The AMPA/kainate glutamate receptor (GluR) antagonist NBQX reduced bone destruction when injected intra-articularly, in rat antigen induced arthritis (AIA) and is similarly protective in rodent models of osteoarthritis. NBQX reduced bone turnover in vivo and reduced mineralization in human primary osteoblasts (HOBs) in vitro. We are developing sustained release GluR antagonist delivery methods, to improve therapeutic effect. DNQX loaded Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were synthesized via double emulsion. DNQX loaded thermosetting hydrogels were synthesised by dissolving Pluronic-F127 (22% w/v) and Carbopol 934 (0.5% w/v) in dH₂O, homogenising with DNQX/NBQX and set in dialysis cassettes at 37˚C. Supernatants from nanoparticles and hydrogels suspended in PBS (37˚C) were analysed using high performance liquid chromatography to determine drug release. Y201 MSCs were differentiated to osteoblasts (DMEM+10% FBS, Dexamethasone, β-Glycerophosphate and Ascorbic acid-2-phosphate) in sustained presence/absence of NBQX (200µM) or DNQX (200 and 400µM). Alizarin red staining quantified mineralisation at 14 days. Nanoparticles encapsulated 2.5mM DNQX (encapsulation efficiency=22%) and released encapsulated drug over 4 weeks. Hydrogels released 2.5mM DNQX load over 24 hours in 37˚C PBS. Y201 alizarin red staining was significantly reduced by both DNQX (p<0.01) and NBQX (p<0.05), compared to untreated controls. PLGA nanoparticles and hydrogels revealed different sustained release profiles. Sustained treatment with GluR antagonists reduced mineralisation in Y201 derived osteoblasts, consistent with effects of NBQX in HOBs. Sustained release of NBQX and DNQX in nanoparticles and hydrogels may improve efficacy of AMPA/kainate GluR antagonists in reducing bone remodelling and enhancing their bone protective potential in the treatment of joint disease.

Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

Knee osteoarthritis (KOA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in KOA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n=51) with Kellgren-Lawrence grade 2–3 KOA through Support Vector Machine (SVM) and a regulation network model (RNM). Clinical descriptors (i.e., pain catastrophism (CA); depression (DE); functionality (FU); joint pain (JP); rigidity (RI); sensitization (SE); synovitis (SY)) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are KOA descriptors, synovial fluid (SL) proteomic measurements (n=25), and transcription factors (TF) activation obtained from RNM [2] stimulated with the SL measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through AUC-ROC analysis. The best classifier with clinical data is CA (AUC = 0.9), highly influenced by FU and SE, suggesting that kinesophobia is involved in pain perception. With SL input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When TF are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, FU has an AUC of 0.7 with strong importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and RNM shall help to map objectively KOA descriptors. Acknowledgements: Catalan & Spanish governments 2020FI_b00680; STRATO-PID2021126469ob-C21-2, European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828). ICREA Academia

Introduction and Objective. TKA have shown both excellent long-term survival rate and symptoms and knee function improvement. Despite the good results, the literature reports dissatisfaction rates around 20%. This rate of dissatisfaction could be due to the overstuff that mechanically aligned prostheses could produce during the range of motion. Either size discrepancy between bone resection and prosthetic component and constitutional mechanical tibiofemoral alignment (MTFA) alteration might increase soft tissue tension within the joint, inducing pain and functional limitation. Materials and Methods. Total knee arthroplasties performed between July 2019 and September 2020 were examined and then divided into two groups based on the presence (Group A) or absence (Group B) of patellofemoral overstuff, defined as a thickness difference of more than 2 mm between chosen component and bone resection performed, taking into account at least one of the following: femoral medial and lateral condyle, medial or lateral trochlea and patella. Based on pre and post-operative MTFA measurements, Group A was further divided into two subgroups whether the considered alignment was modified or not. Patients were assessed pre-operatively and at 6 months post-op using the Knee Society Score (KSS), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), Visual Analogue Scale (VAS) and Range of Motion (ROM). Results. One hundred total knee arthroplasties were included in the present study, 69 in Group A and 31 in group B. Mean age and BMI of patients was respectively 71 and 29.2. The greatest percentage of Patellofemoral Overstuff was found at the distal lateral femoral condyle. OKS, KSS functional score, and FJS were statistically significant higher in patients without Patellofemoral Overstuff. Therefore, Group A patients with a non-modified MTFA demonstrated statistically significant better KSS, ROM and FJS. Conclusions. Patellofemoral Overstuff decrease post-operative clinical scores in patients treated with TKA. The conventional mechanically aligned positioning of TKA components might be the primary cause of prosthetic overstuffing leading to worsened clinical results. Level of evidence: III; Prospective Cohort Observational study;

