Aims. The aim of this study was to evaluate antegrade autologous bone grafting with the preservation of articular cartilage in the treatment of symptomatic osteochondral lesions of the talus with subchondral cysts. Patients and Methods. The study involved seven men and five women; their mean age was 35.9 years (14 to 70). All lesions included full-thickness articular cartilage extending through subchondral bone and were associated with subchondral cysts. Medial lesions were exposed through an oblique medial malleolar osteotomy, and one lateral lesion was exposed by expanding an anterolateral arthroscopic portal. After refreshing the subchondral cyst, it was grafted with autologous cancellous bone from the distal tibial metaphysis. The fragments of cartilage were fixed with 5-0 nylon sutures to the surrounding cartilage. Function was assessed at a mean follow-up of 25.3 months (15 to 50), using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot outcome score. The radiological outcome was assessed using MRI and CT scans. Results. The mean AOFAS score improved from 65.7 (47 to 81) preoperatively to 92 (90 to 100) at final follow-up, with 100% patient satisfaction. The radiolucent area of the cysts almost disappeared on plain radiographs in all patients immediately after surgery, and there were no recurrences at the most recent follow-up. The medial malleolar screws were removed in seven patients, although none had symptoms. At this time, further arthroscopy was undertaken, when it was found that the mean International Cartilage Repair Society (ICRS) arthroscopic score represented near-normal cartilage. Conclusion. Autologous bone grafting with fixation of chondral fragments preserves the original cartilage in the short term, and could be considered in the treatment for adult patients with symptomatic osteochondral defect and subchondral cysts. Cite this article: Bone Joint J 2018;100-B:590–5

Aims. Hip displacement, common in patients with cerebral palsy (CP), causes pain and hinders adequate care. Hip reconstructive surgery (HRS) is performed to treat hip displacement; however, only a few studies have quantitatively assessed femoral head sphericity after HRS. The aim of this study was to quantitatively assess improvement in hip sphericity after HRS in patients with CP. Methods. We retrospectively analyzed hip radiographs of patients who had undergone HRS because of CP-associated hip displacement. The pre- and postoperative migration percentage (MP), femoral neck-shaft angle (NSA), and sphericity, as determined by the Mose hip ratio (MHR), age at surgery, Gross Motor Function Classification System level, surgical history including Dega pelvic osteotomy, and triradiate cartilage status were studied. Regression analyses using linear mixed model were performed to identify factors affecting hip sphericity improvement. Results. A total of 108 patients were enrolled. The mean preoperative MP was 58.3% (SD 31.7%), which improved to 9.1% (SD 15.6%) at the last follow-up. NSA and MHR improved from 156.5° (SD 11.5°) and 82.3% (SD 8.6%) to 126.0° (SD 18.5°) and 89.1% (SD 9.0%), respectively. Factors affecting the postoperative MHR were preoperative MP (p = 0.005), immediate postoperative MP (p = 0.032), and history of Dega osteotomy (p = 0.046). Conclusion. We found that hip sphericity improves with HRS. Preoperative MP, reduction quality, and acetabular coverage influence femoral head remodelling. We recommend that surgeons should consider intervention early before hip displacement progresses and that during HRS, definite reduction and coverage of the femoral head should be obtained. Cite this article: Bone Joint J 2021;103-B(1):198–203

Objectives. Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis. Materials and Methods. A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis. Results. Animals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animals. Conclusion. Our data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture. Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193

