Aims. The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. Methods. We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model. Results. A total of 45 of 398 (11.3%) eligible patients were taking an oral bisphosphonate at the time of knee surgery, with a mean age of 75.8 years (SD 6.2) in bisphosphonate users and 75.7 years (SD 6.8) in non-users. The mean joint space narrowing rate was 0.04 mm/year (SD 0.11) in bisphosphonate users and 0.12 mm/year (SD 0.25) in non-users (p < 0.001). In the multivariate model, age (standardized coefficient = 0.0867, p = 0.016) and the use of a bisphosphonate (standardized coefficient = −0.182, p < 0.001) were associated with the joint space narrowing rate. After successfully matching 43 bisphosphonate users and 86 non-users, the joint narrowing rate was smaller in bisphosphonate users (p < 0.001). Conclusion. The use of bisphosphonates is associated with decreased joint degeneration in non-arthritic hips after knee arthroplasty. Bisphosphonates slow joint degeneration, thus maintaining the thickness of joint cartilage in the normal joint or during the early phase of osteoarthritis. Cite this article: Bone Joint Res 2022;11(11):826–834

Purpose: Section of the anterior cruciate ligament (ACL) is classically used to induce experimental joint degeneration in animal models (dog, rabbit, rat…), but the contribution of physical activity to the course of the cartilage damage observed in this model remains unknown. We studied the influence of moderate physical activity on the course of experimental knee joint degeneration induced by section of the ACL in the rat. Material and methods: The right knee ACL was sectioned with and arthrotome in 60 male Wistar rats (180 g) under general anaesthesia. Full section of the ACL, performed with a fine lancet, was verified clinically by demonstrating anterior drawer. The non-operated knee served as a control. The rats were separated at random into two groups, with or without exercise. Exercise was calibrated on a treadmill running at constant speed (30 cm/s for 30 min, i.e. 15 km for 28 days). Rats were sacrificed on days 7, 14 and 28. Macroscopic inspection, histological analysis and immunohistochemistry tests (Caspase 3) were performed on each knee segment. NO was also assayed in the synovial fluid. Results: No cartilage damage was observed in the non-operated knees after running 15 km. Marked synovitis was observed in the knees with a sectioned ACL starting on day 7, associated with fibrillary surface formations. The severity of the cartilage damage increased from day 14 to day 28, predominantly on the medial tibial plateau and to a lesser extent on the adjacent femoral condyle, in the weight-bearing zone. Damage was minimal on the patella. Chondrocyte apoptotic phenomena were also observed, reaching maximum on day 7 and sustained thereafter. Physical activity had a significant effect on these parameters showing an improvement in the macroscopic and histological lesions from day 14 to day 28, and improvement in chondrocyte apoptosis from day 7 to day 14 and to day 28. Discussion: This novel work confirms the beneficial effect of moderate physical activity in an experimental joint degeneration rat model. Elsewhere, it has been well established experimentally that intense joint activity has a deleterious effect on chondral lesions after meniscectomy and/or section of the ACL. This unfavourable effect of intense physical activity has also been observed clinically in high-level athletes. Our experimental data suggest that moderate physical activity does not increase the risk of joint degeneration and could, under certain conditions, have a beneficial effect, as has been suggested by certain recent clinical data

Purpose: Arthroscopic tenotomy of the long head of the biceps brachial is indicated for pain relief in the treatment of unrepairable tears of the rotator cuff. The purpose of our study was to evaluate clinical and radiological outcome. Material and methods: This retrospective study included 38 patients (21 women and 17 men) mean age 65 years (44–78) who presented rotator cuff tears that could not be repaired by suture. These patients underwent arthroscopic tenotomy associated with acromioplasty in eight cases. Preoperative imaging included arthroscan and standard radiograms to assess retraction of the supraspinatus stump and fatty degeneration. The clinical outcome was assessed with the Constant score and search for loss of biceps force (estimated in comparision of an age- and gender-matched cohort). Modifications of the subarcomial height and the stage of joint degeneration were assessed on AP radiograms (standing and reclining position). Results: Mean follow-up was 31 months. There were no complications related to the operation. The overall constant score improved 19 points from 39 to 58 (pain +7 and motion +6.1 increased most). The activity score improved 6 points. Active joint motion in antepulsion, abduction, and lateral rotation (elbow to body) increased 36.5°, 13.1° and 20.8° respectively. The sub acromial height decreased very little (from 7.4 mm preoperatively to 7.4 mm postoperatively). We observed a 37% decrease in arm force in flexion/supination on the operated side (6.05 kg vs 9.65 kg). Subjectively, 85% of the patients were very satisfied or satisfied, 10% were disappointed and 2.5% were discontent. For 88% of the patients the decision for surgical intervention was wise. Discussion: Tenotomy of the long head of the brachial biceps is effective for pain relief and consequently joint motion. It is a technically simple procedure which does not accelerate degeneration of the excentered joint, at the follow-up considered. It does however reduce flexion force of the arm