Objectives. In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models. Methods. OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score. Results. Both models showed an increase in joint pain as indicated by a significant (p < 0.05) decrease in the values of %HLWD at one week post-surgery. In the osteochondral injury model, the %HLWD returned to normal within three weeks, while in the ACLT model, a significant decrease in the %HLWD was persistent over an eight-week period. In addition, OA progression was more advanced in the ACLT model than in the osteochondral injury model. Furthermore, the ACLT model exhibited a higher mean OA score than that of the osteochondral injury model at 12 weeks. Conclusion. The development of pain patterns in the ACLT and osteochondral injury models is different in that the OA progression was significant in the ACLT model. Although both can be used as models for a post-traumatic injury of the knee, the selection of appropriate models for OA in preclinical studies should be specified and relevant to the clinical scenario. Cite this article: T. Tawonsawatruk, O. Sriwatananukulkit, W. Himakhun, W. Hemstapat. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Joint Res 2018;7:244–251. DOI: 10.1302/2046-3758.73.BJR-2017-0121.R2

Osteoarthritis (OA) is a leading cause of joint pain, deformity and functional limitation. An imbalance of anabolic and catabolic activity results in destruction of the extracellular matrix of articular cartilage. While there is evidence to support the role of DNA methylation in the pathogenesis of OA, the effect of other epigenetic modifications is yet to be described. This study looks at the effect of two novel epigenetic modifiers, PFI-1, a bromodomain inhibitor, and SGC707, a histone methytransferase inhibitor, on gene expression in the pathogenesis of OA. Chondrocytes were extracted from OA femoral heads (n=6), cultured and incubated with increasing concentrations of the compounds. Cells were treated with media alone (control), interleukin 1-beta (IL-1β) plus oncostatin M (OSM) alone, or in combination with PFI-1 or SGC707. Levels of expression of iNOS, COX2, IL8, IL1B, matrix metalloproteinase-13 (MMP13), RUNX2 and COL9A1 were measured using qRT-PCR. PFI-1 (0.5 and 5µM) suppressed expression of catabolic genes in OA chondrocytes, at basal levels and when co-stimulated with IL-1β+OSM. While there was a decrease in catabolic gene expression (iNOS, COX2, IL8, IL1B and MMP13), RUNX2 expression was also supressed. There was no effect on expression of COL9A1, an anabolic chondrocytic gene. SGC707 (0.1 and 1µM) did not induce a reduction in expression of all the catabolic genes, with a less predictable effect on gene expression than PFI-1. This study has demonstrated that the BET inhibitor PFI-1 has a potent protective effect against cartilage degradation, through its action as an epigenetic modifier in modulating the expression of catabolic genes in OA chondrocytes. This further validates the role of epigenetics in OA, with potential implications for therapeutic interventions

Summary Statement. This data may help explain the variability in physical function after primary TKR as compared to primary THR. Introduction. Total knee replacement (TKR) and total hip replacement (THR) reliably relieve pain, restore function, and ensure mobility in patients with advanced joint arthritis; however these results are not uniform across all patient populations. We compared baseline demographic and symptom profiles in patients from a US national cohort undergoing primary TKR and THR. Methods. Patients undergoing primary TKR and THR between 7/1/2011 and 3/30/2012 were identified from the national research consortium which collects comprehensive data on enrolled patients from 120 surgeons across 23 states. Gathered data includes patient demographics, comorbidity (Charlson Comorbidity Index), operative joint pain severity, physical function (SF-36; Physical Component Score (PCS)), emotional health (SF-36 Mental Component Score (MCS)), and musculoskeletal burden of illness (Hip and Knee Disability and Osteoarthritis Outcome Scores; Oswestry Disability Index). Descriptive statistics compared baseline demographic and symptom profiles. Results. Our analysis compared 1362 primary TKR patients and 1013 primary THR patients. US TKR patients were significantly older (66.5 vs. 64.3 years), more obese (BMI 31.7 vs. 29.3), and less educated (p<0.005). TKR patients had higher rates of comorbidities, specifically diabetes, gastrointestinal ulcers, and cerebrovascular disease (p≤0.006). THR patients had significantly worse physical function (PCS 31.6 vs. 33.3), lower back pain (35.6% vs. 30.5% moderate-severe), and operative joint pain, stiffness, and function (p<0.005). Conclusion. US patients undergoing primary TKR are older with more comorbidities, however THR patient baseline functional and musculoskeletal limitations are significantly greater than primary TKR patients

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total hip replacement (THR). We assessed the effectiveness of LAI using a systematic review and a fully powered randomised controlled trial (RCT) with economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving THR. Two reviewers screened abstracts, extracted data, and liaised with authors. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. If feasible, we conducted meta-analysis. In the APEX RCT, we randomised 322 patients awaiting THR to receive additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline) or standard anaesthesia alone. Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, we identified 13 studies (909 patients). Patients undergoing THR receiving LAI experienced greater pain reduction at 24 hours at rest, standardised mean difference (SMD) −0.61 (95%CI −1.05, −0.16; p=0.008) and at 48 hours during activity, SMD −0.43 (95%CI −0.78, −0.09; p=0.014). Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Long-term outcomes were not a focus of these studies. In the APEX RCT, pain levels in hospital were broadly similar between groups, probably due to patient-controlled analgesia. Opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. Patients receiving LAI were less likely to report severe pain at 12 months than those receiving standard care, odds ratio 10.2 (95%CI 2.1, 49.6; p=0.004). Complications were similar between groups. In the economic evaluation, LAI was associated with lower costs and greater cost-effectiveness than standard care. Using a £20,000 per QALY threshold, the incremental net monetary benefit was £1,125 (95%CI £183, £2,067) and the probability of being cost-effective was greater than 98 %. The evidence suggests that peri-operative LAI is a cost-effective intervention for reducing acute and chronic post-surgical pain after THR

Robust evidence on the effectiveness of peri-operative local anaesthetic infiltration (LAI) is required before it is incorporated into the pain management regimen for patients receiving total knee replacement (TKR). To assess the effectiveness of peri-operative LAI for pain management in patients receiving TKR we conducted a systematic review, fully powered randomised controlled trial (RCT) and economic evaluation. We searched MEDLINE, Embase and Cochrane databases for RCTs of peri-operative LAI in patients receiving TKR. Two reviewers screened abstracts and extracted data. Outcomes were pain, opioid use, mobilisation, hospital stay and complications. Authors were contacted if required. When feasible, we conducted meta-analysis with studies analysed separately if a femoral nerve block (FNB) was provided. In the APEX RCT, we randomised 316 patients awaiting TKR to standard anaesthesia which included FNB, or to the same regimen with additional peri-operative LAI (60mls 0.25% bupivacaine plus adrenaline). Post-operatively, all patients received patient-controlled morphine. The primary outcome was joint pain severity (WOMAC-Pain) at 12 months. Patients and outcome assessors were blinded to allocation. Within APEX, cost-effectiveness was assessed from the health and social-care perspective in relation to quality adjusted life years (QALYs) and WOMAC-Pain at 12-months. Resource use was collected from hospital records and patient questionnaires. In the systematic review, 23 studies including 1,439 patients were identified. Compared with patients receiving no intervention, LAI reduced WOMAC-Pain by standardised mean difference (SMD) −0.40 (95%CI −0.58, −0.22; p<0.001) at 24 hours at rest and by SMD −0.27 (95%CI −0.50, −0.05; p=0.018) at 48 hours during activity. In three studies there was no difference in pain at any time point between randomised groups where all patients received FNB. Patients receiving LAI spent fewer days in hospital, used less opioids and mobilised earlier. Complications were similar between groups. Few studies reported long-term outcomes. In the APEX RCT, pain levels in hospital were broadly similar between groups. Overall opioid use was similar between groups. Time to mobilisation and discharge were largely dependent on local protocols and did not differ between groups. There were no differences in pain outcomes between groups at 12 months. In the economic evaluation, LAI was marginally associated with lower costs. Using the NICE £20,000 per QALY threshold, the incremental net monetary benefit was £264 (95%CI, −£710, £1,238) and the probability of being cost-effective was 62%. Although LAI appeared to have some benefit for reduced pain in hospital after TKR there was no evidence of pain control additional to that provided by femoral nerve block, however it would be cost-effective at the current NICE thresholds

Osteoarthritis (OA). is the most common arthritic condition. OA causes joint pain, loss of mobility and significantly affects the quality of life for the affected individual. The major burden to patients with arthritis is pain. However, often radiological joint destruction and the extent of pain do not correlate. This causes a dilemma for clinicians in advising timing for joint replacement surgery. In arthritis, concentrations of the neurotransmitter, glutamate is increased within the synovial fluid activating both peripheral pain mechanisms and pathological processes (1). Other pathological/pain related metabolites are also released into synovial fluid, which provides a real time snap shot of the joint pathology. We have tested the hypothesis that ‘The increased levels of pain and disease-related metabolites within human synovial fluids from arthritic joints can be detected and quantified ex vivo using high resolution 1H-NMR.’. Method. OA synovial fluid samples were obtained during arthroscopy or total knee replacements from patients with varying degrees of pain and pathology (cartilage graded 0-4; n=21). Pain perception was determined using the Oxford knee score and samples sub-classified as mild, moderate and severe pain. All samples were analysed using 500 MHz 1H NMR spectroscopy. Chemical shifts were referenced to a known concentration NMR internal standard (TSP), peaks identified by reference to published synovial fluid NMR spectra (2) and peak integrals measured using the Bruker software Topspin 2.0. Results: Using NMR we were able to detect around 26 metabolite-specific peaks in synovial fluid spectra (such as glutamate/glutamine, isoleucine, acetyl glucoproteins, beta-hydroxbutyrate, CH2 lipids, lactate, glucose). Some specific metabolites varied significantly with pain or pathological score. For example, we found significantly more glutamate/glutamine, isoleucine and beta-hydroxybutyrate (p<0.05, T test) in OA samples reporting mild to moderate levels of pain (n=14) compared to severe pain (n=7). Significantly more CH2 lipids (p<0.05, T-test) were also present in samples indicating severe pain compared to mild/moderate pain. Discussion. Our results have indicated that the metabolic profile of synovial fluid from patients with arthritis can differ depending on degree of pain and disease state. A number of the 26 metabolites assessed showed significant differences between different levels of pain as determined by the Oxford knee score. Both glutamate and isoleucine are known regulators of nociception. Whereas beta-hydroxybutyrate and CH2 lipids levels in synovial fluid may be indicative of alterations in joint metabolism. We have shown for the first time that specific metabolic changes within arthritic synovial fluid that can be detected by NMR may be indicative of pain and pathology. This will provide important new information about the biochemical processes underlying arthritic pain and pathology as well as identify a range of new biomarkers

Background. Osteoarthritis (OA), is characterised with a loss of cartilage and pain in affected joints. It is this pain which most patients associate with their condition. Intra-articular (IA) hyaluronan (HA) has been shown to reduce the pain associated with OA both in animal models and in clinical trials. There are purified HA available and in recent years hyaluronan hydrogels, where the material has been cross-linked into networks, have become available. One of these cross-linked HA hydrogels is Durolane¯. This study has sought to evaluate the effect of Durolane in an in vivo model of osteoarthritis. Methods. Mice (C57BL/6, 12 weeks) were obtained from Jackson Labs and all protocols were approved by Rush IACUC. Joint injury was initiated by TGFb1 injection as described [1]. Mice were given IA injections of 200 ng TGFb1, at days 1 and 3 delivered in a 6 ul volume into the rear right knee joint only. Twenty four hours after the second injection of TGFb1 10 ul of Durolane was injected into the same knee joint. All animals were exercised daily on a treadmill to induce tissue degeneration. Three groups of animals were evaluated: Naïve (n = 4), TGFb1 + saline (n = 5) and TGFb1 + Durolane (n = 5). Running performance was monitored daily and 15 days post injections, gait was assessed quantitatively using the TreadScan gait analysis system (CleverSys). Results. Combined treatment of IA TGFb1 and treadmill running results in rapid and reproducible OA-like joint tissue remodelling in injected knee joints, including cartilage erosion, synovial and joint capsule fibrosis and chondrophyte accumulation along joint margins [2]. It was clear that the injections of TGFb1 + saline into the rear right knee joint caused impairment in gait, such as limping and difficulty to maintain treadmill running. In comparison the TGFb1 + Durolane treated animals showed running behaviours similar to that seen in untreated naïve mice. Quantitative assessment of gait using the TreadScan system, for a number of gait parameters, confirmed that Durolane returned the gait in these animals with induced OA closer to the gait of naïve animals. For example the stance time, described as time elapsed while the foot is in contact with the tread in its stance phase, being 185.81 ms (SD 34.85) for naïve, 249.67 ms (SD 37.58) for TGFb1 + saline and 214.86 ms (SD 28.1) for TGFb1 + Durolane treated animals. Single factor ANOVA for primary comparison between TGFb1 + Durolane and TGFb1 + saline provided a significant improvement for the Durolane group (p < 0.05). Conclusions. This study has demonstrated that a single IA injection of Durolane can improve gait in this non-surgical model of OA confirming earlier data that Durolane provides anti-nociceptive effects in a model of joint pain [3]

Introduction. Patients with knee osteoarthritis (OA) often tell us that they put extra load on the joints of the opposite leg as they walk. Multiple joint OA is common and has previously been related to gait changes due to hip OA (Shakoor et al 2002). The aim of this study was to determine whether patients with medial compartment knee OA have abnormal biomechanics of the unaffected knee and both hips during normal level gait. Methods. Twenty patients (11 male, 9 female), with severe medial compartment knee OA and no other joint pain were recruited. The control group comprised 20 adults without musculoskeletal pain. Patients were reviewed, x-rays were examined and WOMAC and Oxford knee scores were completed. A 12 camera Vicon (Vicon, Oxford) system was used to collect kinematic data (100Hz) on level walking and the ground reaction force was recorded using three AMTI force plates (1000Hz). Surface electrodes were placed over medial and lateral quadriceps and hamstrings bilaterally to record EMG data (1000Hz). Kinematics and kinetics were calculated using the Vicon ‘plug-in-gait’ model. A co-contraction index was calculated for the EMG signals on each side of the knee, representing the magnitude of the combined readings relative to their maximum contraction during the gait cycle. Statistical comparisons were performed using t-tests with Bonferroni's correction for two variables and ANOVA for more than two variables (SPSS v16). Results. The mean age of the patients was 69 (SD 8.8). Mean gait speed was 0.95m/s (study group) and 1.44m/s (control group). Peak adduction moments for the OA group [OA Knee; Unaffected Knee; Ipsilateral Hip; Contralateral Hip; in Nm/Kg(±95% CI)] were: 0.55(0.06); 0.47(0.06); 0.73(0.09); 0.73(0.08). Control values for peak moments were 0.64 (0.06) for the knee and 0.81(0.07) at the hip. Mid-stance adduction moments for the OA group (listed as before) were: 0.44(0.08); 0.33(0.06); 0.64(0.06); 0.61(0.08). Control values for mid-stance moments were 0.14(0.03) and 0.40(0.04). [OA group vs. Controls: p=NS for peak moments at all 4 joints; p<0.01 for mid-stance moments at all joints]. Co-contraction indices for hamstrings and quads, [OA knee medial; and lateral; unaffected knee medial; and lateral; control medial; and lateral; 0<X. Discussion. Although the affected subjects all had only single joint OA, abnormal moments were present in the hips and knees of both legs during normal level gait, despite the reduced gait speed of the OA cohort. Abnormal hamstring and quadriceps co-contraction occurs bilaterally in patient with single joint OA. Increased trunk sway is a recognised compensation in knee OA and may be the cause of the abnormal hip and contra-lateral knee loading found in this study. Further investigation is warranted and may lead to improvements in the long term outcome for these patients. Acknowledgement. The study was funded by the North Wales NHS Trust

Objectives

The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01).

Objectives

This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model.

Objectives

This study reports on a secondary exploratory analysis of the early clinical outcomes of a randomised clinical trial comparing robotic arm-assisted unicompartmental knee arthroplasty (UKA) for medial compartment osteoarthritis of the knee with manual UKA performed using traditional surgical jigs. This follows reporting of the primary outcomes of implant accuracy and gait analysis that showed significant advantages in the robotic arm-assisted group.

Objectives

Whilst gait speed is variable between healthy and injured adults, the extent to which speed alone alters the 3D in vivo knee kinematics has not been fully described. The purpose of this prospective study was to understand better the spatiotemporal and 3D knee kinematic changes induced by slow compared with normal self-selected walking speeds within young healthy adults.

Objectives

The aim of this study was to systematically review the literature on measurement of muscle strength in patients with femoroacetabular impingement (FAI) and other pathologies and to suggest guidelines to standardise protocols for future research in the field.

Objectives

The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA.