Aims. Within healthcare, several measures are used to quantify and compare the severity of health conditions. Two common measures are disability weight (DW), a context-independent value representing severity of a health state, and utility weight (UW), a context-dependent measure of health-related quality of life. Neither of these measures have previously been determined for developmental dysplasia of the hip (DDH). The aim of this study is to determine the DW and country-specific UWs for DDH. Methods. A survey was created using three different methods to estimate the DW: a preference ranking exercise, time trade-off exercise, and visual analogue scale (VAS). Participants were fully licensed orthopaedic surgeons who were contacted through national and international orthopaedic organizations. A global DW was calculated using a random effects model through an inverse-variance approach. A UW was calculated for each country as one minus the country-specific DW composed of the time trade-off exercise and VAS. Results. Over a four-month period, 181 surgeons participated in the survey, with 116 surgeons included in the final analysis. The global DW calculated to be 0.18 (0.11 to 0.24), and the country-specific UWs ranged from 0.26 to 0.89. Conclusion. This is the first time that a global disability weight and country-specific utility weights have been estimated for DDH, which should assist in economic evaluations and the development of health policy. The methodology may be applied to other orthopaedic conditions. Cite this article: Bone Jt Open 2023;4(3):120–128

Aims. No predictive model has been published to forecast operating time for total knee arthroplasty (TKA). The aims of this study were to design and validate a predictive model to estimate operating time for robotic-assisted TKA based on demographic data, and evaluate the added predictive power of CT scan-based predictors and their impact on the accuracy of the predictive model. Methods. A retrospective study was conducted on 1,061 TKAs performed from January 2016 to December 2019 with an image-based robotic-assisted system. Demographic data included age, sex, height, and weight. The femoral and tibial mechanical axis and the osteophyte volume were calculated from CT scans. These inputs were used to develop a predictive model aimed to predict operating time based on demographic data only, and demographic and 3D patient anatomy data. Results. The key factors for predicting operating time were the surgeon and patient weight, followed by 12 anatomical parameters derived from CT scans. The predictive model based only on demographic data showed that 90% of predictions were within 15 minutes of actual operating time, with 73% within ten minutes. The predictive model including demographic data and CT scans showed that 94% of predictions were within 15 minutes of actual operating time and 88% within ten minutes. Conclusion. The primary factors for predicting robotic-assisted TKA operating time were surgeon, patient weight, and osteophyte volume. This study demonstrates that incorporating 3D patient-specific data can improve operating time predictions models, which may lead to improved operating room planning and efficiency. Cite this article: Bone Jt Open 2022;3(5):383–389

Aims. Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection. Methods. Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 10. 7. colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling. Results. Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed. Conclusion. Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage. Cite this article: Bone Joint Res 2022;11(9):669–678

Aims. Obesity is associated with an increased risk of hip osteoarthritis, resulting in an increased number of total hip arthroplasties (THAs) performed annually. This study examines the peri- and postoperative outcomes of morbidly obese (MO) patients (BMI ≥ 40 kg/m. 2. ) compared to healthy weight (HW) patients (BMI 18.5 to < 25 kg/m. 2. ) who underwent a THA using the anterior-based muscle-sparing (ABMS) approach. Methods. This retrospective cohort study observes peri- and postoperative outcomes of MO and HW patients who underwent a primary, unilateral THA with the ABMS approach. Data from surgeries performed by three surgeons at a single institution was collected from January 2013 to August 2020 and analyzed using Microsoft Excel and Stata 17.0. Results. This study compares 341 MO to 1,140 HW patients. Anaesthesia, surgery duration, and length of hospital stay was significantly lower in HW patients compared to MO. There was no difference in incidence of pulmonary embolism, periprosthetic fracture, or dislocation between the two groups. The rate of infection in MO patients (1.47%) was significantly higher than HW patients (0.14%). Preoperative patient-reported outcome measures (PROMs) show a significantly higher pain level in MO patients and a significantly lower score in functional abilities. Overall, six-week and one-year postoperative data show higher levels of pain, lower levels of functional improvement, and lower satisfaction scores in the MO group. Conclusion. The comorbidities of obesity are well studied; however, the implications of THA using the ABMS approach have not been studied. Our peri- and postoperative results demonstrate significant improvements in PROMs in MO patients undergoing THA. However, the incidence of deep infection was significantly higher in this group compared with HW patients. Cite this article: Bone Jt Open 2023;4(5):299–305

Aims. The purpose of this survey study was to examine the demographic and lifestyle factors of women currently in orthopaedic surgery. Methods. An electronic survey was conducted of practising female orthopaedic surgeons based in the USA through both the Ruth Jackson Society and the online Facebook group “Women of Orthopaedics”. Results. The majority of surveyed female orthopaedic surgeons reported being married (76.4%; 285/373) and having children (67.6%; 252/373). In all, 66.5% (247/373) were collegiate athletes; 82.0% (306/373) reported having no female orthopaedic surgeon mentors in undergraduate and medical school. Their mean height is 65.8 inches and average weight is 147.3 lbs. Conclusion. The majority of female orthopaedic surgeons did not have female mentorship during their training. Additionally, biometrically, their build is similar to that of the average American woman. Cite this article: Bone Jt Open 2024;5(5):419–425

Aims. Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. Methods. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes. Results. TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as interleukin 15 receptor subunit alpha (IL15RA) (PTWAS = 0.040, PmRNA = 0.010). Moreover, 71 common GO terms were detected for the enrichment results of TWAS and mRNA expression profiles, such as negative regulation of cell differentiation (LogP value = −2.811). Conclusion. This study revealed the genetic mechanism behind the pathological changes in LSS, and may provide novel insights for the early diagnosis and intervention of LSS. Cite this article: Bone Joint Res 2023;12(6):387–396

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

Aims. It is important to analyze objectively the hammering sound in cup press-fit technique in total hip arthroplasty (THA) in order to better understand the change of the sound during impaction. We hypothesized that a specific characteristic would present in a hammering sound with successful fixation. We designed the study to quantitatively investigate the acoustic characteristics during cementless cup impaction in THA. Methods. In 52 THAs performed between November 2018 and April 2022, the acoustic parameters of the hammering sound of 224 impacts of successful press-fit fixation, and 55 impacts of unsuccessful press-fit fixation, were analyzed. The successful fixation was defined if the following two criteria were met: 1) intraoperatively, the stability of the cup was retained after manual application of the torque test; and 2) at one month postoperatively, the cup showed no translation on radiograph. Each hammering sound was converted to sound pressures in 24 frequency bands by fast Fourier transform analysis. Basic patient characteristics were assessed as potential contributors to the hammering sound. Results. The median sound pressure (SP) of successful fixation at 0.5 to 1.0 kHz was higher than that of unsuccessful fixation (0.0694 (interquartile range (IQR) 0.04721 to 0.09576) vs 0.05425 (IQR 0.03047 to 0.06803), p < 0.001). The median SP of successful fixation at 3.5 to 4.0 kHz and 4.0 to 4.5 kHz was lower than that of unsuccessful fixation (0.0812 (IQR 0.05631 to 0.01161) vs 0.1233 (IQR 0.0730 to 0.1449), p < 0.001; and 0.0891 (IQR 0.0526 to 0.0891) vs 0.0885 (IQR 0.0716 to 0.1048); p < 0.001, respectively). There was a statistically significant positive relationship between body weight and SP at 0.5 to 1.0 kHz (p < 0.001). Multivariate analyses indicated that the SP at 0.5 to 1.0 kHz and 3.5 to 4.0 kHz was independently associated with the successful fixation. Conclusion. The frequency bands of 0.5 to 1.0 and 3.5 to 4.0 kHz were the key to distinguish the sound characteristics between successful and unsuccessful press-fit cup fixation. Cite this article: Bone Jt Open 2024;5(3):154–161

Aims. It is important to analyze objectively the hammering sound in cup press-fit technique in total hip arthroplasty (THA) in order to better understand the change of the sound during impaction. We hypothesized that a specific characteristic would present in a hammering sound with successful fixation. We designed the study to quantitatively investigate the acoustic characteristics during cementless cup impaction in THA. Methods. In 52 THAs performed between November 2018 and April 2022, the acoustic parameters of the hammering sound of 224 impacts of successful press-fit fixation, and 55 impacts of unsuccessful press-fit fixation, were analyzed. The successful fixation was defined if the following two criteria were met: 1) intraoperatively, the stability of the cup was retained after manual application of the torque test; and 2) at one month postoperatively, the cup showed no translation on radiograph. Each hammering sound was converted to sound pressures in 24 frequency bands by fast Fourier transform analysis. Basic patient characteristics were assessed as potential contributors to the hammering sound. Results. The median sound pressure (SP) of successful fixation at 0.5 to 1.0 kHz was higher than that of unsuccessful fixation (0.0694 (interquartile range (IQR) 0.04721 to 0.09576) vs 0.05425 (IQR 0.03047 to 0.06803), p < 0.001). The median SP of successful fixation at 3.5 to 4.0 kHz and 4.0 to 4.5 kHz was lower than that of unsuccessful fixation (0.0812 (IQR 0.05631 to 0.01161) vs 0.1233 (IQR 0.0730 to 0.1449), p < 0.001; and 0.0891 (IQR 0.0526 to 0.0891) vs 0.0885 (IQR 0.0716 to 0.1048); p < 0.001, respectively). There was a statistically significant positive relationship between body weight and SP at 0.5 to 1.0 kHz (p < 0.001). Multivariate analyses indicated that the SP at 0.5 to 1.0 kHz and 3.5 to 4.0 kHz was independently associated with the successful fixation. Conclusion. The frequency bands of 0.5 to 1.0 and 3.5 to 4.0 kHz were the key to distinguish the sound characteristics between successful and unsuccessful press-fit cup fixation. Cite this article: Bone Jt Open 2024;4(3):154–161

Aims. Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results. Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion. Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection. Cite this article: Bone Joint Res 2024;13(3):101–109

Aims. To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. Methods. A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme. Results. The bench test showed that a weight loading < 500 g did not affect the operation of experimental device. The compression test demonstrated that the stiffness of the device was sufficient to keep the uncontrollable motion between fracture ends, resulting from the rat’s daily activities, within 1% strain. In vivo results on 15 rats prove that the device works reliably, without overburdening the experimental animals, and provides standardized micromotion reproductively at the fracture site according to the set parameters. Conclusion. Our device was able to investigate the effect of micromotion parameters on fracture healing by generating standardized micromotion to small animal models. Cite this article: Bone Joint Res 2021;10(11):714–722

Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and hormonal factors. Anatomical and hormonal factors have been identified and investigated as significant contributors including osseous anatomy, ligament laxity, and hamstring muscular recruitment. Postural stability and impact absorption are associated with the stabilizing effort and stress on the ACL during sport activity, increasing the risk of noncontact pivot injury. Female patients have smaller diameter hamstring autografts than males, which may predispose to increased risk of re-rupture following ACL reconstruction and to an increased risk of chondral and meniscal injuries. The addition of an extra-articular tenodesis can reduce the risk of failure; therefore, it should routinely be considered in young elite athletes. Prevention programs target key aspects of training including plyometrics, strengthening, balance, endurance and stability, and neuromuscular training, reducing the risk of ACL injuries in female athletes by up to 90%. Sex disparities in access to training facilities may also play an important role in the risk of ACL injuries between males and females. Similarly, football boots, pitches quality, and football size and weight should be considered and tailored around females’ characteristics. Finally, high levels of personal and sport-related stress have been shown to increase the risk of ACL injury which may be related to alterations in attention and coordination, together with increased muscular tension, and compromise the return to sport after ACL injury. Further investigations are still necessary to better understand and address the risk factors involved in ACL injuries in female athletes. Cite this article: Bone Jt Open 2024;5(2):94–100

Aims. The aim of this study was to investigate whether anterior pelvic plane-pelvic tilt (APP-PT) is associated with distinct hip pathomorphologies. We asked: is there a difference in APP-PT between young symptomatic patients being evaluated for joint preservation surgery and an asymptomatic control group? Does APP-PT vary among distinct acetabular and femoral pathomorphologies? And does APP-PT differ in symptomatic hips based on demographic factors?. Methods. This was an institutional review board-approved, single-centre, retrospective, case-control, comparative study, which included 388 symptomatic hips in 357 patients who presented to our tertiary centre for joint preservation between January 2011 and December 2015. Their mean age was 26 years (SD 2; 23 to 29) and 50% were female. They were allocated to 12 different morphological subgroups. The study group was compared with a control group of 20 asymptomatic hips in 20 patients. APP-PT was assessed in all patients based on supine anteroposterior pelvic radiographs using validated HipRecon software. Values in the two groups were compared using an independent-samples t-test. Multiple regression analysis was performed to examine the influences of diagnoses and demographic factors on APP-PT. The minimal clinically important difference (MCID) for APP-PT was defined as > 1 SD. Results. There were no significant differences in APP-PT between the control group and the overall group (1.1° (SD 3.0°; -4.9° to 5.9°) vs 1.8° (SD 3.4°; -6.9° to 13.2°); p = 0.323). Acetabular retroversion and overcoverage groups showed higher mean APP-PTs compared with the control group (p = 0.001 and p = 0.014) and were the only diagnoses with a significant influence on APP-PT in the stepwise multiple regression analysis. All differences were below the MCID. The age, sex, height, weight, and BMI showed no influence on APP-PT. Conclusion. APP-PT showed no radiologically significant variation across different pathomorphologies of the hip in patients being assessed for joint-preserving surgery. Cite this article: Bone Joint J 2024;106-B(5 Supple B):3–10

Aims. Treatment outcomes for methicillin-resistant Staphylococcus aureus (MRSA) periprosthetic joint infection (PJI) using systemic vancomycin and antibacterial cement spacers during two-stage revision arthroplasty remain unsatisfactory. This study explored the efficacy and safety of intra-articular vancomycin injections for PJI control after debridement and cement spacer implantation in a rat model. Methods. Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation. Results. Rats receiving intra-articular vancomycin showed the best outcomes among the four treatment groups, with negative bacterial cultures, increased weight gain, increased capacity for weightbearing activities, increased residual bone volume preservation, and reduced inflammatory reactions in the joint tissues, indicating MRSA eradication in the knee. The vancomycin-spacer and/or systemic vancomycin failed to eliminate the MRSA infections following a two-week antibiotic course. Serum vancomycin levels did not reach nephrotoxic levels in any group. Mild renal histopathological changes, without changes in serum creatinine levels, were observed in the intraperitoneal vancomycin group compared with the intra-articular vancomycin group, but no changes in hepatic structure or serum alanine aminotransferase or aspartate aminotransferase levels were observed. No local complications were observed, such as sinus tract or non-healing surgical incisions. Conclusion. Intra-articular vancomycin injection was effective and safe for PJI control following debridement and spacer implantation in a rat model during two-stage revision arthroplasties, with better outcomes than systemic vancomycin administration. Cite this article: Bone Joint Res 2022;11(6):371–385

Aims. The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs. Methods. Patients aged younger than 55 years diagnosed with ONFH after FNF were retrospectively reviewed. Overall, 65 hips (38 males and 27 females; mean age 32.6 years (SD 12.2)) met the inclusion criteria. Patients with stage 1 or 4 ONFH, as per the Association Research Circulation Osseous classification, were excluded. The ratios of anterior and posterior viable areas and necrotic areas of the femoral head to the articular surface were calculated by setting the femoral head centre as the reference point. The PTA was measured using Palm’s method. The association between the PTA and viable or necrotic areas of the femoral head was assessed using Spearman’s rank correlation analysis (median PTA 6.0° (interquartile range 3 to 11.5)). Results. We identified a negative correlation between PTA and anterior viable areas (rho −0.477; p = 0.001), and no correlation between PTA and necrotic (rho 0.229; p = 0.067) or posterior viable areas (rho 0.204; p = 0.132). Conclusion. Our results suggest that residual posterior tilt after FNF could affect the anteroposterior localization of necrosis. Cite this article: Bone Jt Open 2024;5(5):394–400

Aims. Bi-unicondylar arthroplasty (Bi-UKA) is a bone and anterior cruciate ligament (ACL)-preserving alternative to total knee arthroplasty (TKA) when the patellofemoral joint is preserved. The aim of this study is to investigate the clinical outcomes and biomechanics of Bi-UKA. Methods. Bi-UKA subjects (n = 22) were measured on an instrumented treadmill, using standard gait metrics, at top walking speeds. Age-, sex-, and BMI-matched healthy (n = 24) and primary TKA (n = 22) subjects formed control groups. TKA subjects with preoperative patellofemoral or tricompartmental arthritis or ACL dysfunction were excluded. The Oxford Knee Score (OKS) and EuroQol five-dimension questionnaire (EQ-5D) were compared. Bi-UKA, then TKA, were performed on eight fresh frozen cadaveric knees, to investigate knee extensor efficiency under controlled laboratory conditions, using a repeated measures study design. Results. Bi-UKA walked 20% faster than TKA (Bi-UKA mean top walking speed 6.7 km/h (SD 0.9),TKA 5.6 km/h (SD 0.7), p < 0.001), exhibiting nearer-normal vertical ground reaction forces in maximum weight acceptance and mid-stance, with longer step and stride lengths compared to TKA (p < 0.048). Bi-UKA subjects reported higher OKS (p = 0.004) and EQ-5D (p < 0.001). In vitro, Bi-UKA generated the same extensor moment as native knees at low flexion angles, while reduced extensor moment was measured following TKA (p < 0.003). Conversely, at higher flexion angles, the extensor moment of TKA was normal. Over the full range, the extensor mechanism was more efficient following Bi-UKA than TKA (p < 0.028). Conclusion. Bi-UKA had more normal gait characteristics and improved patient-reported outcomes, compared to matched TKA subjects. This can, in part, be explained by differences in extensor efficiency. Cite this article: Bone Joint Res 2021;10(11):723–733

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. The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Methods. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies. Results. There was a total of 2,214 cases of ACL and PCL injury and 519,869 controls within the two cohorts, with three loci demonstrating a genome-wide significant association in the meta-analysis: INHBA, AEBP2, and LOC101927869. Of the eight candidate genes previously studied in the literature, six were present in the current dataset, and only COL3A1 (rs1800255) showed a significant association (p = 0.006). Conclusion. Genetic markers in three novel loci in this study and one previously-studied candidate gene were identified as potential risk factors for ACL and PCL injury and deserve further validation and investigation of molecular mechanisms. Cite this article: Bone Jt Open 2021;2(6):414–421

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

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