Aims. The aim of this study was to develop a core outcome set of what to measure in all future clinical research on hand fractures and joint injuries in adults. Methods. Phase 1 consisted of steps to identify potential outcome domains through systematic review of published studies, and exploration of the patient perspective through qualitative research, consisting of 25 semi-structured interviews and five focus groups. Phase 2 involved key stakeholder groups (patients, hand surgeons, and hand therapists) prioritizing the outcome domains via a three-round international Delphi survey, with a final consensus meeting to agree the final core outcome set. Results. The systematic review of 160 studies identified 74 outcome domains based on the World Health Organization International Classification of Functioning, Disability, and Health. Overall, 35 domains were generated through thematic analysis of the patient interviews and focus groups. The domains from these elements were synthesised to develop 37 outcome domains as the basis of the Delphi survey, with a further four generated from participant suggestions in Round 1. The Delphi survey identified 20 outcome domains as ‘very important’ for the core outcome set. At the consensus meeting, 27 participants from key stakeholder groups selected seven outcomes for the core outcome set: pain/discomfort with activity, pain/discomfort with rest, fine hand use/dexterity, self-hygiene/personal care, return to usual work/job, range of motion, and patient satisfaction with outcome/result. Conclusion. This set of core outcome domains is recommended as a minimum to be reported in all clinical research on hand fractures and joint injuries in adults. While this establishes what to measure, future work will focus on determining how best to measure these outcomes. By adopting this patient-centred core outcome set, consistency and comparability of studies will be improved, aiding meta-analysis and strengthening the evidence base for management of these common and impactful injuries. Cite this article: Bone Jt Open 2023;4(2):87–95

Aims

To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms.

Cite this article: Bone Joint Res 2022;11(8):514–517.

Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2

Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis, which occurs secondary to traumatic joint injury which is known to cause pathological changes to the osteochondral unit. Articular cartilage degradation is a primary hallmark of OA, and is normally associated with end-stage disease. However, subchondral bone marrow lesions are associated with joint injury, and may represent localized bone microdamage. Changes in the osteochondral unit have been traditionally studied using explant models, of which the femoral-head model is the most common. However, the bone damage caused during harvest can confound studies of microdamage. Thus, we used a novel patellar explant model to study osteochondral tissue dynamics and mechanistic changes in bone-cartilage crosstalk. Firstly, we characterized explants by comparing patella with femoral head models. Then, the patellar explants (n=269) were subjected to either mechanical or inflammatory stimulus. For mechanical stimulus 10% strain was applied at 0.5 and 1 Hz for 10 cycles. We also studied the responses of osteochondral tissues to 10ng/ml of TNF-α or IL-1β for 24hrs. In general the findings showed that patellar explant viability compared extremely well to the femoral head explant. Following IL-1β or TNF-α treatment, MMP13, significantly increased three days post exposure, furthermore we observed a decrease in sulfate glycoaminoglycan (sGAG) content. Bone morphometric analysis showed no significant changes. Contrastingly, mechanical stimulation resulted in a significant decrease sGAG particularly at 0.5Hz, where an increase in MMP13 release 24hrs post stimulation and an upregulation of bone and cartilage matrix degradation markers was observed. Furthermore, mechanical stimulus caused increases in TNF-α, MMP-8, VEGF expression. In summary, this study demonstrates that our novel patella explant model is an excellent system for studying bone-cartilage crosstalk, which responds well to both mechanical and inflammatory stimulus and is thus of great utility in the study of PTOA

Senescent chondrocyte and subchondral osteoclast overburden aggravate inflammatory cytokine and pro-catabolic proteinase overproduction, accelerating extracellular matrix degradation and pain during osteoarthritis (OA). Fibronectin type III domain containing 5 (FNDC5) is found to promote tissue homeostasis and alleviate inflammation. This study aimed to characterize what role Fndc5 may play in chondrocyte aging and OA development. Serum and macroscopically healthy and osteoarthritic cartilage were biopsied from patients with knee OA who received total knee replacement. Murine chondrocytes were transfected with Fndc5 RNAi or cDNA. Mice overexpressing Fndc5 (Fndc5Tg) were operated to have destabilized medial meniscus mediated (DMM) joint injury as an experimental OA model. Cellular senescence was characterized using RT-PCR analysis of p16INK4A, p21CIP1, and p53 expression together with ß-galactosidase activity staining. Articular cartilage damage and synovitis were graded using OARSI scores. Osteophyte formation and mechanical allodynia were quantified using microCT imaging and von Frey filament, respectively. Osteoclast formation was examined using tartrate-resistant acid phosphatase staining. Senescent chondrocyte and subchondral osteoclast overburden together with decreased serum FNDC5 levels were present in human osteoarthritic cartilage. Fndc5 knockdown upregulated senescence program together with increased IL-6, MMP9 and Adamts5 expression, whereas Alcian blue-stained glycosaminoglycan production were inhibited. Forced Fndc5 expression repressed senescence, apoptosis and IL-6 expression, reversing proliferation and extracellular matrix production in inflamed chondrocytes. Fndc5Tg mice showed few OA signs, including articular cartilage erosion, synovitis, osteophyte formation, subchondral plate sclerosis and mechanical allodynia together with decreased IL-6 production and few senescent chondrocytes and subchondral osteoclast formation during DMM-induced joint injury. Mechanistically, Fndc5 reversed histone H3K27me3-mediated IL-6 transcription repression to reduce reactive oxygen species production. Fndc5 loss correlated with OA development. It was indispensable in chondrocyte growth and anabolism. This study sheds light onto the anti-ageing and anti-inflammatory actions of Fndc5 to chondrocytes; and highlights the chondroprotective function of Fndc5 to compromise OA

The August 2023 Children’s orthopaedics Roundup. 360. looks at: DDH: What can patients expect after open reduction?; Femoral head deformity associated with hip displacement in non-ambulatory cerebral palsy; Bony hip reconstruction for displaced hips in patients with cerebral palsy: is postoperative immobilization indicated?; Opioid re-prescriptions after ACL reconstruction in adolescents are associated with subsequent opioid use disorder; Normative femoral and tibial lengths in a modern population of USA children; Retrospective analysis of associated anomalies in 636 patients with operatively treated congenital scoliosis; Radiological hip shape and patient-reported outcome measures in healed Perthes’ disease; Significantly displaced adolescent posterior sternoclavicular joint injuries

Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493

Development of osteoarthritis (OA) correlates with epigenetic alteration in chondrocytes. H3K27me3 demethylase UTX is known to regulate tissue homeostasis, but its role in the homeostasis of articulating joint tissue is poorly understood. Forced UTX expression upregulated H3K27me3 enrichment at the Sox9 promoter region to inhibit key extracellular matrix (ECM) molecules, like e.g. type II collagen, aggrecan, and glycosaminoglycans in articular chondrocytes. Utx loss in vitro altered the H3K27me3-binding epigenomic landscape, which contributes to mitochondrial activity, cellular senescence, and cartilage development. Functional target genes of Utx comprise insulin-like growth factor 2 (Igf2) and polycomb repressive complex 2 (PRC2) core components Eed and Suz12. Specifically, Utx deletion promoted Tfam transcription, mitochondrial respiration, ATP production and Igf2 transcription, but inhibited Eed and Suz12 expression. Igf2 inhibition or forced Eed or Suz12 expression increased H3K27 trimethylation and H3K27me3 enrichment at the Sox9 promoter, compromising Utx loss-induced ECM overproduction. Overexpression of Utx in murine knee joints aggravated OA development, including articular cartilage damage, synovitis, osteophyte formation, and subchondral bone loss. Transgenic mice with a chondrocytespecific Utx knockout develop thicker articular cartilage as compared to wild-type controls and show fewer gonarthrotic symptoms during destabilized medial meniscus- and collagenase-induced joint injury. In summary, UTX represses chondrocytic activity and accelerates cartilage degradation during OA, while Utx loss promotes cartilage integrity through epigenetic stimulation of mitochondrial biogenesis and Igf2 transcription. This highlights a novel noncanonical role of Utx that regulates articular chondrocyte anabolism and OA development

Glenohumeral joint injuries frequently result in shoulder instability. However, the biomechanical effect of cartilage loss on shoulder stability remains unknown. The aim of the current study was to investigate biomechanically the effect of two severity stages of cartilage loss in different dislocation directions on shoulder stability. Joint dislocation was provoked for 11 human cadaveric glenoids in seven different dislocation directions between 3 o'clock (anterior) to 9 o'clock (posterior) dislocation. Shoulder stability ratio (SSR) and concavity gradient were assessed in intact condition, and after 3 mm and 6 mm simulated cartilage loss. The influence of cartilage loss on SSR and concavity gradient was statistically evaluated. Between intact state and 6 mm cartilage loss, both SSR and concavity gradient decreased significantly in every dislocation direction (p≤0.038), except the concavity gradient in 4 o'clock dislocation direction (p=0.088). Thereby, anterior-inferior dislocation directions were associated with the highest loss of SSR and concavity gradient of up to 59.0% and 49.4%, respectively, being significantly higher for SSR compared to all other dislocation directions (p≤0.04). The correlations between concavity gradient and SSR for pooled dislocation directions were significant for all three conditions of cartilage loss (p<0.001). From a biomechanical perspective, articular cartilage of the glenoid contributes significantly to the concavity gradient, correlating strongly with the associated loss in glenohumeral joint stability. The highest effect of cartilage loss was observed in anterior-inferior dislocation directions, suggesting that surgical intervention should be considered for recurrent shoulder dislocations in the presence of cartilage loss

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA. Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CRE. ERT2. ;Piezo1. fl/fl. Piezo2. fl/fl. ) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria. Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology. Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice

Abstract. Objectives. The syndesmosis joint, located between the tibia and fibula, is critical to maintaining the stability and function of the ankle joint. Damage to the ligaments that support this joint can lead to ankle instability, chronic pain, and a range of other debilitating conditions. Understanding the kinematics of a healthy joint is critical to better quantify the effects of instability and pathology. However, measuring this movement is challenging due to the anatomical structure of the syndesmosis joint. Biplane Video Xray (BVX) combined with Magnetic Resonance Imaging (MRI) allows direct measurement of the bones but the accuracy of this technique is unknown. The primary objective is to quantify this accuracy for measuring tibia and fibula bone poses by comparing with a gold standard implanted bead method. Methods. Written informed consent was given by one participant who had five tantalum beads implanted into their distal tibia and three into their distal fibula from a previous study. Three-dimensional (3D) models of the tibia and fibula were segmented (Simpleware Scan IP, Synopsis) from an MRI scan (Magnetom 3T Prisma, Siemens). The beads were segmented from a previous CT and co-registered with the MRI bone models to calculate their positions. BVX (125 FPS, 1.25ms pulse width) was recorded whilst the participant performed level gait across a raised platform. The beads were tracked, and the bone position of the tibia and fibula were calculated at each frame (DSX Suite, C-Motion Inc.). The beads were digitally removed from the X-rays (MATLAB, MathWorks) allowing for blinded image-registration of the MRI models to the radiographs. The mean difference and standard deviation (STD) between bead-generated and image-registered bone poses were calculated for all degrees of freedom (DOF) for both bones. Results. The absolute mean tibia and fibula bone position differences (Table 1) between the bead and BVX poses were found to be less than 0.5 mm for both bones. The bone rotation differences were found to be less than 1° for all axes except for the fibula Z axis rotation which was found to be 1.46°. One study. 1. has reported the kinematics of the syndesmosis joint and reported maximum ranges of motion of 9.3°and translations of 3.3mm for the fibula. The results show that the accuracy of the methodology is sufficient to quantify these small movements. Conclusions. BVX combined with MRI can be used to accurately measure the syndesmosis joint. Future work will look at quantifying the accuracy of the talus to provide further understanding of normal ankle kinematics and to quantify the kinematics across a healthy population to act as a comparator for future patient studies. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Hip Osteoarthritis (HOA) is the most common joint disorder and a major cause of disability in the adult population, leading to total hip replacement (THR). Recently, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early OA in the non-dysplastic hip. FAI is a pathological mechanical process, caused by abnormalities of the acetabulum and/or femur leading to damage the soft tissue structures. FAI can determine chondro-labral damage and groin pain in young adults and can accelerate HOA progression in middle-aged adults. The aim of the study was to determine if the presence of calcium crystal in synovial fluid (SF) at the time of FAI surgery affects the clinical outcomes to be used as diagnostic and predictive biomarker. 49 patients with FAI undergoing arthroscopy were enrolled after providing informed consent; 37 SFs were collected by arthrocentesis at the time of surgery and 35 analyzed (66% males), median age 35 years with standard deviation (SD) 9.7 and body mass index (BMI) 23.4 kg/m. 2. ; e SD 3. At the time of surgery, chondral pathology using the Outerbridge score, labral pathology and macroscopic synovial pathology based on direct arthroscopic visualization were evaluated. Physical examination and clinical assessment using the Hip disability & Osteoarthritis Outcome Score (HOOS) were performed at the time of surgery and at 6 months of follow up. As positive controls of OA signs, SF samples were also collected from cohort of 15 patients with HOA undergoing THR and 12 were analysed. 45% FAI patients showed CAM deformity; 88% presented labral lesion or instability and 68% radiographic labral calcification. 4 patients out of 35 showed moderate radiographic signs of OA (Kellegren-Lawrence score = 3). Pre-operative HOOS median value was 61.3% (68.10-40.03) with interquartile range (IQR) of 75-25% and post-operative HOOS median value 90% with IQR 93.8-80.60. In both FAI and OA patients the calcium crystal level in SFs negatively correlated with glycosaminoglycan (component of the extracellular matrix) released, which is a marker of cartilage damage (Spearman rho=-0.601, p<0.001). In FAI patients a worst articular function after surgery, measured with the HOOS questionnaire, was associated with both acetabular and femoral chondropathy and degenerative labral lesion. Moreover, radiographic labral calcification was also significantly associated with pain, worst articular function and labral lesion. Calcium crystal level in SFs was associated with labral lesions and OA signs. We concluded that the levels of calcium crystals in FAI patients are correlated with joint damage, OA signs and worst post-operative outcome. The presence of calcium crystals in SF of FAI patients might be a potential new biomarker that might help clinicians to make an early diagnosis, evaluate disease progression and monitor treatment response

