Failed internal fixation of a fracture of the proximal humerus produces many challenges with limited surgical options. The aim of this study was to evaluate the clinical outcomes after the use of a reverse shoulder arthroplasty under these circumstances. Between 2007 and 2012, 19 patients (15 women and four men, mean age 66 years; 52 to 82) with failed internal fixation after a proximal humeral fracture, underwent implant removal and reverse shoulder arthroplasty (RSA). The mean follow-up was 36 months (25 to 60). The mean American Shoulder and Elbow Score improved from 27.8 to 50.1 (p = 0.019). The mean Simple Shoulder Test score improved from 0.7 to 3.2 (p = 0.020), and the mean visual analogue scale for pain improved from 6.8 to 4.3 (p = 0.012). Mean forward flexion improved from 58.7° to 101.1° (p < 0.001), mean abduction from 58.7° to 89.1° (p = 0.012), mean external rotation from 10.7° to 23.1° (p = 0.043) and mean internal rotation from buttocks to L4 (p = 0.034). A major complication was recorded in five patients (26%) (one intra-operative fracture, loosening of the humeral component in two and two peri-prosthetic fractures). A total of 15 patients (79%) rated their outcome as excellent or good, one (5%) as satisfactory, and three (16%) as unsatisfactory. . An improvement in outcomes and pain can be expected when performing a RSA as a salvage procedure after failed internal fixation of a fracture of the proximal humerus. Patients should be cautioned about the possibility for major complications following this technically demanding procedure. Cite this article: Bone Joint J 2015;97-B:967–72

Aims. The aim of this study was to compare the characteristics and outcomes of L-shaped and reverse L-shaped rotator cuff tears. Methods. A total of 82 shoulders (81 patients) after arthroscopic rotator cuff repair were retrospectively enrolled. The mean age of the patients was 62 years (SD 6), 33 shoulders (40.2%) were in male patients, and 57 shoulders (69.5%) were the right shoulder. Of these, 36 shoulders had an L-shaped tear (group L) and 46 had a reverse L-shaped tear (group RL). Both groups were compared regarding characteristics, pre- and postoperative pain, and functional outcomes. Muscle status was assessed by preoperative MRI, and re-tear rates by postoperative ultrasonography or MRI. Results. Patients in group RL were significantly older than in group L (p = 0.008), and group RL was significantly associated with female sex (odds ratio 2.5 (95% confidence interval 1.03 to 6.32); p = 0.041). Mean postoperative pain visual analogue scale (VAS) score was significantly greater (group L = 0.8 (SD 1.5), group RL = 1.7 (SD 2.2); p = 0.033) and mean postoperative American Shoulder and Elbow Surgeons (ASES) score was significantly lower in group RL than group L (group L = 91.4 (SD 13.1), group RL = 83.8 (SD 17.9); p = 0.028). However, postoperative mean VAS for pain and ASES score were not lower than the patient-acceptable symptom state scores. Mean retracted tear length was significantly larger in group L (group L = 24.6 mm (SD 6.5), group RL = 20.0 mm (SD 6.8); p = 0.003). Overall re-tear rate for 82 tears was 11.0% (nine shoulders), and re-tear rates in group L and RL were similar at 11.1% (four shoulders) and 10.9% (five shoulders), respectively (p = 1.000). No significant intergroup difference was found for fatty degeneration (FD) or muscle atrophy. Within group L, postoperative FD grades of supraspinatus and subscapularis worsened significantly (p = 0.034 and p = 0.008, respectively). Mean postoperative pain VAS (male = 1.2 (SD 1.8), female = 1.3 (SD 2.0)) and ASES scores (male = 88.7 (SD 15.5), female = 86.0 (SD 16.8)) were similar in male and female patients (p = 0.700 and p = 0.475, respectively). Regression analysis showed age was not a prognostic factor of postoperative pain VAS or ASES scores (p = 0.188 and p = 0.150, respectively). Conclusion. Older age and female sex were associated with reverse L-shaped tears. Although the postoperative functional outcomes of patients with reverse L-shaped tears were satisfactory, the clinical scores were poorer than those of patients with L-shaped tears. Surgeons should be aware of the differences in clinical outcome between L-shaped and reverse L-shaped rotator cuff tears. Cite this article: Bone Joint J 2022;104-B(3):394–400

Aims. Patients with a failed reverse shoulder arthroplasty (RSA) have limited salvage options. The aim of this study was to determine the outcome of revision RSA when used as a salvage procedure for a failed primary RSA. Patients and Methods. We reviewed all revision RSAs performed for a failed primary RSA between 2006 and 2012, excluding patients with a follow-up of less than two years. A total of 27 revision RSAs were included in the study. The mean age of the patients at the time of revision was 70 years (58 to 82). Of the 27 patients, 14 (52% were female). The mean follow-up was 4.4 years (2 to 10). Results. Six patients (22%) developed complications requiring further revision surgery, at a mean of 1.7 years (0.1 to 5.3) postoperatively. The indication for further revision was dislocation in two, glenoid loosening in one, fracture of the humeral component in one, disassociation of the glenosphere in one, and infection in one. The five-year survival free of further revision was 85%. Five additional RSAs developed complications that did not need surgery, including dislocation in three and periprosthetic fracture in two. Overall, patients who did not require further revision had excellent pain relief, and significant improvements in elevation and external rotation of the shoulder (p < 0.01). The mean postoperative American Shoulder and Elbow Surgeons (ASES), and simple shoulder test (SST) scores were 66 and 7, respectively. Radiological results were available in 26 patients (96.3%) at a mean of 4.3 years (1.5 to 9.5). At the most recent follow-up, six patients (23%) had glenoid lucency, which were classified as grade III or higher in three (12%). Smokers had a significantly increased risk of glenoid lucency (p < 0.01). Conclusion. Revision RSA, when used to salvage a failed primary RSA, can be a successful procedure. At intermediate follow-up, survival rates are reasonable, but dislocation and glenoid lucency remain a concern, particularly in smokers. Cite this article: Bone Joint J 2018;100-B:1493–98

Aims. Instability is a common cause of failure after total hip arthroplasty. A novel reverse total hip has been developed, with a femoral cup and acetabular ball, creating enhanced mechanical stability. The purpose of this study was to assess the implant fixation using radiostereometric analysis (RSA), and the clinical safety and efficacy of this novel design. Methods. Patients with end-stage osteoarthritis were enrolled in a prospective cohort at a single centre. The cohort consisted of 11 females and 11 males with mean age of 70.6 years (SD 3.5) and BMI of 31.0 kg/m. 2. (SD 5.7). Implant fixation was evaluated using RSA as well as Western Ontario and McMaster Universities Osteoarthritis Index, Harris Hip Score, Oxford Hip Score, Hip disability and Osteoarthritis Outcome Score, 38-item Short Form survey, and EuroQol five-dimension health questionnaire scores at two-year follow-up. At least one acetabular screw was used in all cases. RSA markers were inserted into the innominate bone and proximal femur with imaging at six weeks (baseline) and six, 12, and 24 months. Independent-samples t-tests were used to compare to published thresholds. Results. Mean acetabular subsidence from baseline to 24 months was 0.087 mm (SD 0.152), below the critical threshold of 0.2 mm (p = 0.005). Mean femoral subsidence from baseline to 24 months was -0.002 mm (SD 0.194), below the published reference of 0.5 mm (p < 0.001). There was significant improvement in patient-reported outcome measures at 24 months with good to excellent results. Conclusion. RSA analysis demonstrates excellent fixation with a predicted low risk of revision at ten years of this novel reverse total hip system. Clinical outcomes were consistent with safe and effective hip replacement prostheses. Cite this article: Bone Jt Open 2023;4(5):385–392

Aims. We present our experience of using a metal-backed prosthesis and autologous bone graft to treat gross glenoid bone deficiency. Patients and Methods. A prospective cohort study of the first 45 shoulder arthroplasties using the SMR Axioma Trabecular Titanium (TT) metal-backed glenoid with autologous bone graft. Between May 2013 and December 2014, 45 shoulder arthroplasties were carried out in 44 patients with a mean age of 64 years (35 to 89). The indications were 23 complex primary arthroplasties, 12 to revise a hemiarthroplasty or resurfacing, five for aseptic loosening of the glenoid, and five for infection. Results. Of the 45 patients, 16 had anatomical shoulder arthroplasties (ASA) and 29 had reverse shoulder arthroplasties (RSA). Postoperatively, 43/45 patients had a CT scan. In 41 of 43 patients (95%), the glenoid peg achieved > 50% integration. In 40 of 43 cases (93%), the graft was fully or partially integrated. There were seven revisions (16%) but only four (9%) required a change of baseplate. Four (25%) of the 16 ASAs were revised for instability or cuff failure. At two-year radiological follow-up, five of the 41 cases (11%) showed some evidence of lucent lines. Conclusion. The use of a metal baseplate with a trabecular titanium surface in conjunction with autologous bone graft is a reliable method of addressing glenoid bone defects in primary and revision RSA setting in the short term. ASAs have a higher rate of complications with this technique

Aims. This study aimed to evaluate implant survival of reverse hybrid total hip arthroplasty (THA) at medium-term follow-up. Patients and Methods. A consecutive series of 1082 THAs in 982 patients with mean follow-up of 7.9 years (5 to 11.3) is presented. Mean age was 69.2 years (21 to 94). Of these, 194 (17.9%) were in patients under 60 years, 663 (61.3%) in female patients and 348 (32.2%) performed by a trainee. Head size was 28 mm in 953 hips (88.1%) or 32 mm in 129 hips (11.9%). Survival analysis was performed and subgroups compared using log rank tests. Results. Ten-year survival (122 hips at risk) was 97.2% (95% confidence interval (CI) 95.77 to 98.11) for all-cause revision. There was no difference in survival by age (p = 0.50), gender (p = 0.78), head size (p = 0.63) or surgeon grade (p = 0.36). No acetabular components underwent revision for aseptic loosening in the entire series. Four (0.4%) aseptic stem failures occurred early at a mean of 2.5 years (0.6 to 4.8) and were associated with age under 60 years (p = 0.015). There was no difference in survival by gender (p = 0.12), head size (p = 0.43) or surgeon grade (p = 0.77) for stem revision. Conclusion. This is the largest reported study into reverse hybrid THA and it confirms successful outcomes, irrespective of age, gender, head size and surgeon grade. Cite this article: Bone Joint J 2018;100-B:1010–17

Aims. The aim of this study was to use national registry database information to estimate cumulative rates and relative risk of revision due to infection after reverse shoulder arthroplasty. Patients and Methods. We included 17 730 primary shoulder arthroplasties recorded between 2004 and 2013 in The Nordic Arthroplasty Register Association (NARA) data set. With the Kaplan–Meier method, we illustrated the ten-year cumulative rates of revision due to infection and with the Cox regression model, we reported the hazard ratios as a measure of the relative risk of revision due to infection. Results. In all, 188 revisions were reported due to infection during a mean follow-up of three years and nine months. The ten-year cumulative rate of revision due to infection was 1.4% overall, but 3.1% for reverse shoulder arthroplasties and 8.0% for reverse shoulder arthroplasties in men. Reverse shoulder arthroplasties were associated with an increased risk of revision due to infection also when adjusted for sex, age, primary diagnosis, and year of surgery (relative risk 2.41 (95% confidence interval 1.26 to 5.59); p = 0.001). Conclusion. The overall incidence of revision due to infection was low. The increased risk in reverse shoulder arthroplasty must be borne in mind, especially when offering it to men. Cite this article: Bone Joint J 2019;101-B:702–707

