Aims. The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA). Methods. Between 2016 and 2019, 363 patients with troublesome pain, defined as a score of ≤ 14 on the Oxford Knee Score pain subscale, three months after TKA from eight UK NHS hospitals, were recruited into the Support and Treatment After Replacement (STAR) clinical trial. Self-reported neuropathic pain and postoperative pain was assessed at three, nine, and 15 months after surgery using the painDETECT and Douleur Neuropathique 4 (DN4) questionnaires collected by postal survey. Results. Symptoms of neuropathic pain were common among patients reporting chronic pain at three months post-TKA, with half reporting neuropathic pain on painDETECT (191/363; 53%) and 74% (267/359) on DN4. Of those with neuropathic pain at three months, half continued to have symptoms over the next 12 months (148/262; 56%), one-quarter had improved (67/262; 26%), and for one-tenth their neuropathic symptoms fluctuated over time (24/262; 9%). However, a subgroup of participants reported new, late onset neuropathic symptoms (23/262; 9%). Prevalence of neuropathic symptoms was similar between the screening tools when the lower cut-off painDETECT score (≥ 13) was applied. Overall, mean neuropathic pain scores improved between three and 15 months after TKA. Conclusion. Neuropathic pain is common in patients with chronic pain at three months after TKA. Although neuropathic symptoms improved over time, up to half continued to report painful neuropathic symptoms at 15 months after TKA. Postoperative care should include screening, assessment, and treatment of neuropathic pain in patients with early chronic postoperative pain after TKA. Cite this article: Bone Joint J 2024;106-B(6):582–588

Aims. This systematic review aims to identify 3D predictors derived from biplanar reconstruction, and to describe current methods for improving curve prediction in patients with mild adolescent idiopathic scoliosis. Methods. A comprehensive search was conducted by three independent investigators on MEDLINE, PubMed, Web of Science, and Cochrane Library. Search terms included “adolescent idiopathic scoliosis”,“3D”, and “progression”. The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool (QUIPS) and Appraisal tool for Cross-Sectional Studies (AXIS), and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. In all, 915 publications were identified, with 377 articles subjected to full-text screening; overall, 31 articles were included. Results. Torsion index (TI) and apical vertebral rotation (AVR) were identified as accurate predictors of curve progression in early visits. Initial TI > 3.7° and AVR > 5.8° were predictive of curve progression. Thoracic hypokyphosis was inconsistently observed in progressive curves with weak evidence. While sagittal wedging was observed in mild curves, there is insufficient evidence for its correlation with curve progression. In curves with initial Cobb angle < 25°, Cobb angle was a poor predictor for future curve progression. Prediction accuracy was improved by incorporating serial reconstructions in stepwise layers. However, a lack of post-hoc analysis was identified in studies involving geometrical models. Conclusion. For patients with mild curves, TI and AVR were identified as predictors of curve progression, with TI > 3.7° and AVR > 5.8° found to be important thresholds. Cobb angle acts as a poor predictor in mild curves, and more investigations are required to assess thoracic kyphosis and wedging as predictors. Cumulative reconstruction of radiographs improves prediction accuracy. Comprehensive analysis between progressive and non-progressive curves is recommended to extract meaningful thresholds for clinical prognostication. Cite this article: Bone Jt Open 2024;5(3):243–251