Aims. The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child’s distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach. Methods. A total of 30 children with a chondroblastoma of the distal femur who had been treated by intraregional curettage and bone grafting were retrospectively reviewed. An intercondylar approach was used in 16 patients (group A) and an epiphyseal approach in 14 (group B). Limb function was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system and Sailhan’s functional criteria. Results. At final follow-up, the mean MSTS score was 29.1 (SD 0.9) in group A and 26.7 (SD 1.5) in group B (p = 0.006). According to Sailhan’s criteria, the knee function was good and fair in 14 (87.5%) and two (12.5%) patients of group A, and eight (57.1%) and six (42.9%) patients of group B, respectively (p = 0.062). The lesion had recurred in one patient (6.2%) in group A and four patients (28.6%) in group B. Limb shortening > 1 cm was recorded in one patient (6.2%) from group A and six patients (42.8%) from group B. Joint degeneration was noted in one patient from group A and three patients from group B. Conclusion. An intercondylar approach to a chondroblastoma of the middle two-quarters of the distal femoral epiphysis results in better outcomes than a medial or lateral epiphyseal approach: specifically, better limb function, a lower rate of recurrence, and a lower rate of physeal damage and joint degeneration. Cite this article: Bone Joint J 2024;106-B(2):195–202

Aims. cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. Methods. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Results. CREB1 was hyperactive in osteoarthritic articular cartilage, interleukin (IL)-1β-treated cartilage explants, and IL-1β- or carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-treated chondrocytes. 666-15 enhanced cell viability of OA-like chondrocytes and alleviated IL-1β- or CCCP-induced chondrocyte injury through inhibition of mitochondrial dysfunction-associated apoptosis. Moreover, inhibition of CREB1 by 666-15 suppressed expression of ADAMTS4. Additionally, 666-15 alleviated joint degeneration in an ACLT mouse model. Conclusion. Hyperactive CREB1 played a critical role in OA development, and 666-15 exerted anti-IL-1β or anti-CCCP effects in vitro as well as joint-protective effects in vivo. 666-15 may therefore be used as a promising anti-OA drug. Cite this article: Bone Joint Res 2024;13(1):4–18

Introduction. Transfemoral osseointegration (TFOI) for amputees has substantial literature proving superior quality of life and mobility versus a socketed prosthesis. Some amputees have hip arthritis that would be relieved by a total hip replacement (THR). No other group has reported performing a THR in association with TFOI (THR+TFOI). We report the outcomes of eight patients who had THR+TFOI, followed for an average 5.2 years. Materials & Methods. Our osseointegration registry was retrospectively reviewed to identify all patients who had TFOI and also had THR, performed at least two years prior. Six patients had TFOI then THR, one simultaneous, one THR then TFOI. All constructs were in continuity from hip to prosthetic limb. Outcomes were: complications prompting surgical intervention, and changes in subjective hip pain, K-level, daily prosthesis wear hours, Questionnaire for Persons with a Transfemoral Amputation (QTFA), and Short Form 36 (SF36). All patients had clinical follow-up, but one patient did not have complete mobility and quality of life survey data at both time periods. Results. Four (50%) were male, average age 52.7±14.8 years. Three patients (38%) had amputation for trauma, three for osteosarcoma, one each (13%) infected total knee and persistent infection after deformity surgery. One patient died one year after THR+TOFA from subsequently diagnosed pancreatic cancer. One patient had superficial debridement for infection with implant retention after five years. No implants were removed, no fractures occurred. All patients reported severe hip pain preoperatively versus full relief of hip pain afterwards. K-level improved from 0/8=0% K>2 (six were wheelchair-bound) to 5/8=63% (p=.026). At least 8 hours of prosthesis wear was reported by 2/7=29% before TOFA vs 5/7=71% after (p=.286). The QTFA improved in all categories, but not significantly: Global (40.0±21.6 vs 60.0±10.9, p=.136), Problem (50.2±33.2 vs 15.4±8.4, p=.079), and Mobility (35.9±26.8 vs 58.3±30.7, p=.150). The SF36 also improved minimally and not significantly: Mental (53.6±12.0 vs 54.7±4.6, p=.849) and Physical (32.5±10.9 vs 36.3±11.2, p=.634). Conclusions. THR+TFOI is a successful reconstruction option for amputees who desire relief from severe pain related to hip joint degeneration, and also the opportunity for improved mobility and quality of life that TFOI typically confers. In our cohort, the procedure proved safe: no associated deaths, no removals, one soft tissue debridement. Mobility improved markedly. Quality of life improved, but not to significant thresholds as measured by the surveys. THR+TFOI appears safe and reasonable to offer to transfemoral amputees with painful hip joint degeneration

Aims. The ulna is an extremely rare location for primary bone tumours of the elbow in paediatrics. Although several reconstruction options are available, the optimal reconstruction method is still unknown due to the rarity of proximal ulna tumours. In this study, we report the outcomes of osteoarticular ulna allograft for the reconstruction of proximal ulna tumours. Methods. Medical profiles of 13 patients, who between March 2004 and November 2021 underwent osteoarticular ulna allograft reconstruction after the resection of the proximal ulna tumour, were retrospectively reviewed. The outcomes were measured clinically by the assessment of elbow range of motion (ROM), stability, and function, and radiologically by the assessment of allograft-host junction union, recurrence, and joint degeneration. The elbow function was assessed objectively by the Musculoskeletal Tumor Society (MSTS) score and subjectively by the Toronto Extremity Salvage Score (TESS) and Mayo Elbow Performance Score (MEPS) questionnaire. Results. The mean follow-up of patients was 60.3 months (SD 28.5). The mean elbow flexion-extension ROM was 95.8° (SD 21). The mean MSTS of the patients was 84.4 (SD 8.2), the mean TESS was 83.8 (SD 6.7), and the mean MEPS was 79.2 (SD 11.5). All the patients had radiological union at the osteotomy site. Symptomatic osteoarthritic change was observed in three patients (23%), one of whom ended up with elbow joint fusion. Two patients (15.4%) had recurrence during the follow-up period. Surgical complications included two allograft fractures, two plate fractures, three medial instabilities, and two infections. Conclusion. Osteoarticular ulna allograft reconstruction provides acceptable functional outcomes. Despite a high rate of complications, it is still a valuable reconstruction method, particularly in skeletally immature patients who need their distal humerus physis for the rest of hand growth. Cite this article: Bone Jt Open 2024;5(9):749–757

Syndesmotic ankle lesions involve disruption of the osseous tibiofibular mortise configuration as well as ligamentous structures stabilizing the ankle joint. Incomplete diagnosis and maltreatment of these injuries is frequent, resulting in chronic pain and progressive instability thus promoting development of ankle osteoarthritis in the long term. Although the pathogenesis is not fully understood, abnormal mechanics has been implicated as a principal determinant of ankle joint degeneration after syndesmotic ankle lesions. Therefore, the focus of this presentation will be on our recent development of a computationally efficient algorithm to calculate the contact pressure distribution in patients with a syndesmotic ankle lesion, enabling us to stratify the risk of OA development in the long term and thereby guiding patient treatment

Stimulation of the mechanosensitive ion channel, Piezo1 promotes bone anabolism and SNPs in the Piezo1 locus are associated with changes in fracture risk. Osteocytes function as critical regulators of bone homeostasis by sensing mechanical signals. The current study used a human, cell-based physiological, 3D in vitro model of bone to determine whether loading of osteocytes in vitro results in upregulation of the Piezo1 pathway. Human Y201 MSCs, embedded in type I collagen gels and differentiated to osteocytes for 7-days, were subjected to pathophysiological load (5000 µstrain, 10Hz, 5 mins; n=6) with unloaded cells as controls (n=4). RNA was extracted 1-hr post load and assessed by RNAseq analysis. To mimic mechanical load and activate Piezo1, cells were differentiated to osteocytes for 13 days and treated ± Yoda1 (5µM, 2- and 24-hs, n=4); vehicle treated cells served as controls (n=4). RNA was subjected to RT-qPCR and data normalised to the housekeeping gene, YWHAZ. Media was analysed for IL6 release by ELISA. Mechanical load upregulated Piezo1 gene expression (16.5-fold, p<0.001) and expression of the transcription factor NFATc1, and matricellular protein CYR61, known regulators of Piezo1 mechanotransduction (3-fold; p= 5.0E-5 and 6.8-fold; p= 6.0E-5, respectively). After 2-hrs, Yoda1 increased the expression of the early mechanical response gene, cFOS (11-fold; p=0.021), mean Piezo1 expression (2.3-fold) and IL-6 expression (103-fold, p<0.001). Yoda1 increased the release of IL6 protein after 24 hours (7.5-fold, p=0.001). This study confirms Piezo1 as an important mechanosensor in osteocytes. Piezo1 activation mediated an increase in IL6, a cytokine that drives inflammation and bone resorption providing a direct link between mechanical activation of Piezo1, bone remodeling and inflammation, which may contribute to mechanically induced joint degeneration in diseases such as osteoarthritis. Mechanistically, we hypothesize this may occur through promoting Ca2+ influx and activation of the NFATc1 signaling pathway

Aim. Prosthetic joint replacement is more commonly done in the elderly group of patients due to an increase pathology related to joint degeneration that comes with age. In this age group is also more frequent having underling condition that may predispose to a prosthetic joint infection. Also, the pharmacological intervention in those patients may play an important role as a risk factor for infection after joint replacement surgery. The use of oral anticoagulants seems to be particularly increased in elderly patients but there aren't enough data published to support an association between prosthetic joint infection and the use of oral anticoagulants. Identifying risk factors in elderly patients age >75 years old with a special focus on the oral anticoagulation therapy is the aim of the study. Methods. In a retrospective study from 2011 till 2018 all the patients >75 years old with knee and hip replacement surgery have been review looking for acute prosthetic infection and risk factors that may be predispose to it. Patients with previous surgery or any other mechanical complication that needed intervention on the same area have been excluded. Results. A total of 1220 patients have been included (801 knee replacement surgery and 419 hip replacement surgery). The mean age was 79.5 ± 3.44 years and most of the patients were women (72,6%). The infection rate was 2,5%. Several factors have been identified to be associated with acute infection. (Table.1.). The patients receiving oral anticoagulants had an increased risk of infection (OR 3.63 (1.60–7.74), p=0.002). Conclusions. Even all the risk factors associated with risk infection have been described previously, the relevant aspect is the increased risk of prosthetic joint infection in patients receiving oral anticoagulants

Introduction. Osteogenesis imperfect (OI) is a geno- and phenotypically heterogeneous group of congenital collagen disorders characterized by fragility and microfractures resulting in long bone deformities. OI can lead to progressive femoral coxa vara from bone and muscular imbalance and continuous microfracture about the proximal femur. If left untreated, patients develop Trendelenburg gait, leg length discrepancy, further stress fracture and acute fracture at the apex of the deformity, impingement and hip joint degeneration. In the OI patient, femoral coxa vara cannot be treated in isolation and consideration must be given to protecting the whole bone with the primary goal of verticalization and improved biomechanical stability to allow early loading, safe standing, re-orientation of the physis and avoidance of untreated sequelae. Implant constructs should therefore be designed to accommodate and protect the whole bone. The normal paediatric femoral neck shaft angle (FNSA) ranges from 135 to 145 degrees. In OI the progressive pathomechanical changes result in FNSA of significantly less than 120 degrees and decreased Hilgenreiner epiphyseal angles (HEA). Proximal femoral valgus osteotomy is considered the standard surgical treatment for coxa vara and multiple surgical techniques have been described, each with their associated complications. In this paper we present the novel technique of controlling femoral version and coronal alignment using a tubular plate and long bone protection with the use of teleoscoping rods. Methodology. After the decision to operate had been made, a CT scan of the femur was performed. A 1:1 scale 3D printed model (AXIAL3D, Belfast, UK) was made from the CT scan to allow for accurate implant templating and osteotomy planning. In all cases a subtrochanteric osteotomy was performed and fixed using a pre-bent 3.5 mm 1/3 tubular plate. The plate was bent to allow one end to be inserted into the proximal femur to act as a blade. A channel into the femoral neck was opened using a flat osteotome. The plate was then tapped into the femoral neck to the predetermined position. The final position needed to allow one of the plate holes to accommodate the growing rod. This had to be determined pre operatively using the 3D printed model and the implants. The femoral canal was reamed, and the growing rod was placed in the femur, passing through the hole in the plate to create a construct that could effectively protect both the femoral neck and the full length of the shaft. The distal part of the plate was then fixed to the shaft using eccentric screws around the nail to complete the construct. Results. Three children ages 5,8 and 13 underwent the procedure. Five coxa vara femurs have undergone this technique with follow-up out to 62 months (41–85 months) from surgery. Improvements in the femoral neck shaft angle (FNSA) were av. 18. o. (10–38. o. ) with pre-op coxa vara FNSA av. 99. o. (range 87–114. o. ) and final FNSA 117. o. (105–125. o. ). Hilgenreiner's epiphyseal angle was improved by av. 29. o. (2–58. o. ). However only one hip was restored to <25. o. In the initial technique employed for 3 hips, the plates were left short in the neck to avoid damaging the physis. This resulted in 2 of 3 hips fracturing through the femoral neck above the plate at approximately 1 year. There were revisions of the 3 hips to longer plates to prevent intra-capsular stress riser. All osteotomies united and both intracapsular fractures healed. No further fractures have occurred within the protected femurs and no other repeat operations have been required. Conclusions. Surgical correction of the OI coxa vara hip is complex. Bone mineral density, multiplanar deformity, a desire to maintain physeal growth and protection of the whole bone all play a role in the surgeon's decision making process. Following modifications, this technique demonstrates a novel method in planning and control of multiplanar proximal femoral deformity, resulting in restoration of the FNSA to a more appropriate anatomical alignment, preventing long bone fracture and improved femoral verticalization in the medium term follow-up

Introduction. Angular deformity in the lower extremities can result in pain, gait disturbance, deformity and joint degeneration. Guided growth modulation uses the tension band principle with the goal of treatment being to normalise the mechanical axis. To assess the success of this procedure we reviewed our results in an attempt to identify patients who may not benefit from this simple and elegant procedure. Materials and Methods. We reviewed the surgical records and imaging in our tertiary children's hospital to identify all patients who had guided growth surgery since 2007. We noted the patient demographics, diagnosis, peri-operative experience and outcome. All patients were followed until skeletal maturity or until metalwork was removed. Results. 173 patients with 192 legs were assessed for eligibility. Six were excluded due to inadequate follow-up or loss of records. Of the 186 treated legs meeting criteria for final assessment 19.8% were unsuccessful, the other 80.2% were deemed successful at final follow up. Complications included infection and metal-work failure. Those with a pre-treatment diagnosis of idiopathic genu valgum/ varum had a success rate of 83.6%. Conclusions. In our hands, guided growth had an 80-percent success rate when all diagnosis were considered. Those procedures that were unlikely to be successful included growth disturbances due to mucopolysaccharide storage disease, Blounts disease and achondroplasia. Excluding those three diagnoses, success rate was 85.4%. We continue to advocate the use of guided growth as a successful treatment option for skeletally immature patients with limb deformity

Aims. Cam and pincer morphologies are potential precursors to hip osteoarthritis and important contributors to non-arthritic hip pain. However, only some hips with these pathomorphologies develop symptoms and joint degeneration, and it is not clear why. Anterior impingement between the femoral head-neck contour and acetabular rim in positions of hip flexion combined with rotation is a proposed pathomechanism in these hips, but this has not been studied in active postures. Our aim was to assess the anterior impingement pathomechanism in both active and passive postures with high hip flexion that are thought to provoke impingement. Methods. We recruited nine participants with cam and/or pincer morphologies and with pain, 13 participants with cam and/or pincer morphologies and without pain, and 11 controls from a population-based cohort. We scanned hips in active squatting and passive sitting flexion, adduction, and internal rotation using open MRI and quantified anterior femoroacetabular clearance using the β angle. Results. In squatting, we found significantly decreased anterior femoroacetabular clearance in painful hips with cam and/or pincer morphologies (mean -11.3° (SD 19.2°)) compared to pain-free hips with cam and/or pincer morphologies (mean 8.5° (SD 14.6°); p = 0.022) and controls (mean 18.6° (SD 8.5°); p < 0.001). In sitting flexion, adduction, and internal rotation, we found significantly decreased anterior clearance in both painful (mean -15.2° (SD 15.3°); p = 0.002) and painfree hips (mean -4.7° (SD 13°); p = 0.010) with cam and/pincer morphologies compared to the controls (mean 7.1° (SD 5.9°)). Conclusion. Our results support the anterior femoroacetabular impingement pathomechanism in hips with cam and/or pincer morphologies and highlight the effect of posture on this pathomechanism. Cite this article: Bone Jt Open 2021;2(11):988–996

Abstract. Cranial cruciate ligament (CrCL) disease/rupture causes pain and osteoarthritis (OA) in dogs. α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 and kainate (KA)-1 glutamate receptors (GluR) and the excitatory amino acid transporter-1 (EAAT-1) and EAAT-3 are expressed in joint tissues from OA patients and rodent arthritis models and represent potential therapeutic targets. Objectives. To evaluate glutamate signalling in canine diseased and normal CrCL and meniscus by immunohistochemistry (IHC). Methods. Surgical waste (CrCL, n=5 and medial meniscus, n=3) were obtained from canines with CrCL disease (RCVS ethics approval:2017/14/Alves) and normal analogous tissues (n=2). IHC optimization was performed for rabbit polyclonal (AMPA-2:ab52176, KA-1:ab67402, EAAT-1:ab416) and monoclonal (EAAT-3:ab124802) antibodies from Abcam. IHC was optimised over antibody dilutions from 1:100 to 1:5000 alongside equivalent IgG isotype controls (ab37415 and ab172730) and negative controls (TBS/Tween buffer without primary antibodies). IHC staining was compared in diseased and normal tissues and disclosed with 3,3’-Diaminobenzidine (DAB). Results. Specific immunostaining was observed for all primary antibodies, at concentrations between 2.0×10. −4. mg/mL to 1.0×10. −2. mg/mL, depending on the tissue and primary antibody. All GluR and transporters were expressed in the cellular membrane, in the normal and diseased CrCL and meniscus. Healthy CrCL showed a well-organized microstructure, with normal positively labelled ligamentocytes, whereas diseased CrCL microstructure was disrupted, with many positively stained fibroblastic cells in the epiligamentous region and evident neovascularization, indicative of ongoing repair. The normal and diseased meniscal tissues showed similar chondrocytes-like cells labelling and microstructure. Negative controls demonstrated no labelling. Conclusions. GluR and transporters expression is altered in canine diseased CrCLs, implicating glutamate signalling in this pathology. Since AMPA/KA GluR antagonists alleviate joint degeneration in post-traumatic OA in rodent models, they may be useful for the treatment of CrCL disease in dogs, as well as translated to other veterinary and human orthopaedic diseases

Abstract. Objectives. Osteocytes function as critical regulators of bone homeostasis by sensing mechanical signals. Stimulation of the mechanosensitive ion channel, Piezo1 promotes bone anabolism and deletion of Piezo1 in osteoblasts and osteocytes decreases bone mass and bone strength in mice. This study determined whether loading of osteocytes in vitro results in upregulation of the Piezo1 pathway. Methods. Human MSC cells (Y201), embedded in type I collagen gels and differentiated to osteocytes in osteogenic media for 7-days, were subjected to pathophysiological load (5000 µstrain, 10Hz, 5 mins; n=6) with unloaded cells as controls (n=4). RNA was extracted 1-hr post load and Piezo1 activation assessed by RNAseq analysis (NovaSeq S1 flow cell 2 × 100bp PE reads). To mimic mechanical load and activate Piezo1, Y201s were differentiated to osteocytes in 3D gels for 13 days and treated, with Yoda1 (5µM, 2 hours, n=4); vehicle treated cells served as controls (n=4). Extracted RNA was subjected to RT-qPCR and data analysed by Minitab. Results. Low mRNA expression of PIEZO1 in unloaded cells was upregulated 5-fold following 1-hr of mechanical load (p=0.003). In addition, the transcription factor NFATc1, a known regulator of Piezo1 mechanotransduction, was also upregulated by load (2.4-fold; p=0.03). Y201 cells differentiated in gels expressed the osteocyte marker, SOST. Yoda1 upregulated PIEZO1 (1.7-fold; p=0.057), the early mechanical response gene, cFOS (4-fold; p=0.006), COL1A1 (3.9-fold; p=0.052), and IL-6 expression (7.7-fold; p=0.001). Discussion. This study reveals PIEZO1 as an important mechanosenser in osteocytes. Piezo 1 mediated increases in the bone matrix protein, type I collagen, and IL-6, a cytokine that drives inflammation and bone resorption. This provides a direct link between mechanical activation of Piezo 1, bone remodelling and inflammation, which may contribute to mechanically-induced joint degeneration in osteoarthritis. Mechanistically, we hypothesise this may occur through promoting Ca2+ influx and activation of the NFAT1 signalling pathway

Background. The only existing classification of Müller-Weiss Disease (MWD), based solely on Méary's angle, serves neither as guide for prognosis nor treatment. This accounts for lack of gold standard in its management. Methods. Navicular compression, medial extrusion, Kite's angle and metatarsal lengths were measured on all radiographs of 95 feet with MWD. Joints involved, presence and location of navicular fracture were recorded. Results. We identified three distinct groups. Group 1 comprises 11 “early-onset” MWD feet, aged 9 to 29 years. These had the greatest compression and medial extrusion, and lowest Kite's angles. All except 1 were index minus and had a lateral navicular fracture. None has required surgery to date. Only 1 has moderate talonavicular joint (TNJ) degeneration. Group 2 comprises 23 “Müller-Weissoid” feet with radiologically normal navicular in their fifties and developing MWD, on average, 4.5 years later. These had the lowest compression and extrusion, and highest Kite's angles. None had complete fracture. All had TNJ arthritis, with early changes at lateral naviculocuneiform joint (NCJ) in 43%. Group 3 “late-onset” MWD, presenting in the sixth decade, is subdivided into 3 sub-groups. Only TNJ is involved in group 3A (16). Group 3B denotes affection of TNJ more than NCJ (20). In group 3C “reverse Müller-Weiss disease”, which affects NCJ more than TNJ (25), second metatarsal overlength is highest of all groups. No difference in age, compression, extrusion and Kite's angle exists among the 3 subgroups. No fracture occurred in group 3A compared to 65% and 32% in groups 3B and 3C, respectively. Conclusions. With a need to compare like-for-like pathology, the proposed classification provides a common platform for reporting outcomes of different treatment modalities, operative or nonoperative. We theorize pathogenetic pathways in the different groups and propose systematic surgical approaches for each category

Aims. Knee osteonecrosis in advanced stages may lead to joint degeneration. Total knee arthroplasty (TKA) for osteonecrosis has traditionally been associated with suboptimal results. We analyzed outcomes of contemporary TKAs for osteonecrosis, with particular emphasis on: survivorship free from aseptic loosening, any revision, and any reoperation plus the clinical outcomes, complications, and radiological results. Patients and Methods. In total, 156 patients undergoing 167 primary TKAs performed for osteonecrosis between 2004 and 2014 at a single institution were reviewed. The mean age at index TKA was 61 years (14 to 93) and the mean body mass index (BMI) was 30 kg/m. 2. (18 to 51) The mean follow-up was six years (2 to 12). A total of 110 TKAs (66%) were performed for primary osteonecrosis and 57 TKAs (34%) for secondary osteonecrosis. Overall, 15 TKAs (9%) had tibial stems, while 12 TKAs (7%) had femoral stems. Posterior-stabilized designs were used in 147 TKAs (88%) of TKAs. Bivariate Cox regression analysis was conducted to identify risk factors for revision and reoperation. Results. Survivorship free from aseptic loosening, any revision, and any reoperation at ten years was 97% (95% confidence interval (CI) 93 to 100), 93% (95% CI 85 to 100), and 82% (95% CI 69 to 93), respectively. No factors, including age, sex, BMI, primary versus secondary osteonecrosis, stem utilization, and constraint, were identified as risk factors for reoperation. Four TKAs (2%) underwent revision, most commonly for tibial aseptic loosening (n = 2). Excluding revisions and reoperations, there was a total of 11 complications (7%), with the most common being a manipulation under anaesthesia (six TKAs, 4%). Mean Knee Society Scores (Knee component) significantly improved from 57 (32 to 87) preoperatively to 91 (49 to 100) postoperatively (p < 0.001). No unrevised TKAs had complete radiolucent lines or radiological evidence of loosening. Conclusion. Contemporary cemented TKAs with selective stem utilization for osteonecrosis resulted in durable survivorship, a low complication rate, and reliable improvement in clinical outcomes. Cite this article: Bone Joint J 2019;101-B:1356–1361

Abstract. Objectives. Osteoarthritis (OA) is a painful and debilitating disorder of diarthroidal joints. Progressive degeneration of the cartilage extracellular matrix (ECM) together with abnormal chondrocyte characteristics occur leading to a switch to a fibroblast-like phenotype and production of mechanically-weak cartilage. Early changes to chondrocytes within human cartilage have been observed including chondrocyte swelling. [1]. together with the development of thin cytoplasmic processes which increase in number and length with degeneration. [2]. Changes to chondrocyte phenotype in degenerate cartilage are associated with F-actin redistribution and stress fibres (SF) formation, leading to morphologically-dedifferentiated (fibroblast-like) chondrocytes. [3,4]. It is unclear if these processes are a consequence of ‘passive’ cell swelling into a defective ECM or an ‘active’ event driven by changes in cell metabolism resulting in alterations to cell shape. To address this, we have quantified and compared the distribution and levels of F-actin, a key cytoskeletal protein involved in the formation of cytoplasmic processes, within in situ chondrocytes in non-degenerate and mildly degenerate human cartilage. Methods. Human femoral head cartilage was obtained from 21 patients [15 females, 6 males, average age 69.6yrs, (range 47–90yrs)] following femoral neck fracture, with Ethical Approval and patient's permission. Cartilage explants were removed from areas graded non-degenerate grade 0 (G0) or mildly degenerate grade 1 (G1) and cultured for up to 3wks in Dulbecco's Modified Eagle's Medium (DMEM) +/− 25% human serum (HS). In situ chondrocytes were stained with CMFDA (5-chloromethylfluoresceindiacetate, Cell-Tracker Green®) and phalloidin (F-actin labelling) and imaged by confocal microscopy and analysed quantitatively using ImageJ and Imaris® software. Results. There were significant increases in the total amount (TA) of F-actin and its distribution [intense punctuate (IP) and intense areas (IA)] between the whole chondrocyte populations of G0 and G1 cartilage (P=0.0356; 0.0112; 0.016, respectively). Where the volume of chondrocytes was divided into normal (<1000 µm³) and swollen (≥1000 µm³) cells, F-actin TA increased in swollen cells (P=0.036 within G0 and G1, and P=0.0009 between grades) compared to chondrocytes of normal volume in each grade. Moreover, IP and IA within and between G0 and G1 were higher compared to normal chondrocytes (with P<0.0001 for IP and P<0.001 for IA). In addition, tissue culture experiments demonstrated that 90% of chondrocytes with cytoplasmic processes had strong F-actin intensity (either IP or IA with P<0.0001). Furthermore, 83% of this F-actin was associated with cytoplasmic processes, with >65% situated at the base of the process (P<0.0001). Conclusions. The increases in chondrocyte F-actin levels (TA) and its localisation (IP, IA) appear to be associated with cell swelling and development of cytoplasmic processes, which are both characteristics of early OA cartilage. [1]. This suggests the formation of chondrocyte cytoplasmic processes is an ‘active’ event potentially involving changes to matrix metabolism rather than a ‘passive’ cell swelling into a defective extracellular matrix. 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

Abstract. OBJECTIVES. Abnormal joint mechanics have been proposed as adversely affecting natural hip joint tribology, whereby increased stress on the articular cartilage from abnormal loading leads to joint degeneration. The aim of this project was to assess the damage caused by different loading conditions on the articular surfaces of the porcine hip joint in an experimental simulator. METHODS. Porcine hip joints were dissected and mounted in a single station hip simulator (SimSol, UK) and tested under loading scenarios (that corresponded to equivalent of different body mass index's’ (BMI) in humans), as follows:“Normal” (n=4), the loading cycle consisted of a simplified gait cycle based on a scaled version of a simplified twin-peak human gait cycle, the peak load was 900N (representative of a healthy BMI). Representative of an “Overweight” BMI (n=3), as the normal cycle with a peak load of 1,130N Representative of an “Obese” BMI (n=1), as the normal cycle with a peak load of 1,340N Tests were conducted at 1Hz for 14,400 cycles in Ringers solution; photogrammetry was used to characterise the appearance of the cartilage and labrum pre, during and post simulation. the appearance and location of damage was recorded. RESULTS. No significant damage was observed for samples tested under normal conditions. Following “overweight” condition testing, tears and detachment of the labrum were observed during testing in two (of three) samples. In addition to damaged observed in “overweight” tested samples the “obese” showed similar damage and also cartilage bruising and wear tracks on the articular surface of the acetabulum. DISCUSSION. The absence of damage in “normal” loading provides evidence that this is an appropriate methodology and loading regime for porcine hips. Increased damage with increasing loads demonstrates the potential to develop further this experimental simulation to assess adverse loading in natural hip joints. 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

Abstract. OBJECTIVES. Although surgical periacetabular osteotomy (PAO) for hip dysplasia aims to optimise acetabular coverage and restore hip function, it is unclear how surgery affects capsular mechanics and joint stability. The purpose was to examine how the reoriented acetabular coverage affects capsular mechanics and joint stability in dysplastic hips. METHODS. Twelve cadaveric dysplastic hips (n = 12) were denuded to the capsule and mounted onto a robotic tester. The robot positioned each hip in multiple flexion angles (Extension, Neutral 0°, Flexion 30°, Flexion 60°, Flexion 90°) and performed internal-external rotations and abduction-adduction to 5 Nm in each rotational or planar direction. Each hip underwent a PAO, preserving the capsule, and was retested postoperatively in the robot. Paired sample t-tests compared the range of motion before and after PAO surgery (CI = 95%). RESULTS. Pre-operatively, the dysplastic hips demonstrated large ranges of internal-external rotations and abduction-adduction motions throughout all flexion positions. Post-operatively, the PAO slackenend the anterosuperior capsule and tightened the inferior capsule. This increased external rotation in Flexion 60° and Flexion 90° (∆. ER. = +16 and +23%) but provided lateral coverage to decrease internal rotation at Flexion 90° (∆. IR. = –15%). The PAO also reduced abduction throughout, but increased adduction in Neutral 0°, Flexion 30°, and Flexion 60° (∆. ADD. = +34, +30%, +29% respectively). CONCLUSIONS. The PAO provided crucial osseous structural coverage to the femoral head, decreasing hypermobility and adverse loading at extreme hip flexion-extension. However, it also slackened the anterosuperior capsule and increased adduction and external rotation, which may lead to ischiofemoral impingement and adductor irritations. Capsular instability may be secondary to acetabular undercoverage, thus capsular alteration may be warranted for larger corrections or rotational osteotomies. To preserve native hip and delay joint degeneration, it is crucial to preserve capsule and elucidate amount of reorientation needed without causing iatrogenic instability. 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