Aims. This study aimed to assess the impact of using the metal-augmented glenoid baseplate (AGB) on improving clinical and radiological outcomes, as well as reducing complications, in patients with superior glenoid wear undergoing reverse shoulder arthroplasty (RSA). Methods. From January 2016 to June 2021, out of 235 patients who underwent primary RSA, 24 received a superior-AGB after off-axis reaming (Group A). Subsequently, we conducted propensity score matching in a 1:3 ratio, considering sex, age, follow-up duration, and glenoid wear (superior-inclination and retroversion), and selected 72 well-balanced matched patients who received a standard glenoid baseplate (STB) after eccentric reaming (Group B). Superior-inclination, retroversion, and lateral humeral offset (LHO) were measured to assess preoperative glenoid wear and postoperative correction, as well as to identify any complications. Clinical outcomes were measured at each outpatient visit before and after surgery. Results. There were no significant differences in demographic data and preoperative characteristics between the two groups. Both groups showed significant improvements in patient-reported outcome measures (visual analogue scale for pain, visual analogue scale for function, American Shoulder and Elbow Surgeons, Constant, and Simple Shoulder Test scores) from preoperative to final assessment (p < 0.001). However, AGB showed no additional benefit. Notably, within range of motion, Group B showed significant postoperative decrease in both external rotation and internal rotation, unlike Group A (p = 0.028 and 0.003, respectively). Both groups demonstrated a significant correction of superior-inclination after surgery, while patients in Group B exhibited a significant decrease in LHO postoperatively (p = 0.001). Regarding complications, Group A experienced more acromial stress fractures (3 cases; 12.5%), whereas Group B had a higher occurrence of scapular notching (24 cases; 33.3%) (p = 0.008). Conclusion. Both eccentric reaming with STB and off-axis reaming with AGB are effective methods for addressing superior glenoid wear in RSA, leading to improved clinical outcomes. However, it is important to be aware of the potential risks associated with eccentric reaming, which include excessive bone loss leading to reduced rotation and scapular notching. Cite this article: Bone Joint J 2024;106-B(3):268–276

Aims. The purpose of this study was to evaluate the cost of reverse shoulder arthroplasty (RSA) for patients with a proximal humerus fracture, using time-driven activity based costing (TDABC), and to compare treatment costs with reimbursement under the Healthcare Resource Groups (HRGs). Methods. TDABC analysis based on the principles outlined by Kaplan and a clinical pathway that has previously been validated for this institution was used. Staffing cost, consumables, implants, and overheads were updated to reflect 2019/2020 costs. This was compared with the HRG reimbursements. Results. The mean cost of a RSA is £7,007.46 (£6,130.67 to £8,824.67). Implants and staffing costs were the primary cost drivers, with implants (£2,824.80) making up 40% of the costs. Staffing costs made up £1,367.78 (19%) of overall costs. The total tariff, accounting for market force factors and high comorbidities, reimburses £4,629. If maximum cost and minimum reimbursement is applied the losses to the trust are £4,828.67. Conclusion. RSA may be an effective and appropriate surgical option in the treatment of proximal humerus fractures; however, a cost analysis at our centre has demonstrated the financial burden of this surgery. Given its increasing use in trauma, there is a need to work towards generating an HRG that adequately reimburses providers. Cite this article: Bone Jt Open 2020;1-12:731–736

The outcome of an anatomical shoulder replacement depends on an intact rotator cuff. In 1981 Grammont designed a novel large-head reverse shoulder replacement for patients with cuff deficiency. Such has been the success of this replacement that it has led to a rapid expansion of the indications. We performed a systematic review of the literature to evaluate the functional outcome of each indication for the reverse shoulder replacement. Secondary outcome measures of range of movement, pain scores and complication rates are also presented

Aims. The aim of this study was to report the outcomes of different treatment options for glenoid loosening following reverse shoulder arthroplasty (RSA) at a minimum follow-up of two years. Patients and Methods. We retrospectively studied the records of 79 patients (19 men, 60 women; 84 shoulders) aged 70.4 years (21 to 87) treated for aseptic loosening of the glenosphere following RSA. Clinical evaluation included pre- and post-treatment active anterior elevation (AAE), external rotation, and Constant score. Results. From the original cohort, 29 shoulders (35%) were treated conservatively, 27 shoulders (32%) were revised by revision of the glenosphere, and 28 shoulders (33%) were converted to hemiarthroplasty. At last follow-up, conservative treatment and glenoid revision significantly improved AAE, total Constant score, and pain, while hemiarthroplasty did not improve range of movement or clinical scores. Multivariable analysis confirmed that conservative treatment and glenoid revision achieved similar improvements in pain (glenoid revision vs conservative, beta 0.44; p = 0.834) but that outcomes were significantly worse following hemiarthroplasty (beta -5.00; p = 0.029). Conclusion. When possible, glenoid loosening after RSA should first be treated conservatively, then by glenosphere revision if necessary, and last by salvage hemiarthroplasty. Cite this article: Bone Joint J 2019;101-B:461–469

Wear of polyethylene is associated with aseptic loosening of orthopaedic implants and has been observed in hip and knee prostheses and anatomical implants for the shoulder. The reversed shoulder prostheses have not been assessed as yet. We investigated the volumetric polyethylene wear of the reversed and anatomical Aequalis shoulder prostheses using a mathematical musculoskeletal model. Movement and joint stability were achieved by EMG-controlled activation of the muscles. A non-constant wear factor was considered. Simulated activities of daily living were estimated from in vivo recorded data. After one year of use, the volumetric wear was 8.4 mm. 3. for the anatomical prosthesis, but 44.6 mm. 3. for the reversed version. For the anatomical prosthesis the predictions for contact pressure and wear were consistent with biomechanical and clinical data. The abrasive wear of the polyethylene in reversed prostheses should not be underestimated, and further analysis, both experimental and clinical, is required

Reversed shoulder prostheses are increasingly being used for the treatment of glenohumeral arthropathy associated with a deficient rotator cuff. These non-anatomical implants attempt to balance the joint forces by means of a semi-constrained articular surface and a medialised centre of rotation. A finite element model was used to compare a reversed prosthesis with an anatomical implant. Active abduction was simulated from 0° to 150° of elevation. With the anatomical prosthesis, the joint force almost reached the equivalence of body weight. The joint force was half this for the reversed prosthesis. The direction of force was much more vertically aligned for the reverse prosthesis, in the first 90° of abduction. With the reversed prosthesis, abduction was possible without rotator cuff muscles and required 20% less deltoid force to achieve it. This force analysis confirms the potential mechanical advantage of reversed prostheses when rotator cuff muscles are deficient

Short uncemented humeral stems can preserve humeral bone stock and facilitate revision surgery but may be prone to malalignment or loosening, especially when used in reverse total shoulder replacement (TSR). We undertook a retrospective review of 44 patients with a mean age of 76 years (59 to 92) who underwent primary reverse TSR with a short uncemented humeral stem. There were 29 females. The indications for joint replacement included cuff tear associated arthropathy (33), avascular necrosis (six), post-traumatic arthritis (two), and inflammatory arthritis (three). At a mean follow-up of 27 months (24 to 40), pain was rated as mild or none in 43 shoulders (97.7%). The mean active elevation improved from 54° . (sd. 20°) to 142° (. sd . 25°) and the mean active external rotation from 14° (. sd. 13°) to 45° (. sd. 9°). The outcome, as assessed by the modified Neer score, was excellent in 27 (61.3%), satisfactory in 15 (34.1%), and unsatisfactory in two shoulders (4.5%). Stems were well-positioned, without evidence of significant valgus or varus malalignment in 42 TSRs (95.5%). There was no radiological evidence of loosening of the humeral stem in any patient; 13 TSRs (29.5%) had evidence of proximal humeral remodelling and scapular notching was noted in three (6.8%). Cite this article: Bone Joint J 2014;96-B:526–9

Objectives. To date, no study has considered the impact of acromial morphology on shoulder range of movement (ROM). The purpose of our study was to evaluate the effects of lateralization of the centre of rotation (COR) and neck-shaft angle (NSA) on shoulder ROM after reverse shoulder arthroplasty (RSA) in patients with different scapular morphologies. Methods. 3D computer models were constructed from CT scans of 12 patients with a critical shoulder angle (CSA) of 25°, 30°, 35°, and 40°. For each model, shoulder ROM was evaluated at a NSA of 135° and 145°, and lateralization of 0 mm, 5 mm, and 10 mm for seven standardized movements: glenohumeral abduction, adduction, forward flexion, extension, internal rotation with the arm at 90° of abduction, as well as external rotation with the arm at 10° and 90° of abduction. Results. CSA did not seem to influence ROM in any of the models, but greater lateralization achieved greater ROM for all movements in all configurations. Internal and external rotation at 90° of abduction were impossible in most configurations, except in models with a CSA of 25°. Conclusion. Postoperative ROM following RSA depends on multiple patient and surgical factors. This study, based on computer simulation, suggests that CSA has no influence on ROM after RSA, while lateralization increases ROM in all configurations. Furthermore, increasing subacromial space is important to grant sufficient rotation at 90° of abduction. In summary, increased lateralization of the COR and increased subacromial space improve ROM in all CSA configurations. Cite this article: A. Lädermann, E. Tay, P. Collin, S. Piotton, C-H Chiu, A. Michelet, C. Charbonnier. Effect of critical shoulder angle, glenoid lateralization, and humeral inclination on range of movement in reverse shoulder arthroplasty. Bone Joint Res 2019;8:378–386. DOI: 10.1302/2046-3758.88.BJR-2018-0293.R1

Aims. Reverse shoulder arthroplasty (RSA) reliably improves shoulder pain and function for a variety of indications. However, the safety and efficacy of RSA in elderly patients is largely unknown. The purpose of this study was to report the mortality, morbidity, complications, reoperations, and outcomes of primary RSA in patients aged > 80 years. Patients and Methods. Between 2004 and 2013, 242 consecutive primary RSAs were performed in patients aged > 80 years (mean 83.3 years (. sd. 3.1)). Of these, 53 were lost to follow-up before two years and ten had died within two years of surgery, leaving 179 for analysis of survivorship, pain, motion, and strength at a minimum of two years or until revision surgery. All 242 patients were considered for the analysis of 90-day, one-year, and overall mortality, medical complications (90-day and overall), surgical complications, and reoperations. The indications for surgery included rotator cuff arthropathy, osteoarthritis, fracture, the sequela of trauma, avascular necrosis, and rheumatoid arthritis. A retrospective review of the medical records was performed to collect all variables. Survivorship free of revision surgery was calculated at two and five years. Results. One patient (0.4%) died within the first 90 days. A total of 45 patients (19%) were known to have died at the time of the final follow-up, with a median time to death of 67.7 months (interquartile range 40.4 to 94.7) postoperatively. Medical complications occurred in six patients (3%) and surgical complications occurred in 21/179 patients (12%). Survivorship free from revision was 98.9% at two years and 98.3% at five years; survivorship free from loosening was 99.5% at final follow-up. The presence of peripheral vascular disease correlated with a higher complication rate. Conclusion. Primary RSA was safe and effective in patients aged > 80 years, with a relatively low rate of medical and surgical complications. Thus, age alone should not be a contraindication to primary RSA in patients aged > 80 years. However, a careful evaluation of comorbidities is required in this age group when considering primary RSA. Cite this article: Bone Joint J 2019;101-B:1520–1525

Aim. We present the medium-term clinical results of a reverse total shoulder arthroplasty with a trabecular metal glenoid base plate. Patients and Methods. We reviewed 125 consecutive primary reverse total shoulder arthroplasties (RTSA) implanted in 124 patients for rotator cuff arthropathy. There were 100 women and 24 men in the study group with a mean age of 76 years (58 to 89). The mean follow-up was 32 months (24 to 60). No patient was lost to follow-up. Results. There were statistically significant improvements in the mean range of movement and Oxford Shoulder Score (p < 0.001). Kaplan-Meier survivorship at five years was 96.7% (95% confidence interval 91.5 to 98.7) with aseptic glenoid failure as the end point. . Radiologically, 63 shoulders (50.4%) showed no evidence of notching, 51 (40.8%) had grade 1 notching, ten (8.0%) had grade 2 notching and one (0.8%) had grade 4 notching. Radiolucency around the glenoid base plate was found in one patient (0.8%) and around the humeral stem in five (4.0%). In all, three RTSA (2.4%) underwent revision surgery for aseptic mechanical failure of the glenoid within 11 months of surgery due to malseating of the glenosphere. Conclusion. The clinical results of this large independent single unit series are comparable to those from previous series of RTSA reported in the literature. A trabecular metal base plate is safe and effective in the medium-term. Cite this article: Bone Joint J 2016;98-B:969–75

Aims. Acromial fractures following reverse shoulder arthroplasty (RSA) have a wide range of incidences in reported case series. This study evaluates their incidence following RSA by systematically reviewing the current literature. Materials and Methods. A systematic review using the search terms “reverse shoulder”, “reverse total shoulder”, or “inverted shoulder” was performed using PubMed, Web of Science, and Cochrane databases between 1 January 2010 and 31 March 2018. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Studies were included if they reported on RSA outcomes and the incidence rate of acromial and/or scapular spine fractures. The rate of these fractures was evaluated for primary RSA, revision RSA, RSA indications, and RSA implant design. Results. The review included 90 articles out of 686 identified after exclusions. The incidence rate of acromial and/or scapular spine fractures was 2.8% (253/9048 RSAs). The fracture rate was similar for primary and revision RSA (2.8% vs 2.1%; p = 0.4). Acromial fractures were most common after RSA for inflammatory arthritis (10.9%) and massive rotator cuff tears (3.8%). The incidence was lowest in RSA for post-traumatic arthritis (2.1%) and acute proximal humerus fractures (0%). Lateralized glenosphere design had a significantly higher rate of acromial fractures compared with medial glenosphere designs. Conclusion. Based on current English literature, acromial and/or scapular spine fractures occur at a rate of 2.8% after RSA. The incidence is slightly more common after primary compared with revision arthroplasty. Also, higher rates of acromial fractures are reported in RSA performed for inflammatory arthritis and in the lateralized glenoid design. Cite this article: Bone Joint J 2019;101-B:627–634