Aims. The aim of the study was to investigate whether the primary stability of press-fit acetabular components can be improved by altering the impaction procedure. Methods. Three impaction procedures were used to implant acetabular components into human cadaveric acetabula using a powered impaction device. An impaction frequency of 1 Hz until complete component seating served as reference. Overimpaction was simulated by adding ten strokes after complete component seating. High-frequency implantation was performed at 6 Hz. The lever-out moment of the acetabular components was used as measure for primary stability. Permanent bone deformation was assessed by comparison of double micro-CT (µCT) measurements before and after impaction. Acetabular component deformation and impaction forces were recorded, and the extent of bone-implant contact was determined from 3D laser scans. Results. Overimpaction reduced primary acetabular component stability (p = 0.038) but did not significantly increase strain release after implantation (p = 0.117) or plastic deformations (p = 0.193). Higher press-fits were associated with larger polar gaps for the 1 Hz reference impaction (p = 0.002, R. 2. = 0.77), with a similar trend for overimpaction (p = 0.082, R. 2. = 0.31). High-frequency impaction did not significantly increase primary stability (p = 0.170) at lower impaction forces (p = 0.001); it was associated with smaller plastic deformations (p = 0.035, R. 2. = 0.34) and a trend for increased acetabular component relaxation between strokes (p = 0.112). Higher press-fit was not related to larger polar gaps for the 6 Hz impaction (p = 0.346). Conclusion. Overimpaction of press-fit acetabular components should be prevented since additional strokes can be associated with increased bone damage and reduced primary stability as shown in this study. High-frequency impaction at 6 Hz was shown to be beneficial compared with 1 Hz impaction. This benefit has to be confirmed in clinical studies. Cite this article: Bone Joint J 2023;105-B(3):261–268

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article: Bone Joint Res 2020;9(7):368–385

Aims. Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods. A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results. Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion. This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties. Cite this article: Bone Joint J 2024;106-B(3 Supple A):51–58

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

Aims. Pelvic incidence (PI) is a position-independent spinopelvic parameter traditionally used by spinal surgeons to determine spinal alignment. Its relevance to the arthroplasty surgeon in assessing patient risk for total hip arthroplasty (THA) instability preoperatively is unclear. This study was undertaken to investigate the significance of PI relative to other spinopelvic parameter risk factors for instability to help guide its clinical application. Methods. Retrospective analysis was performed of a multicentre THA database of 9,414 patients with preoperative imaging (dynamic spinopelvic radiographs and pelvic CT scans). Several spinopelvic parameter measurements were made by engineers using advanced software including sacral slope (SS), standing anterior pelvic plane tilt (APPT), spinopelvic tilt (SPT), lumbar lordosis (LL), and PI. Lumbar flexion (LF) was determined by change in LL between standing and flexed-seated lateral radiographs. Abnormal pelvic mobility was defined as ∆SPT ≥ 20° between standing and flexed-forward positions. Sagittal spinal deformity (SSD) was defined as PI-LL mismatch > 10°. Results. PI showed a positive correlation with parameters of SS, SPT, and LL (r-value range 0.468 to 0.661). Patients with a higher PI value showed higher degrees of standing LL, likely as a compensatory measure to maintain sagittal spine balance. There was a positive correlation between LL and LF such that patients with less standing LL had decreased LF (r = 0.49). Similarly, there was a positive correlation between increased SSD and decreased LF (r = 0.54). PI in isolation did not show any significant correlation with lumbar (r = 0.04) or pelvic mobility (r = 0.02). The majority of patients (range 89.4% to 94.2%) had normal lumbar and pelvic mobility regardless of the PI value. Conclusion. The PI value alone is not indicative of either spinal or pelvic mobility, and thus in isolation may not be a risk factor for THA instability. Patients with SSD had higher rates of spinopelvic stiffness, which may be the mechanism by which PI relates to THA instability risk, but further clinical studies are required. Cite this article: Bone Joint J 2022;104-B(3):352–358

Aims. Highly polished stems with force-closed design have shown satisfactory clinical results despite being related to relatively high early migration. It has been suggested that the minimal thickness of cement mantles surrounding the femoral stem should be 2 mm to 4 mm to avoid aseptic loosening. The line-to-line cementing technique of the femoral stem, designed to achieve stem press-fit, challenges this opinion. We compared the migration of a highly polished stem with force-closed design by standard and line-to-line cementing to investigate whether differences in early migration of the stems occur in a clinical study. Methods. In this single-blind, randomized controlled, clinical radiostereometric analysis (RSA) study, the migration pattern of the cemented Corail hip stem was compared between line-to-line and standard cementing in 48 arthroplasties. The primary outcome measure was femoral stem migration in terms of rotation and translation around and along with the X-, Y-, and Z- axes measured using model-based RSA at three, 12, and 24 months. A linear mixed-effects model was used for statistical analysis. Results. Results from mixed model analyses revealed a lower mean retroversion for line-to-line (0.72° (95% confidence interval (CI) 0.38° to 1.07°; p < 0.001), but no significant differences in subsidence between the techniques (-0.15 mm (95% CI -0.53 to 0.227; p = 0.429) at 24 months. Radiolucent lines measuring < 2 mm wide were found in three and five arthroplasties cemented by the standard and line-to-line method, respectively. Conclusion. The cemented Corail stem with a force-closed design seems to settle earlier and better with the line-to-line cementing method, although for subsidence the difference was not significant. However, the lower rate of migration into retroversion may reduce the wear and cement deformation, contributing to good long-term fixation and implant survival. Cite this article: Bone Joint J 2022;104-B(1):19–26

Aims. This study sought to estimate the clinical outcomes and describe the nationwide variation in practice, as part of the feasibility workup for a National Institute for Health and Care Excellence (NICE) recommended randomized clinical trial to determine the optimal treatment of torus fractures of the distal radius in children. Methods. Prospective data collection on torus fractures presenting to our emergency department. Patient consent and study information, including a copy of the Wong-Baker Faces pain score, was issued at the first patient contact. An automated text message service recorded pain scores at days 0, 3, 7, 21, and 42 postinjury. A cross-sectional survey of current accident and emergency practice in the UK was also undertaken to gauge current practice following the publication of NICE guidance. Results. In all, 30 patients with a mean age of 8.9 years were enrolled over a six-week period. Of the 150 potential data points, data was captured in 146, making the data 97.3% complete. Pain scores were recorded at day 0 (mean 6.5 (95% confidence interval (CI) 5.7 to 7.3)), day 3 (4.4 (95% CI 3.5 to 5.2)), day 7 (3.0 (95% CI 2.3 to 3.6)), day 21 (1.2 (95% CI 0.7 to 1.7)) and day 42 (0.4 (95% CI 0.1 to 0.7)). Of the 100 units who participated in the nationwide survey, 38% were unaware of any local or national protocols regarding torus fractures, 41% treated torus fractures with cast immobilization, and over 60% of patients had follow-up arranged, both contradictory to national guidelines. Conclusion. We have demonstrated the severity, recovery trajectory, and variation in pain scores among children with torus fractures. We demonstrate excellent follow-up of patient outcomes using text messages. Despite national guidelines, there is significant variation in practice. This data directly informed the development of an ongoing nationwide randomized clinical trial – the FORearm Fracture Recovery in Children Evaluation (FORCE) study

Aims. The follow-up interval of a study represents an important aspect that is frequently mentioned in the title of the manuscript. Authors arbitrarily define whether the follow-up of their study is short-, mid-, or long-term. There is no clear consensus in that regard and definitions show a large range of variation. It was therefore the aim of this study to systematically identify clinical research published in high-impact orthopaedic journals in the last five years and extract follow-up information to deduce corresponding evidence-based definitions of short-, mid-, and long-term follow-up. Methods. A systematic literature search was performed to identify papers published in the six highest ranked orthopaedic journals during the years 2015 to 2019. Follow-up intervals were analyzed. Each article was assigned to a corresponding subspecialty field: sports traumatology, knee arthroplasty and reconstruction, hip-preserving surgery, hip arthroplasty, shoulder and elbow arthroplasty, hand and wrist, foot and ankle, paediatric orthopaedics, orthopaedic trauma, spine, and tumour. Mean follow-up data were tabulated for the corresponding subspecialty fields. Comparison between means was conducted using analysis of variance. Results. Of 16,161 published articles, 590 met the inclusion criteria. Of these, 321 were of level IV evidence, 176 level III, 53 level II, and 40 level I. Considering all included articles, a long-term study published in the included high impact journals had a mean follow-up of 151.6 months, a mid-term study of 63.5 months, and a short-term study of 30.0 months. Conclusion. The results of this study provide evidence-based definitions for orthopaedic follow-up intervals that should provide a citable standard for the planning of clinical studies. A minimum mean follow-up of a short-term study should be 30 months (2.5 years), while a mid-term study should aim for a mean follow-up of 60 months (five years), and a long-term study should aim for a mean of 150 months (12.5 years). Level of Evidence: Level I. Cite this article: Bone Jt Open 2021;2(5):344–350

