The signaling molecule prostaglandin E2 (PGE2), synthesized by cyclooxygenase-2 (COX-2), is immunoregulatory and reported to be essential for skeletal stem cell function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in osteoarthritis (OA) analgesia, but cohort studies suggested that long-term use may accelerate pathology. Interestingly, OA chondrocytes secrete high amounts of PGE2. Mesenchymal stromal cell (MSC) chondrogenesis is an in vitro OA model that phenocopies PGE2 secretion along with a hypertrophic OA-like cell morphology. Our aim was to investigate cause and effects of PGE2 secretion in MSC-based cartilage neogenesis and hypertrophy and identify molecular mechanisms responsible for adverse effects in OA analgesia. Human bone marrow-derived MSCs were cultured in chondrogenic medium with TGFβ (10ng/mL) and treated with PGE2 (1µM), celecoxib (COX-2 inhibitor; 0.5µM), AH23848/AH6809 (PGE2 receptor antagonists; 10µM), or DMSO as a control (n=3–4). Assessment criteria were proteoglycan deposition (histology), chondrocyte/hypertrophy marker expression (qPCR), and ALP activity. PGE2 secretion was measured (ELISA) after TGFβ withdrawal (from day 21, n=2) or WNT inhibition (2µM IWP-2 from day 14; n=3). Strong decrease in PGE2 secretion upon TGFβ deprivation or WNT inhibition identified both pathways as PGE2 drivers. Homogeneous proteoglycan deposition and COL2A1 expression analysis showed that MSC chondrogenesis was not compromised by any treatment. Importantly, hypertrophy markers (COL10A1, ALPL, SPP1, IBSP) were significantly reduced by PGE2 treatment, but increased by all inhibitors. Additionally, PGE2 significantly decreased ALP activity (2.9-fold), whereas the inhibitors caused a significant increase (1.3-fold, 1.7-fold, 1.8-fold). This identified PGE2 as an important inhibitor of chondrocyte hypertrophy. Although TGFβ and WNT are known pro-arthritic signaling pathways, they appear to induce a PGE2-mediated antihypertrophic effect that can counteract pathological cell changes in chondrocytes. Hampering this rescue mechanism via COX inhibition using NSAIDs thus risks acceleration of OA progression, indicating the need of OA analgesia adjustment

The development of a representative human, in vitro OA model could deepen understanding of disease mechanisms. Our research aimed to reprogram healthy and OA-derived synoviocytes to induced pluripotent stem cells (iPSCs), thereby generating a novel OA in vitro model. Comparison between the two models shall enable research into underlying processes with potential for clinical translation. A meta-analysis of OA synovial biomarkers was conducted, identifying up to thirteen relevant pathophysiology-related factors, including, amongst others, IL-13, IL-10, IL-6, PIICP, and HA, with PIICP demonstrating the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001). With these findings in mind, human fibroblast-like synoviocytes (HFLS) from healthy and OA patients were transduced using Sendai viral reprogramming. Two clones for each of the resulting iPSC lines were expanded and preliminarily analysed in triplicate by ICC and RT-qPCR for pluripotency characteristics. Healthy HFLS-derived and OA-HFLS-derived iPSC (UoS-B and UoS-C lines, respectively) were generated, indicating successful reprogramming. Morphological observations demonstrated typical iPSC appearance, and ICC confirmed presence of pluripotency markers Tra-1-60, Oct3/4 and Nanog. Expression of Oct3/4, Nanog and Sox2 were confirmed by RT-qPCR with OA-iPSC lines expressing higher levels of all markers compared to non-OA iPSC. In particular, expression of Oct3/4 and Sox2 was 3.5 fold and 4.6 fold higher (p <0.001) in OA-iPSCs (UoS-C) vs. non-OA iPSCs (UoS-B), respectively. Sendai virus clearance was confirmed by passage 4. The successfully obtained OA and non-OA iPSCs can be differentiated towards mesenchymal lineages, including chondrocyte and bone progenitor cells, enabling phenotypic comparison and biomarker analysis as identified in meta-analysis. Cell bank dissemination of these cell lines could deepen further in vitro OA research, with potential impact for clinical translation via the identification of novel cellular and molecular targets

Osteoarthritis (OA) is the most common degenerative joint disease causing joint immobility and chronic pain. Treatment is mainly based on alleviating pain and reducing disease progression. During OA progression the chondrocyte undergoes a hypertrophic switch in which extracellular matrix (ECM) -degrading enzymes are released, actively degrading the ECM. However, cell biological based therapies to slow down or reverse this katabolic phenotype are still to be developed. Bone morphogenetic protein 7 (BMP-7) has been shown to have OA disease-modifying properties. BMP-7 suppresses the chondrocyte hypertrophic and katabolic phenotype and may be the first biological treatment to target the chondrocyte phenotype in OA. However, intra-articular use of BMP-7 is at risk in the proteolytic and hydrolytic joint-environment. Weekly intra-articular injections are necessary to maintain biological activity, a frequency unacceptable for clinical use. Additionally, production of GMP-grade BMP-7 is challenging and expensive. To enable its clinical use, we sought for BMP-7 mimicking peptides better compatible with the joint-environment while still biologically active and which potentially can be incorporated in a drug-delivery system. We hypothesized that human BMP-7 derived peptides are able to mimic the disease modifying properties of the full-length human BMP-7 protein on the OA chondrocyte phenotype. A BMP-7 peptide library was synthesized consisting of overlapping 20-mer peptides with 18 amino-acids overlap between sequential peptides. OA human articular chondrocytes (HACs) were isolated from OA cartilage from total knee arthroplasty (n=18 donors). HACs were exposed to BMP-7 (1 nM) or BMP-7 library peptides at different concentrations (1, 10, 100 or 1000 nM). Gene-expression levels of important chondrogenic-, hypertrophic-, cartilage degrading- and inflammatory mediators were determined by RT-qPCR. GAG and ALP activity were determined using a colorimetric assay and PGE levels were measured by EIA. During the BMP-7 peptide library screening human BMP-7 derived peptides were screened for their full-length human BMP-7 mimicking properties at different concentrations (1, 10, 100 or 1000nM) on a pool of human chondrocytes. Gene expression as well as GAG, ALP and PGE2 level analysis revealed two distinct peptide regions in the BMP-7 protein based on their pro-chondrogenic and anti-OA phenotype actions on human OA chondrocytes. The two most promising peptides were further analysed for their OA chondrocyte disease modifying properties in the presence of OA synovial fluid, showing similar OA phenotype suppressive activity. Conclusively, we successfully identified two peptide regions in the BMP-7 protein with in vitro OA suppressive actions. Further biochemical fine-tuning of the peptides, and in vivo evaluation, will potentially result in the first peptide-based experimental OA treatment, addressing the hypertrophic and katabolic chondrocyte phenotype in OA

Glenohumeral osteoarthritis (OA) is a challenging clinical problem in young patients. Given the possibility of early glenoid component loosening in this population with total shoulder arthroplasty (TSA), and subsequent need for early revision, alternative treatment options are often recommended to provide pain relief and improved range of motion. While nonoperative modalities including nonsteroidal anti-inflammatory medications and physical therapy focusing on rotator cuff strengthening and scapular stabilization may provide some symptomatic relief, young patients with glenohumeral OA often need surgery for improved outcomes. Joint preserving techniques, such as arthroscopic debridement with removal of loose bodies and capsular release, with or without biceps tenotomy or tenodesis, remains a viable nonarthroplasty option in these patients. Clinical studies evaluating the outcomes of arthroscopic debridement for glenohumeral OA in young patients have had favorable outcomes. Evidence suggests that earlier stages of glenohumeral OA have more favorable outcomes with arthroscopic debridement procedures, with worse outcomes being observed in patients with complete joint space loss and bipolar chondral lesions. More advanced arthroscopic options include inferior osteophyte excision and axillary neurolysis or microfracture of chondral lesions, both of which have demonstrated favorable early clinical outcomes. Patients with some preserved joint space and small osteophytes can avoid arthroplasty and have improved functional outcomes after arthroscopic debridement for glenohumeral OA. Caution should be advised when indicating this procedure for patients with large osteophytes, grade IV bipolar lesions, biconcave glenoids, and complete loss of joint space

Introduction. Osteoarthritis (OA) involves pathological change in all joint tissues, including cartilage degradation and synovitis. Synovial inflammation is significantly associated with pain severity and incidence in knee OA. It is becoming evident that synovitis also plays an active role in the initiation and progression of cartilage erosion in OA, through direct secretion of catabolic enzymes as well as factors that stimulate chondrocyte catabolic activity. Therapeutic agents that target both synovitis and cartilage pathology are likely to be maximally beneficial in treating pain and slowing cartilage breakdown in OA. We have previously shown that an amide-derivative of HA (HYMOVIS™) was superior to native HA of the same MW in improving gait, and reducing synovial hyperplasia in a sheep OA model. In the present study the mechanisms whereby the chemically modified HA may be beneficial were examined using chondrocytes and synovial fibroblasts from knees of OA patients. Patients & Methods. Chondrocytes (HAC, n=6) and synovial fibroblasts (HSF, n=6) were isolated from OA patients at the time of knee replacement. HYMOVIS™ (0, 0.5, 1.0 or 1.5mg/mL) was added to simultaneously or 1 hour before interleukin-1β (IL1, 2ng/mL). Cultures were terminated 30 minutes later for Bioplex. ®. quantitation of p-JNK, p-NFκB and p-p38; or 24 hours later for RNA isolation and analysis of gene expression by real time RT-PCR, and measurement of MMP13 activity in the media. Only statistically significant results are reported. Results. In HAC in the absence of IL1, HYMOVIS™ decreased MMP13, ADAMTS5, PTGS2 and IL6 and increased COL2A1 mRNA (2–10fold). In HSF in absence of IL1, HYMOVIS™ decreased TIMP1, TIMP3, CD44, IL6 and increased PTGS2 (2–3fold). In HAC and HSF, IL1 increased expression of MMP1, MMP13, PTGS2, IL6 (>100fold), ADAMTS4 (∼10 fold), all phosphoproteins (3–10fold), and APMA-activated MMP13 activity in media. IL1 increased expression of ADAMTS5 (∼10fold) only in HSF. As expected, IL1 reduced expression of the key matrix proteins in HAC (2–3 fold decrease in COL2A1 and ACAN) and HSF (2 fold decrease in COL1A1). When added simultaneously with IL1, HYMOVIS™ decreased expression of MMP13, ADAMTS5, PTGS2, IL6 expression, and normalised matrix protein expression in both HAC and HAS. Pre-incubation with HYMOVIS™ for 1 hour inhibited IL1-stimulated p-JNK, p-NFκB and p-p38 in both cell types (excluding p-JNK in HSF). In HAC, HYMOVIS™ pre-incubation was superior to simultaneous addition in reducing expression of MMP1, MMP13, ADAMTS4, PTGS2, and IL6 expression. There was a less dramatic effect of HYMOVIS™ pre-incubation on gene expression in HSF compared with HAC. The inhibitory effects of HYMOVIS™ on IL1 stimulated gene expression in HAC and HSF was partially ameliorated by pre-incubation with a CD-44 blocking antibody. Discussion/Conclusions. The present studies have demonstrated several potential key mechanisms whereby the intra-articular injection of a hexadecylamide-derivative of HA (HYMOVIS™) may have both symptom and disease-modifying effects in OA. The previously described increased joint retention of the hexadecylamide-derivative, might act in a similar manner to the pre-incubation studies in our cell culture studies, to reduce the initiation of degradative events with recurrent/cyclic inflammatory episodes that typify OA