Children with congenital vertical talus (CVT) have been treated with extensive soft-tissue releases, with a high rate of complications. Recently, reverse Ponseti-type casting followed by percutaneous reduction and fixation has been described, with excellent results in separate cohorts of children with CVT, of either idiopathic or teratological aetiology. There are currently no studies that compare the outcome in these two types. We present a prospective cohort of 13 children (21 feet) with CVT of both idiopathic and teratological aetiology, in which this technique has been used. Clinical, radiological and parent-reported outcomes were obtained at a mean follow-up of 36 months (8 to 57). Six children (nine feet) had associated neuromuscular conditions or syndromes; the condition was idiopathic in seven children (12 feet). Initial correction was achieved in all children, with significant improvement in all radiological parameters. Recurrence was seen in ten feet. Modification of the technique to include limited capsulotomy at the initial operation may reduce the risk of recurrence. The reverse Ponseti-type technique is effective in the initial correction of CVT of both idiopathic and teratological aetiology. Recurrence is a problem in both these groups, with higher rates than first reported in the original paper. However, these rates are less than those reported after open surgical release. Cite this article: Bone Joint J 2014;96-B:274–8

Aims. The purpose of this study was to determine whether there were long-term differences in outcomes of reverse shoulder arthroplasty (RSA) undertaken for acute proximal humeral fracture versus rotator cuff deficiency with a minimum follow-up of five years. Methods. This was a prospective cohort study comparing 67 patients with acute complex proximal humeral fracture and 64 patients with irreparable rotator cuff deficiency who underwent primary RSA. In the fracture group, there were 52 (77.6%) females and 15 (22.4%) males, with a mean age of 73.5 years (51 to 85), while in the arthropathy group, there were 43 (67.1%) females and 21 (32.9%) males, with a mean age of 70.6 years (50 to 84). Patients were assessed by the Constant score, University of California Los Angeles shoulder score (UCLA), short version of the Disability of the Arm Shoulder and Hand score (QuickDASH), and visual analogue scales (VAS) for pain and satisfaction. Radiological evaluation was also performed. Results. Mean follow-up was 8.4 years (5 to 11). There were no significant differences in mean absolute (p = 0.125) or adjusted (p = 0.569) Constant, UCLA (p = 0.088), QuickDASH (p = 0.135), VAS-pain (p = 0.062), or range of movement at the final follow-up. However, patient satisfaction was significantly lower in the fracture group (p = 0.002). The complication rate was 1.5% (one patient) versus 9.3% (six patients), and the revision rate was 1.5% (one patient) versus 7.8% (five patients) in the fracture and arthropathy groups, respectively. The ten-year arthroplasty survival was not significantly different (p = 0.221). Conclusion. RSA may be used not only for patients with irreparable rotator cuff deficiencies, but also for those with acute complex proximal humeral fractures. We found that RSA provided similar functional outcomes and a low revision rate for both indications at long-term. However, satisfaction is lower in patients with an acute fracture. Cite this article: Bone Joint J 2020;102-B(11):1555–1559

Aims

Rates of reverse total shoulder arthroplasty (rTSA) continue to grow. Glenoid bone loss and deformity remains a technical challenge to the surgeon and may reduce improvements in patients’ outcomes. However, there is no consensus as to the optimal surgical technique to best reconstruct these patients’ anatomy. This review aims to compare the outcomes of glenoid bone grafting versus augmented glenoid prostheses in the management of glenoid bone loss in primary reverse total shoulder arthroplasty.

Inherent disadvantages of reverse shoulder arthroplasty designs based on the Grammont concept have raised a renewed interest in less-medialised designs and techniques. The aim of this study was to evaluate the outcome of reverse shoulder arthroplasty (RSA) with the fully-constrained, less-medialised, Bayley–Walker prosthesis performed for the treatment of rotator-cuff-deficient shoulders with glenohumeral arthritis. A total of 97 arthroplasties in 92 patients (53 women and 44 men, mean age 67 years (standard deviation (. sd. ) 10, (49 to 85)) were retrospectively reviewed at a mean follow-up of 50 months ((. sd. 25) (24 to 96)). The mean Oxford shoulder score and subjective shoulder value improved from 47 (. sd. 9) and 24 points (. sd. 18) respectively before surgery to 28 (. sd. 11) and 61 (. sd. 24) points after surgery (p <  0.001). The mean pain at rest decreased from 5.3 (. sd. 2.8) to 1.5 (. sd. 2.3) (p < 0.001). The mean active forward elevation and external rotation increased from 42. °. (. sd. 30) and 9. °. (. sd. 15) respectively pre-operatively to 78. °. (. sd. 39) and 24. °. (. sd. 17) post-operatively (p < 0.001). A total of 20 patients required further surgery for complications; 13 required revision of components. No patient developed scapular notching. The Bayley–Walker prosthesis provides reliable pain relief and reasonable functional improvement for patients with symptomatic cuff-deficient shoulders. Compared with other designs of RSA, it offers a modest improvement in forward elevation, but restores external rotation to some extent and prevents scapular notching. A longer follow-up is required to assess the survival of the prosthesis and the clinical performance over time. Cite this article: Bone Joint J 2014;96-B:936–42

Aims. The aim of this study was to analyze the results of reverse shoulder arthroplasty (RSA) in patients with type 1 sequelae of a fracture of the proximal humerus in association with rotator cuff deficiency or severe stiffness of the shoulder. Patients and Methods. A total of 38 patients were included: 28 women and ten men. Their mean age at the time of arthroplasty was 73 years (54 to 91). Before the RSA, 18 patients had been treated with open reduction and internal fixation following a fracture. A total of 22 patients had a rotator cuff tear and 11 had severe stiffness of the shoulder with < 0° of external rotation. The mean follow-up was 4.3 years (1.5 to 10). The Constant score and the range of movement of the shoulder were recorded preoperatively and at final follow-up. Preoperatively, radiographs in two planes were performed, as well as CT or arthro-CT scans; radiographs were also performed at final follow-up. Results. The mean Constant score improved from 25 points (5 to 47) preoperatively to 57 points (15 to 81) postoperatively. The mean forward elevation of the shoulder increased from 73° (10° to 130°) preoperatively to 117° (15° to 170°) postoperatively. Previous surgery did not influence the outcome. Patients with rotator cuff tears had lower Constant scores than patients without (p = 0.037). Those with preoperative stiffness of the shoulder had lower postoperative external rotation compared with patients without stiffness (p = 0.046). There was no radiographic evidence of loosening. Three complications occurred, leading to revision surgery in two patients. In all, 17 patients rated their result as very good (45%), another 17 as good (45%), two as satisfactory (5%), and two as unsatisfactory (5%). Discussion. RSA is an effective form of treatment for patients with type 1 sequelae of a fracture of the proximal humerus associated with rotator cuff deficiency or stiffness of the shoulder, with high rates of satisfaction. Rotator cuff tears and stiffness of the shoulder had an adverse effect on the clinical outcome. Cite this article: Bone Joint J 2018;100-B:318–23

Aims. Shoulder arthroplasty using short humeral components is becoming increasingly popular. Some such components have been associated with relatively high rates of adverse radiological findings. The aim of this retrospective review was to evaluate the radiological humeral bone changes and mechanical failure rates with implantation of a short cementless humeral component in anatomical (TSA) and reverse shoulder arthroplasty (RSA). Patients and Methods. A total of 100 shoulder arthroplasties (35 TSA and 65 RSA) were evaluated at a mean of 3.8 years (3 to 8.3). The mean age at the time of surgery was 68 years (31 to 90). The mean body mass index was 32.7 kg/m. 2. (17.3 to 66.4). Results. Greater tuberosity stress shielding was noted in 14 shoulders (two TSA and 12 RSA) and was graded as mild in nine, moderate in two, and severe in three. Medial calcar resorption was noted in 23 shoulders (seven TSA and 16 RSA), and was graded as mild in 21 and moderate in two. No humeral components were revised for loosening or considered to be loose radiologically. Nine shoulders underwent reoperation for infection (n = 3), fracture of the humeral tray (n = 2), aseptic glenoid loosening (n = 1), and instability (n = 3). No periprosthetic fractures occurred. Conclusion. Implantation of this particular short cementless humeral component at the time of TSA or RSA was associated with a low rate of adverse radiological findings on the humeral side at mid-term follow-up. Our data do not raise any concerns regarding the use of a short stem in TSA or RSA. Cite this article: Bone Joint J 2019;101-B:610–614

Instability after arthroplasty of the shoulder is difficult to correct surgically. Soft-tissue procedures and revision surgery using unconstrained anatomical components are associated with a high rate of failure. The purpose of this study was to determine the results of revision of an unstable anatomical shoulder arthroplasty to a reverse design prosthesis. Between 2004 and 2007, 33 unstable anatomical shoulder arthroplasties were revised to a reverse design. The mean age of the patients was 71 years (53 to 86) and their mean follow-up was 42 months (25 to 71). The mean time to revision was 26 months (4 to 164). Pain scores improved significantly (pre-operative visual analogue scale (VAS) of 7.2 (. sd. 1.6); most recent VAS 2.2 (. sd. 1.9); p = 0.001). There was a statistically significant increase in mean active forward elevation from 40.2° (. sd. 27.3) to 97.0° (. sd. 36.2) (p = 0.001). There was no significant difference in internal (p = 0.93) or external rotation (p = 0.40). Radiological findings included notching in five shoulders (15%) and heterotopic ossification of the inferior capsular region in three (9%). At the last follow-up 31 shoulders (94%) were stable. The remaining two shoulders dislocated at 2.5 weeks and three months post-operatively, respectively. According to the Neer rating system, there were 13 excellent (40%), ten satisfactory (30%) and ten unsatisfactory results (30%). Revision of hemiarthroplasty or anatomical total shoulder replacement for instability using a reverse design prosthesis gives good short-term results. Cite this article: Bone Joint J 2013;95-B:668–72

We have previously described the short-term outcome of the use of reverse shoulder arthroplasty in the treatment of acute complex proximal humeral fractures in the elderly. We now report the clinical and radiological outcome of 36 fractures at a mean of 6.6 years (1 to 16). Previously, at a mean follow-up of 6 years (1 to 12) the mean Constant score was 58.5; this was reduced to 53 points with the further follow-up. A total of 23 patients (63%) had radiological evidence of loosening of the glenoid component. Nevertheless, only one patient had aseptic loosening of the baseplate at 12 years’ follow-up. The reduction in the mean Constant score with longer follow-up and the further development of scapular notching is worrying. New developments in design, bearing surfaces and surgical technique, and further follow-up, will determine whether reverse shoulder arthroplasty has a place in the management of complex proximal humeral fractures in the elderly

Radiological changes and differences between cemented and uncemented components of Grammont reverse shoulder arthroplasties (DePuy) were analysed at a mean follow-up of 9.6 years (8 to 12). Of 122 reverse shoulder arthroplasties implanted in five shoulder centres between 1993 and 2000, a total of 68 (65 patients) were available for study. The indications for reversed shoulder arthroplasty were cuff tear arthropathy in 48 shoulders, revision of shoulder prostheses of various types in 11 and massive cuff tear in nine. The development of scapular notching, bony scapular spur formation, heterotopic ossification, glenoid and humeral radiolucencies, stem subsidence, radiological signs of stress shielding and resorption of the tuberosities were assessed on standardised true anteroposterior and axillary radiographs. A scapular notch was observed in 60 shoulders (88%) and was associated with the superolateral approach (p = 0.009). Glenoid radiolucency was present in 11 (16%), bony scapular spur and/or ossifications in 51 (75%), and subsidence of the stem and humeral radiolucency in more than three zones were present in three (8.8%) and in four (11.8%) of 34 cemented components, respectively, and in one (2.9%) and two (5.9%) of 34 uncemented components, respectively. Radiological signs of stress shielding were significantly more frequent with uncemented components (p < 0.001), as was resorption of the greater (p < 0.001) and lesser tuberosities (p = 0.009)

