Aims. In previous studies, we identified multiple factors influencing the survivorship of hip resurfacing arthroplasties (HRAs), such as initial anatomical conditions and surgical technique. In addition, the University of California, Los Angeles (UCLA) activity score presents a ceiling effect, so a better quantification of activity is important to determine which activities may be advisable or detrimental to the recovered patient. We aimed to determine the effect of specific groups of sporting activities on the survivorship free of aseptic failure of a large series of HRA. Patients and Methods. A total of 661 patients (806 hips) representing 77% of a consecutive series of patients treated with metal-on-metal hybrid HRA answered a survey to determine the types and amounts of sporting activities they regularly participated in. There were 462 male patients (70%) and 199 female patients (30%). Their mean age at the time of surgery was 51.9 years (14 to 78). Their mean body mass index (BMI) was 26.5 kg/m. 2. (16.7 to 46.5). Activities were regrouped into 17 categories based on general analogies between these activities. Scores for typical frequency and duration of the sessions were used to quantify the patients’ overall time spent engaging in sporting activities. Impact and cycle scores were computed. Multivariable models were used. Results. We found no association between any category of activity and a decrease in survivorship. Impact and hip cycle scores also failed to show any association with revision for aseptic failure or wear. Conclusion. Return to sporting activities after surgery is safe for patients treated with well-designed and well-implanted HRA. Cite this article: Bone Joint J 2019;101-B:1186–1191

Aims. Higher osteoblastic bone activity is expected in aseptic loosening and painful unicompartmental knee arthroplasty (UKA). However, insights into normal bone activity patterns after medial UKAs are lacking. The aim of this study was to identify the evolution in bone activity pattern in well-functioning medial mobile-bearing UKAs. Methods. In total, 34 patients (13 female, 21 male; mean age 62 years (41 to 79); BMI 29.7 kg/m. 2. (23.6 to 42.1)) with 38 medial Oxford partial UKAs (20 left, 18 right; 19 cementless, 14 cemented, and five hybrid) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively, and at one and two years postoperatively. Changes in mean osteoblastic activity were investigated using a tracer localization scheme with volumes of interest (VOIs), reported by normalized mean tracer values. A SPECT/CT registration platform additionally explored cortical tracer evolution in zones of interest identified by previous experimental research. Results. Significant reduction of tracer activity from the preoperative situation was found in femoral and anteromedial tibial VOIs adjacent to the UKA components. Temporarily increased osteoblastic bone activity was observed in VOIs comprising the UKA keel structure at one year postoperatively compared to the preoperative activity. Persistent higher tracer uptake was found in the posterior tibial cortex at final follow-up. Multivariate analysis showed no statistical difference in osteoblastic bone activity underneath cemented or cementless components. Conclusion. Well-functioning medial mobile-bearing UKAs showed distinct changes in patterns of normalized bone tracer activity in the different VOIs adjacent to the prosthetic components, regardless of their type of fixation. Compared to the preoperative situation, persistent high bone activity was found underneath the keel and the posterior tibial cortex at final follow-up, with significant reduced activity only being identified in femoral and anteromedial tibial VOIs. Cite this article: Bone Joint J 2022;104-B(1):34–44

Aims. Young adults undergoing total hip arthroplasty (THA) largely have different indications for surgery, preoperative function, and postoperative goals compared to a standard patient group. The aim of our study was to describe young adult THA preoperative function and quality of life, and to assess postoperative satisfaction and compare this with functional outcome measures. Methods. A retrospective cohort analysis of young adults (aged < 50 years) undergoing THA between May 2018 and May 2023 in a single tertiary centre was undertaken. Median follow-up was 31 months (12 to 61). Oxford Hip Score (OHS) and focus group-designed questionnaires were distributed. Searches identified 244 cases in 225 patients. Those aged aged under 30 years represented 22.7% of the cohort. Developmental dysplasia of the hip (50; 45.5%) and Perthes’ disease (15; 13.6%) were the commonest indications for THA. Results. Preoperatively, of 110 patients, 19 (17.2%) were unable to work before THA, 57 (52%) required opioid analgesia, 51 (46.4%) were reliant upon walking aids, and 70 (63.6%) had sexual activity limited by their pathology. One patient required revision due to instability. Mean OHS was 39 (9 to 48). There was a significant difference between the OHS of cases where THA met expectation, compared with the OHS when it did not (satisfied: 86 (78.2%), OHS: 41.2 (36.1%) vs non-satisfied: 24 (21%), OHS: 31.6; p ≤ 0.001). Only one of the 83 patients (75.5%) who returned to premorbid levels of activity did so after 12 months. Conclusion. Satisfaction rates of THA in young adults is high, albeit lower than commonly quoted figures. Young adults awaiting THA have poor function with high requirements for mobility aids, analgesia, and difficulties in working and undertaking leisure activities. The OHS provided a useful insight into patient function and was predictive of satisfaction rates, although it did not address the specific demands of young adults undertaking THA. Function at one year postoperatively is a good indication of overall outcomes. Cite this article: Bone Jt Open 2024;5(4):304–311

Aims. To analyze the potential role of synovial fluid peptidase activity as a measure of disease burden and predictive biomarker of progression in knee osteoarthritis (KOA). Methods. A cross-sectional study of 39 patients (women 71.8%, men 28.2%; mean age of 72.03 years (SD 1.15) with advanced KOA (Ahlbäck grade ≥ 3 and clinical indications for arthrocentesis) recruited through the (Orthopaedic Department at the Complejo Asistencial Universitario de León, Spain (CAULE)), measuring synovial fluid levels of puromycin-sensitive aminopeptidase (PSA), neutral aminopeptidase (NAP), aminopeptidase B (APB), prolyl endopeptidase (PEP), aspartate aminopeptidase (ASP), glutamyl aminopeptidase (GLU) and pyroglutamyl aminopeptidase (PGAP). Results. Synovial fluid peptidase activity varied significantly as a function of clinical signs, with differences in levels of PEP (p = 0.020), ASP (p < 0.001), and PGAP (p = 0. 003) associated with knee locking, PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p = 0.000) with knee failure, and PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p < 0.001) with knee effusion. Further, patients with the greatest functional impairment had significantly higher levels of APB (p = 0.005), PEP (p = 0.005), ASP (p = 0.006), GLU (p = 0.020), and PGAP (p < 0.001) activity, though not of NAP or PSA, indicating local alterations in the renin-angiotensin system. A binary logistic regression model showed that PSA was protective (p = 0.005; Exp (B) 0.949), whereas PEP (p = 0.005) and GLU were risk factors (p = 0.012). Conclusion. These results suggest synovial fluid peptidase activity could play a role as a measure of disease burden and predictive biomarker of progression in KOA. Cite this article: Bone Joint Res 2020;9(11):789–797