DDH with or without previous treatment is the most frequent source of early hip OA in adolescents. Others are hip joint deformation following Legg-Calve-Perthes disease, slipped capital epiphysis or trauma. Secondary OA after rheumatoid arthritis, bacterial infection or as result of an hemophilic hip joint are relatively infrequent. The choice of treatment depends on the type of the deformity and the severity of osteoarthritic changes. Osteotomies are favorably performed in adolescents. Arthrodesis is rarely accepted in this age group. In selected individuals THR is the matter of choice. Pain, limping gait, restricted joint motion and sometimes clicking phemomena are the usual complains. Pain is usually aggravated by running and other sports activities. Residual dysplasia of the hip with a spherical femoral head is best treated by a triple periacetabular osteotomy. The Bernese ostetomy of Ganz (. 3. ) and the triple osteotomy of Tönnis (. 9. ) are popular procedures. They mobilise an acetabular fragment, then reorient and stabilise the fragment in an optimal position. Internal fixation with screws provides stability and allows early mobilisation with partial weight bearing. Chiari’s osteotomy is a supracetabular rotatory displacement osteotomy. Femoral head and joint capsule are medialised and covered by the osteomised iliac bone. The joint capsule in the weight bearing zone is transformed into fibrous cartilage by time. Congruent remodelling of the acetabular roof and fibrous tissue transformation into cartilage are biased by inproper height and orientation of the osteotomy (. 5. ). There is still an indication in severe DDH with subluxation of the femoral head and those with a severely deformed femoral head. In pathomorphologies with aspherical femoral heads femoral osteotomies, usually valgus osteotomies, are required additionally in order to optimize the joint congruency. A dysplastic hip in a high dislocation and moderate to severe OA are contraindications. Radiographic work up includes pelvic ap view and faux profil view. Assessment of the anterior and posterior acetabular rim indicate orientation of the acetabulum in terms of anteversion / retroversion. Orientation of the subchondral sclerosis over the femoral head is an indicator of femoral head coverage as CE-angle and AC-angle. 20°–30° abduction view in neutral rotation mimikes the postoperative acetabulum / femoral head relation. From CT-scans acetabular orientation ( ante-version / retroversion ), degenerative bone cysts, posteroinferior joint space and femoral head deformities and femoral neck osteophytes are depicted. Labrum pathology is dedectable by MRT and MRT-arthrography. After treatment of DDH deformation of the femoral head and neck due to ischaemic necrosis develop in an incidence up to 20 %, depending on the method. Premature closure of the epiphyseal plate can also follow trauma, septic arthritis and Legg-Calve-Perthes disease. Most often an combination of acetabular dysplasia and coxa magna with short femoral neck and a high-standing greater trochanter are typical deformities. Specchiulli’s classification (. 8. ) is very helpful for deformations after avascular necrosis in DDH. Limping gait due to femoral shortening and insufficient strength of the abductor muscels are the major complains of adolescents. Symptoms exacerbate during walking of longer distances and restrict sports activities. Valgus osteotomy, Y-osteotomy, transfer of the greater trochanter alone or in combination with valgus osteotomy are appropiate methods to restore a better function and improve alignment of the mechanical axis to the knee joint. Femoral neck lengthening osteotomies (. 1. ,. 4. ) with distal-lateral transfer of the greater trochanter are advocated by several authors. Restoration of almost normal anatomy muscle function of the hip joint are realistic aims of these methods. If the abductor muscel deficit is dominant and only a minor leg length discrepancy is in slight deformities, e.g. some Specchiulli’s type B2, we do not always need such complex procedures. Isolated transfer of the greater trochanter also improves the lever arm of the abductor muscles and therefore joint function, but does not influence leg length discrepancy. Disappearance of the Tren-delenburg-type gait is the most visible improvement of this procedure (. 7. ). Total hip replacement (=THR) is rarely indicated in adolescents, but sometimes necessary for restoration of a almost normal quality of life. Especially in severe symptomatic OA after septic arthritis or trauma in some individuals remain only two options : arthrodesis or arthroplasty. Arthrodesis is a permanent solution for many years or even life time. Gait function is compromised remarkable (. 6. ) and specific compensatory mechanisms are adopted when walking. Excessive motion in the lumbar spine and ipsilateral knee provokes back and knee pain as well as osteoarthritic changes on the long run. THR in young patients includes the risk of several revisions over life time , due to wear problems particularly in physically active individuals. A deficient acetabular bone stock as usual in severe acetabular dysplasia or poor bone quality after trauma or septic arthritis may compromize primary stability and secondary osteointegration. Nevertheless functional results and outcome (. 2. ) in terms of life quality are superior compared with various non-substituting procedures

Introduction: The Donjoy OA Orthesis has been developed to treat unicompartimental osteoarthrosis of the knee joint. The idea is to reduce the load in the affected joint compartment. Sofar only clinical evaluations and gait analysis have been published. The aim of this study is to use intraarticular pressure sensors in an anatomical model to work out the existing intraarticular pressures. Method: 5 fresh non fixated anatomical knee models were used. The models were prepared leaving the 2/3 of the femur as well as the tibia and fibula. We used a right and left-sided version of the Donjoy OA Orthesis. A defined pressure was applied via the pressure application screw. The dorsal capsule of the knee joint was opened and the meniscus were mobilised in a way that the pressure foils (Fuji typ super low) could be placed between the undersurface of the meniscus and the tibia plateau in each joint compartment. The measurements were recorded in four different joint positions (0°, 30°, 60° flexion and 0° with removed meniscus). Each anatomical model was well fixed in a universal testing machine” (Instron, System ID: 5565 H1703). The used axial pressure in all set ups used was 1500N. We used 4 four different test series:. no pressure, no orthesis. no pressure, with orthesis. with pressure, no orthesis. with pressure, with orthesis. After removing the pressure foils the actual pressure could be estimated by the diameter of the coloured foil. Using the programm Mortphomet it was possible to calculate these pressure areas and give procentual figures. Results: The Antivarus Orthesis could reduce the intraarticular joint pressure between 55–70%. Without pressure:. Knee → 64,37 %. Knee → 55,30 %. Knee → 54,43 %. Knee → 58,75 %. Knee → 44,80 %. Mean value 55%. With pressure:. Knee → 74,59 %. Knee → 74,00 %. Knee → 67,91 %. Knee → 86,34 %. Knee → 49,69 %. mean value 70%. The Antivalgus Orthesis could reduce the intraarticular joint pressure between 46–74%. Without pressure:. Knee → 79,78 %. Knee → 76,22 %. Knee → 75,20 %. Knee → 62,55 %. Knee → 76,49 %. Mean value 74%. With pressure:. Knee → 42,68 %. Knee → 46,24 %. Knee → 64,61 %. Knee → 40,08 %. Knee → 37,20 %. Mean value 46%. Conclusion: This anatomical investigation has proved for the first time via intraarticular pressure measurements that it is possible to considerable reduce the intraarticular pressure using the Donjoy antivarus and antivalgus Orthesis

Fusion remains the standard of care and is associated with a high satisfaction rate. But.… fusion generally requires 6 weeks of restricted weight bearing or immobilization. Potential problems include 1) nonunion, 2) malunion, 3) sesamoid pain (from DJD), 4) late onset IP1 DJD. Complete joint replacement has been performed with a number of different designs since the early 1970's. The metal and poly designed implants are associated with a high failure rate, presumably from high shear loads, eccentric axial loads, poor fixation and bone stock problems. Resurfacing of both sides of the joint with a one piece silicone based crosslinked rubber {“silastic”} in rheumatoid patients appears to function better with use of metal grommets to reduce generation of particle debris and foreign body reaction. These silastic implants are still used by surgeons in select low-demand rheumatoid patients. Salvage after failure of any of these total joint replacements can be challenging because of loss of bone stock. 3 other methods are used to resurface the joint in severe OA: 1) resurfacing the proximal phalangeal side only, 2) resurfacing the metatarsal head only and 3) resurfacing the joint with and interposition arthroplasty. 1) advantage of the proximal phalangeal side resurfacing is simplicity of geometry; the disadvantage is disruption of the FHB attachment and the relative scarcity of severe cartilage damage at that side of the joint. 2) Advantage of the metatarsal head side for resurfacing is that is the typical location of the arthritic change; the disadvantage is potential interference with the sesamoid complex and bulkiness of fixation could lead to a more difficult salvage. 3) The advantage of interposition arthroplasty is the maintenance of bone stock; disadvantages include inconsistent local tissue and somewhat less predictable outcomes. In this talk I will focus primarily on the technique and results of a proximal phalangeal resurfacing approach for OA of the MTP1 joint

Purpose. Patients with anterior cruciate ligament (ACL) deficiency and symptomatic medial compartment osteoarthritis (OA) present a challenge in management. These are often younger than typical primary OA patients and aspire to remain athletically active beyond simple ADLs. Combined ACL reconstruction and valgus tibial osteotomy (ACLHTO) is a well documented surgical option for patients deemed wither too young or too active for total knee arthroplasty. Unicompartmental knee arthroplasty (UKA) is an established surgical treatment for symptomatic medial osteoarthritis of the knee refractory to conservative management. A commonly cited contraindications is symptomatic ACL deficiency because of previous reports detailing premature failure through loosening of the tibial component. Improved results and endoscopic ACL reconstructive procedures have led to an enticing concept of combining ACL reconstruction with medial unicompartmental knee arthroplasty (ACLUKR) for those ACL-deficient medial osteoarthritic (OA) knees. We sought to compare the outcomes in 2 cohorts of patients who underwent either ACLHTO or ACLUKR for this clinical problem. Method. Patients presenting with symptomatic bone on bone medial compartment OA and concomitant ACL deficiency (clinical or asymptomatic) were evaluated for surgery after exhausting non operative management. Patients who were under 40 or had plans to return to high impact loading sports and/or who had more moderate OA were offered combined ACL – medial opening wedge tibia osteotomy as a surgical procedure of choice. Patients were considered for combined ACL Oxford replacement if they were primarily seeking pain relief and were not engaged or aspiring to return to high impact or pivoting sports. All cases but one were concurrent ACL with either HTO or UKR with autogenous hamstring grafts used in all but 2 cases. Results. Thirty of 34 consecutive cases were available for follow-up for a rate of 88%. The median ages for 14 cases of ACLUKR was 51 (range 43 60) whereas 16 patients with ACLHTO had median age 43.4 (range 32 −59). Median FU was 4.65 yrs with minimum 2 year follow up (range 2–8.3). Three of the cases were revision ACL cases all from previous Gore-Tex reconstructions. All but the first patient had concomitant ACL and Oxford unicompartmental knee replacement at 1 surgical sitting and are the subject of this report. The first patient had an autogenous patella bone tendon bone graft performed 6 months prior to the UKA. There were similar change scores for patients in both groups. For ACLUKR, WOMAC pain improvements from 48.1 10.2 SD preoperatively to 79.0 17 SD postop. For ACLHTO, WOMAC improvements from 55.1 13.2 SD preoperatively to 85.0 17 SD postop. To date there have been no cases of infection or bearing dislocation in the ACLUKR group. One patient in the ACLHTO group was revised to TKR for ongoing pain and postoperative flexion contracture. Patient activities ranged from ambulation to vigorous hiking, tennis, and downhill skiing in the UKR group whereas a few in the ACLHTO group were also running mid distances. Overall satisfaction was similar in both groups. Conclusion. ACL reconstruction can safely be combined with medial UKR. The procedure has been used in younger patients with a view toward bone preservation while anticipating need for future revision. Both cohorts showed similar improvements and can be considered. The choice should be geared toward patient athletic demand. While short term results are encouraging though longer term data are necessary to thoroughly evaluate the role of this procedure in patients with medial compartment osteoarthritis and ACL deficiency

There are several case reports or small series of stress tibial fracture around the OA knees in literature. Our study goes on 10 tibial stress fracture in 9 patients. All of the fractures have been distal to proximal tibial methaphysis. 8 of them have been in mid shaft or proximal of mid tibia, only 2 had fractures in distal half of tibia 8 were manage by braces for at least 8 months post TKA. Left side of the Bilateral one was fixed by simple IM nail and in 10 months was changed by TKA. Another very interesting case after failure of plate fixation without revision of knee was fixed by custom – made extended nail that attached to tibial tray. Conclusion: for all patients who are candidate to underwent T K A procedure, an update 3 – joints view is mandatory. Beside of patho anatomy and preoperative planning 3-joints view helps us to assure about peri arthicular stress (pathologic) fractures

Background. The indication of unicompartmental knee arthroplasty (UKA) for end-stage osteoarthritis (OA) remains controversial. This study aimed to investigate patient reported outcomes (PROs) of UKA in patients with severe varus deformity of the knee and compare the results with those of total knee arthroplasty (TKA) at mid-term follow up. Methods. A total of 96 TKAs of 69 patients and 61 UKAs of 50 patients were included. All patients presented with severe knee OA with hip-knee-ankle angle (HKA) ranged from −25 degree to −10 degree, preoperatively. Mean HKAs in TKA group and UKA group were −14.95º and −13.38º, respectively. PROs were assessed using Knee Society Score (KSS 2011), PainDETECT score (PD), and Pain Catastrophizing Scale (PCS) at a mean follow up of 58.65 months for TKA and 58.05 months for UKA. Kaplan-Meier survival analysis was performed to assess implant survival. Complication rate was also assessed. All data were compared between TKA group and UKA group. Results. Mean postoperative knee flexion angle was 124.38 º for TKA group and 133.69 º for UKA group, indicating that knee flexion angle of UKA was significantly greater than that of TKA (p=0.000). There were no statistically differences in KSS and their items, PD, and PCS. Regarding mid-term survivorship, TKA (96.0%) was less than UKA (96.8%), but there was no statistically significance. Major complications of the knee occurred in 4cases (4.0%) for TKA and 7 cases (11.1%) for UKA but there was also no statistically significance. Complications of UKA included 3 cases of OA progression in the lateral compartment. Discussion. Although greater flexion angle was observed in UKA group, there was no significant differences in PROs between the two groups. The survival rate are practically considered worse in TKA and the complication rate are practically considered worse in UKA, but there are no statistically significance. Further assessment should be needed after increasing the number of subjects and follow-up period