Aims. The eccentric glenosphere was principally introduced into reverse shoulder arthroplasty to reduce the incidence of scapular notching. There is only limited information about the influence of its design on deltoid power and joint reaction forces. The aim of our study was to investigate how the diameter and eccentricity of the glenosphere affect the biomechanics of the deltoid and the resultant joint reaction forces. . Methods. Different sizes of glenosphere and eccentricity were serially tested in ten cadaveric shoulders using a custom shoulder movement simulator. Results. Increasing the diameter of the glenosphere alone did not alter the deltoid moment arm. However, using an eccentric glenosphere increased the moment arm of the deltoid, lowered the joint reaction force and required less deltoid force to generate movement. Conclusion. Eccentricity is an independent variable which increases deltoid efficiency and lowers joint reaction forces in a reverse shoulder arthroplasty. Cite this article: Bone Joint J 2016;98-B:218–23

Aims. Scapular notching is a frequently observed radiographic phenomenon in reverse shoulder arthroplasty (RSA), signifying impingement of components. The purposes of this study were to evaluate the effect of glenoid component size and glenosphere type on impingement-free range of movement (ROM) for extension and internal and external rotation in a virtual RSA model, and to determine the optimal configuration to reduce the incidence of friction-type scapular notching. Materials and Methods. Preoperative CT scans obtained in 21 patients (three male, 18 female) with primary osteoarthritis were analyzed using modelling software. Two concurrent factors were tested for impingement-free ROM and translation of the centre of rotation: glenosphere diameter (36 mm vs 39 mm) and type (centred, 2 mm inferior eccentric offset, 10° inferior tilt). Results. Glenosphere size was most predictive of increased extension and external rotation, whereas lateralization of the centre of rotation was the most predictive factor for internal rotation. A larger diameter of glenosphere combined with a 10° tilted configuration demonstrated superior values for extension and external rotation, whereas the eccentric component improved internal rotation by a mean 8.9° (standard deviation 2.7°) compared with a standard concentric glenosphere. Conclusion. Glenosphere configuration can be modified to increase range of movement in RSA. Friction-type scapular notching was most effectively reduced by use of a large-diameter glenosphere with 10° inferior tilt. Cite this article: Bone Joint J 2018;100-B:1182–6

If a modular convertible total shoulder system is used as a primary implant for an anatomical total shoulder arthroplasty, failure of the prosthesis or the rotator cuff can be addressed by converting it to a reverse shoulder arthroplasty (RSA), with retention of the humeral stem and glenoid baseplate. This has the potential to reduce morbidity and improve the results. . In a retrospective study of 14 patients (15 shoulders) with a mean age of 70 years (47 to 83) we reviewed the clinical and radiological outcome of converting an anatomical shoulder arthroplasty (ASA) to a RSA using a convertible prosthetic system (SMR system, Lima, San Daniele, Italy). . The mean operating time was 64 minutes (45 to 75). All humeral stems and glenoid baseplates were found to be well-fixed and could be retained. There were no intra-operative or early post-operative complications and no post-operative infection. The mean follow-up was 43 months (21 to 83), by which time the mean visual analogue scale for pain had decreased from 8 pre-operatively to 1, the mean American Shoulder and Elbow Surgeons Score from 12 to 76, the mean Oxford shoulder score from 3 to 39, the mean Western Ontario Osteoarthritis of the Shoulder Score from 1618 to 418 and the mean Subjective shoulder value from 15 to 61. On radiological review, one patient had a lucency around the humeral stem, two had stress shielding. There were no fatigue fractures of the acromion but four cases of grade 1 scapular notching. . The use of a convertible prosthetic system to revise a failed ASA reduces morbidity and minimises the rate of complications. The mid-term clinical and radiological results of this technique are promising. Cite this article: Bone Joint J 2015;97-B:1662–7

We investigated the functional outcome in patients who underwent reverse shoulder replacement (RSR) after removal of a tumour of the proximal humerus. A total of 16 patients (ten women and six men) underwent this procedure between 1998 and 2011 in our hospital. Five patients died and one was lost to follow-up. Ten patients were available for review at a mean follow-up of 46 months (12 to 136). Eight patients had a primary and two patients a secondary bone tumour. At final follow up the mean range of active movement was: abduction 78° (30° to 150°); flexion 98° (45° to 180°); external rotation 32° (10° to 60°); internal rotation 51° (10° to 80°). The mean Musculoskeletal Tumor Society score was 77% (60% to 90%) and the mean Toronto Extremity Salvage Score was 70% (30% to 91%). Two patients had a superficial infection and one had a deep infection and underwent a two-stage revision procedure. In two patients there was loosening of the RSR; one dislocated twice. All patients had some degree of atrophy or pseudo-atrophy of the deltoid muscle. Use of a RSR in patients with a tumour of the proximal humerus gives acceptable results. Cite this article: Bone Joint J 2013;95-B:1551–5

We report the use of the reverse shoulder prosthesis in the revision of a failed shoulder hemiarthroplasty in 19 shoulders in 18 patients (7 men, 11 women) with severe pain and loss of function. The primary procedure had been undertaken for glenohumeral arthritis associated with severe rotator cuff deficiency. Statistically significant improvements were seen in pain and functional outcome. After a mean follow-up of 44 months (24 to 89), mean forward flexion improved by 26.4° and mean abduction improved by 35°. There were six prosthesis-related complications in six shoulders (32%), five of which had severe bone loss of the glenoid, proximal humerus or both. Three shoulders (16%) had non-prosthesis related complications. The use of the reverse shoulder prosthesis provides improvement in pain and function for patients with failure of a hemiarthroplasty for glenohumeral arthritis and rotator cuff deficiency. However, high rates of complications were associated with glenoid and proximal humeral bone loss

The indications for reverse shoulder arthroplasty (RSA) continue to be expanded. Associated impairment of the deltoid muscle has been considered a contraindication to its use, as function of the RSA depends on the deltoid and impairment of the deltoid may increase the risk of dislocation. The aim of this retrospective study was to determine the functional outcome and risk of dislocation following the use of an RSA in patients with impaired deltoid function. Between 1999 and 2010, 49 patients (49 shoulders) with impairment of the deltoid underwent RSA and were reviewed at a mean of 38 months (12 to 142) post-operatively. There were nine post-operative complications (18%), including two dislocations. The mean forward elevation improved from 50° (. sd. 38; 0° to 150°) pre-operatively to 121° (. sd . 40; 0° to 170°) at final follow-up (p < 0.001). The mean Constant score improved from 24 (. sd. 12; 2 to 51) to 58 (. sd. 17; 16 to 83) (p < 0.001). The mean Single Assessment Numeric Evaluation score was 71 (. sd. 17; 10 to 95) and the rate of patient satisfaction was 98% (48 of 49) at final follow-up. . These results suggest that pre-operative deltoid impairment, in certain circumstances, is not an absolute contraindication to RSA. This form of treatment can yield reliable improvement in function without excessive risk of post-operative dislocation. Cite this article: Bone Joint J 2013;95-B:1106–13

The combination of an irreparable tear of the rotator cuff and destructive arthritis of the shoulder joint may cause severe pain, disability and loss of independence in the aged. Standard anatomical shoulder replacements depend on a functioning rotator cuff, and hence may fail in the presence of tears in the cuff. Many designs of non-anatomical constrained or semi-constrained prostheses have been developed for cuff tear arthropathy, but have proved unsatisfactory and were abandoned. The DePuy Delta III reverse prosthesis, designed by Grammont, medialises and stabilises the centre of rotation of the shoulder joint and has shown early promise. This study evaluated the mid-term clinical and radiological results of this arthroplasty in a consecutive series of 50 shoulders in 43 patients with a painful pseudoparalysis due to an irreparable cuff tear and destructive arthritis, performed over a period of seven years by a single surgeon. A follow-up of 98% was achieved, with a mean duration of 39 months (8 to 81). The mean age of the patients at the time of surgery was 81 years (59 to 95). The female to male ratio was 5:1. During the seven years, six patients died of natural causes. The clinical outcome was assessed using the American Shoulder and Elbow score, the Oxford Shoulder Score and the Short-form 36 score. A radiological review was performed using the Sirveaux score for scapular notching. The mean American Shoulder and Elbow score was 19 (95% confidence interval (CI) 14 to 23) pre-operatively, and 65 (95% CI 48 to 82) (paired t-test, p < 0.001) at final follow-up. The mean Oxford score was 44 (95% CI 40 to 51) pre-operatively and 23 (95% CI 18 to 28) (paired t-test, p < 0.001) at final follow-up. The mean maximum elevation improved from 55° pre-operatively to 105° at final follow-up. There were seven complications during the whole series, although only four patients required further surgery

Aims. Vitamin E-infused highly crosslinked polyethylene (VEPE) has been introduced into total hip arthroplasty (THA) with the aim of further improving the wear characteristics of moderately and highly crosslinked polyethylenes (ModXLPE and HXLPE). There are few studies analyzing the outcomes of vitamin E-infused components in cemented arthroplasty, though early acetabular component migration has been reported. The aim of this study was to measure five-year polyethylene wear and acetabular component stability of a cemented VEPE acetabular component compared with a ModXLPE cemented acetabular component. Methods. In a prospective randomized controlled trial (RCT), we assessed polyethylene wear and acetabular component stability (primary outcome) with radiostereometric analysis (RSA) in 68 patients with reverse hybrid THA at five years follow-up. Patients were randomized to either a VEPE or a ModXLPE cemented acetabular component. Results. Mean polyethylene wear in the proximal direction was 0.17 mm (SD 0.15) for the VEPE group and 0.20 mm (SD 0.09) for the ModXLPE group (p = 0.005) at five years. Annual proximal wear rates were 0.03 mm/year (VEPE) and 0.04 mm/year (ModXLPE). Total 3D wear was 0.21 mm (SD 0.26) and 0.23 mm (SD 0.10) for the VEPE and ModXLPE groups, respectively (p = 0.009). Total 3D cup translation was 0.72 mm (SD 0.70) (VEPE) and 0.50 mm (SD 0.44) (ModXLPE) (p = 0.409). Conclusion. At five years, there was less polyethylene wear in the VEPE group than in the ModXLPE group. Both VEPE and ModXLPE cemented components showed low annual wear rates. Component stability was similar in the two groups and remained constant up to five years. Whether these results will equate to a lower long-term revision rate is still unknown. Cite this article: Bone Joint J 2020;102-B(12):1646–1653

Aims

Reverse total shoulder arthroplasty (rTSA) can be used in complex cases when the glenoid requires reconstruction. In this study, a baseplate with composite bone autograft and a central trabecular titanium peg was implanted, and its migration was assessed for two years postoperatively using radiostereometric analysis (RSA).

We used an inverted shoulder arthroplasty in 43 consecutive patients with a mean age of 78 years (65 to 97) who had sustained a three- or four-part fracture of the upper humerus. All except two were reviewed with a mean follow-up of 22 months (6 to 58). The clinical outcome was satisfactory with a mean active anterior elevation of 97° (35° to 160°) and a mean active external rotation in abduction of 30° (0° to 80°). The mean Constant and the mean modified Constant scores were respectively 44 (16 to 69) and 66% (25% to 97%). Complications included three patients with reflex sympathetic dystrophy, five with neurological complications, most of which resolved, and one with an anterior dislocation. Radiography showed peri-prosthetic calcification in 36 patients (90%), displacement of the tuberosities in 19 (53%) and a scapular notch in ten (25%). Compared with conventional hemiarthroplasty, satisfactory mobility was obtained despite frequent migration of the tuberosities. However, long-term results are required before reverse shoulder arthroplasty can be recommended as a routine procedure in complex fractures of the upper humerus in the elderly

Aims. Radiostereometric analysis (RSA) studies of vitamin E-doped, highly crosslinked polyethylene (VEPE) liners show low head penetration rates in cementless acetabular components. There is, however, currently no data on cemented VEPE acetabular components in total hip arthroplasty (THA). The aim of this study was to evaluate the safety of a new cemented VEPE component, compared with a conventional polyethylene (PE) component regarding migration, head penetration, and clinical results. Patients and Methods. We enrolled 42 patients (21 male, 21 female) with osteoarthritis and a mean age of 67 years (. sd. 5), in a double-blinded, noninferiority, randomized controlled trial. The subjects were randomized in a 1:1 ratio to receive a reverse hybrid THA with a cemented component of either argon-gas gamma-sterilized PE component (controls) or VEPE, with identical geometry. The primary endpoint was proximal implant migration of the component at two years postoperatively measured with RSA. Secondary endpoints included total migration of the component, penetration of the femoral head into the component, and patient-reported outcome measurements. Results. In total, 19 control implants and 18 implants in the VEPE group were analyzed for the primary endpoint. We found a continuous proximal migration of the component in the VEPE group that was significantly higher with a difference at two years of a mean 0.21 mm (95% confidence interval (CI) 0.05 to 0.37; p = 0.013). The total migration was also significantly higher in the VEPE group, but femoral head penetration was lower. We found no difference in clinical outcomes between the groups. Conclusion. At two years, this cemented VEPE component, although having a low head penetration and excellent clinical results, failed to meet noninferiority compared with the conventional implant by a proximal migration above the proposed safety threshold of RSA. The early proximal migration pattern of the VEPE component is a reason for continued monitoring, although a specific threshold for proximal migration and risk for later failure cannot be defined and needs further study. Cite this article: Bone Joint J 2019;101-B:1192–1198

We reviewed 22 children with cubitus varus who had been treated by a reverse V osteotomy and fixation by cross-pinning and wiring. The mean pre-operative humeral-elbow-wrist angle was −16.9° (−25° to +9°) and at the latest follow-up it was +7.3° (−2° to +14°). No child had a lateral prominence greater than 5 mm after correction. An excellent result was achieved in 20 children and a good result in two. We believe that this osteotomy has the advantages of better inherent stability, the avoidance of a prominent lateral condyle after correction and firm fixation allowing early movement

We retrospectively reviewed 21 patients (22 shoulders) who presented with deep infection after surgery to the shoulder, 17 having previously undergone hemiarthroplasty and five open repair of the rotator cuff. Nine shoulders had undergone previous surgical attempts to eradicate their infection. The diagnosis of infection was based on a combination of clinical suspicion (16 shoulders), positive frozen sections (> 5 polymorphonuclear leukocytes per high-power field) at the time of revision (15 shoulders), positive intra-operative cultures (18 shoulders) or the pre-operative radiological appearances. The patients were treated by an extensive debridement, intravenous antibiotics, and conversion to a reverse shoulder prosthesis in either a single- (10 shoulders) or a two-stage (12 shoulders) procedure. At a mean follow-up of 43 months (25 to 66) there was no evidence of recurrent infection. All outcome measures showed statistically significant improvements. Mean abduction improved from 36.1° (. sd. 27.8) pre-operatively to 75.7° (. sd. 36.0) (p < 0.0001), the mean forward flexion from 43.1° (. sd. 33.5) to 79.5° (. sd. 43.2) (p = 0.0003), and mean external rotation from 10.2° (. sd. 18.7) to 25.4° (. sd. 23.5) (p = 0.0037). There was no statistically significant difference in any outcome between the single-stage and the two-stage group

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model

Periprosthetic bone loss after total joint arthroplasty is a major clinical problem resulting in aseptic loosening of the implant. Among many cell types, osteoblasts play a crucial role in the development of peri-implant osteolysis. In this study, we tested the effects of calcitriol (1α,25-dihydroxy-vitamin-D. 3. ) and the bisphosphonate pamidronate on titanium-particle- and TNF-α-induced release of interleukin-6 and suppression of osteoblast-specific gene expressions in bone-marrow-derived stromal cells with an osteoblastic phenotype. We monitored the expression of procollagen α1[1], osteocalcin, osteonectin and alkaline phosphatase mRNAs by Northern blots and real-time reverse transcription and polymerase chain reaction analyses. The release of various cytokines was also analysed by ELISA. We found that calcitriol or pamidronate could only partially recover the altered functions of osteoblasts when added alone. Only a combination of these compounds restored all the tested functions of osteoblasts. The local delivery of these drugs may have therapeutic potential to prevent or to treat periprosthetic osteolysis and aseptic loosening of implants

We describe a congenital deformity of the foot which is characterised by calcaneus at the ankle and valgus at the subtalar joint; spontaneous improvement does not occur and serial casting results in incomplete or impermanent correction of the deformities. Experience with five feet in four children indicates that release of the ligaments and tendons anterior and lateral to the ankle and lateral to the subtalar joint is the minimum surgery necessary; subtalar arthrodesis may be required in addition. The foot deformity described may occur as an isolated condition or in association with multiple congenital anomalies. The possibility of a neurological deficit should always be excluded.

Aims. The aim of this study is to evaluate the change in incidence rate of shoulder arthroplasty, indications, and surgeon volume trends associated with these procedures between January 2003 and April 2021 in the province of Nova Scotia, Canada. Methods. A total of 1,545 patients between 2005 and 2021 were analyzed. Patients operated on between 2003 and 2004 were excluded due to a lack of electronic records. Overall, 84.1% of the surgeries (n = 1,299) were performed by two fellowship-trained upper limb surgeons, with the remainder performed by one of the 14 orthopaedic surgeons working in the province. Results. Total shoulder arthroplasty (TSA) was the most frequent procedure (32.17%; n = 497), followed by stemmed hemiarthroplasty (SHA) (27.7%; n = 428). The most frequent indication for primary shoulder arthroplasty was degenerative osteoarthritis (58.1%; n = 882), followed by acute proximal humerus fracture in 15.11% (n = 245), and rotator cuff arthropathy in 14.18% (n = 220). The overall rate of revision was 7.7% (2.8% to 11.2%). The number of TSAs and reverse shoulder arthroplasties (RSAs) has been increasing since 2016. The amount of revision cases is proportional to the number of operations performed in the same year throughout the study period. Conclusion. The incidence of shoulder arthroplasty in the Maritime Provinces has increased over the last 16 years. Revision rates are similar the those found in other large database registries. Reverse shoulder arthroplasty prevalence has increased since 2016. Cite this article: Bone Jt Open 2023;4(8):567–572

Aims. Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation. Methods. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay. Results. The expression of miR-760 was upregulated in OP tissues, whereas ANKFY1 expression was downregulated. APS stimulated the differentiation and proliferation of hBMSCs by: increasing their viability; upregulating the expression levels of cyclin D1, ALP, OCN, and RUNX2; and inducing osteoblast mineralization. Moreover, APS downregulated the expression of miR-760. Overexpression of miR-760 was found to inhibit the promotive effect of APS on hBMSC differentiation and proliferation, while knockdown of miR-760 had the opposite effect. ANKFY1 was found to be the direct target of miR-760. Additionally, ANKFY1 participated in the APS-mediated regulation of miR-760 function in hBMSCs. Conclusion. APS promotes the osteogenic differentiation and proliferation of hBMSCs. Moreover, APS alleviates the effects of OP by downregulating miR-760 and upregulating ANKFY1 expression. Cite this article: Bone Joint Res 2023;12(8):476–485

Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Aims. The aim of this study was to compare the clinical and radiological outcomes of reverse shoulder arthroplasty (RSA) using small and standard baseplates in Asian patients, and to investigate the impact of a mismatch in the sizes of the glenoid and the baseplate on the outcomes. Methods. This was retrospective analysis of 50 and 33 RSAs using a standard (33.8 mm, ST group) and a small (29.5 mm, SM group) baseplate of the Equinoxe reverse shoulder system, which were undertaken between January 2017 and March 2021. Radiological evaluations included the size of the glenoid, the β-angle, the inclination of the glenoid component, inferior overhang, scapular notching, the location of the central cage in the baseplate within the vault and the mismatch in size between the glenoid and baseplate. Clinical evaluations included the range of motion (ROM) and functional scores. In subgroup analysis, comparisons were performed between those in whom the vault of the glenoid was perforated (VP group) and those in whom it was not perforated (VNP group). Results. Perforation of the vault of the glenoid (p = 0.018) and size mismatch in height (p < 0.001) and width (p = 0.013) were significantly more frequent in the ST group than in the SM group. There was no significant difference in the clinical scores and ROM in the two groups, two years postoperatively (all p > 0.05). In subgroup analysis, the VP group had significantly less inferior overhang (p = 0.009), more scapular notching (p = 0.018), and more size mismatch in height (p < 0.001) and width (p = 0.025) than the VNP group. Conclusion. In Asian patients with a small glenoid, using a 29.5 mm small baseplate at the time of RSA was more effective in reducing size mismatch between the glenoid and the baseplate, decreasing the incidence of perforation of the glenoid vault, and achieving optimal positioning of the baseplate compared with the use of a 33.8 mm standard baseplate. However, longer follow-up is required to assess the impact of these findings on the clinical outcomes. Cite this article: Bone Joint J 2023;105-B(11):1189–1195

Aims. To draw a comparison of the pullout strengths of buttress thread, barb thread, and reverse buttress thread bone screws. Methods. Buttress thread, barb thread, and reverse buttress thread bone screws were inserted into synthetic cancellous bone blocks. Five screw-block constructs per group were tested to failure in an axial pullout test. The pullout strengths were calculated and compared. A finite element analysis (FEA) was performed to explore the underlying failure mechanisms. FEA models of the three different screw-bone constructs were developed. A pullout force of 250 N was applied to the screw head with a fixed bone model. The compressive and tensile strain contours of the midsagittal plane of the three bone models were plotted and compared. Results. The barb thread demonstrated the lowest pullout strength (mean 176.16 N (SD 3.10)) among the three thread types. It formed a considerably larger region with high tensile strains and a slightly smaller region with high compressive strains within the surrounding bone structure. The reverse buttress thread demonstrated the highest pullout strength (mean 254.69 N (SD 4.15)) among the three types of thread. It formed a considerably larger region with high compressive strains and a slightly smaller region with high tensile strains within the surrounding bone structure. Conclusion. Bone screws with a reverse buttress thread design will significantly increase the pullout strength. Cite this article: Bone Joint Res 2021;10(2):105–112

Aims. The role of N,N-dimethylformamide (DMF) in diabetes-induced osteoporosis (DM-OS) progression remains unclear. Here, we aimed to explore the effect of DMF on DM-OS development. Methods. Diabetic models of mice, RAW 264.7 cells, and bone marrow macrophages (BMMs) were established by streptozotocin stimulation, high glucose treatment, and receptor activator of nuclear factor-κB ligand (RANKL) treatment, respectively. The effects of DMF on DM-OS development in these models were examined by micro-CT analysis, haematoxylin and eosin (H&E) staining, osteoclast differentiation of RAW 264.7 cells and BMMs, H&E and tartrate-resistant acid phosphatase (TRAP) staining, enzyme-linked immunosorbent assay (ELISA) of TRAP5b and c-terminal telopeptides of type 1 (CTX1) analyses, reactive oxygen species (ROS) analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), Cell Counting Kit-8 (CCK-8) assay, and Western blot. Results. The established diabetic mice were more sensitive to ovariectomy (OVX)-induced osteoporosis, and DMF treatment inhibited the sensitivity. OVX-treated diabetic mice exhibited higher TRAP5b and c-terminal telopeptides of type 1 (CTX1) levels, and DMF treatment inhibited the enhancement. DMF reduced RAW 264.7 cell viability. Glucose treatment enhanced the levels of TRAP5b, cathepsin K, Atp6v0d2, and H. +. -ATPase, ROS, while DMF reversed this phenotype. The glucose-increased protein levels were inhibited by DMF in cells treated with RANKL. The expression levels of antioxidant enzymes Gclc, Gclm, Ho-1, and Nqo1 were upregulated by DMF. DMF attenuated high glucose-caused osteoclast differentiation by targeting mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signalling in BMMs. Conclusion. DMF inhibits high glucose-induced osteoporosis by targeting MAPK and NF-κB signalling. Cite this article: Bone Joint Res 2022;11(4):200–209

The June 2023 Shoulder & Elbow Roundup. 360. looks at: Proximal humerus fractures: what does the literature say now?; Infection risk of steroid injections and subsequent reverse shoulder arthroplasty; Surgical versus non-surgical management of humeral shaft fractures; Core outcome set needed for elbow arthroplasty; Minimally invasive approaches to locating radial nerve in the posterior humeral approach; Predictors of bone loss in anterior glenohumeral instability; Does the addition of motor control or strengthening exercises improve rotator cuff-related shoulder pain?; Terminology and diagnostic criteria used in patients with subacromial pain syndrome

