectation of daytime pain relief compared with patients undergoing mTKA. However, rTKA was not associated with a clinically significant greater knee-specific function or HRQoL, according to current definitions. Cite this article: Bone Joint J 2024;106-B(5):450–459

Aims. Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. Methods. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene. Results. Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway. Conclusion. Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis. Cite this article: Bone Joint Res 2023;12(11):677–690

Aims. Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Methods. Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay. Results. We found that treatment with DEL-1 suppressed palmitate-induced inflammation, ER stress, and apoptosis in human primary tenocytes. DEL-1 treatment augmented LC3 conversion and p62 degradation as well as AMPK phosphorylation. Moreover, small interfering RNA for AMPK or 3-methyladenine (3-MA), an autophagy inhibitor, abolished the suppressive effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes. Similar to DEL-1, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, also attenuated palmitate-induced inflammation, ER stress, and apoptosis in tenocytes, which 3-MA reversed. Conclusion. These results revealed that DEL-1 suppresses inflammation and ER stress, thereby attenuating tenocyte apoptosis through AMPK/autophagy-mediated signalling. Thus, regular exercise or administration of DEL-1 may directly contribute to improving tendinitis exacerbated by obesity and insulin resistance. Cite this article: Bone Joint Res 2022;11(12):854–861

Aims. To investigate the impact of consecutive perioperative care transitions on in-hospital recovery of patients who had primary total knee arthroplasty (TKA) over an 11-year period. Methods. This observational cohort study used electronic health record data from all patients undergoing preoperative screening for primary TKA at a Northern Netherlands hospital between 2009 and 2020. In this timeframe, three perioperative care transitions were divided into four periods: Baseline care (Joint Care, n = 171; May 2009 to August 2010), Function-tailored (n = 404; September 2010 to October 2013), Fast-track (n = 721; November 2013 to May 2018), and Prehabilitation (n = 601; June 2018 to December 2020). In-hospital recovery was measured using inpatient recovery of activities (IROA), length of stay (LOS), and discharge to preoperative living situation (PLS). Multivariable regression models were used to analyze the impact of each perioperative care transition on in-hospital recovery. Results. The four periods analyzed involved 1,853 patients (65.9% female (1,221/1,853); mean age 70.1 years (SD 9.0)). IROA improved significantly with each transition: Function-tailored (0.9 days; p < 0.001 (95% confidence interval (CI) -0.32 to -0.15)), Fast-track (0.6 days; p < 0.001 (95% CI -0.25 to -0.16)), and Prehabilitation (0.4 days; p < 0.001 (95% CI -0.18 to -0.10)). LOS decreased significantly in Function-tailored (1.1 days; p = 0.001 (95% CI -0.30 to -0.06)), Fast-track (0.6 days; p < 0.001 (95% CI -0.21 to -0.05)), and Prehabilitation (0.6 days; p < 0.001 (95%CI -0.27 to -0.11)). Discharge to PLS increased in Function-tailored (77%), Fast-track (91.6%), and Prehabilitation (92.6%). Post-hoc analysis indicated a significant increase after the transition to the Fast-track period (p < 0.001 (95% CI 3.19 to 8.00)). Conclusion. This study highlights the positive impact of different perioperative care procedures on in-hospital recovery of patients undergoing primary TKA. Assessing functional recovery, LOS, and discharge towards PLS consistently, provides hospitals with valuable insights into postoperative recovery. This can potentially aid planning and identifying areas for targeted improvements to optimize patient outcomes. Cite this article: Bone Joint J 2024;106-B(6):573–581

Aims. Refobacin Bone Cement R and Palacos R + G bone cement were introduced to replace the original cement Refobacin Palacos R in 2005. Both cements were assumed to behave in a biomechanically similar fashion to the original cement. The primary aim of this study was to compare the migration of a polished triple-tapered femoral stem fixed with either Refobacin Bone Cement R or Palacos R + G bone cement. Repeated radiostereometric analysis was used to measure migration of the femoral head centre. The secondary aims were evaluation of cement mantle, stem positioning, and patient-reported outcome measures. Methods. Overall, 75 patients were included in the study and 71 were available at two years postoperatively. Prior to surgery, they were randomized to one of the three combinations studied: Palacos cement with use of the Optivac mixing system, Refobacin with use of the Optivac system, and Refobacin with use of the Optipac system. Cemented MS30 stems and cemented Exceed acetabular components were used in all hips. Postoperative radiographs were used to assess the quality of the cement mantle according to Barrack et al, and the position and migration of the femoral stem. Harris Hip Score, Oxford Hip Score, Forgotten Joint Score, and University of California, Los Angeles Activity Scale were collected. Results. Median distal migration (y-axis) at two years for the Refobacin-Optivac system was -0.79 mm (-2.01 to -0.09), for the Refobacin-Optipac system was -0.75 mm (-2.16 to 0.20), and for the Palacos-Optivac system was -1.01 mm (-4.31 to -0.29). No statistically significant differences were found between the groups. Secondary outcomes did not differ statistically between the groups at the two-year follow-up. Conclusion. At two years, we found no significant differences in distal migration or clinical outcomes between the three groups. Our data indicate that Refobacin Bone Cement R and Palacos R + G are comparable in terms of stable fixation and early clinical outcomes. Cite this article: Bone Joint J 2024;106-B(5):435–441

Aims. Approximately 10% to 20% of knee arthroplasty patients are not satisfied with the result, while a clear indication for revision surgery might not be present. Therapeutic options for these patients, who often lack adequate quadriceps strength, are limited. Therefore, the primary aim of this study was to evaluate the clinical effect of a novel rehabilitation protocol that combines low-load resistance training (LL-RT) with blood flow restriction (BFR). Methods. Between May 2022 and March 2024, we enrolled 45 dissatisfied knee arthroplasty patients who lacked any clear indication for revision to this prospective cohort study. All patients were at least six months post-surgery and had undergone conventional physiotherapy previously. The patients participated in a supervised LL-RT combined with BFR in 18 sessions. Primary assessments included the following patient-reported outcome measures (PROMs): Knee injury and Osteoarthritis Outcome Score (KOOS); Knee Society Score: satisfaction (KSSs); the EuroQol five-dimension five-level questionnaire (EQ-5D-5L); and the pain catastrophizing scale (PCS). Functionality was assessed using the six-minute walk Test (6MWT) and the 30-second chair stand test (30CST). Follow-up timepoints were at baseline, six weeks, three months, and six months after the start. Results. Six weeks of BFR with LL-RT improved all the PROMs except the sports subscale of the KOOS compared to baseline. Highest improvements after six weeks were found for quality of life (QoL) (mean 28.2 (SD 17.2) vs 19 (SD 14.7); p = 0.002), activities of daily living (mean 54.7 (SD 18.7) vs 42.9 (SD 17.3); p < 0.001), and KSSs (mean 17.1 (SD 8.8) vs 12.8 (SD 6.7); p < 0.001). PROMs improvements continued to be present at three-month and six-month follow-up compared to baseline. However, no significant differences were observed in the paired comparisons of the six-week, three-month, and six-month follow-up. The same trends are observed for the 6MWT and 30CST. Conclusion. The reported regime demonstrates improved QoL and function of dissatisfied knee arthroplasty patients. In light of this, the pathway described may provide a valuable and safe treatment option for dissatisfied knee arthroplasty patients for whom therapeutic options are limited. Cite this article: Bone Joint J 2024;106-B(12):1416–1425