Although remnant-preserved ACL reconstruction (ACLR) restores knee joint stability and dampens the problem of acute ACL rupture-induced knee pain, an increasing number of patients still develop post-traumatic osteoarthritis (PTOA) after 10 to 15 years of ACLR. We previously found that remnant-preserved ACLR with concomitant medial and lateral meniscus repair may not prevent cartilage degeneration and weaken muscle strength, while the clinical features of PTOA are not clear. We hypothesized that remnant-preserved ACLR with concomitant medial and lateral meniscus tears is related to early cartilage damage, worse function recovery, patient-reported outcomes (PROs) and delayed duration to return to sports. The aim is to evaluate the remnant-preserved ACLR with complicated meniscal injuries in predicting which patients are at higher risk of osteoarthritic changes, worse function and limited activities after ACLR for 12 months. Human ethical issue was approved by a committee from Xi'an Jiaotong University. 26 young and active patients (24 male, 2 female) with ACL injuries (Sherman type I and II) with concomitant medial and lateral meniscus within 2 months were included from January 2014 to March 2022. The average age of the ACLR+ meniscus repair was 26.77±1.52 (8 right, 5 left) and isolated ACLR control was 31.92±2.61 years old (7 left, 6 right). Remnant-preserved ACLR with a 5- to 6-strand hamstring tendon graft was operated on by the same sports medicine specialists. MRI CUBE-T. 2. scanning with 48 channels was conducted by a professional radiologist. The volume of the ACL graft was created through 3 dimensional MRI model (Mimics 19, Ann Arbor). Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS) was applied to score visible cartilage damage. IKDC 2000 score and VAS were assessed by two blinded researchers. Results were presented as mean± SEM of each group. The cross-sectional area and 3D volume of the ACL graft were greater in the remnant-preserved ACLR+meniscus group compared with isolated ACLR (p=0.01). It showed that ACLR+ meniscus group had early signs of joint damage and delayed meniscus healing regarding ACLOAS compared to control group (p=0.045). MRI CUBE-T. 2. prediction of radiographic cartilage degeneration was not obvious in both groups post remnant-preserved ACLR over 12 months (p>0.05). However, higher VAS scores, lower IKDC scores, and long-last joint swelling were reported in the ACLR+ meniscus repair group at the end of 12 months follow-up. Although remnant-preserved ACLR+ meniscus was able to maintain the restore the knee function, it showed delayed timing (>12 months) to return to play at the pre-injury stage, while no difference between the timing of returning to the normal daily routine of their ACLR knee compared to control (p=0.30). The cost of ACLR+ meniscus (average 10,520.76$) was higher than the control group (6,452.92$, p=0.018). Remnants-preserved ACLR with concomitant injured medial and lateral meniscus repair shows a higher risk of cartilage damage, greater cost, worse functional performance, and longer time for young male patients to return to sports after 12-month follow-up compared to isolated ACLR. Further evidence and long-term follow-up are needed to better understand the association between these results and the risk of development of PTOA in this patient cohort

Abstract. INTRODUCTION. The mechanisms underlying abnormal joint mechanics are poorly understood despite it being a major risk factor for developing osteoarthritis. Glutamate signalling has been implicated in osteoarthritic bone changes and AMPA/kainate glutamate receptor (GluR) antagonists alleviate degeneration in rodent models of osteoarthritis. We investigated whether glutamate signalling molecules are mechanically regulated in a human, cell-based 3D model of bone. METHODS. Human Y201 MSC cells embedded in 3D type I collagen gels (0.05 × 106 cell/gel) differentiated to osteocytes were mechanically loaded in silicone plates (5000 µstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). RNA extracted 1-hr post load was quantified by RTqPCR and RNAseq whole transcriptome analysis (NovaSeq S1 flow cell 2 × 100bp PE reads). Differentially expressed GluRs and glutamate transporters (GluTs) were identified using DEseq2 analysis on normalised count data. Genes were considered differentially expressed if >2 fold change and FDR p<0.05. RESULTS. Cells expressed mature osteocyte markers (E11, sclerostin, DMP-1). DEseq2 analysis, revealed 981 mechanically regulated genes. Mechanical loading upregulated kainate GluRs, GRIK2 (1.6 fold, p=0.024) and GRIK5 (4.2 fold, p=0.045); the NMDA GluR GRIN3B (3.25 fold, p=0.047) and the GluT SLC1A1 (3 fold, p=0.037). Conversely, AMPA GRIA3, NMDA GluRs GRIN2A&C, and the GluT SLC1A2 were down regulated by 50–60%, although not significant. Kainate GRIK3&4; AMPA GRIA2, NMDA GRIN1, and GluTs SLC1A6&A7 were not expressed in control or loaded osteocytes, whereas GluRs (GRIK1, GRIA1&4, GRIN2B&2D&3A) and GluT SLC1A3 were expressed but not regulated by mechanical loading. DISCUSSION. Mechanical loading of human osteocytes in 3D revealed that they regulated expression of glutamate receptors and transporters. This is consistent with our observation that mechanical perturbation after joint injury in rodent models of OA regulates glutamatergic signalling in the bone thus linking mechanical stimuli to inflammatory and nociceptive pathways mediated by glutamate receptors. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Rheumatoid arthritis is the most common inflammatory disease of the joints affecting about 0.5% of adults, women more often than men with a peak age of onset of 35–45 years. It is usually progressive affecting further joints and the destructive disease process causes irreversible bony erosions and the joints become structurally deformed, with long-term pain and disability. It has an early and significant impact on the person’s ability to work and socio-economic status with work capacity restricted in a third within a year and within 3 years almost half 40 may be registered work disabled. The aims of management of rheumatoid arthritis are to reduce pain an inflammation; reduce disability; prevent joint damage and progression; and to reduce the comorbidities that are associated with the disease. As joint damage is irreversible it is important to diagnose the disease and institute disease modifying anti-rheumatic therapy as soon as possible. There is as yet no way of preventing the disease. Lifestyle interventions of avoiding obesity, maintaining physical activity and avoiding smoking may improve outcome. Symptoms can be effectively controlled with analgesics and NSAIDs and joint damage can be reduced with disease modifying antirheumatic therapy with consequent benefits to quality of life. Biological therapies, such as anti TNF, are the latest advance that is dramatically improving the outlook for those developing RA. Rehabilitation interventions can improve and maintain function, including dynamic training. Surgery also has an important role, predominantly arthroplasty when pharmacological therapies have not adequately prevented joint damage. Effective management of rheumatoid arthritis requires early diagnosis and treatment by recognising those with early inflammatory arthritis and for expert assessment within 6 weeks to decide about disease modifying anti-rheumatic therapy. This should be in addition to symptomatic therapy, rehabilitation and education to improve understanding of their chronic disease and to encourage self management. Such management should be provided through a multiprofessional and multidisciplinary group. People with RA need regular monitoring to ensure optimal disease management. This will reduce the risk of longterm joint damage and disability and will lessen indirect costs of RA. This approach requires systems for early diagnosis and for referral to experts, which includes education of primary care physicians to enable them to recognise synovitis. Public education is also needed to ensure early presentation to the primary care physician at the onset of symptoms

Aims. A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients’ quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures. Methods. A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods. Discussion. The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open 2021;2(3):150–163

Aim. Septic arthritis (SA) is considered a medical emergency. The most common etiological agents are glucose consuming bacteria, so we evaluated the clinical utility of synovial fluid (SF) glucose levels and other biochemical parameters for supporting the diagnosis of the disease and their association with a positive bacteria culture and joint destruction. Methods. Adult patients with SA diagnose were enrolled prospectively between July 2018 and October 2019. As control group, adults with knee osteoarthritis, meniscus and/or knee ligaments lesions were enrolled. SF samples were obtained from the joints by arthrocentesis/arthrotomy. Microbiological analyses of SF were performed using Brucella broth blood culture flasks, samples were incubated at 37°C with 5% CO. 2. for 24 hours. Gram stain, chocolate and blood agar were used for the identification and growth of the bacteria. SF glucose levels, pH and leukocyte esterase were measured as biochemical parameters using a glucometer and colorimetric test strips. The Outerbridge classification was used for grading the osteochondral injury. Furthermore, blood samples were collected from patients and control subjects for determining glucose levels. Results. We included 8 subjects with knee ligaments lesions, 6 with meniscus lesions and 5 with osteoarthritis as control group, as well as 20 patients with SA diagnose. The mean age of the patients was 57.8 years with a 65% of male predominance. The most common affected joint was the knee (85%). SF culture was positive in 60% of the cases and the most common etiological agent was Staphylococcus aureus (58.3%). SF glucose levels from patients were lower than the controls (P=0.0018) and showed the lowest concentration in patients with a positive culture (P=0.0004). There was also a difference between blood and SF glucose concentration from the positive culture patients (P<0.0001). Leucocyte esterase presented the highest values in positive culture patients (P=<0.0001) and a more acidic pH was found compared to the control group (P<0.0001). Regarding the osteochondral injury, the lowest concentrations of SF glucose were found in patients with a higher grade in the classification (P = 0.0046). Conclusions. SF glucose and leukocyte esterase concentrations might be a quick and cheap useful parameter for the physician for distinguishing between bacterial infection and not infected joint. In addition, the lowest SF glucose levels might give information about the joint damage due to the disease

Osteoarthritis (OA) is a disease that affects both bone and cartilage. Typically, this disease leads to cartilage degradation and subchondral bone sclerosis but the link between the two is unknown. Also, while OA was traditionally thought of as non-inflammatory condition, it now seems that low levels of inflammation may be involved in the link between these responses. This is particularly relevant in the case of Post-Traumatic OA (PTOA), where an initial phase of synovial inflammation occurs after injury. The inflammatory mediator interleukin 1 beta (IL-1B) is central to this response and contributes to cartilage degradation. However, whether there is a secondary effect of this mediator on subchondral bone, via bone-cartilage crosstalk, is not known. To address this question, we developed a novel patellar explant model, to study bone cartilage crosstalk which may be more suitable than commonly used femoral head explants. The specific aim of this study was to validate this novel patellar explant model by using IL-1B to stimulate the inflammatory response after joint injury and the subsequent development of PTOA. Female Sprague Dawley rats (n=48) were used to obtain patellar explants, under an institutional ethical approval license. Patellae were maintained in high glucose media, under sterile culture conditions, with or without IL-1B (10ng/ml), for 7 days. Contralateral patellae served as controls. One group (n= 12) of patellae were assessed for active metabolism, using two both Live and Dead (L/D) staining and an Alamar Blue assay (AB). A second group (n=12) was used for tissue specific biochemical assays for both bone (Alkaline Phosphatase) and cartilage (sulfated proteoglycan and glycosaminoglycan (sGaG)). Finally, a third group (n=28) of explants were used for histologically analysis. Samples were decalcified, embedded in paraffin and sectioned to 7µm thickness, and then stained using H&E; and Safranin O with fast green. Additionally, toluidine blue and alkaline phosphatase staining were also performed. Our results demonstrate that our system can maintain good explant viability for at least 7 days, but that IL-1B reduces cell viability in patellar cartilage, as measured by both L/D and AB assays after 0, 2, 4 and 7 days in culture. In contrast, sGaG content in cartilage were increased by this treatment. Additionally, ALP, a marker of osteoblastic activity, was increased in IL-1B treated group 4 and 7 days, but was also showed some increase in control groups. Histological analyses showed that IL-1B treatment resulted in reduced proteoglycan staining, demonstrating the powerful effect of this factor in injury response over time. Thus, we conclude that IL-1B affects both bone and cartilage tissues independently in this system, which may have relevance in understanding bone-cartilage crosstalk after injury and how this is involved in PTOA development

Purpose. Operative treatment of Lisfranc joint injuries typically includes reduction and stabilization of the medial and middle columns of the midfoot. Mobility of the lateral column is preserved where possible, such that indications for lateral column stabilization rely upon the surgeons assessment of instability. In this case series, the indication for lateral column stabilization was defined by the results of an intra-operative stress test. The purpose of this study was to determine whether an intra-operative fluoroscopic stress test of the lateral column was sufficient to determine the need for internal fixation of the lateral column in Lisfranc joint injuries. Method. 35 adult patients with Lisfranc injuries operated in our centre by a single surgeon from 2005–2009 were reviewed. All patients had unstable midfoot fracture dislocations, treated by reduction and internal fixation including an intra-operative stress examination to determine the need for lateral column fixation. Patients were contacted for clinical and radiographic review at a mean of 31 months post injury. Functional outcome was assessed using general and joint-specific outcome tools (AOFAS midfoot score and LEM). Radiographic review included analysis of joint displacement and arthritic changes in preoperative, postoperative, and most recent radiographs. Results. Pre-operative imaging demonstrated displacement of the lateral column in 25 / 35 patients. Nineteen of these 25 had a stable reduction of the lateral column following medial and middle column fixation, based upon an intra-operative stress examination. Only 6 patients had persistent instability; these were treated with lateral column stabilization. Reduction of the lateral column was maintained at final follow up in 100 percent of 35 patients. Lateral midfoot pain was present in 5/6 patients requiring lateral fixation, compared to 1/(19) patient who did not require lateral fixation. AOFAS midfoot scores (mean) were 80 15. in patients with no evidence of lateral column instability, 79 15. in patients with preoperative displacement but a negative stress examination, and 77 18 in patients requiring lateral fixation (p>0.05). Post-traumatic arthrosis was present in 3/10 patients with no evidence of lateral column instability, 4/19 patients with preoperative displacement but a negative stress examination, and 4/6 in patients requiring lateral fixation (p>0.05). Conclusion. The decision to stabilize the lateral column during surgery on Lisfranc injuries was aided by an intra-operative fluoroscopic stress examination. Based upon the stress examination, 19 / 25 patients who had a displaced lateral column at the time of presentation avoided lateral fixation. None of these 19 patients treated without lateral fixation lost reduction in the follow up period. A fluoroscopic intra operative stress test safely reduced the need for lateral column fixation in displaced Lisfranc joint injuries

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310

Aim of study Setting an investigation and therapeutical algorythm in paediatric patients with a distal tibiofibular joint injury. Material: The authors present their clinical material collected during the period of last five years (from 1997 to 2001). 222 children with physeal injury of the distal tibia and/or fibula were treated in the Regional Paediatric Trauma Centre in Prague Krè. Methods: In all patients with an injury of the ankle joint, a plain X-ray scanning in two basic planes was performed. In any doubts oblique views or an X-ray scan of the ankle joint in a stress position were added. In some patients it was necessary to complete the investigation by CT scans. Results: Only 9 % of all 222 selected patients sustained the distal tibiofibular joint injury. In 85 % of them the skeletal injury was evident (the juvenile Tillaux fracture of Salter’s type 3 or 4). In the rest 15 % (three cases) there was no skeletal trauma visible on neither plain nor oblique X-ray scans but CT scan showed it. Conclusions: Injury to the distal tibiofibular joint is very rare in the growing skeleton. Most of our patients were of premature age. There is a danger of missing this rare but subsequently serious injury. That’s why we recommend the use of CT in all cases of ankle joint injury in children. Children with fractures (juvenile Tillaux fracture) displaced more than 2 mm should be operated on (closed reduction and internal fixation). In two girls we had to stabilise the distal tibiofibular joint due to severe ligamentous injury

Introduction. Septic arthritis of the native knee often results in irreversible joint damage leading to the need for a total knee arthroplasty (TKA). This study examines the mid-term risk of periprosthetic joint infection (PJI), aseptic revision, any revision, and any reoperation in primary TKAs after septic arthritis of the native knee compared to a control cohort of primary TKAs performed for osteoarthritis (OA). Methods. We retrospectively identified 215 primary TKAs performed between 1971 and 2016 at a single institution following septic arthritis of the native knee. Eighty-two percent (177 cases) were treated in a single setting, whereas a two-stage exchange arthroplasty protocol was utilized in 18% (39 cases) for ongoing or suspected active native knee septic arthritis. Each case was matched 1:1 based on age, sex, body mass index (BMI), and surgical year to a primary TKA for OA. Mean age and BMI were 63 years and 30 kg/m2, respectively. Mean follow-up was 9 years. Results. Survivorship free from any infection (inclusive of PJI and wound infections) at 10 years was 87% in the septic arthritis cohort and 98% for the OA cohort (HR=6.5, p<0.01). Survivorship free of PJI at 10 years was 90% in the septic arthritis and 99% in the OA group (HR=6; p<0.01). There was no difference in the rate of infection when TKA occurred within 5 years of a septic arthritis diagnosis compared to a diagnosis that occurred >5 years from the TKA. The survivorship free of aseptic revision at 10 years was 83% for the septic arthritis cohort and 93% for the OA cohort (HR=2.5, p<0.01). When combining the above survivorships free of aseptic and septic revisions, the survivorship free of any revision at 10 years was 78% in the septic arthritis cohort and 91% in the OA cohort (HR=3, p<0.01). The 10-year survivorship free of any reoperation was 61% in septic arthritis group and 84% in the OA group (HR=3; p<0.01). Preoperative and 2-year postoperative Knee Society scores were similar between groups (p=0.16 and p=0.19, respectively). Conclusion. There was a 6-fold increased risk of PJI in patients undergoing TKA with prior history of septic arthritis when compared to controls who had a TKA for OA, with a cumulative incidence of 9% at 10 years. Moreover, the 10-year survivorships free of aseptic revision, any revision, and any reoperation were significantly worse in the septic arthritis cohort. Summary. A history of septic arthritis prior to primary TKA allows for satisfactory clinical outcomes, but patients had increased risk of PJI, aseptic revision, any revision, and any reoperation compared to a control cohort

Introduction and Aims: Late degeneration of the ACL injured knee may be in part due to repeat injury, but also due to aberrant kinematics altering the wear pattern at the chondral surface. The aim of this study was to use tibio-femoral contact mapping by MRI to examine kinematic changes due to chronic ACL deficiency. Method: Twenty subjects with a recent unilateral ACL deficiency (mean 13 months since injury) and 23 subjects with a chronic ACL deficiency (mean 18 years since injury) were recruited. Passive ligament laxity was quantified using a KT1000® device. Subjects performed a closed-chain leg press, relaxed and against a 15 kg weight. MRI recorded the tibio-femoral contact position at 15-degree intervals from zero to 90 degrees of knee flexion. Tibio-femoral contact points were measured at each position. Damage to the knee was recorded for all subjects by MRI, and at arthroscopy. Results: The tibio-femoral contact pattern of the ACL injured knee was different from the healthy contralateral knee (p = 0.001). The contact pattern of the recently injured knees was different to the chronic ACL deficient knees (p = 0.034). In the recently injured knees the lateral compartment of the knee showed a posterior pattern of femoral contact, and in the chronic ACL deficient knees the medial compartment showed a posterior femoral contact pattern, particularly at zero and 15 degrees of knee flexion (p < 0.01), with the femur two millimetres (mean, SD 3.2mm) posterior on the tibial plateau. There was no difference in passive laxity between the recent and chronic injured knees (side-to-side difference: 5.8mm±2.4 for the recently injured knees, and 4.6±2.8mm for the chronic ACL-deficient knees). Nine of 20 recently injured knees had associated joint damage: three medial and three lateral meniscal tears, two with medial femoral condyle and two with patello-femoral damage. Eleven of 23 chronic ACL deficient subjects had associated joint damage: 15 medial and 16 lateral meniscus tears, 16 with medial and 12 with lateral compartment chondral damage. Greater kinematic changes in the chronic ACL deficient knees were associated with more severe chondral damage in the medial compartment. Conclusion: ACL injury shifts the axis of rotation of the knee medially. In chronic ACL deficiency the tibio-femoral contact pattern is altered in the medial compartment, where it is associated with joint damage. These findings describe the relationship between aberrant kinematics and wear in the ACL deficient knee

Osteoarthritis (OA) is a multifactorial debilitating disease that affects over four million Canadians. Although the mechanism(s) of OA onset is unclear, the biological outcome is cartilage degradation. Cartilage degradation is typified by the progressive loss of extracellular matrix components - aggrecan and type II collagen (Col II) – partly due to the up-regulation of catabolic enzymes - aggrecanases a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS-) 4 and 5 and matrix metalloproteinases (MMPs). There is currently no treatment that will prevent or repair joint damage, and current medications are aimed mostly at pain management. When pain becomes unmanageable arthroplastic surgery is often performed. Interest has developed over the presence of calcium crystals in the synovial fluid of OA patients, as they have been shown to activate synovial fibroblasts inducing the expression of catabolic agents. We recently discovered elevated levels of free calcium in the synovial fluid of OA patients and raised the question on its role in cartilage degeneration. Articular cartilage was isolated from 5 donors undergoing total hip replacement. Chondrocytes were recovered from the cartilage of each femoral head or knee by sequential digestion with Pronase followed by Collagenase and expanded in DMEM supplemented with 10% heat-inactivated FBS. OA and normal human articular chondrocytes (PromoCell, Heidelberg, Germany) were transferred to 6-well plates in culture medium containing various concentrations of calcium (0.5, 1, 2.5, and 5 mM CaCl2), and IL-1β. Cartilage explants were prepared from the same donors and included cartilage with the cortical bone approximately 1 cm2 in dimension. Bovine articular cartilage explants (10 months) were used as a control. Explants were cultured in the above mentioned media, however, the incubation period was extended to 21 days. Immunohistochemistry was performed on cartilage explants to measure expression of Col X, MMP-13, and alkaline phosphatase. The sulfated glycosaminoglycan (GAG, predominantly aggrecan) content of cartilage was analyzed using the 1,9-dimethylmethylene blue (DMMB) dye-binding assay, and aggregan fragmentation was determined by Western blotting using antibody targeted to its G1 domain. Western blotting was also performed on cell lysate from both OA and normal chondrocytes to measure aggrecan, Col II, MMP-3 and −13, ADAMTS-4 and −5. Ca2+ significantly decreased the proteoglycan content of the cartilage explants as determined by the DMMB assay. The presence of aggrecan and Col II also decreased as a function of calcium, in both the human OA and bovine cartilage explants. When normal and OA chondrocytes were cultured in medium supplemented with increasing concentrations of calcium (0.5–5 mM Ca2+), aggrecan and Col II expression decreased dose-dependently. Surprisingly, increasing Ca2+ did not induce the release of MMP-3, and −13, or ADAMTS-4 and-5 in conditioned media from OA and normal chondrocytes. Interestingly, inhibition of the extracellular calcium-sensing receptor CaSR) reversed the effects of calcium on matrix protein synthesis. We provide evidence that Ca2+ may play a direct role in cartilage degradation by regulating the expression of aggrecan and Col II through activation of CaSR

Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments. Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after joint injury and may provide further insight into the role of chondrocyte death in post-traumatic arthritis

The paramount importance of synovial fluid in lubrication and protection of articular joints has long been recognized. Synovial fluid, a dialysate of plasma, forms an interface with both the synovium and cartilage and plays a crucial role in joint lubrication and bearing functions. In an osteoarthritic joint, damage to the articular cartilage causes modifications in the rheological properties of synovial fluid and, reducing the viscoelasticity and increasing the friction between articular surfaces. Viscosupplementation is a treatment for osteoarthritis that uses hyaluronic acid as a (visco)supplement to the diseased joint. The aim of this treatment is to restore the rheological properties of synovial fluid. Osteoarthritis is the most common disease affecting the joints in human population and among the most important causes of pain, disability and economic loss. Therefore, innovative methods are needed to more effectively treat osteoarthritis, directly addressing the disease process. Among various locomotor mechanisms that could serve to illustrate the integrated nature of functional morphology, perhaps none is more complex than the equine locomotor system. Confronting the need for evaluating the current methods to control joint disease, the horse provides an excellent animal model. As it suffers similar clinical manifestations to those seen in human, it may provide tentative biomedical extrapolations

Osteoarthritis (OA) is the most common musculoskeletal disease in the EU and is characterized by cartilage degeneration, pain and restricted movement. Post-Traumatic OA (PTOA) is a specific disease subset that occurs subsequent to traumatic injury, such as ACL rupture and makes up 12% of the overall disease burden. Our current understanding PTOA is that initial injury affects multiple tissues, and many/all contribute to overall ‘joint failure.’ MRI scans show that subchondral bone marrow lesions (BMLs) are present in 80% of ACL rupture cases in the immediate aftermath of joint injury. Their presence indicates an acute consequence in subchondral bone. It has also been suggested that BMLs overlap with, or directly represent, bone microdamage. Microdamage is known to induce osteoclast-mediated remodelling in bone. Therefore, the inhibition of subchondral bone remodelling, particularly in the early phase post-injury, may be a candidate therapeutic approach for preventing PTOA. Finally, the contiguous link between subchondral bone and articular cartilage, can allow transport of small molecules across this boundary, this suggests that bone/cartilage crosstalk is likely to be a key factor in PTOA development after injury. This presentation will summarize recent advances in our understanding these phenomena in both animal and human studies

In least 12% of patients with symptomatic OA, the cause is joint injury that progressed over time to post-traumatic OA. Human adult articular cartilage has a limited innate ability to regenerate. Available treatment options are unable to restore native structure and function of hyaline cartilage. Agili-C (CartiHeal, Israel) is a first-in-class acellular scaffold consisted of two layers corresponding to cartilage and bone that is capable of attracting stem cells and guide a regenerative process in both tissues. Agili-C has been extensively tested in vitro in our laboratory using human normal cartilage and in vivo in preclinical and currently clinical studies. This scaffold consists of a natural crystalline aragonite, derived from corals, to which hyaluronic acid is added. It showed a great ability to induce regeneration of chondral and osteochondral lesions and attract chondrocytes and stems cells to fill the defect area. Cells remained viable over the course of the study (up to 2 months). Signs of the extracellular matrix formation were evident inside 3D structure of the scaffold. PG synthesis and gene expression of collagen type II and aggrecan were elevated by more than 2.5-fold in cartilage with the scaffold vs corresponding controls. Agili-C scaffold displays a potential in the treatment of focal chondral and osteochondral defects

Joint injuries often result in inflammation and cartilage defects. When inflamed, the synovium secretes factors that prevent successful cartilage repair by inhibiting chondrogenic differentiation of progenitor cells. In particular the pro-inflammatory macrophages in the synovium are indicated to contribute to this anti-chondrogenic effect. Thus, we aimed to counteract the anti-chondrogenic effect of inflamed synovium by modulating synovial inflammation and its macrophages. Synovium tissue obtained from osteoarthritic patients undergoing a total knee replacement was cut into explants and cultured for 72 hours +/− 1 µM of the anti-inflammatory drug triamcinolone acetonide (TAA) (Sigma Aldrich). TAA significantly decreased gene expression of TNFA, IL1β and IL6, and increased expression of CCL18, IL1RA in synovial explants (all with p < 0.001). On the other hand, TAA significantly decreased the percentages of pro-inflammatory CD14+/CD80+ and CD14+/CD86+ macrophages in the synovium (both p < 0.001) as assessed by flow cytometry analyses. The percentages of anti-inflammatory CD14+/CD163+ macrophages, is significantly increased (p < 0.001) in TAA treated synovium. Conditioned medium (CM) from synovium explants downregulated the gene expression of cartilage matrix components collagen type-2 and aggrecan expression in chondrogenic MSCs. This chondrogenesis inhibiting effect was reduced by treating synovium with TAA during the production of the CM. Our findings indicate that reducing synovial inflammation might improve the joint environment for better cartilage repair, possibly by modulation of macrophage phenotypes

Onset and progression of osteoarthritis (OA) is affected by a plethora of factors, including joint injury, obesity, aging, and heredity. This multi-factorial etiology obstructs our understanding of driving molecular mechanisms, which likely comprise an interplay between systemic and local factors. Next to biomechanical factors and cytokines, the course of OA appears to be altered by microenvironmental oxidative stress: cumulative evidence now suggests a prominent participation of cell signalling mediated by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master regulator of cellular protective processes, in this process. Nrf2 activation through phosphorylation of mitogen-activated protein kinases (MAPKs) regulates Nrf2 target genes, like hemeoxygenase-1 (HO-1), superoxide dismutase 2 (SOD2), or NAD(P)H Quinone Dehydrogenase 1 (NQO1) in OA chondrocytes. Maintaining high levels of HO-1 appears to be beneficial against OA development. Experimental manipulation of putative antioxidant response element (ARE) binding sites alters the in vitro expression of key transcription factors of chondrocyte markers in promoter-reporter assays. Potentially, Nrf2 is involved in autophagy, intermediary metabolism and unfolded protein response. RNAi-mediated depletion of Nrf2 further significantly abrogated anti-inflammatory and chondroprotective effects and epigenetics link transcriptional pathways of ‘N-factors’, Nrf2 and NFATs, to micro-RNA signalling. Current findings thus reveal novel mechanisms regulating extracellular matrix synthesis by chondrocytes. A further understanding of these pathways and their regulation will lead to important novel targets to slow OA progression

Juvenile idiopathic arthritis (JIA) is a chronic disease of childhood; it causes joint damage which may require surgical intervention, often in the young adult. The aim of this study was to describe the long-term outcome and survival of hip replacement in a group of adult patients with JIA and to determine predictors of survival for the prosthesis. In this retrospective comparative study patients were identified from the database of a regional specialist adult JIA clinic. This documented a series of 47 hip replacements performed in 25 adult patients with JIA. Surgery was performed at a mean age of 27 years (11 to 47), with a mean follow-up of 19 years (2 to 36). The mean Western Ontario and McMaster Universities osteoarthritis index questionnaire (WOMAC) score at the last follow-up was 53 (19 to 96) and the mean Health Assessment Questionnaire score was 2.25 (0 to 3). The mean pain component of the WOMAC score (60 (20 to 100)) was significantly higher than the mean functional component score (46 (0 to 97)) (p = 0.02). Kaplan-Meier survival analysis revealed a survival probability of 46.6% (95% confidence interval 37.5 to 55.7) at 19 years, with a trend towards enhanced survival with the use of a cemented acetabular component and a cementless femoral component. This was not, however, statistically significant (acetabular component, p = 0.76, femoral component, p = 0.45). Cox’s proportional hazards regression analysis showed an implant survival rate of 54.9% at 19 years at the mean of covariates. Survival of the prosthesis was significantly poorer (p = 0.001) in patients who had been taking long-term corticosteroids and significantly better (p = 0.02) in patients on methotrexate

Introduction Late degeneration of the ACL injured knee may be in part due to repeat injury, but also due to aberrant kinematics altering the wear pattern at the chondral surface. The aim of this study was to use tibio-femoral contact mapping by MRI to examine kinematic changes due to chronic ACL deficiency. Methods Twenty-three subjects with a history of chronic ACL deficiency (mean 18 years since injury) performed a closed chain leg press, relaxed and against a 15 kilogram weight. MRI recorded the tibio-femoral contact position at 15° intervals from 0° to 90° of knee flexion. Intra-articular pathology was assessed for all subjects by MRI, and at arthroscopy for 10 subjects. Results The tibio-femoral contact pattern of the ACL injured knee differed from the healthy contralateral knee (p=0.003). This difference was greatest in the medial compartment, particularly at 0° and 15° of knee flexion (p< 0.01), with the femur two millimetres (mean, SD 3.2 mm) posterior on the tibial plateau. Damage to the chondral surface was seen in the medial compartment in 16 subjects and lateral compartment in 12; medial meniscus damage was present in 16 subjects and lateral meniscus in 15. Chondral surface damage correlated with the difference in the tibio-femoral contact pattern between the healthy and injured knee in the medial compartment of the knee. Joint damage was not related significantly to time since injury, or Cincinnati knee score. Joint damage was related to level of sports participation, but probably indicates that as the joint failed, subjects curtailed their activity. Conclusions The kinematic consequences of chronic ACL injury may in part be responsible for the pattern of degenerative change, especially in the medial compartment of the knee. In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source

Ligaments, menisci and joint capsules were obtained from experimental knees with post-traumatic joint contractures and their unoperated contralateral controls in 6 rabbits. Relative mRNA expression was altered for six of seven matrix molecules, growth factors and _-SMA (myofibroblast marker) in the joint capsule, four of seven molecules in the ACL, and two of seven molecules in the MCL and medial meniscus. The joint capsule had the most molecules with altered expression corresponding to it’s acknowledged key role in joint contracture development. Changes in molecular expression of several joint structures in post-traumatic contractures is similar to changes seen following ligament injury. To evaluate alteration of mRNA expression in ligaments, meniscus and joint capsules in post-traumatic contractures. mRNA expression was altered most frequently in the joint capsule. The mRNA expression alterations in the joint capsule reflect it’s significant contribution to contractures. The right knee had a stable intraarticular fracture coupled with Kirschner wire immobilization while the left knee was not surgically manipulated. The rabbits (n=6) were sacrificed two weeks later, and the ACL, MCL, posterior joint capsule and medial meniscus were obtained from both knees. Semiquantitative RT-PCR was used to evaluate relative mRNA expression of selected matrix molecules, growth factors and _-smooth muscle actin (_-SMA), a myofibroblast marker. Glyc-eraldehyde-3-phosphate dehydrogenase, a housekeeping gene, served as a normalization. Optical density measures of the gels were used for analysis. Statistical comparisons were made with a paired t-test. Statistical significance was p< 0.05. Relative mRNA expression was altered for six of seven molecules in the joint capsule, four of seven molecules in the ACL, and two of seven molecules for the MCL and meniscus. For the joint capsule, relative mRNA expression in the contracture capsule was 2-4x greater than the expression in the control capsules, except for TIMP one where the expression in the contracture capsule was 1/3 of the control capsules. As has been noted with other joint injuries (ligament instability), several structures in the joint display altered molecular expression as was found in this model of joint injury, post-traumatic joint contractures. Please contact author for tables and/or graphs

Purpose: The presence of hemarthrosis during joint injury is a potential inciting stimulus in the genesis of joint capsule fibrosis. Using a rabbit model of posttraumatic knee joint contracture, our hypothesis was that, bone marrow-derived elements of hemarthrosis rather than simply the presence of blood in the joint, trigger the induction of capsule fibrosis in post-traumatic joint contracture. Method: 35 Skeletally mature New Zealand White female rabbits (12–18 months old, 5.5 ± 0.5 kg) were randomly assigned to one of five groups: Immobilization-Only (IMO), Immobilization+ Bone Marrow (IMBM), Immobilization+ Peripheral Blood (IMPB), Bone Marrow-Only (BMO), and Controls. Surgeries: Immobilization groups had one knee joint fixed at full flexion with a Kirschner wire drilled through the tibia, passed posterior (extra-articular) to the knee joint and bent around the femur. Bone marrow groups had cortical windows removed from the non-articular cartilage portion of the medial and lateral femoral condyles. In the IMPB group, autologous peripheral venous blood was injected into the immobilized knee joint to recreate a non-traumatic hemarthrosis. The control group did not have any intervention. Joint angle measurements: After 8 weeks, rabbits were euthanized, all muscular tissue was removed and maximum extension angle of the joints with intact capsule was measured using a standard torque applied via a custom made rabbit knee gripping device attached to a MTS TestStar II. Each joint was cycled 5 times (0.2 Nm) and the average of 5 cycles was calculated. Statistical analysis consisted of a one-way ANOVA with posthoc Scheffe test (significance p < 0.05). Data are presented as mean +/ − standard deviation. Results: The IMBM (n=8) and IMPB (n=7) groups had significantly greater contractures (52 +/ − 12 and 58 +/ − 13 degrees, respectively) when compared to the BMO (n=7) and control (n=6) groups (32 +/ − 10 and 32 +/ − 13 degrees, respectively). The IMO group had average contracture measures of 44 +/ − 15 degrees. There was no statistically significant difference between the IMBM and IMPB groups. Conclusion: The present study showed differences in the contracture severity of the immobilized knees associated with hemarthrosis compared to other experimental and control groups. There does not appear to be a difference whether the hemarthrosis arose from a fracture (bone marrow) versus peripheral blood in rabbits. Future work will look at reversibility of contractures in the various groups. Studies on the joint capsule will evaluate myofibroblast numbers in concert with mast cell and neuropeptide distribution based on our previous work. Such knowledge will aid the prevention and treatment of the difficult and disabling problem of contracture formation after joint injury

Osteoarthritis (OA) is associated with biochemical and mechanical processes that release different wear particles into the synovial fluid. Unfortunately, symptoms such as pain, swelling and limited range of motion often do not correlate with the level of OA as observed by X-ray. In addition, the mechanisms of OA and the processes involved are still not clearly understood. Therefore, there is much interest in developing new diagnostic techniques that would provide means to both sensitive, objective determination of joint damage and studying the underlying mechanisms. Such a technique may also aid in evaluating the efficiency of drugs under development objectively and relatively quickly. Bio-ferrography (BF) is a method for magnetic isolation of target cells or particles in a fluid. The current project was aimed at evaluating the applicability of BF for isolation and analysis of specific wear particles in human joints. Synovial fluid aspirates were drawn during either arthroscopy or total joint replacement from 14 patients with either OA or other types of chondropathy. Target components of bone and cartilage (collagen type I and type II, respectively) were labeled with monoclonal antibodies coupled to magnetic beads. The captured particles were isolated on microscope slides by means of BF and characterized by several optical and scanning electron microscopy techniques combined with chemical analysis. The number, size and shape of particles were quantified by image analysis. Results showed that specific labeling of target collagens enables capture of a much higher number of particles in comparison to previous reports. A variety of particles with different morphologies and sizes were documented. The number of captured particles changed in different patients. In addition to bone and cartilage fragments, particles of repaired cartilage that contained collagen I, meniscus particles containing collagens I and II, and magnesium-rich particles that could form during biochemical dissolution of hydroxyapatite or precipitation from body fluids, were identified. Further in-depth characterization of these particles would shade more light on the mechanisms and processes involved in joint degradation. The evaluation of joint damage by BF was found to correlate with clinical observations. It was concluded that BF has the potential of becoming a powerful tool in the study of human joint diseases. Future studies may use even more specific labeling of joint components. BF may become a routine diagnostic technique, aiding the orthopedist in determination of OA level in an objective manner. The ability to draw samples quickly during arthroscopy with little discomfort to the patient could facilitate routine serial assessment of particular joints

Aims

Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection.

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Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

Background. Epigenetic regulation of gene transcription affects metabolism of chondrocytes and synovial fibroblasts and is associated with the prevalence of osteoarthritis (OA) of knees. Histone lysine demethylase (KDMs) reportedly modulates tissue homeostasis and deterioration. This study investigated whether KMD6a inhibitor treatment affected the joint injuries in the progression of OA. Methods. Collagenase-induced OA knees in mice were intra-articular administered with KDM6a inhibitor GSK-J4. Walking patterns and footprints of affected animals were detected by Catwalk. Articular cartilage injury was quantified by OARSI scoring; and subchondral bone microstructure was analysed by μCT imaging. Histopathology and mRNA expression of cartilage, fibrosis and bone matrices in joint micro-compartments were detected by histomorphometry and quantitative RT-PCR. Methylation states of chondrogenic transcription factor SOX9 promoter was detected by methylation-specific PCR and chromatin immuno-precipitation. Results. Declined KDM6a expression and SOX9 gene transcription was associated with the pathogenesis of collagenase-induced joint injures. GSK-J4 administration dose-dependently improved gait profiles and footprint characteristics of affected feet and alleviated histopathology of severe cartilage degradation, synovial inflammation, fibrotic matrix accumulation and subchondral bone microarchitecture deterioration in injured joints. Treatment with GSK-J4 decreased expression of fibrogenic factor (TGF-β1, PLOD2 and TIMP) and restored expression of cartilage and bone matrices (collagen II, I, aggrecan, and osteocalcin). KDM6a inhibitor curtailed the hypomethylation of SOX9 promoter and lysine 27 of histone H3 (H3K27) and restored SOX9 mRNA and protein levels in joint tissues. Conclusions. KDM6a enhanced SOX9 promoter and H3K27 hypomethylation that accelerated the progression of OA. KDM6a inhibitor had mitigated effects on SOX9 promoter demethylation thereby restored SOX9 signaling and stabilised homeostasis of cartilage, synovium and subchondral bone compartments in affected joints. This study sheds a new light on the KDM6a-mediated epigenetic dysfunction in OA joints and has a perspective that pharmaceutical KDM6a inhibitor has therapeutic potential for OA knee pathogenesis. Level of evidence. II

The April 2023 Research Roundup³⁶⁰ looks at: Ear protection for orthopaedic surgeons?; Has arthroscopic meniscectomy use changed in response to the evidence?; Time to positivity of cultures obtained for periprosthetic joint infection; Bisphosphonates for post-COVID-19 osteonecrosis of the femoral head; Missing missed fractures: is AI the answer?; Congenital insensitivity to pain and correction of the knee; YouTube and paediatric elbow injuries.

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The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems.

The February 2024 Trauma Roundup³⁶⁰ looks at: Posterior malleolus fractures: what about medium-sized fragments?; Acute or delayed total hip arthroplasty after acetabular fracture fixation?; Intrawound antibiotics reduce the risk of deep infections in fracture fixation; Does the VANCO trial represent real world patients?; Can a restrictive transfusion protocol be effective beyond initial resuscitation?; What risk factors result in avascular necrosis of the talus?; Pre-existing anxiety and mood disorders have a role to play in complex regional pain syndrome; Three- and four-part proximal humeral fractures at ten years.

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For the increasing number of working-age patients undergoing total hip or total knee arthroplasty (THA/TKA), return to work (RTW) after surgery is crucial. We investigated the association between occupational class and time to RTW after THA or TKA.

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Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA.

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To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

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This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue.

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Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis.

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The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome.

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Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

Introduction. Version abnormalities of the femur, either retroversion or excessive anteversion, cause pain and hip joint damage due to impingement or instability respectively. A retrospective clinical review was conducted on patients undergoing a subtrochanteric derotation osteotomy for either excessive anteversion or retroversion of the femur. Methods. A total of 49 derotation osteotomies were performed in 39 patients. There were 32 females and 7 males. Average age was 29 years (range 14 to 59 years). Osteotomies were performed closed with an intramedullary saw (Figure 1). Fixation was performed with a variety of intramedullary nails. Patients requiring a varus or valgus intertrochanteric osteotomy were excluded. Pure rotational corrections only were performed. Twenty-four percent of patients had a retroversion deformity (average −8° retroversion, range +1 to −23°), 76% had excessive anteversion of the femur (average +36° anteversion, range +22° to +53°). Etiology was post-traumatic in 5 (10%), diplegic cerebral palsy in 4 (8%), fibrous dysplasia in 2 (4%), Prader-Willi Syndrome in 1 (2%) and idiopathic in 37 (76%). Previous surgery had been performed in 51% of hips. Fifty-seven percent underwent concomitant surgery with the index femoral derotation osteotomy, including hip arthroscopy in 39% (labral debridement alone or with femoral neck osteochondroplasty), a tibial derotation osteotomy in 12% and periacetabular osteotomy in 6%. Concomitant tibial osteotomies were performed to correct a compensatory excessive external tibial torsion that would be exacerbated in the correction of excessive femoral anteversion. The modified Harris Hip Score was used to assess the results in patients with a minimum of 24 months follow-up. Results. There were no non-unions. Average time to union was 3.3 months. One late infection occurred 10 months after surgery, treated successfully with hardware removal and antibiotics. Two patients, one with Prader-Willi syndrome and one with Ehlers-Danlos syndrome, were converted to total hip replacement. At an average follow-up of 6.1 years (range 2 to 19.1 years), the modified Harris Hip Score improved by 26 points (p< 0.001, Wilcoxon signed-ranks test). The results were rated as excellent in 71%, good in 22%, fair in 5% and poor in 3%. Subsequent surgery was required in 73%, 93% of which were hardware removals. Discussion and Conclusion. A closed, subtrochanteric derotation osteotomy of the femur is a safe and effective procedure to treat either femoral retroversion or excessive anteversion. Excellent or good results were obtained in 93%, despite the need for subsequent hardware removal in more than two-thirds of the patients. For figures/tables, please contact authors directly.

Aims

Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

Aims. To compare radiographic failure and re-operation rates of anatomical coracoclavicular (CC) ligament reconstructional techniques with non-anatomical techniques after chronic high grade acromioclavicular (AC) joint injuries. . Patients and Methods. We reviewed chronic AC joint reconstructions within a region-wide healthcare system to identify surgical technique, complications, radiographic failure and re-operations. Procedures fell into four categories: (1) modified Weaver-Dunn, (2) allograft fixed through coracoid and clavicular tunnels, (3) allograft loop coracoclavicular fixation, and (4) combined allograft loop and synthetic cortical button fixation. Among 167 patients (mean age 38.1 years, (standard deviation (. sd. ) 14.7) treated at least a four week interval after injury, 154 had post-operative radiographs available for analysis. . Results. Radiographic failure occurred in 33/154 cases (21.4%), with the lowest rate in Technique 4 (2/42 4.8%, p = 0.001). Half the failures occurred by six weeks, and the Kaplan-Meier survivorship at 24 months was 94.4% (95% confidence interval (CI) 79.6 to 98.6) for Technique 4 and 69.9% (95% CI 59.4 to 78.3) for the other techniques when combined. In multivariable survival analysis, Technique 4 had better survival than other techniques (Hazard Ratio 0.162, 95% CI 0.039 to 0.068, p = 0.013). Among 155 patients with a minimum of six months post-operative insurance coverage, re-operation occurred in 9.7% (15 patients). However, in multivariable logistic regression, Technique 4 did not reach a statistically significant lower risk for re-operation (odds ratio 0.254, 95% CI 0.05 to 1.3, p = 0.11). Conclusion. In this retrospective series, anatomical CC ligament reconstruction using combined synthetic cortical button and allograft loop fixation had the lowest rate of radiographic failure. . Take home message: Anatomical coracoclavicular ligament reconstruction using combined synthetic cortical button and allograft loop fixation had the lowest rate of radiographic failure. Cite this article: Bone Joint J 2016;98-B:512–18

Acute septic arthritis of the knee can lead to joint damage or sepsis, if early diagnosis and treatment fail to occur, which includes drainage of the joint, adequate antibiotic coverage and resting of the knee. Classically, drainage of the knee was performed either with multiple aspirations or open arhtrotomy. The arthroscopic approach has becoming widely accepted, as it allows adequate drainage of the pus and debridement with partial or total sinovectomy of the joint. The aim of this study was to evaluate the differences between arthroscopy and open arthrotomy in the clinical outcomes and rate of recurrence in patients with septic arthritis of the knee joint. We reviewed patients with acute septic arthritis of the knee admitted in our center between January 2010 and December 2014. The criteria for diagnosis was report of purulent material when arhtrotomy or arthroscopy was performed or a positive culture of the joint fluid. Patients with recent surgery or documented osteomyelitis of the femur or tíbia were excluded. We used the Oxford Knee Score (OKS) to classify the clinical outcomes in the end of follow-up, and registered the rate of recurrence in each group. The statistical evaluation of the results was performed using Student's t-test. 65 patients were treated during this period, 37 by an open arthrotomy through a lateral supra-patellar aproach, and 28 by arthroscopy through 2 standard anterior portals. All the patients were imobilized with a cast or orthosis in the immediate post-operation period for a mean period of 13 days in the arthrotomy group (8–15) and 9 days in the arthroscopy group (6–12) and received endovenous antibiotics for at least 10 days, followed by oral antibiotics for a mean total of 36 days in the the arthrotomy group (30–48) and 32 days in the arthroscopy group (22–36). The mean follow-up was 22 months in the arthrotomy group (8–28 months) and 18 months in the arthroscopy group (14–24). The mean OKS was 31 in the the arthrotomy group (21–39) and 35 in the arthroscopy group (25–44). There was 1 recurrence in the arthrotomy group and 1 recurrence in the arthroscopic group, both managed by knee arthrotomy. Drainage is a key step in treatment of knee pyoarthrosis, either through an open or an arthroscopic approach. Both seem to be equally effective, with no significant statistical difference in terms of recurrence. The functional results tend to favour the arthroscopic approach, but with no statistical significance

Hip arthroscopy is particularly attractive in children as it confers advantages over arthrotomy or open surgery, such as shorter recovery time and earlier return to activity. Developments in surgical technique and arthroscopic instrumentation have enabled extension of arthroscopy of the hip to this age group. Potential challenges in paediatric and adolescent hip arthroscopy include variability in size, normal developmental change from childhood to adolescence, and conditions specific to children and adolescents and their various consequences. Treatable disorders include the sequelae of traumatic and sports-related hip joint injuries, Legg–Calve–Perthes’ disease and slipped capital femoral epiphysis, and the arthritic and septic hip. Intra-articular abnormalities are rarely isolated and are often associated with underlying morphological changes. This review presents the current concepts of hip arthroscopy in the paediatric and adolescent patient, covering clinical assessment and investigation, indications and results of the experience to date, as well as technical challenges and future directions

Septic arthritis is a therapeutic emergency with a high mortality rate (about 11%)(1). Inadequate treatment can cause permanent joint damage. Management of the septic arthritis includes prompt antibiotic treatment as well as joint-decompression and removal of purulent material(2). It is still discussed controversially and there is little evidence which surgical concept is preferable: arthroscopy with lavage and debridement or open arthrotomy with synovectomy(3,4). The aim of the study was to compare efficacy of arthroscopy and arthrotomy in patients with septic gonarthritis. We evaluated 70 consecutive patients who underwent arthroscopy or arthrotomy at our clinic, because of a bacterial monarthritis of the knee between 2002 and 2010. Our primary outcome was the early recurrence of infection (> 3 months after surgery), which made a second surgery necessary. We compared patients who suffered reinfection and those who did not, in regard to the surgery type as well as potential confounders like comorbidity (measured by Charlson comorbidity index), age, body mass index (BMI), Gächter's -, Kellgren and Lawrence - and Outerbridge classification, duration of symptoms and inflammatory parameters. Furthermore we evaluated differences of the confounders between the surgery groups. From the 70 patients 41 were treated arthroscopic and 29 with arthrotomy. In total eight patients (11.4%) had to undergo a second surgery because of early reinfection. The rate was significantly higher in patients treated with arthrotomy (n=6; 20.7%) compared to those treated with arthroscopy (n=2; 4.9%) (p=0.041). Whereas we found no significant influence of potential confounders between the reinfection group and the group where primary eradication was achieved. Patients who underwent arthrotomy were significantly older, had more comorbidities (both p<0.001) and higher grades of osteoarthritis according to Kellgren and Lawrence classification (p=0.023). In order to adjust the study population towards confounders we performed a subgroup analysis on patients of the second and third age percentile. When we repeated our analysis we still found a significant higher reinfection rate in the arthrotomy group (p=0.036). At the same time there were no differences in prevalence of confounders, neither between the two surgery groups, nor between the reinfection and the primary eradication group. Patients with bacterial monarthritis of the knee who were treated with arthroscopy had a significantly lower reinfection rate than those treated with arthrotomy. As arthroscopy is the less invasive and more sufficient method it should be considered the routine treatment according to our data

Young adults with hip pain secondary to femoroacetabular impingement (FAI) are rapidly being recognised as an important cohort of orthopaedic patients. Interest in FAI has intensified over the last decade since its recognition as a precursor to arthritis of the hip and the number of publications related to the topic has increased exponentially in the last decade. Although not all patients with abnormal hip morphology develop osteoarthritis (OA), those with FAI-related joint damage rapidly develop premature OA. There are no explicit diagnostic criteria or definitive indications for surgical intervention in FAI. Surgery for symptomatic FAI appears to be most effective in younger individuals who have not yet developed irreversible OA. The difficulty in predicting prognosis in FAI means that avoiding unnecessary surgery in asymptomatic individuals, while undertaking intervention in those that are likely to develop premature OA poses a considerable dilemma. FAI treatment in the past has focused on open procedures that carry a potential risk of complications. Recent developments in hip arthroscopy have facilitated a minimally invasive approach to the management of FAI with few complications in expert hands. Acetabular labral preservation and repair appears to provide superior results when compared with debridement alone. Arthroscopic correction of structural abnormalities is increasingly becoming the standard treatment for FAI, however there is a paucity of high-level evidence comparing open and arthroscopic techniques in patients with similar FAI morphology and degree of associated articular cartilage damage. Further research is needed to develop an understanding of the natural course of FAI, the definitive indications for surgery and the long-term outcomes. Cite this article: Bone Joint J 2013;95-B, Supple A:26–30

Introduction. In this study we decided to observe the incidence of osteoarthritis following ORIF of Lisfranc joint injury. We also intended to point out the influence of different factors such as late diagnosis of the fracture, co-fractures, and open or close fractures on the incidence of osteoarthritis. Methods. Patients with a dislocation more than 2 millimeters in simple AP, lateral and oblique radiograms of the foot who went through ORIF were included. Patients were classified according to: Anatomic or non-anatomic reduction, open or close fractures, presence of other fractures and early or late diagnosis (up to 6 weeks). The incidence of osteoarthritis was then compared in these groups. Results. In 20 patients (45%), post traumatic osteoarthritis occurred. In the 10 patients with non-anatomic reduction, 8 (80%) experienced osteoarthritis, when from the 34 patients with anatomic reduction 12(35%) did so (p = 0.004). Discussion. 9% of the cases were not diagnosed in the 1st visit and 22% attended the hospital with delay. According to the findings, having either open or close fracture or delayed diagnosis up to 6 weeks has no influence on the prevalence of osteoarthritis after trauma, and the only important factor affecting the prevalence of post-traumatic osteoarthritis is anatomic reduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA.

Cite this article: Bone Joint Res 2021;10(4):285–297.

Osteoarticular loss in a major weightbearing joint is one of the many consequences of military conflict. While minor in terms of life and limb salvage, when rehabilitation is being planned, a small amount of joint damage can make a large impact on the level of long term disability. Reconstruction methods include allograft, massive replacement, arthrodesis and amputation. We have been developing a suite of technologies that contribute to the reconstruction of such injuries including assessment of disability in a fully instrumented gait lab, modelling of the injury using low dose CT, analysis of the extent of loss and creation of stereolithograph files of the bones, planning of the surgical procedure including implants as needed, custom manufacture of osteotomy guides and prostheses if required and technology assisted surgery, including active constraint robots. We report 3 cases of soldiers who have suffered osteoarticular loss to part of the knee, two from high velocity rounds and one from an IED. All 3 have received custom partial knee replacements preserving their cruciates, the other compartment and the patella-femoral joint. No major technical issues have been encountered. The surgery is quick and recovery simple, with the prospect of normal painfree pedestrian life. Exchange of the bearing will be necessary. It is expected and planned for once a decade as a day case procedure. While the surgery is expensive, it is highly cost-effective, as it restores near normal gait. It does not appear to be particularly risky, as the volume of tissue being excised is small, and highly constrained. The same approach is now being developed for deployment in civilian life for post traumatic osteoarthritis

We have reviewed 41 children under 15 years of age with a fracture of the radius and disruption of the inferior radio-ulnar joint. Despite the fact that the joint injury had not at first been recognised in 41% of cases and a variety of treatments had been used, the final results of conservative management were generally good. The more distal the radial fracture, the greater were the problems encountered

Introduction. Lisfranc joint injuries account for only 0.2% of all fractures but early diagnosis improves the chances of a better outcom]. Radiographic signs, such as diastasis (>2mm) of the 1–2 interspace, are subtle and. often missed, leading to a poorer outcome. We present a new radiographic sign, less likely to result in missed diagnoses. Null nypothesis: The intermetarsal angle remains unchanged in Lisfranc injuries. Method. A series of radiographs demonstrating Lisfranc injury were interspersed with normal and postoperative cases. Evidence of fixation was obscured. A selection of Foundation and Core Trainee medical staff measured the intermetatarsal angle (IMA) on two separate occasions. The measuring technique was demonstrated with no explanation for the reason behind the measurement. Results. The intra-class correlation (ICC) between observers was 0.96 and a mean 0.86 (range 0.69–0.96) for individual observers. IMA on comparative weight bearing AP views of injured and normal side, using Wilcoxon-signed rank test demonstrated a P< 0.0001 with mean values of 6.6 degrees (normal) versus 4.85 degrees (injured) and standard deviation of 1.97 & 1.91 degrees respectively. Conclusion. The high ICC value suggests that this radiographic sign is easily taught, reliable and reproducible. Analysis of individual angles suggests that there is a significant difference between the normal and pathological IMA. We therefore reject our null hypothesis. The data supports our proposition that that the IMA becomes more parallel in Lisfranc injuries and that this is an easily recognised sign, which could help reduce the incidence of missed injuries. Elucidation of the exact anatomical pathology responsible is the basis for further, anatomical, studies

Introduction: Hot swollen knee joints are a common presentation in clinical practice. It has wide differential diagnoses, the most serious being septic arthritis. Delayed or inadequate treatment leads to joint damage. Arthroscopic lavage should be planned appropriately after proper clinical assessment and investigation. Other differential diagnoses like crystal arthritis, reactive arthritis, monoarticular inflammatory arthritis should be considered. Patients and Methods: This retrospective audit involved 44 patients who had arthroscopic knee lavage for suspected septic arthritis from January 2005 to May 2007. Analysis included the aspects of adequate backup supportive evidence for the procedure, the time from diagnosis to operation and postoperative antibiotic regime. Results: There were 29 males and 15 females with age group ranging from 11 to 91 yrs. Fever was present in 15 patients(34%), preoperative joint aspiration done in 22(50%), peri-operatively pus found in 11(25%). 13 patients(29.5%) had procedure done within 6hrs, causal organism identified in 25%. Follow-up ranged upto 12 months without persistence or reactivation. Discussion: Arthroscopic lavage is a useful adjunct in treatment of septic arthritis of knees but proper patient selection with systematic approach considering other possible differential diagnoses is important for avoiding unnecessary operations

Aims

Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour.

1 . A specific mechanism of injury can produce a tear of the articular disc of the wrist without any associated bony lesion. 2. Torn discs have been found associated with Colles's fractures and with dislocation of the inferior radio-ulnar joint. 3. The injury gives rise to clear-cut symptoms and definite physical signs. 4. Operation in fourteen cases has shown five types of tear of the disc. 5. Arthrographs of the wrist are helpful in establishing the diagnosis. 6. In isolated tears removal ofthe disc relieves the symptoms and does not prejudice function. 7. If there is other joint injury, removal of the disc cannot be expected to give as satisfactory a result

1. Twenty cases of tarso-metatarsal joint injury have been studied with regard to the mechanism of injury, and experiments have been done on cadavers to confirm clinical impressions. 2. Injuries of the tarso-metatarsal joints occur by direct and indirect mechanisms, the latter being more common. 3. Indirect injuries occur in at least two ways-namely, acute abduction of the forefoot and plantar-flexion of the forefoot. 4. Most of the indirect injuries occur when the ankle joint is in a plantar-flexed position. 5. Whereas this foot injury once gained prominence on the field of battle amongst cavalrymen, it is currently associated with the motor car, the step ladder, the toboggan, the joy-rider, and commonly the simple misguided step

Introduction: Early treatment with antibiotics is advocated in the management of septic arthritis. Whilst some argue for mandatory arthrotomy we have used arthrotomy selectively. The results of this approach over a ten year period were reported 20-years ago. Aim: To review the outcome of joint aspiration and selective rather than mandatory arthrotomy for the management of septic arthritis in children. Method: We compared the outcome for cases of septic arthritis in children reported from this centre in the decade 1982–1991 (Group I) with a contemporary cohort, from 1997–2006 (Group II) using the same criteria for diagnosis and the same treatment principles. Results: Group I comprised 61 children, Group II 42. The mean incidence of septic arthritis in children (< 13 years old) was similar for Groups I and II (2.9/100,000 and 3.1/100,000). Infection caused by Haemophilus species declined from 10 of 56 (18%) in Group I to none in Group II. Staphylococcus Aureus reduced from 27/56(48%) in Group I to 13(31%) in Group II. As previously, infections particularly of the infant hip were at highest risk of causing permanent joint damage. There were eleven (18%) sequellae in Group I and two (5%) in group II. Conclusions: These results continue to support joint aspiration for the management of early acute septic arthritis in children. However involvement of the hip in infants requires arthrotomy, as does late (≥4 days) diagnosis in older children

Purpose of the Study:. Spontaneous intraarticular haemorrhages are the most frequent bleeding episodes encountered in the haemophiliac population, causing pain, joint deformity and arthropathy. Chronic haemophiliac arthropathy is characterised by persistent joint swelling, proliferative synovitis, and damage to or loss of articular cartilage. Elimination of the synovitis is the key to prevention of recurrent intraarticular haemorrhages and joint damage. The purpose of the study was to investigate the indications for, and outcome of, radioactive synoviorthesis for haemophiliac arthropathy. Methods:. A retrospective study was done to assess the results of 12 intra-articular injections of radioactive Yttrium-90 colloid, performed in 10 patients from November 1993 to December 2006. Patients were referred by the Haematology Unit if they had a target joint, as defined as >2 bleeds into the same joint in the preceding 6 months. Follow up was conducted at 6 monthly intervals, assessing clinical and radiological outcomes. The radiological involvement of the target joint, the pre- and post-treatment range of movement, presence of synovitis and bleeding events were compared from presentation to that at follow up. Range of movement of each target joint was assessed and compared to that at follow-up. Results:. The average age at time of injection was 10.6 years (range 6–15). The duration of follow-up was 35 months (range 6 to 60 months). The involved joints had an average of 2 bleeds each in the 6 months preceding the injection (24 events). Following Yttrium injection only 1 out of 12 joints had a bleed in the subsequent 6 months (1 event). Synovitis of the target joint resolved in 11 of 12 joints. Nine target joints (75%) showed a favourable improvement in range of movement. Those with a favourable radiological score had a better clinical outcome, but even those with a poor score showed improvement. Conclusion:. In this study, intra-articular injection of radioactive Yttrium-90 colloid was shown to:. –. Significantly reduce bleeding events in a Haemophiliac cohort. –. Resolve synovitis in 11 out of 12 joints with haemophiliac arthropathy. –. Improve range of movement in the majority of patients. –. This was best in those with a better radiological appearance at presentation. –. Those with a poorer radiological grade also showed some improvement suggesting that while results are less certain, patients may still benefit from the intervention

Introduction: Unstable Lisfranc (tarsometatarsal) joint injuries are increasingly being treated by open reduction and internal fixation. Hypothesis: A good outcome is achievable by anatomical reduction and internal fixation of these injuries. Methods: This was a retrospective outcome-analysis involving 21 patients. Six were treated non-operatively. There sere eight ligamentous and seven ligamentous/osseous injuries. The patients’ outcomes were assessed with the use of the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score and the long-form Musculoskeletal Function Assessment (MFA) score. Results: The average follow-up was11 months. One patient developed a post-operative infection, and another developed a deep-vein thrombosis. The average AOFAS score was 71 and the average MFA score was 32. The study group as a whole sustained their injuries through low-energy trauma, therefore comparison with other studies should take this into account. Conclusions: Follow-up in this study was short an this was reflected in the scoring. Longer follow-up will allow a greater evaluation of final outcome

Osteoarthritis (OA) is a disease of the joints stemming from a variety of factors, including joint injuries and abnormally high mechanical loading. Although the traditional treatment alternatives for end-stage OA are arthroplasty in the case of the hip and knee, and arthroplasty or arthrodesis in the case of the ankle, these options are not ideal for younger, more active patients. For these patients, joint prostheses would be expected to fail relatively quickly, and ankle fusion is not amenable to maintaining their active lifestyles. In these cases, joint distraction has attracted investigative attention as a conservative OA treatment for younger patients. 9-14. . Based on the principle that decreasing the mechanical load on cartilage stimulates its regeneration. 15. , distraction treatment calls for reduced loading of the joint during a period of typically 3 months, during which time the load customarily passing through the joint is taken up by an external fixator spanning the joint . By mounting the fixator components to the bone on each side of the joint, and then lengthening the rods connecting the proximal and distal portions of the fixator, the joint is distracted. Assuming the fixation is appropriately stiff, any load passes through the fixator instead of the joint, and the two articular surfaces will not be allowed to contact each other under physiologic loading. The exact mechanisms leading to cartilage regeneration during distraction are not yet understood. A possible negative consequence of joint fixation is cartilage degeneration due to immobilization during the treatment. It has been shown by Haapala et al. and others that long-term immobilization can be detrimental to articular cartilage. 16-18. . Conversely, joint motion during fixation (even passive motion) is thought to stimulate or encourage cartilage regeneration. 19-22. Toward this end, considerable effort has been invested in the application of hinges to external fixation for joints Joint motion has also been suggested as a potentially beneficial factor in distraction treatment, as well. 10. This is borne out by data from an RCT comparing the use of a rigid vs motion external fixator. Change in joint biology due to resorption of cysts may be responsible for reversal of symptoms

Objectives: Injury is a major cause of morbidity in children, but can be prevented if at-risk groups are identified and proper precautions taken. Our study aims to identify the patterns of paediatric fractures in terms of at-risk bone, age, type of fracture, seasonal variations and attempts to look at the role of prevention. Methods: Retrospective study of the children with fractures presented to A& E and admitted to the paediatric ward at the University Hospital of Hartlepool during August 2004 to August 2005. As used elsewhere we categorised data into injury types. Results: From the total of 1067 children reviewed,564 were boys and 503, girls. Age incidence-highest in the group of 10–14 years (462), with highest presentation in April, May, June months. Of all orthopaedic injuries, 918 were closed fractures, 38 – open fractures, 40 – dislocations, 71- joint injuries. Upper limb (797) were much common than lower limb fractures (270), with wrist being the commonest site (209). Amongst the 198 admissions, 153 had upper limb and 45 lower limb fractures, with forearm being commonest (117) of whom 51 required surgery. In-patient bed-days occupied were 336. Discussion: Information about the patterns of injuries in children is important in planning injury prevention. Incidence of paediatric injuries can be reduced with public education, implementation of safety strategies and government legislation. Orthopaedists can be instrumental in reducing incidence of paediatric injuries by participating in patient education, research, and programs that promote safe play

Introduction. Lisfranc joint injuries are increasingly recognised in elite soccer and rugby players. Currently no evidence-based guidelines exist on timeframes for return to training and competition following surgical treatment. This study aimed to see whether return to full competition following surgery for Lisfranc injuries was possible in these groups and to assess times to training, playing and possible related factors. Material/Methods. Over 46-months, a consecutive series of fifteen professional soccer (6) and rugby(9) players in the English Premierships/Championship, was assessed using prospectively collected data. All were isolated injuries, sustained during competitive matches. Each had clinical and radiological evidence of injury and was treated surgically within thirty-one days. A standardised postoperative regime was used. Results. Follow-up was obtained in all fifteen cases. Eight cases were ligamentous injuries and seven were bony. Time from injury to fixation ranged from 10–31 days. One athlete retired following a ligamentous injury. All remaining fourteen returned to training and full competition. Excluding the retired case, mean return to training time was 20.2 weeks and to full competition was 25.6 weeks. No significant difference existed between the mean return to competition time for rugby (27.8 weeks) and soccer(24.7 weeks). A significant difference existed between the mean return to competition time for ligamentous (23.7 weeks) compared to bony(27.6 weeks) injuries(p = 0.012). Three patients suffered deep peroneal nerve sensation loss, two of which fully recovered. Discussion/Conclusion. Return to competitive elite-level soccer and rugby is possible following surgically treated Lisfranc injuries. Return to training can take up to 24 weeks and playing up to 31 weeks, with bony injuries taking longer. To our knowledge this is the largest series of its kind and whilst we recognise it contains small numbers, we feel it provides some guidance on rehabilitative timeframes for those who treat and those who sustain these injuries. Evidence Level: 4

Between 1985 and 1994, 1223 patients with malleolar fractures of the ankle were treated by open reduction and internal fixation with absorbable pins and screws, of whom 74 (6.1%) had an obvious inflammatory foreign-body reaction to the implants. Of these 74, ten later developed moderate to severe osteoarthritis of the ankle despite no evidence of incongruity of the articular surface. The implants used in these patients were made from polyglycolide, polylactide or glycolidelactide copolymer. The joint damage seemed to be due to polymeric debris entering the articular cavity through an osteolytic extension of an implant track. The ten patients had a long clinical course which included a vigorous local foreign-body reaction, synovial irritation and subsequent degeneration. At a follow-up of three to nine years, ankle arthrodesis had been necessary in two patients and is being considered for another two. The incidence of these changes in the whole series was 0.8%, which is not high, but awareness of this possible late complication is essential

Our work is based on the analysis of 104 patients with suppurative posttraumatic osteoarthritis of the ankle joint. By prolonged septic arthritis with degradation of articular surfaces of ankle and shin bones we used necrectomia with osteoarthrotomy and compression arthrodesis in the mechanism of external fixation, which allows to radically sanify the nidus of infection and eliminate the inflammatory process all together. This operation was performed for 68 patients. Surgical treatment for 18 patients with septic arthritis of the ankle joint with considerable involvement of ankle joint metaepiphysis was performed in the following way. We performed segmental resection of the shin bone distal part, put in external fixation mechanism with the possibility of defect building, and then we performed the osteotomy of the shin bone in its upper one-third. On the 10th day we started performing building of defect by Ilizarov. For six patients with ankle joint septic arthritis with considerable involvement of ankle bone we performed its subtotal resection and compression arthrodesis in the external fixation mechanism. For patients with total overall affection of the ankle bone we performed ankle bone excision and tibialcalcaneal fusion. For three patients we performed ankle bone excision with tibialcalcaneal fusion and external fixation. For nine patients where it was not possible to perform a single-stage fusion of shin and heel bones we used external fixation mechanism with the possibility to move the shin bone fragment. Then we performed open fusion of shin and heel bones. The result was considered to be position (92% of patients) in case of extremity support ability recovery, suppurative process elimination and bony ankylosis achievement. Original ankle joint injury nature and localization are very important in selecting the necessary surgical treatment variant. Differential surgical treatment tactics selection for patients with suppurative ankle joint osteoarthritis together with adequate usage of conservative therapy allow to eliminate active purulo-necrotic process and restore the extremity support function for most patients

Introduction: Treatment of choice in osteogenesis imperfecta (O.I.) patients presenting severe deformities of lower limbs is endomedular nailing with previous corrective osteotomy. Fassier-Duval telescopic rod permits anterograde nailing without the need of distal arthrotomy and thus, joint damage. MATERIAL AND Methods: We retrospectively revised the first 14 rods implanted in 9 patients at our service, 6 males and 3 females. Average age of 6.14 years. Sillence type III: 5, type IV: 4. Six right femurs, 7 left femurs and one tibia were nailed. In 5 of the 14 cases surgery was performed on acute fractures on previous deformities, in 9 cases because of progressive deformities. Corrective osteotomies were performed in all cases. Seven of 9 patients were receiving treatment with palmidronate prior to surgery. Improvement in quality of life with Bleck scale was assessed. Results: Six of 14 operations were salvage procedures because of failure of other implants. Complications included a transient sciatic palsy, lack of telescoping in one case, one acute fracture with implant failure and one delay in consolidation. Two reoperations were needed. Global Bleck score improved from 7.37 to 12.75 (p=0.024), walking score improved from 1.25 to 2.87 (p=0.038). DISCUSSION AND Conclusions: Fassier-Duval telescopic rod is a safe and useful implant for the treatment of deformities in the lower limbs in patients with O.I. There was a significant improvement in both global quality of life score and walking score

Summary Statement. Using a weight-bearing force control task, age-related changes in muscle action were observed in osteoarthritic subjects, however, greater activation of rectus femoris and medial hamstring muscles in the OA group compared to control indicates greater cocontraction and varied stabilisation strategies. Introduction. Osteoarthritis (OA) is the most debilitating condition among older adults. OA is thought to be mechanically driven by altering the stabilising integrity of the joint. The main contributor to knee joint stability is that of muscular contraction. In cases where the history of a traumatic knee joint injury is not a causal factor, a change in muscle function, resulting in reduced strength and force control in believed to induce OA development and progression. Since age is also a determining factor of OA, the purpose of this study was to investigate the muscle activation patterns of young healthy adults (YC), older healthy adults (OC), and adults with OA during a standing isometric force control task. Patients & Methods. A force matching protocol was used to evaluate muscle activation patterns of 41 YC (23.1±1.9 years of age) 18 OC (59.7±5.14 years), and 19 OA (63.5±8.1 years). Subjects stood with their leg of interest fixed to a force platform and modulated ground reaction forces while exposing equal body weight to each leg. Surface electromyography (EMG) of 8 muscles that cross the knee joint, kinetics and kinematics were recorded while subjects generated 30% of their maximal force in 12 different directions, corresponding to various combinations of medial-lateral-anterior-posterior ground reaction forces. Processed EMG was normalised to previously recorded maximum voluntary isometric contraction (MVIC) and ensemble averaged into group means for each loading direction. Muscle activation patterns were displayed in EMG polar plots and were quantified with symmetry analyses, mean activation levels (X. EMG. ), directions (Φ), and specificity indices (SI). Group differences were tested with independent T-tests at the p<0.05 level. Results. Muscle activation patterns were similar between groups (i.e. symmetry and Φ). However, X. EMG. of 7 muscles was significantly greater in both the OA and OC groups compared to YC. OA group also demonstrated significantly greater X. EMG. in the rectus femoris and tensor fascia lata as well as lower SI in semitendinosus hamstrings compared to OC. Discussion/Conclusion. Our results indicate that regardless of loading direction, both OC and OA groups have greater levels of muscle co-contraction than YC. This is suggested to be an adaptive response to age-related changes in muscle strength and force control. Since individuals with OA have reduced muscle strength and force control compared to age-matched controls, our results suggest that the OA group's greater, less specific activation of knee joint muscles relative to the OC is this “stiffening” response adapted by the OA group, however, to an extent that may expose the joint to detrimental loading conditions, contributing to the progression of OA. Further investigation regarding age-related neuromuscular changes and their influence on joint loading conditions and development of OA is warranted

Knowledge of joint kinematics in the lower limb is important for understanding joint injuries and diseases and evaluating treatment outcomes. However, limited information is available about the joint kinematics required for high flexion activities necessary for floor sitting life style. In this study, the hip and knee joint kinematics of ten healthy male and ten healthy female subjects were investigated using an electromagnetic motion tracking system. We measured the hip and knee joints' functions moving into 1) kneeling on knees with legs parallel without using arms, 2) kneeling on knees with legs parallel with using arms, 3) kneeling on knees with one foot forward without using arms, 4) cross-legged sitting, 5) kneeling with legs to the side, 6) sitting with legs stretched out, and 7) deep squatting, and moving out of the above seven conditions. Conditions 1) through 3) were Japanese seiza style. On conditions 4) through 7), arms were not used. We further measured the functions of putting on and taking off a sock under such conditions as 8) with standing position and 9) sitting position (Fig 1). Here special attention was paid for flexion and extension motion. The data were used to produce the pattern of joint angulation against the percentage of the cycle for each individual conducting each activity. The kinematic curves were split into 3 phases: moving into the rest position, the rest position and out of the rest position. It should be noted that the moving into and the rest phases were split at the moment when the peak value was determined during the moving into phase. Thus the initiation of the rest phase on the curve was not coinciding with the moment the subject reached at the rest position. This was necessary in order not for the mean kinematic curve to become too dull in shape. Same was true when the end of rest phase was determined. The maximum hip and knee joint angles during the cycle were determined. Further a relationship between the hip and knee joint excursions were investigated. The results indicated condition 8) requires the maximum flexion angles to the hip among all conditions, 157.5 ± 20.4° and condition 3) to the knee joint, 157.1 ± 10.0° respectively (Fig 2). The results also indicated in many activities, the maximum joint angles were recorded not during the rest phase but during the moving into or out of phase. In any conditions even including donning on and off a sock, a strong relationship was found between the hip and knee joints motion (Fig 3), indicating the bi-articular muscles' co-contraction during the sit to stand activities. The data presented in this study will increase the knowledge of high-flexion needs especially in non-Western cultures and provide an initial characterization of the prosthesis kinematics in high flexion

The correction of axial deviation of the lower limbs in paediatric patients requires complete patient history and clinical examination. The correct approach to the deformity must consider:radiology,evolution,associated joint damage, neurologic diseases and surgical planning. Timing and choice of operation (osteotomy, assimetric epiphyseal distraction, hemiepiphysodesis, epiphysiodesis) are critical. Thirty-four paediatric patients with an average age of 10 years (range 2–18) were treated with a monolateral external fixator: 16 femoral osteotomies (nine post-traumatic, four congenital, one after radiotherapy for neoplastic diesease, one Ollier’s disease, one multiple exostosis) and 18 tibial osteotomies (eight congential, four post-traumatic, two multiple exostosis, two osteogenesis imperfecta, one neoplasm, one Ollier’s disease) were performed. The knowledge of normal physiologic values, angles and anatomical and mechanical axes are fundamentally important. In choosing which operation to perfom in patients with post-traumatic deviation, the controlateral limb, functional necessity, symptoms and possible compensation must be considered. External fixation appears to be necessary in the correction of lower limb deformities because of patient comfort in the femur, because it allows osteotomy in the apex of the deformity and because it is possible to perform lengthening and correction when necessary. We suggest performing lengthening and correction osteotomy at the same level when it is possible, whereas it is dangerous to perform it at the distal metaphyseal femur and distal third of the tibia

We present an all arthroscopic technique for modified Weaver Dunn reconstruction of symptomatic chronic type III ACJ joint injuries. Over a one year period we performed 12 all arthroscopic modified Weaver-Dunn procedures. All patients had failed non-operative management for at least 6 months. The technique involved excision of the lateral end of clavicle, stabilisation with a suture cerclage technique from 2 anchors placed in the base of the coracoid and coracoacromial ligament transfer from the acromion to lateral end of clavicle. Post-operatively the patients were immobilised for six weeks, followed by an active rehabilitation programme and return to work and sports at 3 months. We have currently performed this technique in 12 patients, all male. The average age at operation was 25.8yrs at a mean interval of 11 months post injury. The mean Constant score preoperatively was 49 (44–54). The mean 3 month postoperative Constant score was 88.6 (84–96). There have been no complications, and the 2 professional sportsmen within our cohort returned to full contact at 3 months. Due to an irreducible clavicle, one patient required an open excision of lateral clavicle, with the rest of the procedure performed arthroscopically. Arthroscopic Weaver-Dunn has a number of advantages over the corresponding open procedure. It avoids the detachment of deltoid needed to gain exposure and also the morbidity from the wound. From our experience is that it enables patients to regain their function more rapidly with an earlier return to sporting activities. The early results from our initial experience have been excellent, with no complications. With this technique an anatomic reconstruction can be achieved with excellent cosmesis, low morbidity and potentially accelerated rehabilitation

Summary Statement. IL-1β stimulation of human OA chondrocytes induces NFκB, ERK1/2, c-JUN, IκB and P38 signalling pathways. Pre-treatment with cannabinoid WIN-55 for 48 hours inhibits certain pathways, providing mechanisms for cannabinoids inhibitory actions on IL-1β induced cartilage degradation. Matrix metalloproteinases (MMPs) are involved in extracellular matrix (ECM) breakdown in osteoarthritis (OA) and their expression is regulated by nuclear factor kappa B (NFκB). In addition signalling pathways ERK1/2, c-JUN, IκB and P38 are activated in OA and are induced by inflammatory cytokine interleukin 1 (IL-1). Cannabinoids have been shown to reduce joint damage in animal models of arthritis. Synthetic cannabinoid WIN-55, 212-2 mesylate (WIN-55) significantly reduces IL-1β induced expression of MMP-3 and -13 in human OA chondrocytes, indicating a possible mechanism via which cannabinoids may act to prevent ECM breakdown. Here the effects of WIN-55 on IL-1β induced NFκB, ERK1/2, c-JUN, IκB and P38 phosphorylation in human OA chondrocytes has been investigated. Primary human chondrocytes were obtained from articular cartilage removed from patients with symptomatic OA during total knee replacement (Ethic approval:SMB002). Cartilage tissue was graded macroscopically 0–4 using the Outerbridge Classification method. Chondrocytes isolated from grade 2 cartilage and cultured in monolayer were pre-treated with 10 μM WIN-55 for 1 hour prior to stimulation with 10 ng/ml IL-1β for 30 minutes for investigation of NFκB, c-JUN, IκB and P38 phosphorylation. In addition chondrocytes were pre-treated with 10 μM WIN-55 for 30 minutes, 1, 3, 6, 24 and 48 hours prior to 10 ng/ml IL-1β stimulation for 30 minutes to investigate ERK1/2 phosphorylation. Dimethyl sulfoxide (DMSO) was used as a vehicle control at 0.1%. Immunocytochemistry was used to investigate the phosphorylation and translocation of NFκB. ERK1/2, c-JUN, IκB, and P38 activation was investigated using cell based ELISA. Immunocytochemical analysis showed chondrocytes stimulated with IL-1β induced NFκB phosphorylation and translocation to the nucleus. Chondrocytes treated with IL-1β with WIN-55 for 1 hour pre-treatment showed no inhibition of the IL-1β induced NFκB phosphorylation and translocation to the nucleus. WIN-55 treatment alone for 1 hour stimulated NFκB phosphorylation in the cytoplasm but not the nucleus. ELISA showed that phosphorylation of ERK1/2, c-JUN, IκB, and P38 was significantly induced by IL-1β following 30 minutes stimulation (p<0.05). Pre-treatment with WIN-55 for 1 hour had no significant effect on this IL-1β induced phosphorylation. However WIN-55 pre-treatment for 48 hours prior to IL-1β stimulation for 30 minutes, resulted in a significant decrease in ERK1/2 phosphorylation compared to IL-1β stimulation alone (p<0.05). WIN-55 treatment alone for 1 hour significantly induced c-JUN phosphorylation (p<0.05), but had no effect on IκB and P38 phosphorylation compared to DMSO control. IL-1β stimulation of ERK1/2 phosphorylation was not significantly affected by WIN-55 pre-treatment of 30 minutes, 1, 3, 6 and 24 hours. WIN-55 treatment alone for 48 hours significantly reduced ERK1/2 phosphorylation compared to DMSO control (p<0.05). WIN-55 treatment alone for 30 min, 1, 3, 6 and 24 hours had no significant effect on ERK1/2 phosphorylation compared to DMSO control. The results show that following 48 hours pre-treatment WIN-55 inhibits IL-1β induced ERK1/2 phosphorylation in human OA chondrocytes. Thus inhibitory effects of cannabinoids on IL-1β induced cartilage degradation may be mediated via modulation of ERK1/2 signalling

Introduction:. The sealing function of the acetabular labrum is central to the stability of the hip and the health of the joint. Disruption of the labrum has been shown to reduce intra-articular pressure and increase the rate of cartilage consolidation during static loading. Functional activities require movement of the hip through wide ranges of joint motion which disrupt joint congruency, and thus may alter the seal. This study was performed to test the hypothesis that the sealing function of the labrum varies with the position of the hip during functional activities. Methods:. Six fresh cadaveric hip joint specimens were obtained from donors of average age 45.5 ± 16.1 years (range 25–63 years). Each specimen was dissected free of soft tissue, leaving the capsule and labrum intact, potted in mounting fixtures, and placed in a loading apparatus. Catheters were inserted into the central and peripheral compartments of each hip to allow infusion of fluid and monitoring of compartment pressures via miniature transducers (OMEGA Engineering, Inc). After application of a joint load of 0.50 BW, fluid was introduced into the central compartment at a constant rate until transport was indicated by a rise in pressure within the peripheral compartment. These measurements were performed with each hip placed in 10 functional positions ranging from −5 to 105 degrees of flexion, −5 to 13 degrees of abduction, and −25 to 35 degrees of external rotation simulating the sequential stages of gait, stooping, and pivoting. Motion analysis was performed via reflective marker arrays attached to the femur and pelvis to allow computer visualization of the position of the pelvis and femur using CT reconstructions. In each hip position, we measured the peak pressure (kPA) developed within the central compartment prior to fluid transfer to the peripheral compartment. Results:. The sealing capacity of the labrum varied wit hip joint position (p = 0.003). Peak pressures were greatest during pivoting (average peak central compartment pressure: 33.9 ± 5.0 kPa; p = 0.001), compared to both gait (22.5 ± 4.1 kPa; p = 0.047) and stoop (9.6 ± 3.6 kPa; p = 0.004). During the pivoting maneuver, peak pressures increased in a linear fashion with increasing hip extension and external rotation. Conversely, the sealing capacity of the labrum was reduced during stooping once hip flexion exceeded 70° and internal rotation was greater than 15°. The positions simulating gait consisted of minimal to no joint rotation, and peak pressures varied little between the four positions. Discussion:. The sealing ability of the labral seal increases with external rotation of the hip joint, and decreases with increased flexion combined with internal rotation. Changes in joint congruency that occur when the hip is placed in high flexion and internal rotation may be responsible for the loss of sealing function of the labrum during stooping. Our results reveal the importance of joint position during functional activities on the ability of the labrum to seal the central compartment of the hip. Future research will further assess the relationship between these positions and joint injury

Objectives:. Experimental disruption of the labrum has been shown to compromise its sealing function and alter cartilage lubrication. However, it is not known whether pathological changes to the labrum secondary to femoro-acetabular impingement (FAI) have a similar impact on labral function. This study was performed to determine the effect of natural labral damage secondary to abnormal femoral morphology on the labral seal. Methods:. Ten intact hip specimens were obtained from male donors (47.8 ± 1.5 yrs) for use in this study. CT reconstructions demonstrated that 6 specimens were of normal morphology, while 4 displayed morphology typical of cam-FAI. Specimens were dissected free of the overlying soft tissue, leaving the capsule and labrum intact. Each specimen was potted and placed in a loading apparatus (0.5 BW). Pressures developed within the central and peripheral compartments were monitored with miniature pressure transducers. The sealing capacity of the labrum was measured by introducing fluid into the central compartment at a constant rate until transport was detected from the central to the peripheral compartment. These measurements were performed in 10 functional positions simulating sequential stages of gait, stooping, and pivoting. During testing, the 3D motion of the femoral head in the acetabulum was measured with motion analysis combined with computer visualization. Peak pressures were compared between specimens with and without labral damage for each of the three activities (p < 0.05). Results:. Visual observation following testing showed that each specimen with CAM morphology exhibited secondary damage of the labrum and the adjacent chondral surface, while specimens of normal morphology were undamaged. Average peak central compartment pressure was affected by the presence of labral damage secondary to impingement. The specimens with labral damage exhibited reduced peak central compartment pressure during pivot (15.2 ± 2.6 vs. 42.3 ± 7.7 kPa; p = 0.007) when compared to intact specimens. Conversely, no differences in peak pressure were detected between specimens with and without labral damage during simulated gait (21.1 ± 6.0 vs. 22.0 ± 4.2 kPA; p = 0.9) and stooping (8.6 ± 2.4 vs. 7.5 ± 2.6 kPa; p = 0.78). Conclusions:. The acetabular seal, quantified by intra-articular pressure, was affected by the presence of labral damage secondary to impingement. The reduction in ultimate pressure occurred during pivoting; however, the seal was maintained during gait and stooping. These results are in contrast to previous studies which reported a complete negation of the seal in response to experimentally-created labral disruption. As degeneration is progressive with repetitive impingement, loss of the seal starts to be seen during pivoting and may progress from there, but at this time point (50 years), the seal remains intact during gait and stooping. Our study highlights the importance of using clinically relevant joint injury models to study labral function

Summary. The ideal therapy for post-traumatic osteoarthritis (PTOA) must be mechanism-based and target multiple anabolic and catabolic pathways. Our results suggest an innovative combination of known pro-anabolic and anti-catabolic biologics to treat post-traumatic cartilage degeneration. Introduction. Untreated joint injuries can result in cartilage wear and the development of PTOA. Previous studies identified the mechanisms that may govern the progression to PTOA. Here we hypothesised that targeted biologic interventions combined based on the type/time of cellular responses may constitute an effective novel treatment algorithm to arrest PTOA. Methods. Eleven human donor normal tali, age 19–71 yo, from the Gift of Hope Organ & Tissue Donor Network were impacted using a 4mm cylindrical indenter with the impulse of 1N as discribed. 8mm cartilage explants (4mm impacted core + 4mm non-impacted adjacent ring) were removed from the joint and cultured for 14 days in 5% fetal bovine serum with or without selected biologics. Treatment groups consisted of 1) Impacted control (IC), 2) Un-impacted control (UIC); 3–5) Impaction + three combinations of BMP-7/OP-1 (100ng/ml), P188 (8 ug/ml) and tumor necrosis factor-α (TNF-α) antagonist (100ng/ml) defined as Combo1, Combo2, and Combo3. All treatments were administered according to previously reported post-injury cellular responses. Combo1: P188 administered at day 0 for 48hrs + BMP-7 administered at day 0 for 48hrs and at days 7–14 + anti-TNF-α administered at days 0–7; Combo2: All three agents administered at day 0 for 48hrs and anti-TNF-α and BMP-7 administered again at day 7 for 48hrs; Combo3: All agents administered simultaneously at day 0 for 48hrs. Tissue and media were collected on days 0, 2, 7, and 14 and analyzed for cell viability, Safranin O staining, and proteoglycan (PG) synthesis. Results. A single impact to articular cartilage resulted in cell death within the superficial layer of impacted region, which if untreated, expanded to the adjacent non-impacted area. It reduced cell viability by more than 2-fold (p<0.01) and triggered elevation of pro-inflammatory mediators within the first 24–48 hrs and again around day 10. Initial anabolic responses characterised by the synthesis of superficial zone protein, endogenous BMP-7 and PGs were initiated at days 5–7. Cell survival in the superficial layer was improved under the individual or combined treatments with the most pronounced sustained effect under Combo1 & 2 (∼1.5-fold increase vs IC, p<0.05). Combo1 and to a lesser extend Combo 2 markedly improved cell survival in the entire cartilage thickness, which increased from 59% in IC to 84% in Combo1, p=0.006. Both Combo1 & 2 had a stronger effect on Safranin O staining and preservation of matrix integrity than Combo 3. Contrary, Combo3 exhibited the highest effect on PG synthesis (1.8-fold increase vs IC or other two combinations; p<0.05). Combo1 & 2 were less effective. Discussion. Current study reports two important findings: 1) the same combination of agents, but administered at various treatment regimens, can induce different effects. Prolonged administration of anti-TNF-α and BMP-7 (Combo1) had a strong effect on cell survival and matrix preservation, but was less effective in inducing chondrocyte synthetic activity suggesting that overstimulation/overdosing can have a detrimental effect on chondrocyte anabolism; 2) a window of opportunity exists to arrest cell death and delay/prevent cartilage degeneration

Introduction and aims: Osteoarthritis (OA) of the knee is a widespread problem, yet there is little known about the kinematics of the osteoarthritic knee, and nothing about the tibio-femoral contact pattern. This study aimed to describe the role of tibio-femoral interface events in articular surface wear and degenerative change. Method: Fourteen subjects with symptomatic OA in one knee, and no pain or injury in the contralateral knee were recruited. The tibio-femoral contact pattern was recorded for both knees, while performing a supine leg-press from 0 to 90 degrees flexion against a 150N load. Severity of osteoarthritis was measured by Kellgren Lawrence grade, bone mineral density (BMD) using Dual Energy X-ray Absorptiometry close to the subchondral bone, diagnostic MRI, and joint damage recorded at knee arthroplasty. Pain and disability was recorded using a WOMAC questionnaire. Results: Severity of OA in the knees ranged from grade two to four (mode=4) in the symptomatic knee, and from zero to three (mode=0) in the contralateral knee. Contact in the lateral compartment of the knee was more anterior on the tibial plateau than healthy knees (p≤ 0.01), and this was associated with severity of OA (p≤ 0.01). Contact in the medial compartment was also more anterior on the tibial plateau, and this was associated with severity of OA. Abnormality in tibio-femoral contact patterns was associated with disability reported by the WOMAC score (r= 0.54). There was no significant difference in BMD between the OA and contralateral knees. However, the BMD was correlated with pain and physical function of the WOMAC score, that is, as function decreased, bone density increased in the arthritic compartment (r = 0.49 to 0.63; p≤ 0.01). Conclusion: Severity of osteoarthritis was associated with loss of rollback normally coupled with flexion, especially in the lateral compartment. Consequently longitudinal rotation was lost. In severe osteoarthritis, ACL integrity did not affect the contact pattern. Kinematic abnormalities may explain loss of range of motion, and patterns of wear in osteoarthritic knees

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: Acromioclavicular (AC) joint injuries are common in both the sporting and working populations. Most injuries are grade I in severity and settle with an appropriate non-operative treatment program. Arthroscopic soft tissue debridement of the AC Joint without excising the distal clavicle, is a bone sparing procedure that, to our knowledge, has never been reported in the literature. This paper is a retrospective review of patients with chronic recalcitrant AC joint injuries, who underwent arthroscopic soft tissue debridement of the AC joint. Materials and Methods: Fourteen patients underwent arthroscopic AC joint soft tissue debridement. All patients had failed a non-operative treatment program including physiotherapy, anti-inflammatory tablets and corticosteroid injections. All patients had been symptomatic for a minimum of four months prior to surgery. The surgery involves a glenohumeral joint arthroscopy, subacromial bursoscopy and AC joint arthroscopy. Excision of the torn AC joint meniscus, AC joint synovectomy and soft tissue clearance were performed in all cases. Surgery was performed as a day-only procedure. Results: Ten out of fourteen patients obtained good pain relief and a corresponding increase in function. One patient was lost to follow-up. One patient subsequently underwent an open AC joint reconstruction for chronic instability. Five patients had previously undiagnosed SLAP tears. Conclusion. Arthroscopic soft tissue debridement for recalcitrant AC joint injuries gave good results in 77% of cases. Arthroscopy of the glenohumeral joint in patients with presumed isolated AC joint disease is important as there is a significant proportion of patients who have associated significant superior labral tears. Soft tissue arthroscopic AC joint debridement allows quick post-operative rehabilitation, an early return to sport and work and avoids having to excise bone from the distal clavicle. Arthroscopic AC joint debridement is contraindicated in patients who have grade II or grade III AC joint instability

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Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

Purpose: Recurrent hemarthrosis is a common clinical entity in hemophiliacs. They not only interfere with daily life but also trigger hemophilic arthropathy. Synovial hypertrophy has a pivot role in hemarthrosis related joint damage and ablation of the synovium prevents further deterioration. Current treatment strategy is to ablate synovium in the early stages in order to prevent progression of the arthropathy. We report a series of hemophilia patients with advanced arthropathy who had been treated with radionuclide synoviorthesis. Materials and Methods: The patients who had been treated with radionuclide synoviorthesis for either knee or elbow disease between 2002 and 2004 were included in this study. The inclusion criteria were having > 1 hemarthrosis episode per month in the index joint, chronic synovial hypertrophy, advanced degenerative changes of grade III and IV as defined by Arnold-Hilgartner Classification, F8 inhibitor level < 3. The frequency of hemarthrosis, range of motion of the affected joint, pain level that was evaluated by visual analog scale, was recorded during each follow-up. 90Y was used for the synoviorthesis of the knee, whereas 186Re was used for the elbow cases. Patients were screened for radionuclide leak by using a gamma camera following the injection. Results: Twenty radionuclide synoviorthesis were performed in 14 knees. The average age was 20 (range, 10–31) with an average follow-up of 17 months (range, 3–29). There were 12 severe hemophilia A and 2 severe hemophilia B patients. The frequency of intaarticular bleeding episodes was significantly reduced at the final follow-up (p< 0,05). Although the range of motion and the pain scores were improved, the change was not statistically significant (p> 0,05). Six patients required repeated treatment because of inadequate response. No radioactive material leakage were detected at the draining lymph nodes. Conclusions: Our results demonstrate that radionuclide synoviorthesis significantly reduces the number of the bleeding episodes even in the knees presenting with advanced arthritis, and increases the quality of life. Although most patients respond to single injection, some patients may require more than one injection, to achieve a satisfactory clinical outcome

Osteoarthritis (OA) involves pathology in both articular cartilage and subchondral bone. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa beta ligand (RANK-L) balance is known to modulate bone turnover. We compared the bony changes in human total knee arthroplasty (TKA) and cadaveric controls. A qualitative increase in subchondral and ligamentous insertional bone mineral density was observed on micro-CT sections of TKA bone compared with cadaveric controls. In-situ hybridization of digoxygenase (DIG)-labelled OPG riboprobes showed selective uptake in osteoblasts but not osteocytes or osteoclasts in TKA bone. Those data suggested that the upregulation of OPG expression by osteoblasts may have precipitated the bony hypertrophy of end-stage OA. Altered joint mechanics produced by periarticular bone remodelling may precede the cartilage changes of osteoarthritis (OA). Recently, receptor activator of nuclear factor kappa beta (RANK), along with its soluble ligand (RANK-L), have been shown to induce both maturation and activation of bone-degrading osteoclasts. Activation of RANK on osteoclast cells by RANK-L is opposed by another soluble factor, osteoprotegerin (OPG). Thus RANK/OPG balance is important in regulating bone turnover. Here, we compared periarticular bone from patients with end-stage OA undergoing total knee arthroplasty (TKA) with those of cadaveric controls. We assessed bony, histological and molecular changes that are important in the pathogenesis of OA. Using in-situ hybridization, we found increased staining of digoxygenase (DIG)-labelled OPG in osteoblasts of TKA bone. A corresponding increase in subchondral and insertional bone was seen on micro-CT (μCT) sections from TKA bone in comparison with cadaveric controls. Those changes were accompanied by marked articular cartilage degeneration on histology. This study is the first of which we are aware that directly assessed the role of OPG in inducing the bony changes seen in human end-stage OA. We used μCT to compare corresponding samples qualitatively from TKA and cadaveric bone. Adjacent sections underwent hybridization of digoxygenase (DIG)-labelled OPG riboprobes to assess gene expression in situ. Finally, samples were stained and analysed for histology. Bony hypertrophy may be a result of overexpression of OPG that occurs as an important feature of OA pathophysiology. Funding: This work was supported by a grant from the Hip Hip Hooray Fund of the Canadian Orthopaedic Research Foundation (CORF) and the Wood Professorship in Joint Injury Research. There was no commercial funding for this research project

Osteoarthritis is a slowly progressive musculoskeletal disorder that can occur in any joint and is characterised by symptoms of pain, stiffness or loss of function. Studies showed that the work related disability rate with osteoarthritis varied from 30 to 50%, it is also a frequent cause of early retirement. Age is the strongest predictor of the development and progression of radiographic osteoarthritis. Further risk factors are physical activity, injuries, high bone mass index and intensive sport activities. Targets that are most important in the prevention or management of osteoarthritis are to reduce pain, disability and to prevent radiological progression. There are various life style factors that increase the risk of developing osteoarthritis, increase its rate of progression and may increase pain and functional limitation. Preventable or modifyable risk factors are obesity and mechanical aspects of the joint f.e. joint laxity or malalignment. Tears of menisci or ligaments may lead to at normal loading of articular cartilage and result in the increased deveopment of osteoarthritis. Further risk factors are certain occupations (f.e. farmers for hip- and knee osteoarthritis), intensive sport participation, muscle weakness and nutritional factors. Pharmacological interventions are mainly to treat the symptom of pain and have nearly no effect on tissue damage. Nevertheless activity and participation is improved as well as using simple analgesics, antiinflammatory drugs, disease modifying therapies, hyaluronic acid and intraarticular steroids. There is no evidence that pharmacological interventions can prevent osteoarthritis as defined by radiological changes. Biomechanic deficiencies may lead to joint damage and result in pain and disability. Therefore surgical correction of these abnormalities can relief pain and improve function. Further surgical interventions to reduce the impact of osteoarthritis include cartilage repair and joint preserving surgeries. For severely damaged joints, partial or total replacement of the joint is now possible for all those joints that are commonly affected by osteoarthritis. Osteoarthritis is commonly associated with limited function that can be improved with a wide variety of rehabilitative interventions. Symptoms of pain may be reduced by joint specific exercises, transient immobilisation, heat or cold packings and braces or other devices. Further attention can be put on modifiying the environment as adaptions at home and at work, support services or other social interventions. Eduction and self managements play an important role as well in early as in late stages of the disease

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Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Methods of study: Prospective Controlled Animal Study. Objectives: Evaluation of the feasibility of embryonal epiphyses transplantation in a xenogeneic model for reconstruction of adult articular cartilage in a rabbit model. Introduction: Articular cartilage reconstruction has been the goal for many years of orthopaedic research. Current acceptable techniques include the use of allografts, autologous chondrocytes transplantation and osteochondral cylinder grafting. Reconstruction of articular cartilage defects using adult osteochondral allografts is an established clinical procedure, whose principal drawback is lack of lateral integration of the grafts to the surrounding tissue. Autologous chondrocytes transplantation is a sophisticated technique requiring cell culture and a staged operation. Its main draw back is the lack of mechanical strength early on and the prolonged rehabilitation period. This study was conducted in order to evaluate the possibility of using embryonal epiphyses as a cartilage reconstruction tissue. Methods: A xenogeneic human to rabbit sub-acute osteochondral defect model was designed to evaluate the possibility of allogeneic implantation in humans. The following procedures were performed (n=5): transplantation of: 1. live epiphyses, 2. live epiphyses with autogeneic periosteum, 3. devitalized epiphyses, and 4. devitalized epiphyses with autogeneic articular chondrocytes. A fifth control group did not receive any implant. Animals were followed for 3 months after transplantation and than sacrificed. The histological specimens were evaluated by image analysis after immuno-histochemical stains were performed (including the following antigens – collagen type II, collagen type I, collagen type III, collagen type X, S-100, alkaline phosphatase, osteocalcin, osteopontin, nitric oxide synthase). Results: Animals in groups 1 and 2 had a viable reconstruction of the articular surface with little evidence of rejection and without pannus formation. Animals in groups 3 and 4 became severely arthrotic and the graft was resorbed. Nitric oxide synthase accumulation was reduced in group 1 and 2 as compared to groups 3, 4, and 5, indicating a joint preserving function of the epiphyseal grafts. Discussion: Epiphyseal grafts appear to be a feasible procedure for reconstruction of articular cartilage defects even in a xenogeneic model. The restoration of articular cartilage even with a xenogeneic graft appears to prevent nitric oxide synthesis and the resulting destruction of unafflicted articular cartilage. This is a major pathway leading to secondary osteoarthritis after joint injury. Blocking this pathway might prevent degenerative changes

Background and Purpose: There is a high incidence of arthritis in the hand, but joint replacement technology in the wrist and other small joints is still in its infancy compared with the larger joints. The wrist is the most complex small joint and so there is a need for fundamental research into the way in which it works. At present there is no generally agreed upon satisfactory explanation for the complex movement patterns of the carpal bones. The purpose of the work was to test a new hypothesis on wrist kinematics. The basis of the hypothesis was that the bones of the wrist move in such a manner as to maximise total contact area in the joint, thereby minimising contact stress. Such a strategy would minimise the bone mass requirements, thereby minimising the biological “cost” of creating and maintaining the joint. This agrees with the minimum energy principle, which governs many natural processes. Methods: A computer model was created to test the hypothesis. A cadaveric wrist was dissected and 3D faceted models of the carpal bones were created using laser digitisation. The model contained a program to evaluate the closeness of packing of the carpal bones and an optimisation algorithm [. 1. ] to maximise this quantity by adjusting the positions of the bones. The evaluation program computed the contact area and level of intersection between nine pairs of interacting bones. Rotation in the radial-ulnar deviation plane was applied in 1.0° increments to four rigidly connected bones defining the overall posture of the wrist, and an optimisation algorithm was used to maximise the contact area by adjusting the positions and orientations of the remaining bones. Results: The results of the work are encouraging because certain known characteristics of carpal behaviour were clearly predicted by the model. The results for the scaphoid in particular were similar to the characteristic movements of this bone in both radial and ulnar deviation. During 20° of unlar deviation, the bone demonstrated 14.3° of extension, which is near to the 20.4° reported by an experimental study [. 2. ]. In 10° of radial deviation, the bone underwent 6.4° of flexion, which again is close to the 8.1° experimental result. Conclusion: Although the computer model predicted certain aspects of carpal behaviour, the initial hypothesis was not conclusively proved. This is due in part to the computational complexity of the task. Despite some simplifying assumptions, there were still a large number of degrees of freedom, and it is almost certain that the optimisation process was afflicted with local minima problems. If the technical hurdles can be overcome and the hypothesis is proved correct, then we will gain a new explanation of the laws governing the kinematics of the wrist joint, which are not fully understood at present. This will provide invaluable information for surgical applications, where a thorough understanding of normal kinematics is essential for the treatment of joint injury and instability

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The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in Kingella kingae septic arthritis when compared with those of other organisms, and whether this difference needs to be considered when assessing children in whom a diagnosis of septic arthritis is suspected.

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Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres.

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This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA).

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Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method.