Aims. It is important to understand the rate of complications associated with the increasing burden of revision shoulder arthroplasty. Currently, this has not been well quantified. This review aims to address that deficiency with a focus on complication and reoperation rates, shoulder outcome scores, and comparison of anatomical and reverse prostheses when used in revision surgery. Methods. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review was performed to identify clinical data for patients undergoing revision shoulder arthroplasty. Data were extracted from the literature and pooled for analysis. Complication and reoperation rates were analyzed using a meta-analysis of proportion, and continuous variables underwent comparative subgroup analysis. Results. A total of 112 studies (5,379 shoulders) were eligible for inclusion, although complete clinical data was not ubiquitous. Indications for revision included component loosening 20% (601/3,041), instability 19% (577/3,041), rotator cuff failure 17% (528/3,041), and infection 16% (490/3,041). Intraoperative complication and postoperative complication and reoperation rates were 8% (230/2,915), 22% (825/3,843), and 13% (584/3,843) respectively. Intraoperative and postoperative complications included iatrogenic humeral fractures (91/230, 40%) and instability (215/825, 26%). Revision to reverse total shoulder arthroplasty (TSA), rather than revision to anatomical TSA from any index prosthesis, resulted in lower complication rates and superior Constant scores, although there was no difference in American Shoulder and Elbow Surgeons scores. Conclusion. Satisfactory improvement in patient-reported outcome measures are reported following revision shoulder arthroplasty; however, revision surgery is associated with high complication rates and better outcomes may be evident following revision to reverse TSA. Cite this article: Bone Jt Open 2021;2(8):618–630

The February 2023 Shoulder & Elbow Roundup. 360. looks at: Arthroscopic capsular release or manipulation under anaesthesia for frozen shoulder?; Distal biceps repair through a single incision?; Distal biceps tendon ruptures: diagnostic strategy through physical examination; Postoperative multimodal opioid-sparing protocol vs standard opioid prescribing after knee or shoulder arthroscopy: a randomized clinical trial; Graft healing is more important than graft technique in massive rotator cuff tear; Subscapularis tenotomy versus peel after anatomic shoulder arthroplasty; Previous rotator cuff repair increases the risk of revision surgery for periprosthetic joint infection after reverse shoulder arthroplasty; Conservative versus operative treatment of acromial and scapular spine fractures following reverse total shoulder arthroplasty

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. 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. After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA. Methods. Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed. Results. Coexpression of both transgenes (SV40 and hTERT) were observed in the nuclei of transduced chondrocytes. Generated chondrocyte cell lines showed a high proliferation capacity and less than 2% of senescent cells. These cell lines were able to form 3D aggregates analogous to those generated by primary articular chondrocytes, but were unsuccessful in synthesizing cartilage-like tissue when seeded on type I collagen sponges. However, generated chondrocyte cell lines maintained the potential to respond to IL-1β stimulation. Conclusion. Through SV40LT and hTERT transduction, we successfully immortalized chondrocytes. These immortalized chondrocytes were able to overcome senescence in vitro, but were incapable of synthesizing cartilage-like tissue under the experimental conditions. Nonetheless, these chondrocyte cell lines could be advantageous for OA investigation since, similarly to primary articular chondrocytes, they showed capacity to upregulate inflammatory mediators in response to the IL-1β cytokine. Cite this article: Bone Joint Res 2023;12(1):46–57

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

Aims. Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood. Methods. MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay. Results. miR-19a-3p was identified as one of the key regulators in the osteogenic differentiation of BMSCs, and was found to be downregulated in the alcohol-fed mouse model of fracture healing. In vitro, miR-19a-3p expression was downregulated after ethanol administration in both BMSCs and HUVECs. Vascularization and osteogenic differentiation were independently suppressed by ethanol and reversed by miR-19a-3p. In addition, the luciferase reporter assay showed that FOXF2 is the direct binding target of miR-19a-3p. In vivo, miR-19a-3p agomir stimulated callus transformation and improved the alcohol-impaired fracture healing. Conclusion. This study is the first to demonstrate that the miR-19a-3p/FOXF2 axis has a pivotal role in alcohol-impaired fracture healing, and may be a potential therapeutic target. Cite this article: Bone Joint Res 2022;11(6):386–397

Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440

Aims. To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment. Methods. Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue. Results. This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as CHL1 (false discovery rate (FDR) = 2.11 × 10. -11. ), RIC8A (FDR = 7.05 × 10. -4. ), and SOX12 (FDR = 1.43 × 10. -3. ). Additionally, RIC8A and CHL1 were hypermethylated in responders, while SOX12 was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in TESPA1 and ATP11A exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells. Conclusion. Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients. Cite this article: Bone Joint Res 2024;13(5):237–246

Aims. Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. Methods. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR). Results. Local delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN. Conclusion. We demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males. Cite this article: Bone Joint Res 2024;13(1):28–39

Aims. Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis. Methods. Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology. Results. Berberine inhibited proliferation and adhesion of RA-FLS cells, and significantly reduced the expression of MMP-1, MMP-3, RANKL, and TNF-α. Transcriptional results suggested that berberine intervention mainly regulated forkhead box O (FOXO) signal pathway, prolactin signal pathway, neurotrophic factor signal pathway, and hypoxia-inducible factor 1 (HIF-1) signal pathway. Conclusion. The effect of berberine on RA was related to the regulation of RAS/mitogen-activated protein kinase/FOXO/HIF-1 signal pathway in RA-FLS cells. Cite this article: Bone Joint Res 2023;12(2):91–102

The June 2024 Shoulder & Elbow Roundup. 360. looks at: Reverse versus anatomical total shoulder replacement for osteoarthritis? A UK national picture; Acute rehabilitation following traumatic anterior shoulder dislocation (ARTISAN): pragmatic, multicentre, randomized controlled trial; acid for rotator cuff repair: a systematic review and meta-analysis of randomized controlled trials; Metal or ceramic humeral head total shoulder arthroplasty: an analysis of data from the National Joint Registry; Platelet-rich plasma has better results for long-term functional improvement and pain relief for lateral epicondylitis: a systematic review and meta-analysis of randomized controlled trials; Quantitative fatty infiltration and 3D muscle volume after nonoperative treatment of symptomatic rotator cuff tears: a prospective MRI study of 79 patients; Locking plates for non-osteoporotic proximal humeral fractures in the long term; A systematic review of the treatment of primary acromioclavicular joint osteoarthritis

Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137

Aims. Favourable short-term outcomes have been reported following latissimus dorsi tendon transfer for patients with an irreparable subscapularis (SSC) tendon tear. The aim of this study was to investigate the long-term outcomes of this transfer in these patients. Methods. This was a retrospective study involving 30 patients with an irreparable SSC tear and those with a SSC tear combined with a reparable supraspinatus tear, who underwent a latissimus dorsi tendon transfer. Clinical scores and active range of motion (aROM), SSC-specific physical examination and the rate of return to work were assessed. Radiological assessment included recording the acromiohumeral distance (AHD), the Hamada grade of cuff tear arthropathy and the integrity of the transferred tendon. Statistical analysis compared preoperative, short-term (two years), and final follow-up at a mean of 8.7 years (7 to 10). Results. There were significant improvements in clinical scores, in the range and strength of internal rotation and aROM compared with the preoperative values in the 26 patients (87%) who were available for long-term follow-up. These improvements were maintained between short- and long-term follow-ups. Although there was a decreased mean AHD of 7.3 mm (SD 1.5) and an increased mean Hamada grade of 1.7 (SD 0.5) at final follow-up, the rate of progression of cuff tear arthropathy remained low-grade. Comparison between the isolated SSC and combined SSC and reparable supraspinatus tear groups showed no significant differences. At final follow-up, one patient (3.8%) had undergone revision surgery to a reverse shoulder arthroplasty (RSA). No neurological complications were associated with the procedure. Conclusion. Latissimus dorsi transfer for an irreparable SSC tendon tear resulted in a significant clinical improvement, particularly in pain, range and strength of internal rotation and aROM, which were maintained over a mean of 8.7 years following surgery. Given that this was a long-term outcome study, there was a low-grade progression in the rate of cuff tear arthropathy. Thus, the long-term clinical efficacy of latissimus dorsi tendon transfer in patients with irreparable SSC was confirmed as a joint-preserving procedure for these patients, suggesting it as an effective alternative to RSA in young, active patients without degenerative changes of the glenohumeral joint. Cite this article: Bone Joint J 2024;106-B(9):957–963

Aims. Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Methods. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. Results. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28. Conclusion. Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting. Cite this article: Bone Joint Res 2024;13(3):91–100

Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion. Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351

Aims. Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. Methods. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers. Results. C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes: bone remodelling subtype (C1), immune metabolism subtype (C2), and cartilage degradation subtype (C3). The number of macrophage M0 and activated mast cells of C2 subtype was significantly higher than those of the other two subtypes. COL2A1 has significant differences in different subtypes. The expression of COL2A1 is related to age, and trafficking protein particle complex subunit 2 is related to the sex of OA patients. Conclusion. This study linked different tissues with gene expression profiles, revealing different molecular subtypes of patients with knee OA. The relationship between clinical characteristics and OA-related genes was also studied, which provides a new concept for the diagnosis and treatment of OA. Cite this article: Bone Joint Res 2023;12(12):702–711

Aims. The aim of this study was to examine perioperative blood transfusion practice, and associations with clinical outcomes, in a national cohort of hip fracture patients. Methods. A retrospective cohort study was undertaken using linked data from the Scottish Hip Fracture Audit and the Scottish National Blood Transfusion Service between May 2016 and December 2020. All patients aged ≥ 50 years admitted to a Scottish hospital with a hip fracture were included. Assessment of the factors independently associated with red blood cell transfusion (RBCT) during admission was performed, alongside determination of the association between RBCT and hip fracture outcomes. Results. A total of 23,266 individual patient records from 18 hospitals were included. The overall rate of blood transfusion during admission was 28.7% (n = 6,685). There was inter-hospital variation in transfusion rate, ranging from 16.6% to 37.4%. Independent perioperative factors significantly associated with RBCT included older age (90 to 94 years, odds ratio (OR) 3.04 (95% confidence interval (CI) 2.28 to 4.04); p < 0.001), intramedullary fixation (OR 7.15 (95% CI 6.50 to 7.86); p < 0.001), and sliding hip screw constructs (OR 2.34 (95% CI 2.19 to 2.50); p < 0.001). Blood transfusion during admission was significantly associated with higher rates of 30-day mortality (OR 1.35 (95% CI 1.19 to 1.53); p < 0.001) and 60-day mortality (OR 1.54 (95% CI 1.43 to 1.67); p < 0.001), as well as delays to postoperative mobilization, higher likelihood of not returning to their home, and longer length of stay. Conclusion. Blood transfusion after hip fracture was common, although practice varied nationally. RBCT is associated with adverse outcomes, which is most likely a reflection of perioperative anaemia, rather than any causal effect. Use of RBCT does not appear to reverse this effect, highlighting the importance of perioperative blood loss reduction. Cite this article: Bone Joint J 2022;104-B(11):1266–1272

Aims. Circular RNA (circRNA) S-phase cyclin A-associated protein in the endoplasmic reticulum (ER) (circSCAPER, ID: hsa_circ_0104595) has been found to be highly expressed in osteoarthritis (OA) patients and has been associated with the severity of OA. Hence, the role and mechanisms underlying circSCAPER in OA were investigated in this study. Methods. In vitro cultured human normal chondrocyte C28/I2 was exposed to interleukin (IL)-1β to mimic the microenvironment of OA. The expression of circSCAPER, microRNA (miR)-140-3p, and enhancer of zeste homolog 2 (EZH2) was detected using quantitative real-time polymerase chain reaction and Western blot assays. The extracellular matrix (ECM) degradation, proliferation, and apoptosis of chondrocytes were determined using Western blot, cell counting kit-8, and flow cytometry assays. Targeted relationships were predicted by bioinformatic analysis and verified using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The levels of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein were detected using Western blot assays. Results. CircSCAPER was highly expressed in OA cartilage tissues and IL-1β-induced chondrocytes. Knockdown of circSCAPER reduced IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes. Mechanistically, circSCAPER directly bound to miR-140-3p, and miR-140-3p inhibition reversed the effects of circSCAPER knockdown on IL-1β-induced chondrocytes. miR-140-3p was verified to target EZH2, and overexpression of miR-140-3p protected chondrocytes against IL-1β-induced dysfunction via targeting EZH2. Additionally, we confirmed that circSCAPER could regulate EZH2 through sponging miR-140-3p, and the circSCAPER/miR-140-3p/EZH2 axis could activate the PI3K/AKT pathway. Conclusion. CircSCAPER promoted IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes via regulating miR-140-3p/EZH2 axis, which gained a new insight into the pathogenesis of OA. Cite this article: Bone Joint Res 2022;11(2):61–72