Aims. The purpose of this exploratory study was to investigate if the 24-hour activity profile (i.e. waking activities and sleep) objectively measured using wrist-worn accelerometry of patients scheduled for total hip arthroplasty (THA) improves postoperatively. Patients and Methods. A total of 51 THA patients with a mean age of 64 years (24 to 87) were recruited from a single public hospital. All patients underwent THA using the same surgical approach with the same prosthesis type. The 24-hour activity profiles were captured using wrist-worn accelerometers preoperatively and at 2, 6, 12, and 26 weeks postoperatively. Patient-reported outcomes (Hip Disability and Osteoarthritis Outcome Score (HOOS)) were collected at all timepoints except two weeks postoperatively. Accelerometry data were used to quantify the intensity (sedentary, light, moderate, and vigorous activities) and frequency (bouts) of activity during the day and sleep efficiency. The analysis investigated changes with time and differences between Charnley class. Results. Patients slept or were sedentary for a mean of 19.5 hours/day preoperatively and the 24-hour activity pattern did not improve significantly postoperatively. Outside of sleep, the patients spent their time in sedentary activities for a mean of 620 minutes/day (. sd. 143) preoperatively and 641 minutes/day (. sd. 133) six months postoperatively. No significant improvements were observed for light, moderate, and vigorous intensity activities (p = 0.140, p = 0.531, and p = 0.407, respectively). Sleep efficiency was poor (< 85%) at all timepoints. There was no postoperative improvement in sleep efficiency when adjusted for medications (p > 0.05). Patient-reported outcome measures showed a significant improvement with time in all domains when compared with preoperative levels. There were no differences with Charnley class at six months postoperatively. However, Charnley class C patients were more sedentary at two weeks postoperatively when compared with Charnley class A patients (p < 0.05). There were no further differences between Charnley classifications. Conclusion. This study describes the 24-hour activity profile of THA patients for the first time. Prior to THA, patients in this cohort were inactive and slept poorly. This cohort shows no improvement in 24-hour activity profiles at six months postoperative. Cite this article: Bone Joint J 2019;101-B:415–425

Aims. The reduction in mobility due to hip diseases in children is likely to affect their physical activity (PA) levels. Physical inactivity negatively influences quality of life and health. Our aim was to objectively measure PA in children with hip disease, and correlate it with the Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility Score. Methods. A total of 28 children (12 boys and 16 girls) with hip disease aged between 8and 17 years (mean 12 (SD 3)) were studied between December 2018 and July 2019. Children completed the PROMIS Paediatric Item Bank v. 2.0 – Mobility Short Form 8a and wore a hip accelerometer (ActiGraph) for seven consecutive days. Sedentary time (ST), light PA (LPA), moderate to vigorous PA (MVPA), and vigorous PA were calculated from the accelerometers' data. The PROMIS Mobility score was classified as normal, mild, and moderate functions, based on the PROMIS cut scores on the physical function metric. A one-way analysis of covariance (ANCOVA) was used to assess differences among mobility (normal; mild; moderate) and measured PA and relationships between these variables were assessed using bivariate Pearson correlations. Results. Children classified as normally functioning on the PROMIS had less ST (p = 0.002), higher MVPA, (p = 0.002) and VPA (p = 0.004) compared to those classified as mild or moderate function. A moderate correlation was evident between the overall PROMIS score and daily LPA (r = 0.462, n = 28; p = 0.013), moderate-to-vigorous PA (r = 0.689, n = 28; p = 0.013) and vigorous PA (VPA) (r = 0.535, n = 28; p = 0.013). No correlation was evident between the mean daily ST and overall PROMIS score (r = -0.282, n = 28; p = 0.146). Conclusion. PROMIS Pediatric Mobility tool correlates well with experimentally measured levels of physical activity in children with hip disease. We provide external validity for the use of this tool as a measure of physical activity in children. Cite this article: Bone Joint J 2021;103-B(2):405–410

Aims. Total hip arthroplasty (THA) has well known subjective benefits, but little is known objectively about the recovery of mobility in the early post-operative period. Patients and Methods. A total of 33 patients aged > 60 years who underwent elective primary THA had their activity monitored for 30 days post-operatively using an at-home (Fitbit) ankle accelerometer. Their mean age was 70.7 years (61 to 86); 15 (45.5%) were female. The rate of compliance and the mean level of activity were determined. Comparisons between subgroups based on age, body mass index (BMI), surgical approach, and the destination of the patients when discharged were also performed. Results. The mean compliance over the 30 days was 26.7 days (16 to 30; 89%) of use. The mean number of steps increased from 235 (5 to 1152) to 2563 (87 to 7280) (p < 0.001) between the first and the 30th post-operative day. Age < 70 years and an anterior surgical approach were significantly associated with higher levels of activity (1600 to 2400 (p = 0.016 to 0.031) and 1000 to 1800 (p = 0.017 to 0.037) more steps per day, respectively) between the second and the fourth week post-operatively. There was also a trend towards higher levels of activity in those who were discharged to their home rather than to a nursing facility (a mean of 1500 more steps per day, p = 0.02). BMI greater or less than 30 kg/m. 2. was not predictive of activity (p = 0.45 to 0.98). Conclusion. At-home remote mobility monitoring using existing commercially available technology is feasible in patients who have undergone THA. It showed a clear trend towards increased activity with the passage of time. Additionally, the remote device was able to detect differences in levels of activity clearly between patients in relation to variables of interest including age, BMI, surgical approach, and the destination of the patient at the time of discharge from hospital. Such monitoring may allow for the early identification and targeted intervention in patients who recover slowly. Cite this article: Bone Joint J 2016;98-B:1450–4

There is evidence that high levels of physical activity following arthroplasty of the hip or knee can lead to early revision. However, the term ‘highly active’ is not well defined. . A validated ankle accelerometer was used to quantify activity in 13 patients, who had undergone a total of 20 arthroplasties of the lower limbs and who had active lifestyles. The assessments were taken at a mean of 8.7 years post-operatively (1.8 to 15.8). The mean gait cycles per day was 8273 (5964 to 12 557), which extrapolates to 3.0 million cycles per year (cpy) (2.2 to 4.6). The mean percentage of time spent in high activity mode was 4.3%, or about one hour per day. The mean percentage of cycles in high activity was 40%. . Based on these data, we propose the following definitions of high activity: > 3 million cpy; one hour per day in high activity mode; 40% of cycles in high activity mode. . Extrapolating the sample of activity over the time since operation, the mean cycles per arthroplasty was 25.2 million, with a maximum of 44.1 million. No joint has been revised, or shows evidence of impending failure. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):95–7

Aims. The removal of the cruciate ligaments in total knee arthroplasty (TKA) has been suggested as a potential contributing factor to patient dissatisfaction, due to alteration of the in vivo biomechanics of the knee. Bicruciate retaining (BCR) TKA allows the preservation of the cruciate ligaments, thus offering the potential to reproduce healthy kinematics. The aim of this study was to compare in vivo kinematics between the operated and contralateral knee in patients who have undergone TKA with a contemporary BCR design. Methods. A total of 29 patients who underwent unilateral BCR TKA were evaluated during single-leg deep lunges and sit-to-stand tests using a validated computer tomography and fluoroscopic imaging system. In vivo six-degrees of freedom (6DOF) kinematics were compared between the BCR TKA and the contralateral knee. Results. During single-leg deep lunge, BCR TKAs showed significantly less mean posterior femoral translation (13 mm; standard deviation (SD) 4) during terminal flexion, compared with the contralateral knee (16.6 mm, SD 3.7; p = 0.001). Similarly, BCR TKAs showed significantly less mean femoral rollback (11.6 mm (SD 4.5) vs 14.4 mm (SD 4.6); p < 0.043) during sit-to-stand. BCR TKAs showed significantly reduced internal rotation during many parts of the strenuous flexion activities particularly during high-flexion lunge (4° (SD 5.6°) vs 6.5° (SD 6.1°); p = 0.051) and during sit-to-stand (4.5° (SD 6°) vs 6.9° (SD 6.3°); p = 0.048). Conclusion. The contemporary design of BCR TKA showed asymmetrical flexion-extension and internal-external rotation, suggesting that the kinematics are not entirely reproduced during strenuous activities. Future studies are required to establish the importance of patient factors, component orientation and design, in optimizing kinematics in patients who undergo BCR TKA. Cite this article: Bone Joint J 2020;102-B(6 Supple A):59–65

Aims. Altered alignment and biomechanics are thought to contribute to the progression of osteoarthritis (OA) in the native compartments after medial unicompartmental knee arthroplasty (UKA). The aim of this study was to evaluate the bone activity and remodelling in the lateral tibiofemoral and patellofemoral compartment after medial mobile-bearing UKA. Patients and Methods. In total, 24 patients (nine female, 15 male) with 25 medial Oxford UKAs (13 left, 12 right) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively and at one and two years postoperatively, along with standard radiographs and clinical outcome scores. The mean patient age was 62 years (40 to 78) and the mean body mass index (BMI) was 29.7 kg/m2 (23.6 to 42.2). Mean osteoblastic activity was evaluated using a tracer localization scheme with volumes of interest (VOIs). Normalized mean tracer values were calculated as the ratio between the mean tracer activity in a VOI and background activity in the femoral diaphysis. Results. Significant reduction of normalized tracer activity was observed one year postoperatively in tibial and femoral VOIs adjacent to the joint line in the lateral compartment. Patellar VOIs and remaining femoral VOIs demonstrated a significant, diminished normalized tracer activity at final follow-up. Conclusion. The osteoblastic bone activity in the native compartments decreased significantly after treatment of medial end-stage OA with a UKA, implying reduced stress to the subchondral bone in the retained compartments after a UKA. Cite this article: Bone Joint J 2019;101-B:915–921

Objectives. The medially spherical GMK Sphere (Medacta International AG, Castel San Pietro, Switzerland) total knee arthroplasty (TKA) was previously shown to accommodate lateral rollback while pivoting around a stable medial compartment, aiming to replicate native knee kinematics in which some coronal laxity, especially laterally, is also present. We assess coronal plane kinematics of the GMK Sphere and explore the occurrence and pattern of articular separation during static and dynamic activities. Methods. Using pulsed fluoroscopy and image matching, the coronal kinematics and articular surface separation of 16 well-functioning TKAs were studied during weight-bearing and non-weight-bearing, static, and dynamic activities. The closest distances between the modelled articular surfaces were examined with respect to knee position, and proportions of joint poses exhibiting separation were computed. Results. Overall, 1717 joint poses were analyzed. At a 1.0 mm detection threshold, 37 instances of surface separation were observed in the lateral compartment and four medially (p < 0.001). Separation was activity-dependent, both laterally and medially (p < 0.001), occurring more commonly during static deep flexion in the lateral compartment, and during static rotation in the medial compartment. Lateral separation occurred more frequently than medial during kneeling (7/14 lateral vs 1/14 medial; p = 0.031) and stepping (20/1022 lateral vs 0/1022 medial; p < 0.001). Separation varied significantly between individuals during dynamic activities. Conclusion. No consistent association between closest distances of the articular surfaces and knee position was found during any activity. Lift-off was infrequent and depended on the activity performed and the individual knee. Lateral separation was consistent with the design rationale. Medial lift-off was rare and mostly in non-weight-bearing activities. Cite this article: S. Key, G. Scott, J. G. Stammers, M. A. R. Freeman†, V. Pinskerova, R. E. Field, J. Skinner, S. A. Banks. Does lateral lift-off occur in static and dynamic activity in a medially spherical total knee arthroplasty? A pulsed-fluoroscopic investigation. Bone Joint Res 2019;8:207–215. DOI: 10.1302/2046-3758.85.BJR-2018-0237.R1

Aims. In Asia and the Middle-East, people often flex their knees deeply in order to perform activities of daily living. The purpose of this study was to investigate the 3D kinematics of normal knees during high-flexion activities. Our hypothesis was that the femorotibial rotation, varus-valgus angle, translations, and kinematic pathway of normal knees during high-flexion activities, varied according to activity. Materials and Methods. We investigated the in vivo kinematics of eight normal knees in four male volunteers (mean age 41.8 years; 37 to 53) using 2D and 3D registration technique, and modelled the knees with a computer aided design program. Each subject squatted, kneeled, and sat cross-legged. We evaluated the femoral rotation and varus-valgus angle relative to the tibia and anteroposterior translation of the medial and lateral side, using the transepicodylar axis as our femoral reference relative to the perpendicular projection on to the tibial plateau. This method evaluates the femur medially from what has elsewhere been described as the extension facet centre, and differs from the method classically applied. . Results. During squatting and kneeling, the knees displayed femoral external rotation. When sitting cross-legged, femurs displayed internal rotation from 10° to 100°. From 100°, femoral external rotation was observed. No significant difference in varus-valgus angle was seen between squatting and kneeling, whereas a varus position was observed from 140° when sitting cross-legged. The measure kinematic pathway using our methodology found during squatting a medial pivoting pattern from 0° to 40° and bicondylar rollback from 40° to 150°. During kneeling, a medial pivot pattern was evident. When sitting cross-legged, a lateral pivot pattern was seen from 0° to 100°, and a medial pivot pattern beyond 100°. Conclusion. The kinematics of normal knees during high flexion are variable according to activity. Nevertheless, our study was limited to a small number of male patients using a different technique to report the kinematics than previous publications. Accordingly, caution should be observed in generalizing our findings. Cite this article: Bone Joint J 2018;100-B:50–5