Aims. Recent studies have suggested that corticosteroid injections into the knee may harm the joint resulting in cartilage loss and possibly accelerating the progression of osteoarthritis (OA). The aim of this study was to assess whether patients with, or at risk of developing, symptomatic osteoarthritis of the knee who receive intra-articular corticosteroid injections have an increased risk of requiring arthroplasty. Methods. We used data from the Osteoarthritis Initiative (OAI), a multicentre observational cohort study that followed 4,796 patients with, or at risk of developing, osteoarthritis of the knee on an annual basis with follow-up available up to nine years. Increased risk for symptomatic OA was defined as frequent knee symptoms (pain, aching, or stiffness) without radiological evidence of OA and two or more risk factors, while OA was defined by the presence of both femoral osteophytes and frequent symptoms in one or both knees. Missing data were imputed with multiple imputations using chained equations. Time-dependent propensity score matching was performed to match patients at the time of receving their first injection with controls. The effect of corticosteroid injections on the rate of subsequent (total and partial) knee arthroplasty was estimated using Cox proportional-hazards survival analyses. Results. After removing patients lost to follow-up, 3,822 patients remained in the study. A total of 249 (31.3%) of the 796 patients who received corticosteroid injections, and 152 (5.0%) of the 3,026 who did not, had knee arthroplasty. In the matched cohort, Cox proportional-hazards regression resulted in a hazard ratio of 1.57 (95% confidence interval (CI) 1.37 to 1.81; p < 0.001) and each injection increased the absolute risk of arthroplasty by 9.4% at nine years’ follow-up compared with those who did not receive injections. Conclusion. Corticosteroid injections seem to be associated with an increased risk of knee arthroplasty in patients with, or at risk of developing, symptomatic OA of the knee. These findings suggest that a conservative approach regarding the treatment of these patients with corticosteroid injections should be recommended. Cite this article: Bone Joint J 2020;102-B(5):586–592

Aims. To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. Methods. Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways. Results. Arthritic mice improved their physical fitness by 42.5% after PE intervention; it induced the differential expression of 2,554 genes. The bioinformatic analysis showed that the downregulated genes (n = 1,371) were significantly associated with cellular processes that mediate the inflammation, including Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT), Notch, and cytokine receptor interaction signalling pathways. Moreover, the protein interaction network showed that the downregulated inflammatory mediators interleukin (IL) 4, IL5, IL2 receptor alpha (IL2rα), IL2 receptor beta (IL2rβ), chemokine ligand (CXCL) 9, and CXCL12 were interacting in several pathways associated with the pathogenesis of arthritis. The upregulated genes (n = 1,183) were associated with processes involved in the remodelling of the extracellular matrix and bone mineralization, as well as with the processes of aerobic metabolism. At the histological level, PE attenuated joint inflammatory infiltrate and cartilage erosion. Conclusion. Physical exercise influences parameters intimately linked to inflammatory arthropathies. Research on the effect of PE on the pathogenesis process of arthritis is still necessary for animal and human models. Cite this article:Bone Joint Res. 2020;9(1):36–48

Aims. 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. Methods. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets. Results. Four noteworthy RA-related modules were identified, revealing the immune- and infection-related biological processes and pathways involved in RA. HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, BLNK, BTK, CD3D, CD4, IL2RG, INPP5D, LCK, PTPRC, RAC2, SYK, and VAV1 were recognized as the key hub genes with high connectivity in gene regulation networks and gene pathway networks. Moreover, the long noncoding RNAs (lncRNAs) in the RA-related modules, such as FAM30A and NEAT1, were identified as the indispensable interactors with the hub genes. Finally, candidate drugs were screened by developing a cumulatively scoring approach based on the selected modules. Niclosamide and the other compounds of T-type calcium channel blocker, IKK inhibitor, and PKC activator, HIF activator, and proteasome inhibitor, which harbour the similar gene signature with niclosamide, were promising drugs with high specificity and broad coverage for the RA-related modules. Conclusion. This study provides not only the promising targets and drugs for RA but also a novel methodological insight into the target and drug screening. Cite this article: Bone Joint Res 2020;9(8):501–514

Advanced MRI cartilage imaging such as T. 1. -rho (T1ρ) for the diagnosis of early cartilage degradation prior to morpholgic radiological changes may provide prognostic information in the management of joint disease. This study aimed first to determine the normal T1ρ profile of cartilage within the hip, and secondly to identify any differences in T1ρ profile between the normal and symptomatic femoroacetabular impingement (FAI) hip. Ten patients with cam-type FAI (seven male and three female, mean age 35.9 years (28 to 48)) and ten control patients (four male and six female, mean age 30.6 years (22 to 35)) underwent 1.5T T1ρ MRI of a single hip. Mean T1ρ relaxation times for full thickness and each of the three equal cartilage thickness layers were calculated and compared between the groups. The mean T1ρ relaxation times for full cartilage thickness of control and FAI hips were similar (37.17 ms (. sd.  9.95) and 36.71 ms (. sd. 6.72), respectively). The control group demonstrated a T1ρ value trend, increasing from deep to superficial cartilage layers, with the middle third having significantly greater T1ρ relaxation values than the deepest third (p = 0.008). The FAI group demonstrated loss of this trend. The deepest third in the FAI group demonstrated greater T1ρ relaxation values than controls (p = 0.028). These results suggest that 1.5T T1ρ MRI can detect acetabular hyaline cartilage changes in patients with FAI

Cartilage defects of the hip cause significant pain and may lead to arthritic changes that necessitate hip replacement. We propose the use of fresh osteochondral allografts as an option for the treatment of such defects in young patients. Here we present the results of fresh osteochondral allografts for cartilage defects in 17 patients in a prospective study. The underlying diagnoses for the cartilage defects were osteochondritis dissecans in eight and avascular necrosis in six. Two had Legg-Calve-Perthes and one a femoral head fracture. Pre-operatively, an MRI was used to determine the size of the cartilage defect and the femoral head diameter. All patients underwent surgical hip dislocation with a trochanteric slide osteotomy for placement of the allograft. The mean age at surgery was 25.9 years (17 to 44) and mean follow-up was 41.6 months (3 to 74). The mean Harris hip score was significantly better after surgery (p < 0.01) and 13 patients had fair to good outcomes. One patient required a repeat allograft, one patient underwent hip replacement and two patients are awaiting hip replacement. Fresh osteochondral allograft is a reasonable treatment option for hip cartilage defects in young patients. Cite this article: Bone Joint J 2014;96-B(11 Supple A):11–16

Aims. Medial unicompartmental knee arthroplasty (UKA) is associated with successful outcomes in carefully selected patient cohorts. We hypothesised that severity and location of patellofemoral cartilage lesions significantly influences functional outcome after Oxford medial compartmental knee arthroplasty. Patients and Methods. We reviewed 100 consecutive UKAs at minimum eight-year follow-up (96 to 132). A single surgeon performed all procedures. Patients were selected based on clinical and plain radiographic assessment. All patients had end-stage medial compartment osteoarthritis (OA) with sparing of the lateral compartment and intact anterior cruciate ligaments. None of the patients had end-stage patellofemoral OA, but patients with anterior knee pain or partial thickness chondral loss were not excluded. There were 57 male and 43 female patients. The mean age at surgery was 69 years (41 to 82). At surgery the joint was carefully inspected for patellofemoral chondral loss and this was documented based on severity of cartilage loss (0 to 4 Outerbridge grading) and topographic location (medial, lateral, central, and superior or inferior). Functional scores collected included Oxford Knee Score (OKS), patient satisfaction scale and University College Hospital (UCH) knee score. Intraclass correlation was used to compare chondral damage to outcomes. Results. All patients documented significant improvement in pain and improved functional scores at mid-term follow-up. There were four revisions (mean 2.9 years, 2 to 4; standard deviation (. sd). 0.9) in this cohort, three for tibial loosening and one for femoral loosening. There was one infection that was treated with debridement and insert exchange. The mean OKS improved from 23.2 (. sd. 7.1) to 39.1 (. sd. 6.9); p < 0.001. The cohort with central and lateral grade 3 patellofemoral OA documented lower mean satisfaction with pain (90, . sd.  11.8) and function (87.5, . sd. 10.3) on the patient satisfaction scale. On the UCH scale, patients reported significantly decreased mean overall scores (7.3, . sd. 1.2 vs 9, . sd. 2.3) as well as stair climb task (3.5, . sd. 0.3 vs 5, . sd. 0.1) when cartilage lesions were located centrally or laterally on the PFJ. Patients with medial chondral PFJ lesions behave similar to patients with no chondral lesions. Conclusion. Topographical location and severity of cartilage damage of the patella can significantly influence function after successful Oxford medial UKA. Surgeons should factor this in when making their operative decision, and undertake to counsel patients appropriately. Cite this article: Bone Joint J 2016;98-B(10 Suppl B):11–15

With medial unicompartmental osteoarthritis (OA) there is occasionally a full-thickness ulcer of the cartilage on the medial side of the lateral femoral condyle. It is not clear whether this should be considered a contraindication to unicompartmental knee replacement (UKR). The aim of this study was to determine why these ulcers occur, and whether they compromise the outcome of UKR. Case studies of knees with medial OA suggest that cartilage lesions on the medial side of the lateral condyle are caused by impingement on the lateral tibial spine as a result of the varus deformity and tibial subluxation. Following UKR the varus and the subluxation are corrected, so that impingement is prevented and the damaged part of the lateral femoral condyle is not transmitting load. An illustrative case report is presented. Out of 769 knees with OA of the medial compartment treated with the Oxford UKR, 59 (7.7%) had partial-thickness cartilage loss and 20 (2.6%) had a full-thickness cartilage deficit on the medial side of the lateral condyle. The mean Oxford Knee Score (OKS) at the last follow-up at a mean of four years was 41.9 (13 to 48) in those with partial-thickness cartilage loss and 41.0 (20 to 48) in those with full-thickness loss. In those with normal or superficially damaged cartilage the mean was 39.5 (5 to 48) and 39.7 (8 to 48), respectively. There were no statistically significant differences between the pre-operative OKS, the final review OKS or of change in the score in the various groups. We conclude that in medial compartment OA, damage to the medial side of the lateral femoral condyle is caused by impingement on the tibial spine and should not be considered a contraindication to an Oxford UKR, even if there is extensive full-thickness ulceration of the cartilage

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To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis.

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Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

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To fully quantify the effect of posterior tibial slope (PTS) angles on joint kinematics and contact mechanics of intact and anterior cruciate ligament-deficient (ACLD) knees during the gait cycle.

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To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics.

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Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters.

Osteochondritis Dissecans (OCD) is a condition for which the aetiology remains unknown. It affects subchondral bone and secondarily its overlying cartilage and is mostly found in the knee. It can occur in adults, but is generally identified when growth remains, when it is referred to as juvenile OCD. As the condition progresses, the affected subchondral bone separates from adjacent healthy bone, and can lead to demarcation and separation of its associated articular cartilage. Any symptoms which arise relate to the stage of the disease. Early disease without separation of the lesion results in pain. Separation of the lesion leads to mechanical symptoms and swelling and, in advanced cases, the formation of loose bodies. Early identification of OCD is essential as untreated OCD can lead to the premature degeneration of the joint, whereas appropriate treatment can halt the disease process and lead to healing. Establishing the stability of the lesion is a key part of providing the correct treatment. Stable lesions, particularly in juvenile patients, have greater propensity to heal with non-surgical treatment, whereas unstable or displaced lesions usually require surgical management. This article discusses the aetiology, clinical presentation and prognosis of OCD in the knee. It presents an algorithm for treatment, which aims to promote healing of native hyaline cartilage and to ensure joint congruity. Take home message: Although there is no clear consensus as to the best treatment of OCD, every attempt should be made to retain the osteochondral fragment when possible as, with a careful surgical technique, there is potential for healing even in chronic lesions. Cite this article: Bone Joint J 2016;98-B:723–9

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Hip arthroscopy (HA) has become the treatment of choice for femoroacetabular impingement (FAI). However, less favourable outcomes following arthroscopic surgery are expected in patients with severe chondral lesions. The aim of this study was to assess the outcomes of HA in patients with FAI and associated chondral lesions, classified according to the Outerbridge system.

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Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear.

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Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.

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This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).