Aims. Patients with abnormal spinopelvic mobility are at increased risk for instability. Measuring the change in sacral slope (ΔSS) can help determine spinopelvic mobility preoperatively. Sacral slope (SS) should decrease at least 10° to demonstrate adequate posterior pelvic tilt. There is potential for different ΔSS measurements in the same patient based on sitting posture. The purpose of this study was to determine the effect of sitting posture on the ΔSS in patients undergoing total hip arthroplasty (THA). Methods. In total, 51 patients undergoing THA were reviewed to quantify the variability in preoperative spinopelvic mobility when measuring two different sitting positions using SS for planning. Results. A total of 32 patients had standardized relaxed sitting radiographs, while 35 patients had standardized flexed sitting images. Of the 32 patients with relaxed sitting views, the mean ΔSS was 20.7° (SD 8.9°). No patients exhibited an increase in SS during relaxed sitting (i.e. anterior pelvic tilt or so-called reverse accommodation). Of the 35 patients with flexed sitting radiographs, the mean ΔSS was only 2.1° (SD 9.7°) with 16/35 (45.71%) showing anterior pelvic tilt, or so-called reverse accommodation, unexpectedly increasing the sitting SS compared to the standing SS. Overall, 18 patients had both relaxed sitting and flexed sitting radiographs. In patients with both types of sitting radiographs, the mean relaxed sit to stand ΔSS was 18.06° (SD 6.07°), while only a 3.00° (SD 10.53°) ΔSS was noted when flexed sitting. There was a mean ΔSS difference of 15.06° (SD 7.67°) noted in the same patient cohort depending on sitting posture (p < 0.001). Conclusion. A 15° mean difference was noted depending on the sitting posture of the patient. Since decisions on component position can be made on preoperative lateral sit-stand radiographs, postural standardization is crucial. If using ΔSS for preoperative planning, the relaxed sitting radiograph is preferred. Cite this article: Bone Joint J 2020;102-B(7 Supple B):41–46

Aims. Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. Methods. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). Results. PARP-1 expression level significantly increased in the cartilage of the established OA rat model. sh-PARP-1 treatment suppressed PARP-1 levels, decreased the Δ Force (the difference between the weight on ipsilateral limb and contralateral limb) and the knee joint width, inhibited cartilage matrix catabolic enzymes, and ameliorated OA cartilage degradation and attenuated inflammatory response. Conclusion. PARP-1 inhibition attenuates OA cartilage inflammatory response in the OA rat model. Cite this article: Bone Joint Res 2021;10(7):401–410

Aims. Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Methods. High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. Results. More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-β1) was downregulated, while that of TGF-β2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. Conclusion. DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558–570

Aims. The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. Methods. Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency. Results. IBA1 and cyclin D1 in the ipsilateral spinal horn increased in a time-dependent fashion. Spinal microglia proliferated in BCP rats. The microglia inhibitor minocycline attenuated the pain behaviour in BCP rats. The cyclin-dependent kinase inhibitor flavopiridol inhibited the proliferation of spinal microglia, and was associated with an improvement in pain behaviour in BCP rats. Conclusion. Our results revealed that the inhibition of spinal microglial proliferation was associated with a decrease in pain behaviour in a rat model of BCP. Cyclin D1 acts as a key regulator of the proliferation of spinal microglia in a rat model of BCP. Disruption of cyclin D1, the restriction-point control of cell cycle, inhibited the proliferation of microglia and attenuated the pain behaviours in BCP rats. Cyclin D1 and the proliferation of spinal microglia may be potential targets for the clinical treatment of BCP. Cite this article: Bone Joint Res 2022;11(11):803–813

Aims. Corticosteroid injections are often used to manage glenohumeral arthritis in patients who may be candidates for future total shoulder arthroplasty (TSA) or reverse shoulder arthroplasty (rTSA). In the conservative management of these patients, corticosteroid injections are often provided for symptomatic relief. The purpose of this study was to determine if the timing of corticosteroid injections prior to TSA or rTSA is associated with changes in rates of revision and periprosthetic joint infection (PJI) following these procedures. Methods. Data were collected from a national insurance database from January 2006 to December 2017. Patients who underwent shoulder corticosteroid injection within one year prior to ipsilateral TSA or rTSA were identified and stratified into the following cohorts: < three months, three to six months, six to nine months, and nine to 12 months from time of corticosteroid injection to TSA or rTSA. A control cohort with no corticosteroid injection within one year prior to TSA or rTSA was used for comparison. Univariate and multivariate analyses were conducted to determine the association between specific time intervals and outcomes. Results. In total, 4,252 patients were included in this study. Among those, 1,632 patients (38.4%) received corticosteroid injection(s) within one year prior to TSA or rTSA and 2,620 patients (61.6%) did not. On multivariate analysis, patients who received corticosteroid injection < three months prior to TSA or rTSA were at significantly increased risk for revision (odds ratio (OR) 2.61 (95% confidence interval (CI) 1.77 to 3.28); p < 0.001) when compared with the control cohort. However, there was no significant increase in revision risk for all other timing interval cohorts. Notably, Charlson Comorbidity Index ≥ 3 was a significant independent risk factor for all-cause revision (OR 4.00 (95% CI 1.40 to 8.92); p = 0.036). Conclusion. There is a time-dependent relationship between the preoperative timing of corticosteroid injection and the incidence of all-cause revision surgery following TSA or rTSA. This analysis suggests that an interval of at least three months should be maintained between corticosteroid injection and TSA or rTSA to minimize risks of subsequent revision surgery. Cite this article: Bone Joint J 2022;104-B(5):620–626

Aims. MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. Methods. Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. Results. miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. Conclusion. Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557

Aims. Long-term outcomes following the use of human dermal allografts in the treatment of symptomatic irreparable rotator cuff tears are not known. The aim of this study was to evaluate these outcomes, and to investigate whether this would be a good form of treatment in young patients in whom a reverse shoulder arthroplasty should ideally be avoided. Methods. This prospective study included 47 shoulders in 45 patients who underwent an open reconstruction of the rotator cuff using an interposition GraftJacket allograft to bridge irreparable cuff tears, between January 2007 and November 2011. The Oxford Shoulder Score (OSS), pain score, and range of motion (ROM) were recorded preoperatively and at one year and a mean of 9.1 years (7.0 to 12.5) postoperatively. Results. There was significant improvement in the mean OSS from 24.7 (SD 5.4) preoperatively to 42.0 (SD 6.3) at one year, and this improvement was maintained at 9.1 years (p < 0.001), with a score of 42.8 (SD 6.8). Similar significant improvements in the pain score were seen and maintained at the final follow-up from 6.1 (SD 1.6) to 2.1 (SD 2.3) (p < 0.001). There were also significant improvements in the ROM of the shoulder, and patient satisfaction was high. Conclusion. The use of an interposition human dermal allograft in patients with an irreparable rotator cuff tear leads to good outcomes that are maintained at a mean of nine years postoperatively. Cite this article: Bone Joint J 2022;104-B(1):91–96

Aims. The aims of this study were: firstly, to investigate the influence of the thickness of cartilage at the sigmoid notch on the inclination of the distal radioulnar joint (DRUJ), and secondly, to compare the sensitivity and specificity of MRI with plain radiographs for the assessment of the inclination of the articular surface of the DRUJ in the coronal plane. . Patients and Methods. Contemporaneous MRI images and radiographs of 100 wrists from 98 asymptomatic patients (mean age 43 years, (16 to 67); 52 male, 53%) with no history of a fracture involving the wrist or surgery to the wrist, were reviewed. The thickness of the cartilage at the sigmoid notch, inclination of the DRUJ and Tolat Type of each DRUJ were determined. . Results. The assessment using MRI scans and cortical bone correlated well with radiographs, with a kappa value of 0.83. The mean difference between the inclination using the cortex and cartilage on MRI scans was 12°, leading to a change of Tolat type of inclination in 66% of wrists. No reverse oblique (Type 3) inclinations were found when using the cartilage to assess inclination. . Conclusion . These data revealed that when measuring the inclination of the DRUJ using cartilage, reverse oblique inclinations might not exist. The data suggest that performing an ulna shortening osteotomy might be reasonable even in distal radioulnar joints where the plain radiographic appearance suggests an unfavourable reverse oblique inclination in the coronal plane. We recommend using MRI to validate radiographs in those that appear to be reverse oblique (Tolat Type 3), as the true inclination might be different, thereby removing one possible contraindication to ulnar shortening. Cite this article: Bone Joint J 2017;99-B:369–75

Aims. The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. Methods. Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted. Results. A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss. Conclusion. Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article: Bone Joint Res 2021;10(1):51–59

Aims. Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. Methods. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay. Results. The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2. Conclusion. In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: Bone Joint Res 2020;9(11):821–826

Aims. The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). Methods. TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR. Results. UAC altered the histological structure and extracellular matrix content of cartilage in the temporomandibular joint (TMJ), and KO of MiR21 alleviated this effect (p < 0.05). Upregulation of MiR21 influenced the expression of TMJ-OA related molecules in mandibular condylar chondrocytes via targeting Gdf5 (p < 0.05). Gdf5 overexpression significantly decreased matrix metalloproteinase 13 (MMP13) expression (p < 0.05) and reversed the effects of MiR21 (p < 0.05). Conclusion. MiR21, which acts as a critical regulator of Gdf5 in chondrocytes, regulates TMJ-OA related molecules and is involved in cartilage matrix degradation, contributing to the progression of TMJ-OA. Cite this article: Bone Joint Res 2020;9(10):689–700

Aims. To investigate the impact of the Charlson and Elixhauser comorbidity indices on patient-reported outcomes measures (PROMs) following shoulder arthroplasty. Methods. Patients undergoing total shoulder arthroplasty (TSA), reverse shoulder arthroplasty (RSA), or hemiarthroplasty (HA) from 2016 to 2018 were identified, along with the Charlson and Elixhauser comorbidities listed as their secondary diagnoses in the electronic medical records. Patients were matched to our institution’s registry to obtain their PROMs, including shoulder-specific (American Shoulder and Elbow Society (ASES) and Shoulder Activity Scale (SAS)) and general health scales (12-Item Short Form Survey (SF-12) and Patient-Reported Outcomes Measurement Information System-Pain Interference). Linear regression models adjusting for age and sex were used to evaluate the association between increasing number of comorbidities and PROM scores. A total of 1,817 shoulder arthroplasties were performed: 1,017 (56%) TSA, 726 (40%) RSA, and 74 (4%) HA. The mean age was 67 years (SD 10), and 936 (52%) of the patients were female. Results. The most common comorbidities were obesity (1,256, 69%) and hypertension (990, 55%). Patients with more comorbidities had lower ASES and SAS scores at baseline (p < 0.001). Elixhauser comorbidities continued to negatively impact ASES and SAS scores at one year (p = 0.002) and two-year follow-up (p = 0.002). Patients with more comorbidities reported greater pain interference on PROMIS at baseline (p = 0.007), but not at two years. Higher number of Charlson comorbidities were associated with lower scores on the SF-12 mental component at baseline (p < 0.001) and two years (p = 0.020). Higher number of Elixhauser comorbidities were associated with lower SF-12 physical component scores at baseline (p < 0.001) and two years (p = 0.004). Conclusion. Higher number of comorbidities was associated with lower baseline scores and worse outcomes on both shoulder-specific and general health PROMs. The presence of specific comorbidities may be used during shared decision-making to manage expectations for patients undergoing shoulder arthroplasty. Cite this article: Bone Joint J 2021;103-B(5):964–970

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

Aims. The risk to patients and healthcare workers of resuming elective orthopaedic surgery following the peak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been difficult to quantify. This has prompted governing bodies to adopt a cautious approach that may be impractical and financially unsustainable. The lack of evidence has made it impossible for surgeons to give patients an informed perspective of the consequences of elective surgery in the presence of SARS-CoV-2. This study aims to determine, for the UK population, the probability of a patient being admitted with an undetected SARS-CoV-2 infection and their resulting risk of death; taking into consideration the current disease prevalence, reverse transcription-polymerase chain reaction (RT-PCR) testing, and preassessment pathway. Methods. The probability of SARS-CoV-2 infection with a false negative test was calculated using a lower-end RT-PCR sensitivity of 71%, specificity of 95%, and the UK disease prevalence of 0.24% reported in May 2020. Subsequently, a case fatality rate of 20.5% was applied as a worst-case scenario. Results. The probability of SARS-CoV-2 infection with a false negative preoperative test was 0.07% (around 1 in 1,400). The risk of a patient with an undetected infection being admitted for surgery and subsequently dying from the coronavirus disease 2019 (COVID-19) is estimated at approximately 1 in 7,000. However, if an estimate of the current global infection fatality rate (1.04%) is applied, the risk of death would be around 1 in 140,000, at most. This calculation does not take into account the risk of nosocomial infection. Conversely, it does not factor in that patients will also be clinically assessed and asked to self-isolate prior to surgery. Conclusion. Our estimation suggests that the risk of patients being inadvertently admitted with an undetected SARS-CoV-2 infection for elective orthopaedic surgery is relatively low. Accordingly, the risk of death following elective orthopaedic surgery is low, even when applying the worst-case fatality rate. Cite this article: Bone Joint J 2020;102-B(9):1256–1260

Aims. To describe the incidence of adverse clinical outcomes related to COVID-19 infection following corticosteroid injections (CSI) during the COVID-19 pandemic. To describe the incidence of positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) testing, positive SARS-COV2 IgG antibody testing or positive imaging findings following CSI at our institution during the COVID-19 pandemic. Methods. A retrospective observational study was undertaken of consecutive patients who had CSI in our local hospitals between 1 February and 30June 2020. Electronic patient medical records (EPR) and radiology information system (RIS) database were reviewed. SARS-CoV-2 RT-PCR testing, SARS-COV2 IgG antibody testing, radiological investigations, patient management, and clinical outcomes were recorded. Lung findings were categorized according to the British Society of Thoracic Imaging (BSTI) guidelines. Reference was made to the incidence of lab-confirmed COVID-19 cases in our region. Results. Overall, 1,656 lab-confirmed COVID-19 cases were identified in our upper tier local authority (UTLA), a rate of 306.6 per 100,000, as of 30June 2020. A total of 504 CSI injections were performed on 443 patients between 1 February and 30June 2020. A total of 11 RT-PCR tests were performed on nine patients (2% of those who had CSI), all of which were negative for SARS-CoV-2 RNA, and five patients (1.1%) received an SARS-CoV-2 IgG antibody test, of which 2 (0.5%) were positive consistent with prior COVID-19 infection, however both patients were asymptomatic. Seven patients (1.6%) had radiological investigations for respiratory symptoms. One patient with indeterminate ground glass change was identified. Conclusion. The incidence of positive COVID-19 infection following corticosteroid injections was very low in our cohort and no adverse clinical outcomes related to COVID-19 infection following CSI were identified. Our findings are consistent with CSI likely being low risk during the COVID-19 pandemic. The results of this small observational study are supportive of the current multi-society guidelines regarding the judicious use of CSI. Cite this article: Bone Joint Open 2020;1-9:605–611

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

Aims. Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD. Methods. The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between COMP-overexpression groups and control groups were examined after cell transfection. Results. The mRNA and protein expression levels of COMP were significantly lower in KBD chondrocytes than control chondrocytes. After the T-2 toxin intervention, the COMP mRNA expression of C28/I2 chondrocyte reduced and the protein level of COMP in three intervention groups was significantly lower than in the control group. MTT assay showed that the survival rate of COMP overexpression KBD chondrocytes were notably higher than in the blank control group. The mRNA expression levels of Survivin, SOX9, Caspase-3, and type II collagen were also significantly different among COMP overexpression, negative control, and blank control groups. Conclusion. Our study results confirmed the functional relevance of COMP with KBD. COMP may play an important role in the excessive chondrocytes apoptosis of KBD patients. Cite this article: Bone Joint Res 2020;9(9):578–586

Objectives. Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb. Methods. The medial and lateral cartilage samples of the tibial plateau from 12 osteoarthritis (OA) patients were collected. Ob-Rb messenger RNA (mRNA) was detected in these samples. The Ob-Rb-overexpressing chondrocytes and controls were treated with different doses of leptin for two days. The activation of the p53/p21 pathway and the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells were evaluated. The mammalian target of rapamycin (mTOR) signalling pathway and autophagy were detected after the chondrocytes were treated with a high dose of leptin. Results. In total, 12 cases were found to have severe medial cartilage wear compared with the lateral cartilage. Immunofluorescence showed that the expression of Ob-Rb in the medial cartilage of the tibial plateau was high. High levels of leptin led to cell cycle arrest and inhibited autophagy. After overexpression of Ob-Rb, the physiological dose of leptin induced cell senescence in the chondrocytes. High doses of leptin inhibited autophagy by activating the mTOR signalling pathway. Blockade of the mTOR signalling pathway could restore autophagy and partially reverse senescence induced by leptin in chondrocytes. Conclusion. In summary, the present study demonstrated that high doses of leptin induce cell senescence by activating the mTOR pathway in chondrocytes from OA cartilage. Highly expressed Ob-Rb accelerates chondrocyte senescence by activating the leptin pathway in OA. Cite this article: X. Zhao, P. Huang, G. Li, L. Zhendong, G. Hu, Q. Xu. Activation of the leptin pathway by high expression of the long form of the leptin receptor (Ob-Rb) accelerates chondrocyte senescence in osteoarthritis. Bone Joint Res 2019;8:425–436. DOI: 10.1302/2046-3758.89.BJR-2018-0325.R2

Objectives. Osteoporosis is a systemic bone metabolic disease, which often occurs among the elderly. Angelica polysaccharide (AP) is the main component of angelica sinensis, and is widely used for treating various diseases. However, the effects of AP on osteoporosis have not been investigated. This study aimed to uncover the functions of AP in mesenchymal stem cell (MSC) proliferation and osteoblast differentiation. Methods. MSCs were treated with different concentrations of AP, and then cell viability, Cyclin D1 protein level, and the osteogenic markers of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2) were examined by Cell Counting Kit-8 (CCK-8) and western blot assays, respectively. The effect of AP on the main signalling pathways of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/β-catenin was determined by western blot. Following this, si-H19#1 and si-H19#2 were transfected into MSCs, and the effects of H19 on cell proliferation and osteoblast differentiation in MSCs were studied. Finally, in vivo experimentation explored bone mineral density, bone mineral content, and the ash weight and dry weight of femoral bone. Results. The results revealed that AP significantly promoted cell viability, upregulated cyclin D1 and increased RUNX2, OCN, ALP, and BMP-2 protein levels in MSCs. Moreover, we found that AP notably activated PI3K/AKT and Wnt/β-catenin signalling pathways in MSCs. Additionally, the relative expression level of H19 was upregulated by AP in a dose-dependent manner. The promoting effects of AP on cell proliferation and osteoblast differentiation were reversed by H19 knockdown. Moreover, in vivo experimentation further confirmed the promoting effect of AP on bone formation. Conclusion. These data indicate that AP could promote MSC proliferation and osteoblast differentiation by regulating H19. Cite this article: X. Xie, M. Liu, Q. Meng. Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study. Bone Joint Res 2019;8:323–332. DOI: 10.1302/2046-3758.87.BJR-2018-0223.R2

Objectives. The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods. The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results. In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion. This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients. Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290–303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1

Only limited data are available regarding the infiltration of local anaesthetic for total hip arthroplasty (THA), and no studies were performed for THA using the anterior approach. . In this prospective, randomised placebo-controlled study we investigated the effect of both standard and reverse infiltration of local anaesthetic in combination with the anterior approach for THA. The primary endpoint was the mean numeric rating score for pain four hours post-operatively. In addition, we recorded the length of hospital stay, the operating time, the destination of the patient at discharge, the use of pain medication, the occurrence of side effects and pain scores at various times post-operatively. Between November 2012 and January 2014, 75 patients were included in the study. They were randomised into three groups: standard infiltration of local anaesthetic, reversed infiltration of local anaesthetic, and placebo. There was no difference in mean numeric rating score for pain four hours post-operatively (p = 0.87). There were significantly more side effects at one and eight hours post-operatively in the placebo group (p = 0.02; p = 0.03), but this did not influence the mobilisation of the patients. There were no differences in all other outcomes between the groups. We found no clinically relevant effect when the infiltration of local anaesthetic with ropivacaine and epinephrine was used in a multimodal pain protocol for THA using the anterior approach. Cite this article: Bone Joint J 2015; 97-B:734–40

Aims. To investigate the effect of polyethylene manufacturing characteristics and irradiation dose on the survival of cemented and reverse hybrid total hip arthroplasties (THAs). Methods. In this registry study, data from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man (NJR) were linked with manufacturing data supplied by manufacturers. The primary endpoint was revision of any component. Cox proportional hazard regression was a primary analytic approach adjusting for competing risk of death, patient characteristics, head composition, and stem fixation. Results. A total of 290,770 primary THAs were successfully linked with manufacturing characteristics. Overall 4,708 revisions were analyzed, 1,260 of which were due to aseptic loosening. Total radiation dose was identified as a risk factor and included in the Cox model. For statistical modelling of aseptic loosening, THAs were grouped into three categories: G1 (no radiation); G2 ( > 0 to < 5 Mrad); and G3 ( ≥ 5 Mrad). G1 had the worst survivorship. The Cox regression hazard ratio for revision due to aseptic loosening for G2 was 0.7 (95% confidence interval (CI) 0.58 to 0.83), and for G3 0.4 (95% CI 0.30 to 0.53). Male sex and uncemented stem fixation were associated with higher risk of revision and ceramic heads with lower risk. Conclusion. Polyethylene irradiation was associated with reduced risk of revision for aseptic loosening. Radiation doses of ≥ 5 Mrad were associated with a further reduction in risk. Cite this article: Bone Joint Res 2020;9(9):563–571

Objectives. The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results. A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion. Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1

Aims. The number of rotator cuff repairs that are undertaken is increasing. Reverse shoulder arthroplasty (RSA) is the procedure of choice for patients with rotator cuff arthropathy. We sought to determine whether patients who underwent rotator cuff repair and subsequent RSA had different outcomes compared with a matched control group who underwent RSA without a previous rotator cuff repair. Patients and Methods. All patients with a history of rotator cuff repair who underwent RSA between 2000 and 2015 with a minimum follow-up of two years were eligible for inclusion as the study group. Outcomes, including the American Shoulder and Elbow Surgeons (ASES) scores, were compared with a matched control group of patients who underwent RSA without having previously undergone rotator cuff repair. Results. The study group included 45 patients. Their mean age was 69 years (. sd. 8.6) and 27 patients (60%) were women. The mean ASES score improved from 43.1 to 76.6 two years postoperatively, and to 66.9 five years postoperatively. There was no significant difference between the outcomes at two years in the two groups (all p ≥ 0.05), although there was significantly more improvement in ASES scores in the control group (44.5 vs 33.4; p = 0.01). However, there was no significant difference between ASES scores at two and five years when baseline ASES scores were matched in the two groups (p = 0.42 at two years; p = 0.35 at five years). Conclusion. Significant improvements in ASES scores were seen following RSA in patients who had previously undergone rotator cuff repair. They had higher baseline ASES scores than those who had not previously undergone this surgery. However, there was no significant difference in outcomes between the two groups, two years postoperatively. Previous rotator cuff repair does not appear to affect the early outcome after RSA adversely

Aims. Heterotopic ossification (HO) occurs after arthroplasty, especially total hip arthroplasty. In this study we describe the incidence, evolution, morphology and clinical consequences of HO following reverse shoulder arthroplasty. Patients and Methods. This is a single-centre retrospective study of 132 consecutive patients who received a Delta III or Delta Xtend reverse total shoulder arthroplasty between 2006 and 2013 for the treatment of cuff tear arthropathy. There were 96 women and 36 men. Their mean age at the time of surgery was 69 years (49 to 89) and the mean follow-up was 36 months (12 to 84). The incidence, evolution, morphology and clinical consequences of HO using the Constant-Murley score (CS) were analysed. A modified Brooker classification of HO of the hip was used. Results. HO was seen in 39 patients (29.5%). A total of 31 of these patients (81.6%) began to develop HO by three months post-operatively. According to the Hamada classification, 11 patients had grade 1a, eight had grade 1b, six had grade 1c and 14 had grade 2 HO. The HO evolved over a mean of 8.3 months (3 to 21). Patients with HO had a lower mean CS at three (p = 0.017), six (p < 0.001) and 12 months (p < 0.001) post-operatively. HO was not associated with notching (p = 0.675). Conclusion. HO after reverse shoulder arthroplasty is a non-progressive condition without long-term clinical consequences. Only grade 2 HO is clinically relevant with a negative effect on the function of the shoulder during its development. Cite this article: Bone Joint J 2016;98-B:1215–21

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.

Aims

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

Aims

Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders.

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To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis.