Aims. Hereditary haemochromatosis is a genetic disorder that is caused by several known mutations in the human homeostatic iron regulator protein (HFE) gene. Abnormal accumulation of iron causes a joint disease that resembles osteoarthritis (OA), but appears at a relatively younger age and is accompanied by cirrhosis, diabetes, and injury to other organs. Increased serum transferrin saturation and ferritin levels are known markers of haemochromatosis with high positive predictive values. Methods. We have retrospectively analyzed the iron studies of a cohort of 2,035 patients undergoing knee joint arthroplasty due to OA. Results. No patients had HFE gene C282Y, S65C, or H63D mutations testing. In total, 18 patients (2.96%) of the male cohort and 51 (3.58%) of the female cohort had pathologically increased ferritin levels that may be indicative of haemochromatosis. Seven patients (0.34%) had serum transferrin saturation above 45%. Conclusion. The awareness for the diagnosis of this disorder in Orthopaedics is low and needs improvement. Osteoarthritic patients undergoing knee arthroplasty should be routinely screened for haemochromatosis by iron studies and referred to genetic testing when needed. Level of evidence: Level III - Retrospective cohort study. Cite this article: Bone Jt Open 2021;2(12):1062–1066

Aims. Vertebral body tethering (VBT) is a non-fusion technique to correct scoliosis. It allows correction of scoliosis through growth modulation (GM) by tethering the convex side to allow concave unrestricted growth similar to the hemiepiphysiodesis concept. The other modality is anterior scoliosis correction (ASC) where the tether is able to perform most of the correction immediately where limited growth is expected. Methods. We conducted a retrospective analysis of clinical and radiological data of 20 patients aged between 9 and 17 years old, (with a 19 female: 1 male ratio) between January 2014 to December 2016 with a mean five-year follow-up (4 to 7). Results. There were ten patients in each group with a total of 23 curves operated on. VBT-GM mean age was 12.5 years (9 to 14) with a mean Risser classification of 0.63 (0 to 2) and VBT-ASC was 14.9 years (13 to 17) with a mean Risser classification of 3.66 (3 to 5). Mean preoperative VBT-GM Cobb was 47.4° (40° to 58°) with a Fulcrum unbend of 17.4 (1° to 41°), compared to VBT-ASC 56.5° (40° to 79°) with 30.6 (2° to 69°)unbend. Postoperative VBT-GM was 20.3° and VBT-ASC Cobb angle was 11.2°. The early postoperative correction rate was 54.3% versus 81% whereas Fulcrum Bending Correction Index (FBCI) was 93.1% vs 146.6%. The last Cobb angle on radiograph at mean five years’ follow-up was 19.4° (VBT-GM) and 16.5° (VBT-ASC). Patients with open triradiate cartilage (TRC) had three over-corrections. Overall, 5% of patients required fusion. This one patient alone had a over-correction, a second-stage tether release, and final conversion to fusion. Conclusion. We show a high success rate (95%) in helping children avoid fusion at five years post-surgery. VBT is a safe technique for correction of scoliosis in the skeletally immature patient. This is the first report at five years that shows two methods of VBT can be employed depending on the skeletal maturity of the patient: GM and ASC. Cite this article: Bone Jt Open 2022;3(2):123–129