Aims. This study aims to define a set of core outcomes (COS) to allow consistent reporting in order to compare results and assist in treatment decisions for idiopathic clubfoot. Methods. A list of outcomes will be obtained in a three-stage process from the literature and from key stakeholders (patients, parents, surgeons, and healthcare professionals). Important outcomes for patients and parents will be collected from a group of children with idiopathic clubfoot and their parents through questionnaires and interviews. The outcomes identified during this process will be combined with the list of outcomes previously obtained from a systematic review, with each outcome assigned to one of the five core areas defined by the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT). This stage will be followed by a two round Delphi survey aimed at key stakeholders in the management of idiopathic clubfoot. The final outcomes list obtained will then be discussed in a consensus meeting of representative key stakeholders. Conclusion. The inconsistency in outcomes reporting in studies investigating idiopathic clubfoot has made it difficult to define the success rate of treatments and to compare findings between studies. The development of a COS seeks to define a minimum standard set of outcomes to collect in all future clinical trials for this condition, to facilitate comparisons between studies and to aid decisions in treatment. Cite this article: Bone Jt Open 2021;2(4):255–260

Aims. The aim of this study was to investigate the relationship between the Orthopaedic Trauma Society (OTS) classification of open fractures and economic costs. Methods. Resource use was measured during the six months that followed open fractures of the lower limb in 748 adults recruited as part of two large clinical trials within the UK Major Trauma Research Network. Resource inputs were valued using unit costs drawn from primary and secondary sources. Economic costs (GBP sterling, 2017 to 2018 prices), estimated from both a NHS and Personal Social Services (PSS) perspective, were related to the degree of complexity of the open fracture based on the OTS classification. Results. Adjusted mean total NHS and PSS costs were £13,785 following treatment of complex fractures and £3,550 following treatment of simple fractures, where the open fracture wound is closed at the end of the first wound debridement, generating a mean difference of £10,235 (95% confidence interval £8,074 to £12,396). Conclusion. Following previous work correlating clinical outcomes with the OTS classification of open fractures, this study suggests that the new OTS classification also correlates with economic costs estimated from alternative study perspectives. Cite this article: Bone Joint J 2022;104-B(3):408–412

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Aims. The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR. . Materials and Methods. In all, 1879 studies were identified across three databases. Following assessment against strict criteria, 112 studies were included (20 clinical studies; 92 animal studies). . Results. Seven categories of biological interventions were identified: growth factors, biomaterials, stem cells, gene therapy, autologous tissue, biophysical/environmental, and pharmaceuticals. The methodological quality of animal studies was moderate in 97%, but only 10% used clinically relevant outcome measures. The most interventions in clinical trials target the graft-tunnel interface and are applied intraoperatively. Platelet-rich plasma is the most studied intervention, but the clinical outcomes are mixed, and the methodological quality of studies was suboptimal. Other biological therapies investigated in clinical trials include: remnant-augmented ACLR; bone substitutes; calcium phosphate-hybridized grafts; extracorporeal shockwave therapy; and adult autologus non-cultivated stem cells. Conclusion. There is extensive preclinical research supporting the use of biological therapies to augment ACLR. Further clinical studies that meet the minimum standards of reporting are required to determine whether emerging biological strategies will provide tangible benefits in patients undergoing ACLR. Cite this article: Bone Joint J 2018;100-B:271–84

Aims. The aim of this study was to evaluate the epidemiology and treatment of Perthes’ disease of the hip. Methods. This was an anonymized comprehensive cohort study of Perthes’ disease, with a nested consented cohort. A total of 143 of 144 hospitals treating children’s hip disease in the UK participated over an 18-month period. Cases were cross-checked using a secondary independent reporting network of trainee surgeons to minimize those missing. Clinician-reported outcomes were collected until two years. Patient-reported outcome measures (PROMs) were collected for a subset of participants. Results. Overall, 371 children (396 hips) were newly affected by Perthes’ disease arising from 63 hospitals, with a median of two patients (interquartile range 1.0 to 5.5) per hospital. The annual incidence was 2.48 patients (95% confidence interval (CI) 2.20 to 2.76) per 100,000 zero- to 14-year-olds. Of these, 117 hips (36.4%) were treated surgically. There was considerable variation in the treatment strategy, and an optimized decision tree identified joint stiffness and age above eight years as the key determinants for containment surgery. A total of 348 hips (88.5%) had outcomes to two years, of which 227 were in the late reossification stage for which a hip shape outcome (Stulberg grade) was assigned. The independent predictors of a poorer radiological outcome were female sex (odds ratio (OR) 2.27 (95% CI 1.19 to 4.35)), age above six years (OR 2.62 (95% CI (1.30 to 5.28)), and over 50% radiological collapse at inclusion (OR 2.19 (95% CI 0.99 to 4.83)). Surgery had no effect on radiological outcomes (OR 1.03 (95% CI 0.55 to 1.96)). PROMs indicated the marked effect of the disease on the child, which persisted at two years. Conclusion. Despite the frequency of containment surgery, we found no evidence of improved outcomes. There appears to be a sufficient case volume and community equipoise among surgeons to embark on a randomized clinical trial to definitively investigate the effectiveness of containment surgery. Cite this article: Bone Joint J 2022;104-B(4):510–518

Aims. The aim of this study was to explore parents and young people’s experience of having a medial epicondyle fracture, and their thoughts about the uncertainty regarding the optimal treatment. Methods. Families were identified after being invited to participate in a randomized controlled trial of surgery or no surgery for displaced medial epicondyle fractures of the humerus in children. A purposeful sample of 25 parents (22 females) and five young people (three females, mean age 11 years (7 to 14)) from 15 UK hospitals were interviewed a mean of 39 days (14 to 78) from injury. Qualitative interviews were informed by phenomenology and themes identified to convey participants’ experience. Results. The results identify parents’ desire to do the best for their child expressed through two themes: 1) ‘uncertainty’ (being uncertain about the best treatment option); and 2) ‘facilitating recovery’ (sharing the experience). Parents and young people were shocked when confronted with uncertainty about treatment and they felt responsible for the decision. They searched for further information, drew on their own experience, and struggled to weigh up risks of the treatments. Discussion with surgeons provided crucial support for decision-making, and young people were involved to a varying degree. In facilitating recovery, parents balanced increasing activity with protecting their child, but lacked knowledge about pain management, and how to improve strength and function of the arm. They hoped for a return to normal, including competitive sports. Conclusion. Surgeons are aware of the impact of injury on children and their parents; however, they may be less aware of the turmoil created by treatment uncertainty. Confident surgeons who appreciate and contextualize the importance of pre-existing experience and beliefs are best placed to help the family develop confidence to embrace uncertainty, particularly regarding participation in clinical trials. Cite this article: Bone Jt Open 2021;2(6):359–364

Limb alignment in total knee arthroplasty (TKA) influences periarticular soft-tissue tension, biomechanics through knee flexion, and implant survival. Despite this, there is no uniform consensus on the optimal alignment technique for TKA. Neutral mechanical alignment facilitates knee flexion and symmetrical component wear but forces the limb into an unnatural position that alters native knee kinematics through the arc of knee flexion. Kinematic alignment aims to restore native limb alignment, but the safe ranges with this technique remain uncertain and the effects of this alignment technique on component survivorship remain unknown. Anatomical alignment aims to restore predisease limb alignment and knee geometry, but existing studies using this technique are based on cadaveric specimens or clinical trials with limited follow-up times. Functional alignment aims to restore the native plane and obliquity of the joint by manipulating implant positioning while limiting soft tissue releases, but the results of high-quality studies with long-term outcomes are still awaited. The drawbacks of existing studies on alignment include the use of surgical techniques with limited accuracy and reproducibility of achieving the planned alignment, poor correlation of intraoperative data to long-term functional outcomes and implant survivorship, and a paucity of studies on the safe ranges of limb alignment. Further studies on alignment in TKA should use surgical adjuncts (e.g. robotic technology) to help execute the planned alignment with improved accuracy, include intraoperative assessments of knee biomechanics and periarticular soft-tissue tension, and correlate alignment to long-term functional outcomes and survivorship

Aims. The aim of this study was to prepare a scoping review to investigate the use of biologic therapies in the treatment of musculoskeletal injuries in professional and Olympic athletes. Methods. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews and Arksey and O’Malley frameworks were followed. A three-step search strategy identified relevant published primary and secondary studies, as well as grey literature. The identified studies were screened with criteria for inclusion comprising clinical studies evaluating the use of biologic therapies in professional and Olympic athletes, systematic reviews, consensus statements, and conference proceedings. Data were extracted using a standardized tool to form a descriptive analysis and a thematic summary. Results. A total of 202 studies were initially identified, and 35 met criteria for the scoping review; 33 (94.3%) were published within the last eight years, and 18 (51.4%) originated from the USA. Platelet rich plasma was the most studied biologic therapy, being evaluated in 33 (94.3%) studies. Ulnar collateral ligament and hamstring injuries were the conditions most studied (nine (25.7%) studies and seven (20.0%) studies, respectively). Athletes most frequently participated in baseball, soccer, and American football. Only two (5.7%) studies were level 1 evidence, with interpretation and comparison between studies limited by the variations in the injury profile, biologic preparations, and rehabilitation protocols. Conclusion. There is diverse use of biologic therapies in the management of musculoskeletal injuries in professional and Olympic athletes. There is currently insufficient high-level evidence to support the widespread use of biologic therapies in athletes. Further research priorities include the development of condition/pathology-specific preparations of biologic therapies, and of outcome measures and imaging modalities sufficiently sensitive to detect differences in outcomes, should they exist. Cite this article: Bone Joint J 2021;103-B(7):1189–1196

Aims. LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling. Methods. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action. Results. LY3023414 attenuated PI3K/protein kinase B (Akt)/GSK3-dependent activation of β-catenin and nuclear factor-activated T cell 1 (NFATc1) during osteogenesis and osteoclastogenesis, respectively. LY3023414 mainly inhibited osteoclast formation instead of mature osteoclast function. Moreover, it suppressed osteogenesis both in the early stage of differentiation and late stage of calcification. Similarly, gene knockdown of Akt isoforms by siRNA downregulated osteogenic and osteoclastogenic processes, indicating that Akt1 and Akt2 acted synergistically. Conclusion. LY3023414 can suppress osteogenesis and osteoclastogenesis through inhibition of the PI3K/Akt/GSK3 signalling pathway, which highlights the potential benefits and side effects of LY3023414 for future clinical applications. Cite this article: Bone Joint Res 2021;10(4):237–249

Aims. We aimed to determine hip-related quality of life and clinical findings following treatment for neonatal hip instability (NHI) compared with age- and sex-matched controls. We hypothesized that NHI would predispose to hip discomfort in long-term follow-up. Methods. We invited those born between 1995 and 2001 who were treated for NHI at our hospital to participate in this population-based study. We included those that had Von Rosen-like splinting treatment started before one month of age. A total of 96 patients treated for NHI (75.6 %) were enrolled. A further 94 age- and sex-matched controls were also recruited. The Copenhagen Hip and Groin Outcome Score (HAGOS) questionnaire was completed separately for both hips, and a physical examination was performed. Results. The mean follow-up was 18.2 years (14.6 to 22.0). The HAGOS scores between groups were similar and met statistical and clinical significance only in the Symptoms subscale (mean difference 3.80, 95% confidence interval (CI) 0.31 to 7.29; p = 0.033). Those patients who had undergone treatment for NHI had a higher frequency of positive flexion-adduction-internal rotation test (odds ratio (OR) 2.6, 95% CI 1.2 to 5.6; p = 0.014), resisted straight leg rise test (OR 4.5, 95% CI 1.4 to 14.9; p = 0.014), and also experienced more pain in the groin during passive end range hip flexion (OR 2.5, 95% CI 1.2 to 5.3; p = 0.015) than controls. Conclusion. NHI predisposes to hip discomfort in clinical tests, but no clinically relevant differences in experience of pain, physical function, and hip-related quality of life could be observed between the treated group and matched controls in 18 years of follow-up. Cite this article: Bone Joint J 2020;102-B(12):1767–1773