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

In this systematic review, our aim was to explore whether or not patients are able to return to athletic activity following lower limb joint replacement. We also investigated any evidence as to whether participation in athletic activity post-joint replacement increases complications and reduces implant survival. A PubMed, Embase and Sports Discus search was performed using the MeSH terms ‘Sport’, ‘Athletic’, ‘Athlete’, ‘Physical’, ‘Activity’, ‘Arthroplasty’, ‘Total Hip Replacement’, ‘Hip Resurfacing’, ‘Total Knee Replacement’, ‘Unicompartmental Knee Replacement’ and ‘Unicondylar Knee Replacement’. From this search, duplications were excluded, the remaining abstracts were reviewed and any unrelated to the search terms were excluded. The remaining abstracts had their full papers reviewed. Following joint replacement, participation in sporting activity is common principally determined by pre-operative patient activity levels, BMI and patient age. The type of joint replaced is of less significance. Total time spent performing activity does not change but tends to be at a lower intensity. There is little evidence in the literature of an association between high activity levels and early implant failure. Cite this article: Bone Joint J 2014;96-B:923–7

Aims. Tibiofemoral alignment is important to determine the rate of progression of osteoarthritis and implant survival after total knee arthroplasty (TKA). Normally, surgeons aim for neutral tibiofemoral alignment following TKA, but this has been questioned in recent years. The aim of this study was to evaluate whether varus or valgus alignment indeed leads to increased medial or lateral tibiofemoral forces during static and dynamic weight-bearing activities. Patients and Methods. Tibiofemoral contact forces and moments were measured in nine patients with instrumented knee implants. Medial force ratios were analysed during nine daily activities, including activities with single-limb support (e.g. walking) and double-limb support (e.g. knee bend). Hip-knee-ankle angles in the frontal plane were analysed using full-leg coronal radiographs. . Results. The medial force ratio strongly correlated with the tibiofemoral alignment in the static condition of one-legged stance (R² = 0.88) and dynamic single-limb loading (R² = 0.59) with varus malalignment leading to increased medial force ratios of up to 88%. In contrast, the correlation between leg alignment and magnitude of medial compartment force was much less pronounced. A lateral shift of force occurred during activities with double-limb support and higher knee flexion angles. . Conclusion. The medial force ratio depends on both the tibiofemoral alignment and the nature of the activity involved. It cannot be generalised to a single value. Higher medial ratios during single-limb loading are associated with varus malalignment in TKA. The current trend towards a ‘constitutional varus’ after joint replacement, in terms of overall tibiofemoral alignment, should be considered carefully with respect to the increased medial force ratio. Cite this article: Bone Joint J 2017;99-B:779–87

Aims. Little is known about employment following total knee arthroplasty (TKA). This study aims to identify factors which predict return to work following TKA in patients of working age in the United Kingdom. Patients & Methods. We prospectively assessed 289 patients (289 TKAs) aged ≤ 65 years who underwent TKA between 2010 and 2013. There were 148 women. The following were recorded pre-operatively: age, gender, body mass index, social deprivation, comorbidities, indication for surgery, work status and nature of employment, activity level as assessed by the University of California, Los Angeles (UCLA) activity score and Oxford Knee Score (OKS). The intention of patients to return to work or to retire was not assessed pre-operatively. At a mean of 3.4 years (2 to 4) post-operatively, the return to work status, OKS, the EuroQol-5 dimensions (EQ-5D) score, UCLA activity score and Work, Osteoarthritis and joint-Replacement (WORQ) score were obtained. Univariate and multivariate analyses were performed. Results. Of 261 patients (90%) who were working before TKA, 105 (40%) returned to any job, including 89 (34%) who returned to the same job at a mean of 13.5 weeks (2 to 104) post-operatively. A total of 108 (41%) retired following TKA and 18 remained on welfare. Patients not working before the operation did not return to work. Median UCLA scores improved in 125 patients (58%) from 4 (mild activity) to 6 (moderate activity) (p < 0.001). Significant (p < 0.05) factors which were predictive of return to any work included age, heavy or moderate manual work, better post-operative UCLA, OKS and EQ-5D general health scores. Significant predictive factors of return to the same work included age, heavy or moderate manual work and post-operative OKS. Multivariate analysis confirmed heavy or moderate manual work and age to independently predict a return to either any or the same work. All patients aged < 50 years who were working pre-operatively returned to any work as did 60% of those aged between 50 and 54 years, 50% of those aged between 55 and 59 years and 24% those aged between 60 and 65 years. . Conclusion. If working pre-operatively, patients aged < 50 years invariably returned to work following TKA, but only half of those aged between 50 to 60 years returned. High post-operative activity levels and patient reported outcome measures do not predict return to work following TKA. Cite this article: Bone Joint J 2017;99-B:1037–46

Objectives. To elucidate the effects of age on the expression levels of the receptor activator of the nuclear factor-κB ligand (RANKL) and osteoclasts in the periodontal ligament during orthodontic mechanical loading and post-orthodontic retention. Materials and Methods. The study included 20 male Sprague-Dawley rats, ten in the young group (aged four to five weeks) and ten in the adult group (aged 18 to 20 weeks). In each rat, the upper-left first molar was subjected to a seven-day orthodontic force loading followed by a seven-day retention period. The upper-right first molar served as a control. The amount of orthodontic tooth movement was measured after seven-day force application and seven-day post-orthodontic retention. The expression levels of RANKL and the tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were evaluated on day 7 (end of mechanical force loading) and day 14 (after seven days of post-orthodontic retention). Statistical analysis was performed using the t-test, and significance was set at p < 0.05. Results. There was no significant difference between the amount of tooth movement in the young group (0.96, standard deviation (. sd. ) 0.30mm) and that in the adult group (0.80mm, . sd. 0.28) (p > 0.05) after the seven-day force application. On the compression side, the expression of RANKL and TRAP-positive osteoclasts in both the young and the adult groups increased after the application of force for seven days, and then decreased at the end of the seven-day retention period. However, by the end of the period, the expression of RANKL on the compression side dropped to the control level in the young group (p > 0.05), while it was still higher than that on the control side in the adult group (p < 0.05). The expression of RANKL on the compression side did not show significant difference between the young and the adult groups after seven-day force application (p > 0.05), but it was significantly higher in the adult group than that in the young group after seven-day post-orthodontic retention (p < 0.05). Similarly, the decreasing trend of TRAP-positive osteoclasts during the retention period in the adult group was less obvious than that in the young group. Conclusions. The bone-resorptive activity in the young rats was more dynamic than that in the adult rats. The expression of RANKL and the number of osteoclasts in adult rats did not drop to the control level during the post-orthodontic retention period while RANKL expression and the number of osteoclasts in young rats had returned to the baseline. Cite this article: X. Li, M. Li, J. Lu, Y. Hu, L. Cui, D. Zhang, Y. Yang. Age-related effects on osteoclastic activities after orthodontic tooth movement. Bone Joint Res 2016;5:492–499. DOI: 10.1302/2046-3758.510.BJR-2016-0004.R2

The release of various penicillins and other antibiotics from two brands of polymerised bone cement has been studied in vitro and in vivo in mice. Bone cement plugs containing antibiotics demonstrated antibacterial activity as a result of diffusion of antibiotic from the plugs into the surrounding medium. With all antibiotics tested, from 2-5 to 10 per cent of the antibiotic in the cement was released in vitro in active form within twenty-four hours. Most of the activity appeared within three hours of the start of the test, but in some cases low levels of activity were detected after four days. Antibiotic cement plugs implanted in mice and rats produced low concentrations of antibiotic in the blood up to two hours after implantation, but activity was seldom detected subsequently. In general, penicillins and non-penicillin antibiotics showed similar diffusion characteristics, and the pattern of release in vitro and in vivo was consistent with the leaching of antibiotic from, or near, the surface of the bone cement

We conducted a longitudinal study including patients with the same type of primary hybrid total hip replacement and evaluated patient activity and femoral osteolysis at either five or ten years post-operatively. Activity was measured using the University of California, Los Angeles scale. The primary outcome was the radiological assessment of femoral osteolysis. Secondary outcomes were revision of the femoral component for aseptic loosening and the patients’ quality of life. Of 503 hip replacements in 433 patients with a mean age of 67.7 years (30 to 91), 241 (48%) were seen at five and 262 (52%) at ten years post-operatively. Osteolytic lesions were identified in nine of 166 total hip replacements (5.4%) in patients with low activity, 21 of 279 (7.5%) with moderate activity, and 14 of 58 (24.1%) patients with high activity. The risk of osteolysis increased with participation in a greater number of sporting activities. In multivariate logistic regression adjusting for age, gender, body mass index and the inclination angle of the acetabular component, the adjusted odds ratio for osteolysis comparing high vs moderate activity was 3.6 (95% confidence interval 1.6 to 8.3). Stratification for the cementing technique revealed that lower quality cementing increased the effect of high activity on osteolysis. Revision for aseptic loosening was most frequent with high activity. Patients with the highest activity had the best outcome and highest satisfaction. In conclusion, of patients engaged in high activity, 24% had developed femoral osteolysis five to ten years post-operatively

1. A quantitative study of phosphatase distribution in the limb bones of growing rabbits is reported. 2. Alkaline phosphatase is present in high concentrations in areas of deposition of new bone. Both local concentrations and the total alkaline phosphatase content of a bone are found to decrease with age. There is good correlation between total alkaline phosphatase activity and monthly increment of weight. 3. Acid phosphatase is present in these bones in greatly less concentrations than alkaline phosphatase. 4. The acid phosphatase of bone shows nearly full activity in the presence of 0·5 per cent formaldehyde. It can be subdivided into two enzymes with characteristically different distributions by the effect of M/100 tartrate on activity. 5. The formaldehyde-stable and tartrate-stable acid phosphatase of rabbit bone (FTS) has a distribution very similar to that of alkaline phosphatase, though very much less in amount, and, like the latter, declines in activity as the bone matures. 6. Tartrate-inhibited, formaldehyde-stable acid phosphatase (FSTI) is found mainly in red marrow and cancellous bone, and full activity persists in mature bone. This enzyme may be associated with resorption and remodelling of bone, or it may represent residual activity under these conditions of the acid phosphatase of developing erythrocytes in the marrow

The total plasma alkaline phosphatase level has long been recognised as an indicator of osteoblastic activity, but lack of specificity makes it an insensitive index of the progress of disease and the response to treatment. Selective precipitation by wheatgerm lectin allows measurement of the plasma bone-specific alkaline phosphatase. We measured the plasma levels of this isoenzyme in 170 normal Chinese adolescents and adults, in 49 adults with fractures of a long bone, in 15 patients with osteosarcoma and in 38 patients with osteolytic metastases. The enzyme activity was also determined in 39 patients with liver disease. Of the patients with fractures, 94% had increased plasma activity during the healing process. The level was also increased in those with osteosarcoma but not in those with osteolytic bone metastases. There was no significant increase in activity in the patients with liver disease. We conclude that the plasma bone-specific alkaline phosphatase activity is a sensitive and reliable measure of osteoblastic activity

The primary aim of this study was to develop a patient-reported Activity & Participation Questionnaire (the OKS-APQ) to supplement the Oxford knee score, in order to assess higher levels of activity and participation. The generation of items for the questionnaire involved interviews with 26 patients. Psychometric analysis (exploratory and confirmatory factor analysis and Rasch analysis) guided the reduction of items and the generation of a scale within a prospective study of 122 relatively young patients (mean age 61.5 years (42 to 71)) prior to knee replacement. A total of 99, completed pre-operative and six month post-operative assessments (new items, OKS, Short-Form 36 and American Knee Society Score). The eight-item OKS-APQ scale is unidimensional, reliable (Cronbach’s alpha 0.85; intraclass correlation coefficient (ICC) 0.79; or 0.92 when one outlier was excluded), valid (r >  0.5 with related scales) and responsive (effect size 4.16). We recommend that it is used with the OKS with adults of all ages when further detail regarding the levels of activity and participation of a patient is required. Cite this article: Bone Joint J 2014;96-B:332–8

The alkaline phosphatase activity of pre-osseous tibial cartilage of rachitic bone stored in the deep freeze for two weeks at -25 degrees centigrade was only slightly less than that of fresh controls from the same animals. The deep frozen pre-osseous tissue did not calcify in in vitro calcifying media containing either inorganic phosphorus or organic phosphate ester. The fresh controls calcified equally well in both media. In addition, after deep-freeze storage the tissue hydrolysed the organic phosphate to the same degree as did the fresh tissue. Bones heated at 65 degrees centigrade will calcify in vitro after calcium chloride treatment despite the destruction of phosphatase activity. It appears unlikely that a relationship exists between alkaline phosphatase and the minimal system required for calcification of pre-osseous cartilage in vitro. These findings do not exclude the possibility that alkaline phosphatase plays some critical role in vivo

Objectives. Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time. Materials and Methods. Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 minutes, 180 minutes, and 24 hours. Results. The MBEC of acetic acid was found to be: 15%, 11%, 3.2%, and 0.8% following a ten-minute, 20-minute, 180-minute, and 24-hour treatment, respectively. Conclusion. This study found that the MBEC of acetic acid following a 10- or 20-minute treatment time exceeded its safety threshold, making these concentrations unsuitable as a topical debridement adjunct. However, a clinically acceptable concentration (5%) was still found to eliminate 96.1% of biofilm-associated MSSA following a 20-minute treatment time. Cite this article: S. T. J. Tsang, P. J. Gwynne, M. P. Gallagher, A. H. R. W. Simpson. The biofilm eradication activity of acetic acid in the management of periprosthetic joint infection. Bone Joint Res 2018;7:517–523. DOI: 10.1302/2046-3758.78.BJR-2018-0045.R1

Previous studies have identified clinical and demographic risk factors for recurrence in the treatment of idiopathic clubfoot (congenital talipes equinovarus). Evertor muscle activity is not usually considered amongst them. This study aimed to evaluate whether recurrence could be predicted by demographic, clinical and gait parameters. From a series of 103 children with clubfeet, 67 had completed a follow-up of two years: 41 male and 26 female, 38 with idiopathic and 29 with non-idiopathic deformities. The mean age was 3.2 years (2.1 to 6.3). Primary correction was obtained in all 38 children (100%) with an idiopathic deformity, and in 26 of 29 patients (90%) with a non-idiopathic deformity. Overall, 60 children (90%) complied with the abduction brace regime. At a mean follow-up of 31.4 months (24 to 62), recurrence was noted in six children (15.8%) in the idiopathic and 14 children (48.3%) in the non-idiopathic group. Significant correlation was found between poor evertor activity and recurrence in both groups. No statistically significant relationship was found between the rate of recurrence and the severity of the initial deformity, the age at the time of treatment, the number of casts required or the compliance with the brace. After correction of idiopathic and non-idiopathic clubfoot using the Ponseti method, only poor evertor muscle activity was statistically associated with recurrence. The identification of risk factors for recurrent deformity allows clinicians to anticipate problems and advocate early additional treatment to improve muscle balance around the ankle. Cite this article: Bone Joint J 2014;96-B:1264–8

We investigated whether patients who underwent internal fixation for an isolated acetabular fracture were able to return to their previous sporting activities. We studied 52 consecutive patients with an isolated acetabular fracture who were operated on between January 2001 and December 2002. Their demographic details, fracture type, rehabilitation regime, outcome and complications were documented prospectively as was their level and frequency of participation in sport both before and after surgery. Quality of life was measured using the EuroQol-5D health outcome tool (EQ-5D). There was a significant reduction in level of activity, frequency of participation in sport (both p < 0.001) and EQ-5D scores in patients of all age groups compared to a normal English population (p = 0.001). A total of 22 (42%) were able to return to their previous level of activities: 35 (67%) were able to take part in sport at some level. Of all the parameters analysed, the Matta radiological follow-up criteria were the single best predictor for resumption of sporting activity and frequency of participation

We have investigated the level of physical activity of 49 women between the ages of 15 and 45 years who sustained a fracture of the neck of the femur at between 60 and 70 years of age, and compared this with the level of activity reported by 49 control subjects without fracture, who were matched for age and social status. We found that the patients had been significantly less physically active than the controls, especially as regards household duties and professional working conditions

Aims. The aim of this study was to identify predictors of return to work (RTW) after revision lower limb arthroplasty in patients of working age in the United Kingdom. Patients and Methods. We assessed 55 patients aged ≤ 65 years after revision total hip arthroplasty (THA). There were 43 women and 12 men with a mean age of 54 years (23 to 65). We also reviewed 30 patients after revision total knee arthroplasty (TKA). There were 14 women and 16 men with a mean age of 58 years (48 to 64). Preoperatively, age, gender, body mass index, social deprivation, mode of failure, length of primary implant survival, work status and nature, activity level (University of California, Los Angeles (UCLA) score), and Oxford Hip and Knee Scores were recorded. Postoperatively, RTW status, Oxford Hip and Knee Scores, EuroQol-5D (EQ-5D), UCLA score, and Work, Osteoarthritis and Joint-Replacement Questionnaire (WORQ) scores were obtained. Univariate and multivariate analysis was performed. Results. Overall, 95% (52/55) of patients were working before their revision THA. Afterwards, 33% (17/52) RTW by one year, 48% (25/52) had retired, and 19% (10/52) were receiving welfare benefit. RTW was associated with age, postoperative Oxford Hip Score, early THA failure (less than two years), mode of failure dislocation, and contralateral revision (p < 0.05). No patient returned to work after revision for dislocation. Only age remained a significant factor on multivariate analysis (p = 0.003), with 79% (11/14) of those less than 50 years of age returning to work, compared with 16% (6/38) of those aged fifty years or over. Before revision TKA, 93% (28/30) of patients were working. Postoperatively only 7% (2/28) returned to work by one year, 71% (20/28) had retired, and 21% (6/28) were receiving welfare benefits. UCLA scores improved after 43% of revision THAs and 44% of revision TKAs. Conclusion. After revision THA, age is the most significant predictor of RTW: only 16% of those over 50 years old return to work. Fewer patients return to work after early revision THA and none after revision for dislocation. After revision TKA, patients rarely return to work: none return to heavy or moderate manual work. Cite this article: Bone Joint J 2018;100-B:1043–53

A continuous ambulatory activity monitor allows objective measurement of the amount and intensity of physical activity. We examined the reliability and validity of this device in the assessment of seven aspects of function over a period of 24 hours in 20 patients who had undergone limb salvage or amputation for a tumour in the leg. The test-retest reliability was determined by undertaking identical assessments on two separate days. The measurements were compared with other indicators of functional status and quality of life in order to determine the validity of the monitor. Its reliability was satisfactory, with intraclass correlation coefficients ranging from 0.65 to 0.91. Significant correlations were seen between the ‘time spent walking’ and the Musculoskeletal Tumor Society rating scales and the Rand-36 physical functioning score. There was also a significant association between the ‘movement intensity during walking’ and the Musculoskeletal Tumor Society score. The satisfactory reliability and validity of the monitor shows considerable promise for its use as a device for measuring physical activity objectively in patients after surgery for limb-salvage or an amputation

Experimentally produced fractures in long bones studied by light and electron microscopic histochemistry were found to heal by a process of enchondral calcification. There was intense proliferation in the cells of the cambium layer of the periosteum, with differentiation to chondroblasts and osteoblasts, suggesting that this layer was the primary tissue responsible for development of the callus. Cytoplasmic processes of the hypertrophic chondrocytes appeared to bud and produce matrix vesicles. Alkaline phosphatase activity was detected along the plasma membrane of the hypertrophic chondrocytes and around the matrix vesicles, before any signs of mineral deposition. Calcification took place by deposition of hydroxyapatite crystals in and around these matrix vesicles which frequently showed alkaline phosphatase activity. It is suggested that there is a close functional association between alkaline phosphatase activity and calcification in the process of fracture healing, which is another type of enchondral calcification mediated by matrix vesicles

1. In a previous investigation, approximately 40 per cent of so-called "primary" degenerative disease or osteoarthritis of the hip appeared to have been the result of an abnormal joint mechanism caused by minimal epiphysiolysis in adolescence. Males were affected much more commonly than females. The residual abnormality of this disturbance, recognised radiologically, was termed the "tilt deformity" of the femoral head. 2. Three groups of young adult males, with different athletic backgrounds, have now been examined to assess the incidence of this abnormality and its relationship to athletic regimes. The condition was found to be more common in subjects who had been engaged in more active regimes and was also related statistically to a history of "growing pains". The deformity is compared with the gross disturbance of adolescent epiphysiolysis or slipped epiphysis, which is believed basically to be caused by chronic stress. 3. Degenerative disease of the hip of this type has a geographical and racial distribution corresponding to the degree of interest in and encouragement of competitive athletic activities. Many cases are therefore postulated to be the direct result of a minor and usually asymptomatic disturbance of this type, attributable to excess activity during adolescence

The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures

The acid and alkaline phosphatase activity in fluid aspirated from solitary bone cysts in six patients was measured, and large increases in the concentration of acid phosphatase were found. In some cases this increase was reflected in venous blood concentrations. The significance of these findings for the pathogenesis and the management of solitary bone cyst is discussed

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured. Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value

Biopsies of lumbar multifidus muscles were obtained at operation on seventeen patients aged from fifteen to fifty-eight with lumbar spinal derangement, and further material was taken from the cadavers of three subjects aged from nineteen to fifty-one. Sections were prepared to show the presence of ATPase activity, so distinguishing Fast from Slow types of muscle fibre. The normal mosaic pattern arising from the intermingling of fibres from Fast and Slow motor units was seen in sections from cadaveric material and from many of the biopsies. With age and limited lumbar flexibility, the Fast fibres became relatively smaller but with increasing variation in size, suggesting a reduced capacity for phasic activity. The presence of positive root signs was associated with a greater proportion of Slow fibres, and in some patients with the occurrence of atrophied Fast fibres, giving rise to differences in the populations of the two fibres in neighbouring fascicles. The results suggest that multifidus adopts an increasingly postural role with advancing age and with disabling lesions of the lumbar spine

The purpose of this study is to investigate the diagnostic value of evoked spinal cord potentials (ESCPs) and choline acetyltransferase (CAT) activity during exploration of injuries to the brachial plexus. We assessed 25 spinal roots in 19 patients. The results of the two investigations were consistent in all except two roots. Although assessment of ESCPs is easy and quick, it mainly records the nerve potentials along the sensory pathway. Although measurement of CAT activity needs a specimen of the nerve and the availability of a radioisotope laboratory, it gives direct information regarding the motor function of ventral spinal roots. These two techniques should be complementary to each other in order to achieve a more accurate diagnosis

We performed a prospective, randomised double-blind study in 24 patients undergoing high tibial osteotomy to evaluate the effectiveness of human recombinant osteogenic protein (OP-1) on a collagen type-I carrier in a critically-sized fibular defect. The study had two phases, each evaluated by clinical, radiological and DEXA methods during the first postoperative year. The first concerned the validation of the model of the fibular defect, using positive (demineralised bone) and negative (untreated) controls. The second phase concerned the osteogenic potential of OP-1 on collagen type-I ν collagen type-I alone. The results of the first phase established the critically-sized nature of the defect. In the untreated group no bony changes were observed while, in the demineralised bone group, formation of new bone was visible from six weeks onwards. The results of the second phase showed no significant formation of new bone in the presence of collagen alone, while in the OP-1 group, all patients except one showed formation of new bone from six weeks onwards. This proved the osteogenic activity of OP-1 in a validated critically-sized human defect

The presence of the connective tissue components fibronectin and the different types of collagen was demonstrated by histological and immunohistological methods in the granulation and scar tissue of a healing injury in rat muscle. The effects of physical activity on granulation tissue production, scar formation and muscle regeneration at various stages of healing were studied. It was shown that immobilisation after injury accelerates granulation tissue production, but if continued too long, leads to contraction of the scar and to poor structural organisation of the components of regenerating muscle and scar tissue. However, a certain period of immobilisation, about five days for rat muscle, is required to allow newly-formed granulation tissue to cover the injured area and to have sufficient tensile strength to withstand subsequent mobilisation. This mobilisation, at the correct interval, seems essential for the quicker resorption of scar tissue and the better structural organisation of the muscle

Subtotal synovectomy was performed in the knee joints of New Zealand white rabbits. The changes noted in the articular cartilage as manifest by decreased metachromatic staining of the matrix were considered to indicate matrix degradation caused by the altered joint environment. The documentation of the enzyme changes suggests that the histological alteration in the articular cartilage noted after synovectomy may be mediated through the activation of endogenous chondrocyte lysozomal enzymes, particularly cathepsin and acid hydrolases.

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

Aims. Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030

Aims. The COVID-19 pandemic has disrupted the provision of arthroplasty services in England, Wales, and Northern Ireland. This study aimed to quantify the backlog, analyze national trends, and predict time to recovery. Methods. We performed an analysis of the mandatory prospective national registry of all independent and publicly funded hip, knee, shoulder, elbow, and ankle replacements in England, Wales, and Northern Ireland between January 2019 and December 2022 inclusive, totalling 729,642 operations. The deficit was calculated per year compared to a continuation of 2019 volume. Total deficit of cases between 2020 to 2022 was expressed as a percentage of 2019 volume. Sub-analyses were performed based on procedure type, country, and unit sector. Results. Between January 2020 and December 2022, there was a deficit of 158,994 joint replacements. This is equivalent to over two-thirds of a year of normal expected operating activity (71.6%). There were 104,724 (-47.1%) fewer performed in 2020, 41,928 (-18.9%) fewer performed in 2021, and 12,342 (-5.6%) fewer performed in 2022, respectively, than in 2019. Independent-sector procedures increased to make it the predominant arthroplasty provider (53% in 2022). NHS activity was 73.2% of 2019 levels, while independent activity increased to 126.8%. Wales (-136.3%) and Northern Ireland (-121.3%) recorded deficits of more than a year’s worth of procedures, substantially more than England (-66.7%). It would take until 2031 to eliminate this deficit with an immediate expansion of capacity over 2019 levels by 10%. Conclusion. The arthroplasty deficit following the COVID-19 pandemic is now equivalent to over two-thirds of a year of normal operating activity, and continues to increase. Patients awaiting different types of arthroplasty, in each country, have been affected disproportionately. A rapid and significant expansion in services is required to address the deficit, and will still take many years to rectify. Cite this article: Bone Joint J 2024;106-B(8):834–841

Aims. We assessed the long-term outcomes of a large cohort of patients who have undergone a periacetabular osteotomy (PAO), and sought to validate a patient satisfaction questionnaire for use in a PAO cohort. Methods. All patients who had undergone a PAO from July 1998 to February 2013 were surveyed, with several patient-reported outcome measures (PROMs) and radiological measurements of preoperative acetabular dysplasia and postoperative correction also recorded. Patients were asked to rate their level of satisfaction with their operation in achieving pain relief, restoration of activities of daily living, ability to perform recreational activity, and their overall level of satisfaction with the procedure. Results. A total of 143 PAOs were performed between 1998 and 2013. Of those, 90 postoperative surveys were returned. Only 65 patients (73 hips) had both pre- and postoperative radiographs available for measurement. The mean time to follow-up was 15 years (6.5 to 20). Most patients were female (91%), with a mean age of 26.4 years (14.9 to 48.3) at the time of their surgery. A statistically significant improvement in radiological correction was detected in all hips (p < 0.001). A total of 67 patients (92.3%) remained either very satisfied or satisfied with their PAO. The internal consistency of the patient satisfaction questionnaire, measured using Cronbach’s α, ranged from 0.89 to 0.94 indicating ‘good’ to ‘excellent’ reliability. Conclusion. Outcomes of importance to patients undergoing a PAO include several key domains: pain relief, improve activities of daily living, and improve recreational ability. Our study demonstrates high rates of long-term patient satisfaction in all domains, and found the patient satisfaction questionnaire to be a valid and reliable instrument for use in this cohort. Cite this article: Bone Jt Open 2023;4(12):964–969

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. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776

Aims. The primary aim of our study was to assess the influence of age on hip-specific outcome following total hip arthroplasty (THA). Secondary aims were to assess health-related quality of life (HRQoL) and level of activity according to age. Methods. A prospective cohort study was conducted. All patients were fitted with an Exeter stem with a 32 mm head on highly cross-linked polyethylene (X3RimFit) cemented acetabulum. Patients were recruited into three age groups: < 65 years, 65 to 74 years, and ≥ 75 years, and assessed preoperatively and at three, 12, 24, and 60 months postoperatively. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and Hip disability and Osteoarthritis Outcome Score (HOOS), were used to assess hip-specific outcome. EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 36-Item Short Form Survey (SF-36) scores were used to assess HRQoL. The Lower Extremity Activity Scale (LEAS) and Timed Up and Go (TUG) were used to assess level of activity. Results. There were no significant (p > 0.05) differences in the WOMAC scores, HSS, HOOS, or EQ-5D-5L at any postoperative timepoint between the age groups. Patients aged ≥ 75 years had significantly lower physical function (p ≤ 0.010) and physical role (p ≤ 0.047) SF-36 scores at 12, 24, and 60 months, but were equal to that expect of an age-matched population. No differences according to age were observed for the other six domains of the SF-36 (p > 0.060). The ≥ 75 years group had a lower LEAS (p < 0.001) and longer TUG test times (p ≤ 0.032) compared to the < 65 years group, but older age groups had significant (p < 0.001) improvement relative to their preoperative baseline measures. Conclusion. Age did not influence postoperative hip-specific outcome or HRQoL (according to the EQ-5D) following THA. Despite a significant improvement, older patients had lower postoperative activity levels compared to younger patients, but this may be reflective of the overall physical effect of ageing. Cite this article: Bone Jt Open 2022;3(9):692–700

Aims. The influence of metabolic syndrome (MetS) on the outcome after hip and knee arthroplasty is debated. We aimed to investigate the change in patient-reported outcome measure (PROM) scores after hip and knee arthroplasty, comparing patients with and without MetS. Methods. From 1 May 2017 to 30 November 2019, a prospective cohort of 2,586 patients undergoing elective unilateral hip and knee arthroplasty was established in Denmark. Data from national registries and a local database were used to determine the presence of MetS. Patients’ scores on Oxford Hip Score (OHS) or Oxford Knee Score (OKS), EuroQol five-dimension five-level questionnaire (EQ-5D-5L), University of California, Los Angeles (UCLA) Activity Scale, and Forgotten Joint Score (FJS) at baseline, three, 12, and 24 months after surgery were collected. Primary outcome was the difference between groups from baseline to 12 months in OHS and OKS. Secondary outcomes were scores of OHS and OKS at three and 24 months and EQ-5D-5L, UCLA Activity Scale, and FJS at three, 12, and 24 months after surgery. Generalized linear mixed model was applied, adjusting for age, sex, Charlson Comorbidity Index, and smoking to present marginal mean and associated 95% CIs. Results. A total of 62.3% (1,611/2,586) of the cohort met the criteria for MetS. Both groups showed similar increase in mean OHS (MetS group 22.5 (95% CI 21.8 to 23.1), non-MetS group 22.1 (21.3 to 22.8); p = 0.477) and mean OKS (MetS group 18.0 (17.4 to 18.6), non-MetS group 17.8 (17.0 to 18.7); p = 0.722) at 12 months' follow-up. Between groups, similar improvements were seen for OHS and OKS at three and 24 months postoperatively and for the mean EQ-5D-5L, EuroQol-visual analogue scale (EQ-VAS), UCLA Activity Scale, and FJS at every timepoint. Conclusion. Patients meeting the criteria for MetS obtain the same improvement in PROM scores as individuals without MetS up to 24 months after hip and knee arthroplasty. This is important for the clinician to take into account when assessing and advising patients with MetS. Cite this article: Bone Joint J 2024;106-B(10):1074–1083