Aims. The Exeter V40 cemented polished tapered stem system has demonstrated excellent long-term outcomes. This paper presents a systematic review of the existing literature and reports on a large case series comparing implant fractures between the Exeter V40 series; 125 mm and conventional length stem systems. Methods. A systematic literature search was performed adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. In parallel, we performed a retrospective single centre study of Exeter V40 femoral stem prosthetic fractures between April 2003 and June 2020. Results. There are 25 reported cases of such prosthetic fractures confined to small case series and case reports within the literature. We report an additional 19 cases to the literature (mean age 66.3 years (SD 11.7); 12 (63%) females; BMI 32.9 kg/m. 2. (SD 5.9)). The mean time from index procedure to fracture was 7.8 years (SD 3.6; 2.5 to 16.3). Exeter V40 stem fracture incidence was 0.15% and 1.21% for primary and revision arthroplasty, respectively. Incidence was significantly higher in revision arthroplasty (p < 0.001) and 125 mm length stems compared to ≥ 150 mm length stems (1.25% vs 0.13%, respectively; p < 0.001). When comparing different stem length cohorts, 125 mm short-stems were associated with stem-body fractures (92% vs 29%; p = 0.0095), earlier time to fracture (6.2 years vs 11.0 years; p = 0.0018), younger patient age at time of fracture (62.7 years vs 72.6 years; p = 0.037), and female sex (75% vs 43%; p = 0.326). Conclusion. This complication remains rare, although we report a significantly higher incidence at up to 17 years follow-up than in the literature. Short 125 mm length Exeter V40 stems undoubtedly have a role in restoring anatomy and biomechanics in smaller femoral geometries, although the surgeon has to appreciate the higher risk of stem fracture and the associated predisposing factors which may necessitate particular attention to surgical technique and planning. Cite this article: Bone Jt Open 2021;2(6):443–456

Aims. To establish the survivorship, function, and metal ion levels in an unselected series of metal-on-metal hip resurfacing arthroplasties (HRAs) performed by a non-designer surgeon. Methods. We reviewed 105 consecutive HRAs in 83 patients, performed by a single surgeon, at a mean follow-up of 14.9 years (9.3 to 19.1). The cohort included 45 male and 38 female patients, with a mean age of 49.5 years (SD 12.5). Results. At the time of review 13 patients with 15 hips had died from causes unrelated to the hip operation, and 14 hips had undergone revision surgery, giving an overall survival rate of rate of 86.7% (95% confidence interval (CI) 84.2 to 89.1). The survival rate in men was 97.7% (95% CI 96.3 to 98.9) and in women was 73.4% (95% CI 70.6 to 75.1). The median head size of the failed group was 42 mm (interquartile range (IQR) 42 to 44), and in the surviving group was 50 mm (IQR 46 to 50). In all, 13 of the 14 revised hips had a femoral component measuring ≤ 46 mm. The mean blood levels of cobalt and chromium ions were 26.6 nmol/l (SD 24.5) and 30.6 nmol/l (SD 15.3), respectively. No metal ion levels exceeded the safe limit. The mean Oxford Hip Score was 41.5 (SD 8.9) and Harris Hip Score was 89.9 (14.8). In the surviving group, four patients had radiolucent lines around the stem of the femoral component, and one had lysis around the acetabular component; eight hips demonstrated heterotopic ossification. Conclusion. Our results confirm the existing understanding that HRA provides good long-term survival and function in patients with adequate-sized femoral heads. This is evidenced by a 97.7% survival rate among men (larger heads) in our series at a mean follow-up of 14.9 years. Failure is closely related to head sizes ≤ 46 cm. Cite this article: Bone Jt Open 2022;3(1):68–76

Aims. While preoperative bloodwork is routinely ordered, its value in determining which patients are at risk of postoperative readmission following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is unclear. The objective of this study was to determine which routinely ordered preoperative blood markers have the strongest association with acute hospital readmission for patients undergoing elective TKA and THA. Methods. Two population-based retrospective cohorts were assembled for all adult primary elective TKA (n = 137,969) and THA (n = 78,532) patients between 2011 to 2018 across 678 North American hospitals using the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) registry. Six routinely ordered preoperative blood markers - albumin, haematocrit, platelet count, white blood cell count (WBC), estimated glomerular filtration rate (eGFR), and sodium level - were queried. The association between preoperative blood marker values and all-cause readmission within 30 days of surgery was compared using univariable analysis and multivariable logistic regression adjusted for relevant patient and treatment factors. Results. The mean TKA age was 66.6 years (SD 9.6) with 62% being females (n = 85,163/137,969), while in the THA cohort the mean age was 64.7 years (SD 11.4) with 54% being female (n = 42,637/78,532). In both cohorts, preoperative hypoalbuminemia (< 35 g/l) was associated with a 1.5- and 1.8-times increased odds of 30-day readmission following TKA and THA, respectively. In TKA patients, decreased eGFR demonstrated the strongest association with acute readmission with a standardized odds ratio of 0.75 per two standard deviations increase (p < 0.0001). Conclusion. In this population level cohort analysis of arthroplasty patients, low albumin demonstrated the strongest association with acute readmission in comparison to five other commonly ordered preoperative blood markers. Identification and optimization of preoperative hypoalbuminemia could help healthcare providers recognize and address at-risk patients undergoing TKA and THA. This is the most comprehensive and rigorous examination of the association between preoperative blood markers and readmission for TKA and THA patients to date. Cite this article: Bone Jt Open 2021;2(6):388–396

Aims. The aim of this prospective study was to assess the long-term clinical, radiological, functional, and quality of life (QoL)-related outcome of patients treated with the synthetic Ligament Advanced Reinforcement System (LARS) device for anterior cruciate ligament (ACL) rupture. Methods. A total of 41 patients who underwent ACL reconstruction with the LARS device (mean age 39.8 years (SD 12.1 ); 32% females (n = 13)) were prospectively included between August 2001 and March 2005. MRI scans and radiographs were performed at a median follow-up of 2.0 years (interquartile range (IQR) 1.3 to 3.0; n = 40) and 12.8 years (IQR 12.1 to 13.8; n = 22). Functional and QoL-related outcome was assessed in 29 patients at a median follow-up of 12.8 years (IQR 12.0 to 14.0) and clinically reconfirmed at latest median follow-up of 16.5 years (IQR 15.5 to 17.9). International Knee Documentation Committee (IKDC) and Tegner scores were obtained pre- and postoperatively, and Lysholm score postoperatively only. At latest follow-up, range of motion, knee stability tests, 36-Item Short Form Health Survey (SF-36), and IKDC scores were ascertained. Complications and reoperations during follow-up were documented. Results. Cumulative complication rate was 66% (n = 27), with 11 developing within one year from surgery and 16 after one year (including five patients with both early and late complications). Ten graft failures (24%) and eight cases of reactive synovitis were observed (20%). All 11 patients with early complications and ten with late complications underwent reoperation (including five with another surgical procedure for early complications), amounting to a cumulative reoperation rate of 51% (n = 21). Revision ACL reconstruction was performed in one patient (2.4%). Median IKDC at latest follow-up was 89.7 (IQR 78.2 to 93.1), being significantly worse in the event of previous complications. Lachman test was positive in 56% (n = 15) of reconstructed knees. All norm-based SF-36 items were at or above median at latest follow-up, and did not differ depending on development of complications. Conclusion. Despite good functional and QoL-related results in the long term, the cumulative complication rate of 66%, including graft failures and reactive synovitis, has to be viewed with great concern. Cite this article: Bone Joint J 2022;104-B(2):242–248

Aims. Golf is a popular pursuit among those requiring total hip arthroplasty (THA). The aim of this study was to determine if participating in golf is associated with greater functional outcomes, satisfaction, or improvement in quality of life (QoL) compared to non-golfers. Methods. All patients undergoing primary THA over a one-year period at a single institution were included with one-year postoperative outcomes. Patients were retrospectively followed up to assess if they had been golfers at the time of their surgery. Multivariate linear regression analysis was performed to assess the independent association of preoperative golfing status on outcomes. Results. The study cohort consisted of a total of 308 patients undergoing THA, of whom 44 were golfers (14%). This included 120 male patients (39%) and 188 female patients (61%), with an overall mean age of 67.8 years (SD 11.6). Golfers had a greater mean postoperative Oxford Hip Score (OHS) (3.7 (95% confidence interval (CI) 1.9 to 5.5); p < 0.001) and EuroQol visual analogue scale (5.5 (95% CI 0.1 to 11.9); p = 0.039). However, there were no differences in EuroQoL five-dimension score (p = 0.124), pain visual analogue scale (p = 0.505), or Forgotten Joint Score (p = 0.215). When adjusting for confounders, golfers had a greater improvement in their Oxford Hip Score (2.7 (95% CI 0.2 to 5.3); p < 0.001) compared to non-golfers. Of the 44 patients who reported being golfers at the time of their surgery, 32 (72.7%) returned to golf and 84.4% of those were satisfied with their involvement in golf following surgery. Those who returned to golf were more likely to be male (p = 0.039) and had higher (better) preoperative health-related QoL (p = 0.040) and hip-related functional scores (p = 0.026). Conclusion. Golfers had a greater improvement in their hip-specific function compared to non-golfers after THA. However, less than three-quarters of patients return to golf, with male patients and those who had greater preoperative QoL or hip-related function being more likely to return to play. Cite this article: Bone Jt Open 2022;3(2):145–151

Aims. Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA. Methods. We retrospectively identified 256 THAs in 244 patients following septic arthritis of the native hip, which were undertaken between 1969 and 2016 at a single institution. Each case was matched 1:1, based on age, sex, BMI, and year of surgery, to a primary THA performed for OA. The mean age and BMI were 58 years (35 to 84) and 31 kg/m. 2. (18 to 48), respectively, and 100 (39%) were female. The mean follow-up was 11 years (2 to 39). Results. The ten-year survival free of any infection was 91% and 99% in the septic arthritis and OA groups, respectively (hazard ratio (HR) = 13; p < 0.001). The survival free of PJI at ten years was 93% and 99% in the septic arthritis and OA groups, respectively (HR = 10; p = 0.002). There was a significantly higher rate of any infection at ten years when THA was undertaken within five years of the diagnosis of septic arthritis compared with those in whom THA was undertaken > five years after this diagnosis was made (14% vs 5%, respectively; HR = 3.1; p = 0.009), but there was no significant difference in ten-year survival free of aseptic revision (HR = 1.14; p = 0.485). The mean Harris Hip Scores at two and five years postoperatively were significantly lower in the septic arthritis group compared with the OA group (p = 0.001 for both). Conclusion. There was a ten-fold increased risk of PJI in patients with a history of septic arthritis who underwent THA compared with those who underwent THA for OA with a ten-year cumulative incidence of 7%. The risk of any infection had a strong downward trend as the time interval between the diagnosis of septic arthritis and THA increased, highlighted by a 3.1-fold higher risk when THAs were performed within five years of the diagnosis being made. Cite this article: Bone Joint J 2022;104-B(2):227–234

Aims. Open reduction and plate fixation (ORPF) for displaced proximal humerus fractures can achieve reliably good long-term outcomes. However, a minority of patients have persistent pain and stiffness after surgery and may benefit from open arthrolysis, subacromial decompression, and removal of metalwork (ADROM). The long-term results of ADROM remain unknown; we aimed to assess outcomes of patients undergoing this procedure for stiffness following ORPF, and assess predictors of poor outcome. Methods. Between 1998 and 2018, 424 consecutive patients were treated with primary ORPF for proximal humerus fracture. ADROM was offered to symptomatic patients with a healed fracture at six months postoperatively. Patients were followed up retrospectively with demographic data, fracture characteristics, and complications recorded. Active range of motion (aROM), Oxford Shoulder Score (OSS), and EuroQol five-dimension three-level questionnaire (EQ-5D-3L) were recorded preoperatively and postoperatively. Results. A total of 138 patients underwent ADROM; 111 patients were available for long-term follow-up at a mean of 10.9 years (range 1 to 20). Mean age was 50.8 years (18 to 75);79 (57.2%) were female. Mean time from primary ORPF to ADROM was 11.9 months (6 to 19). Five patients developed superficial wound infection; ten developed symptomatic osteonecrosis/post-traumatic arthrosis (ON/PTA); four underwent revision arthrolysis. Median OSS improved from 17 (interquartile range (IQR) 12.0 to 22.0) preoperatively to 40.0 (IQR 31.5 to 48.0) postoperatively, and 39.0 (IQR 31.5 to 46.5) at long-term follow-up (p < 0.001). Median EQ-5D-3L improved from 0.079 (IQR -0.057 to 0.215) to 0.691 (IQR 0.441 to 0.941) postoperatively, and 0.701 (IQR 0.570 to 0.832) at long-term follow-up (p < 0.001). We found that aROM improved in all planes (p < 0.001). Among the variables assessed on multivariable analysis, a manual occupation, worsening Charlson Comorbidity Index and increasing socioeconomic deprivation were most consistently predictive of worse patient-reported outcome scores. Patients who subsequently developed ON/PTA reported significantly worse one-year and late OSS. Conclusion. ADROM in patients with persistent symptomatic stiffness following ORPF can achieve excellent short- and long-term outcomes. More deprived patients, those in a manual occupation, and those with worsening comorbidities have worse outcomes following ADROM. Cite this article: Bone Joint J 2022;104-B(1):157–167

Aims. The outcome following the development of neurological complications after corrective surgery for scoliosis varies from full recovery to a permanent deficit. This study aimed to assess the prognosis and recovery of major neurological deficits in these patients, and to determine the risk factors for non-recovery, at a minimum follow-up of two years. Methods. A major neurological deficit was identified in 65 of 8,870 patients who underwent corrective surgery for scoliosis, including eight with complete paraplegia and 57 with incomplete paraplegia. There were 23 male and 42 female patients. Their mean age was 25.0 years (SD 16.3). The aetiology of the scoliosis was idiopathic (n = 6), congenital (n = 23), neuromuscular (n = 11), neurofibromatosis type 1 (n = 6), and others (n = 19). Neurological function was determined by the American Spinal Injury Association (ASIA) impairment scale at a mean follow-up of 45.4 months (SD 17.2). the patients were divided into those with recovery and those with no recovery according to the ASIA scale during follow-up. Results. The incidence of major deficit was 0.73%. At six-month follow-up, 39 patients (60%) had complete recovery and ten (15.4%) had incomplete recovery; these percentages improved to 70.8% (46) and 16.9% (11) at follow-up of two years, respectively. Eight patients showed no recovery at the final follow-up. The cause of injury was mechanical in 39 patients and ischaemic in five. For 11 patients with misplaced implants and haematoma formation, nine had complete recovery. Fisher’s exact test showed a significant difference in the aetiology of the scoliosis (p = 0.007) and preoperative deficit (p = 0.016) between the recovery and non-recovery groups. A preoperative deficit was found to be significantly associated with non-recovery (odds ratio 8.5 (95% confidence interval 1.676 to 43.109); p = 0.010) in a multivariate regression model. Conclusion. For patients with scoliosis who develop a major neurological deficit after corrective surgery, recovery (complete and incomplete) can be expected in 87.7%. The first three to six months is the time window for recovery. In patients with misplaced implants and haematoma formation, the prognosis is satisfactory with appropriate early intervention. Patients with a preoperative neurological deficit are at a significant risk of having a permanent deficit. Cite this article: Bone Joint J 2022;104-B(1):103–111

Aims. Healthcare systems have been rapidly restructured to meet COVID-19 demand. Clinicians are working to novel clinical guidelines, treating new patient cohorts and working in unfamiliar environments. Trauma and orthopaedics (T&O) has experienced cancellation of routine clinics and operating, with redistribution of the workload and human resources. To date, no studies have evaluated the mental health impact of these changes on the T&O workforce. We report the results of a novel survey on the impact of the pandemic on the mental health of our orthopaedic workforce and the contributory factors. Methods. A 20-question survey-based cross-sectional study of orthopaedic team members was conducted during the COVID-19 pandemic. The primary objective was to identify the impact of the pandemic on mental health in the form of major depressive disorder (MDD) and general anxiety disorder (GAD). The survey incorporated the patient health questionnaire (PHQ-2), which is validated for screening of MDD, and the generalized anxiety disorder questionnaire (GAD-2), which is validated for screening of GAD. Results. There were 62 respondents (18 females and 44 males). As compared to the general population, we noted a greater estimated prevalence of GAD (17.7% vs 5.9%, p = 0.0009297) and MDD (19.4% vs 3.3%, p = 0.0000007731). The prevalence of MDD symptoms was greatest among senior house officers (SHOs) (p = 0.02216). Female respondents scored higher for symptoms of MDD (p = 0.03583) and GAD (p = 0.0001086). Those identifying as ‘Black, African, Caribbean or Black British’ displayed a higher prevalence of GAD symptoms (p = 0.001575) and felt least supported at work (p = 0.001341). Conclusion. Our study, in the first of its kind, shows a significant prevalence of GAD and MDD in the workforce. We found that SHOs, females and those of Black, African, Caribbean, or Black British origin were disproportionately affected. Action should be taken to help prevent adverse mental health outcomes for our colleagues during the pandemic. Cite this article: Bone Joint Open 2020;1-6:316–325

Aims. The aims of the study were to analyze differences in surgical and oncological outcomes, as well as quality of life (QoL) and function in patients with ankle sarcomas undergoing three forms of surgical treatment, minor or major limb salvage surgery (LSS), or amputation. Methods. A total of 69 patients with ankle sarcomas, treated between 1981 and 2017 at two tumour centres, were retrospectively reviewed (mean age at surgery: 46.3 years (SD 22.0); 31 females (45%)). Among these 69 patients 25 were analyzed prospectively (mean age at latest follow-up: 61.2 years (SD 20.7); 11 females (44%)), and assessed for mobility using the Prosthetic Limb Users Survey of Mobility (PLUS-M; for amputees only), the Toronto Extremity Salvage Score (TESS), and the University of California, Los Angeles (UCLA) Activity Score. Individual QoL was evaluated in these 25 patients using the five-level EuroQol five-dimension (EQ-5D-5L) and Fragebogen zur Lebenszufriedenheit/Questions on Life Satisfaction (FLZ). Results. Of the total number of patients in the study, 22 (32%) underwent minor LSS and 22 (32%) underwent major LSS; 25 underwent primary amputation (36%). Complications developed in 26 (38%) patients, and were more common in those with major or minor LSS in comparison to amputation (59% vs 36% vs 20%; p = 0.022). A time-dependent trend towards higher complication risk following any LSS was present (relative risk: 0.204; 95% confidence interval (CI) 0.026 to 1.614; p = 0.095). In the prospective cohort, mean TESS was higher following minor LSS in comparison to amputation (91.0 vs 67.3; p = 0.006), while there was no statistically significant difference between major LSS and amputation (81.6 vs 67.3; p = 0.099). There was no difference in mean UCLA (p = 0.334) between the three groups (p = 0.334). None of the items in FLZ or EQ-5D-5L were different between the three groups (all p > 0.05), except for FLZ item “self-relation”, being lower in amputees. Conclusion. Complications are common following LSS for ankle sarcomas. QoL is comparable between patients with LSS or amputation, despite better mobility scores for patients following minor LSS. We conclude that these results allow a decision for amputation to be made more easily in patients particularly where the principles of oncological surgery would otherwise be at risk. Cite this article: Bone Joint J 2021;103-B(3):553–561

Aims. Gender bias and sexual discrimination (GBSD) have been widely recognized across a range of fields and are now part of the wider social consciousness. Such conduct can occur in the medical workplace, with detrimental effects on recipients. The aim of this review was to identify the prevalence and impact of GBSD in orthopaedic surgery, and to investigate interventions countering such behaviours. Methods. A systematic review was conducted by searching Medline, EMCARE, CINAHL, PsycINFO, and the Cochrane Library Database in April 2020, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to which we adhered. Original research papers pertaining to the prevalence and impact of GBSD, or mitigating strategies, within orthopaedics were included for review. Results. Of 570 papers, 27 were eligible for inclusion. These were published between 1998 and 2020. A narrative review was performed in light of the significant heterogeneity displayed by the eligible studies. A total of 13 papers discussed the prevalence of GBSD, while 13 related to the impact of these behaviours, and six discussed mitigating strategies. GBSD was found to be common in the orthopaedic workplace, with all sources showing women to be the subjects. The impact of this includes poor workforce representation, lower salaries, and less career success, including in academia, for women in orthopaedics. Mitigating strategies in the literature are focused on providing female role models, mentors, and educational interventions. Conclusion. GBSD is common in orthopaedic surgery, with a substantial impact on sufferers. A small number of mitigating strategies have been tested but these are limited in their scope. As such, the orthopaedic community is obliged to participate in more thoughtful and proactive strategies that mitigate against GBSD, by improving female recruitment and retention within the specialty. Cite this article: Bone Joint J 2020;102-B(11):1446–1456

Aims. The aim of this study was to assess the prognostic value of the modified three-group Stulberg classification, which is based on the sphericity of the femoral head, in patients with Perthes’ disease. Methods. A total of 88 patients were followed from the time of diagnosis until a mean follow-up of 21 years. Anteroposterior pelvic and frog-leg lateral radiographs were obtained at diagnosis and at follow-up of one, five, and 21 years. At the five- and 21-year follow-up, the femoral heads were classified using a modified three-group Stulberg classification (round, ovoid, or flat femoral head). Further radiological endpoints at long-term follow-up were osteoarthritis (OA) of the hip and the requirement for total hip arthroplasty (THA). Results. There were 71 males (81%) and 17 females. A total of 13 patients had bilateral Perthes’ disease; thus 101 hips were analyzed. At five-year follow-up, 37 hips were round, 38 ovoid, and 26 flat. At that time, 66 hips (65%) were healed and 91 (90%) were skeletally immature. At long-term follow-up, when the mean age of the patients was 28 years (24 to 34), 20 hips had an unsatisfactory outcome (seven had OA and 13 had required THA). There was a strongly significant association between the modified Stulberg classification applied atfive-year follow-up and an unsatisfactory outcome at long-term follow-up (p < 0.001). Between the five- and 21-year follow-up, 67 hips (76%) stayed in their respective modified Stulberg group, indicating a strongly significant association between the Stulberg classifications at these follow-ups (p < 0.001). Conclusion. The modified Stulberg classification is a strong predictor of long-term radiological outcome in patients with Perthes’ disease. It can be applied at the healing stage, which is usually reached five years after the diagnosis is made and before skeletal maturity. Cite this article: Bone Joint J 2021;103-B(12):1815–1820

Aims. As the first wave of the COVID-19 pandemic began to dip, restarting elective orthopaedics became a challenge. Protocols including surgery at ‘green’ sites, self-isolation for 14 days, and COVID-19 testing were developed to minimize the risk of transmission. In this study, we look at risk effects of 14-day self-isolation on the incidence of venous thromboembolism (VTE) in our green site hospital among patients undergoing total joint replacement (TJR). Methods. This retrospective cohort study included 50 patients who underwent TJR. Basic demographic data was collected including, age, sex, American Society of Anesthesiologists (ASA) grade, body mass index (BMI), type of surgery, and complications at two and four weeks. Univariate and multivariate analysis were used to identify risk factors associated with an increased risk of VTE. Results. A total of 50 patients were included in our study, with 24 males and 26 females. The mean age was 67.86 (SD 11.803). Overall, 8% of patients suffered a VTE complication; symptomatic non-fatal pulmoary embolism was confirmed in 6% of patients (n = 3) as an inpatient, and symptomatic deep vein thrombosis was diagnosed in 2% of patients (n = 1) within two weeks of their operation. All patients were found to be female (p < 0.001), had a BMI > 30 (p = 0.317), and were immobile prior to their operation using walking aids (p = 0.016). Conclusion. The incidence we report is much higher than the reported incidence in the literature, which we believe is related to the 14-day self-isolation period and immobility prior to their operation. We recommend that all patients undergoing TJR that require a period of self-isolation, are pre-assessed prior to self-isolation for their risk of VTE, potentially using mechanical and chemical prophylaxis to reduce the likelihood of developing VTE. Cite this article: Bone Jt Open 2020;1-12:751–756

Aims. The aim of this study was to surveil whether the standard operating procedure created for the NHS Golden Jubilee sufficiently managed COVID-19 risk to allow safe resumption of elective orthopaedic surgery. Methods. This was a prospective study of all elective orthopaedic patients within an elective unit running a green pathway at a COVID-19 light site. Rates of preoperative and 30-day postoperative COVID-19 symptoms or infection were examined for a period of 40 weeks. The unit resumed elective orthopaedic services on 29 June 2020 at a reduced capacity for a limited number of day-case procedures with strict patient selection criteria, increasing to full service on 29 August 2020 with no patient selection criteria. Results. A total of 2,373 cases were planned in the 40-week study period. Surgery was cancelled in 59 cases, six (10.2%) of which were due to having a positive preoperative COVID-19 screening test result. Of the remaining 2,314, 996 (43%) were male and 1,318 (57%) were female. The median age was 67 years (interquartile range 59.2 to 74.6). The median American Society of Anesthesiologists grade was 2. Hip and knee arthroplasties accounted for the majority of the operations (76%). Six patients tested positive for COVID-19 preoperatively (0.25%) and 39 patients were tested for COVID-19 within 30 days after discharge, with only five patients testing positive (0.22%). Conclusion. Through strict application of a COVID-19 green pathway, elective orthopaedic surgery could be safely delivered to a large number of patients with no selection criteria. Cite this article: Bone Jt Open 2021;2(11):951–957

Objectives. Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male versus female cocultures. Methods. A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion. Results. We found that 96 hours of M1 phenotype in male cocultures allowed for maximum matrix mineralization versus 72 hours in female cocultures. ALP activity and osteocalcin secretion were also enhanced with the addition of IL-4 later in male versus female groups. The sex of the cells had a statistically significant effect on the optimal IL-4 addition time to maximize osteogenesis. Conclusion. These results suggest that: 1) a 72- to 96-hour proinflammatory environment is critical for optimal matrix mineralization; and 2) there are immunological differences in this coculture environment due to sex. Optimizing immunomodulation during fracture healing may enhance and expedite the bone regeneration response. These findings provide insight into precise immunomodulation for enhanced bone healing that is sex-specific. Cite this article: K. Nathan, L. Y. Lu, T. Lin, J. Pajarinen, E. Jämsen, J-F. Huang, M. Romero-Lopez, M. Maruyama, Y. Kohno, Z. Yao, S. B. Goodman. Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex. Bone Joint Res 2019;8:481–488. DOI: 10.1302/2046-3758.810.BJR-2018-0231.R2

Aims. Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods. OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. Results. Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. Conclusion. Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704–713

Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667

Aims. Periacetabular osteotomy (PAO) is an established treatment for acetabular dysplasia. It has also been proposed as a treatment for patients with acetabular retroversion. By reviewing a large cohort, we aimed to test whether outcome is equivalent for both types of morphology and identify factors that influenced outcome. Methods. A single-centre, retrospective cohort study was performed on patients with acetabular retroversion treated with PAO (n = 62 hips). Acetabular retroversion was diagnosed clinically and radiologically (presence of a crossover sign, posterior wall sign, lateral centre-edge angle (LCEA) between 20° and 35°). Outcomes were compared with a control group of patients undergoing PAO for dysplasia (LCEA < 20°; n = 86 hips). Femoral version was recorded. Patient-reported outcome measures (PROMs), complications, and reoperation rates were measured. Results. The mean Non-Arthritic Hip Score (NAHS) preoperatively was 58.6 (SD 16.1) for the dysplastic hips and 52.5 (SD 12.7) for the retroverted hips (p = 0.145). Postoperatively, mean NAHS was 83.0 (SD 16.9) and 76.7 (SD 17.9) for dysplastic and retroverted hips respectively (p = 0.041). Difference between pre- and postoperative NAHS was slightly lower in the retroverted hips (18.3 (SD 22.1)) compared to the dysplastic hips (25.2 (SD 15.2); p = 0.230). At mean 3.5 years’ follow-up (SD 1.9), one hip needed a revision PAO and no hips were converted to total hip arthroplasty (THA) in the retroversion group. In the control group, six hips (7.0%) were revised to THA. No differences in complications (p = 0.106) or in reoperation rate (p = 0.087) were seen. Negative predictors of outcome for patients undergoing surgery for retroversion were female sex, obesity, hypermobility, and severely decreased femoral anteversion. Conclusion. A PAO is an effective surgical intervention for acetabular retroversion and produces similar improvements when used to treat dysplasia. Femoral version should be routinely assessed in these patients and when extremely low (< 0°), as an additional procedure to address this abnormality may be necessary. Females with signs of hypermobility should also be consulted of the likely guarded improvement. Cite this article: Bone Jt Open 2021;2(9):757–764