Good mid-term results of Oxford UKA (OxUNI) for anteromedial osteoarthritis (OA) were reported. The designers of prosthesis reported a 98% 10-year survival rate for a combined series of phase I and II, and these findings were supported by published results from other series, with 10-year survival ranging from 91% to 98%. In order to obtain good results, the designers of this prosthesis mentioned the importance of adhering to strict indication for OxUNI, especially only for OA cases with intact anterior cruciate ligament (ACL). OxUNI combined with ACL reconstruction (ACLR) is a viable treatment option for only young active patients, in whom the ACL has been primarily ruptured. On the other hand, it was not clear whether the result of OxUNI combined with ACLR for OA with secondary ruptured ACL was good. In this study we compare the short-term results of OxUNI combined with ACLR for OA with secondary ruptured ACL with that for usual OA with intact ACL. 382 OxUNI were performed at two hospitals by one surgeon between January 2002 and August 2005. Among those, 367 cases, followed over two years postoperatively (272 patients, women: 283, men: 84) were assessed. Follow up ratio was 96.1%. The mean patient age at the time of surgery was 72.0 (47~93) years. The mean follow-up period was 39.3 (24~67) months. Thirty three knees of OA were treated with OxUNI combined with ACLR, by using synthetic graft. Clinical results were assessed by the Oxford Knee Score (OKS) and active range of motion (ROM). Patients are asked a series of 12 questions, and their response scores range from 0 (worse) to 4 (best) for each, yielding an overall score range of 0–48. All living patients were contacted, and the status of the implant was established at the time of last follow from hospital records. We evaluate the survival rate for OxUNI with or without ACLR, using the endpoint of revision for any reason. The pre-and postoperative clinical scores were compared using the paired Student’s t-test. Survivor-ship curves were constructed using the Kaplan-Meier method, and survivorship between groups was compared using logrank and Wilcoxon methods. All analyses were performed using 95% confidence intervals and a P value of < 0.05 was considered significant. The mean OKS at final follow-up was 42.1 (preoperative; 21.7), and the mean active ROM was 125.2° (preoperative; 113.4°). OKS and active ROM were significantly improved. There were no significant differences in OKS and active ROM between OxUNI with ACLR and OxUNI with intact ACL. Fourteen knees among 367 knees were revised; nine for loosening of tibial component, four for dislocation of bearing and one for progression of lateral OA. Overall 5-year survival rate was 95.6%. When survival rate was assessed separately with or without ACLR, that of OxUNI with intact ACL was 96.7% and that of OxUNI with ACLR was 83.8%. There was significant worse survival rate between the two groups (P=0.0071). The 5-year survival rate for OxUNI with intact ACL was 96.7%, which was equivalent to those of original series from Oxford. However, 5-year survival rate for Oxford UKA with ACLR was 83.8% in our series. Four knees in nine of loosening of tibial component were replaced by OxUNI combined with ACLR. Therefore, even if ACL was reconstructed, the results of OxUNI for OA with secondary ruptured ACL was proved to be pessimistic. There was significantly worse survival rate for OxUNI with ACLR, compared with OxUNI with intact ACL. So we conclude that combined ACL reconstruction and OxUNI for anteromedial OA with secondary ruptured ACL is not recommended, which must be treated with TKA

Greater trochanteric pain syndrome (GTPS) is common, yet the impact on function and quality of life has not been measured. The aim of this study was to quantify the impact on function and quality of life, comparing the results to people with severe hip osteoarthritis and an asymptomatic control group. Forty two people with GTPS – including 11 not actively seeking treatment and 11 seeking surgical treatment, 20 with severe hip osteoarthritis (OA), and 23 age and sex matched asymptomatic participants (ASC) where recruited from public and private hospitals, and the community. Upon confirming meeting inclusion and exclusion criteria participants were interviewed. Exclusion criteria included lumbar nerve root signs; inflammatory, neoplastic and metabolic disorders. Measured used were the Harris hip score (HHS); the Oswestry disability index (ODI); the Australian quality of life instrument (AQoL); the Functional co-morbidity index (FCI); and fulltime work assessments. No difference was found between the GTPS and the OA group on the HHS, ODI, AQoL or the FCI measures. Both symptomatic groups were significantly more disabled than the ASC group on the HHS and ODI (p<0.001). The GTPS and OA groups had lower AQoL than the ASC group (p<0.001); and higher FCI results than the ASC group (GTPS vs ASC, p=0.005; OA vs ASC, p=0.019). GTPS participants were least likely to be in full time work; full time work participation probability (95% C.I.): GTPS Prob=0.288 (0.160 to 0.463), OA Prob= 0.518 (0.273 to 0.753); ASC group of Prob=0.676 (0.439 to 0.847). People with GTPS have similar levels of pain, disability and quality of life, but are less likely to be in full time employment than people with severe hip OA which puts them at risk of economic hardship. Research on conservative and surgical treatments should measure pain, disability and work participation

Introduction: Abnormalities of mesenchymal stem cells and osteoblastic cells (Obs) might play a role in producing bone collapse due to insufficient repair of the necrotic area in osteonecrosis of the femoral head (ON). Osteoblast and osteocyte apoptosis should be increased at the osteonecrotic site. Materials and Methods: We compared the TRAIL (TNF-related apoptosis-inducing ligand) cytotoxicity in primary Obs isolated from femoral heads from patients with ON or osteoarthritis (OA) and on two human osteosarcoma cell lines, MG-63 and SaOS. 2. . Results and Discussion: We showed that ON but also OA Obs were sensitive to TRAIL. We also observed TRAIL cytotoxicity on MG-63 but not SaOS. 2. cells. Moreover, we saw that TRAIL negatively regulated Akt and ERK survival pathways in MG-63 cells. We also investigated the IL-6 influences on apoptotic response of Obs to TRAIL. Even though decreased IL-6 and sIL-6R levels were observed at peripheral sites of the ON in regard to the levels produced in the iliac crest, IL-6 had no protective effects on TRAIL-induced apoptosis in ON Obs and only a weak protective effect in MG-63 cells. However, TRAIL stimulated IL-6 production in MG-63 cells and, cells and OA Obs, suggesting to a lesser extend, in SaOS. 2. other roles of TRAIL in the bone environment

Early stabilisation after an anterior cruciate ligament (ACL) rupture reduces future meniscal injury. We may therefore expect protection of articular cartilage from ACL reconstruction, but this has yet to be shown. Our aim wasto determine the effect of meniscal injury on the long term risk of osteoarthritis (OA) following ACL reconstruction using Single Photon Emission Computed Tomography (SPECT, a 3 dimensional radionuclide scan). We studied a prospective series of 31 patients (mean age at injury of 29 years) who had bone-patellar tendon-bone ACL reconstruction for unstable, ACL deficient knees. Mean follow-up was 10 years (range 9-13). Patients were separated into two groups according to the status of their menisci at the time of ACL reconstruction, those with intact menisci in group 1 (n=15) and those who required partial meniscectomy in group 2 (n=16). The contra-lateral normal knee was used as a control. All knees were clinically stable with high clinical scores (mean Lysholm score 93 and mean Tegner activity score 6). In group 1 (intact menisci) only one patient (7%) had clinical symptoms of OA and was the only patient with increased uptake on SPECT compatible with early OA. In group 2 (partial meniscectomy), two had clinical symptoms of osteoarthritis, and five patients (32%) had increased uptake on SPECT compatible with early OA. None of the control knees had early OA on SPECT. The prevalence of OA 10 years post ACL reconstruction, using the most sensitive investigation available, is very low in patients who had intact menisci (7%), but increases 5 fold (32%) if a meniscal tear was present. We recommend early ACL reconstruction to preserve the menisci to minimise the long term risk of OA

Joint load reduction is effective for alleviating OA pain. Treatment options for joint unloading include braces and HTO, both of which may be impractical for patients. The purpose of the present study was to examine the biomechanical rationale of a practical, partial unloading implant (KineSpring® System, Moximed) for knee OA. Device durability was tested by cyclically loading bone-implant constructs through simulated use for at least 10 million cycles. Joint load reduction with the implant was quantified by measuring changes in medial and lateral knee compartment loads generated by cadaver knees in simulated gait. Safety of the device was tested by 3, 6, and 12 month follow-up of implants in an in vivo ovine model. Surgical technique and device safety and efficacy were assessed in human clinical studies. The unloader device survived over 15 million cycles of simulated use without failure. In the simulated gait cadaver model, the unloading device significantly reduced medial compartment (29 ± 13 lbs, p<0.05) and overall knee joint loads during the stance phase of gait testing but did not significantly increase lateral compartment loading. Chronic ovine implants demonstrated good tolerance of the implant with normal wound healing and secure device fixation. Clinical experience (n=49) demonstrated uneventful device implantation. Unlike HTO, the implantation technique for the unloader does not alter joint alignment. This surgical technique avoids removal of bone, ligament, and cartilage, thus preserving future primary arthroplasty, if required. Early-term clinical experience also demonstrates good outcomes for patients, the earliest of whom are beyond 2.6 years with the implant. This unloading device offers a practical and attractive treatment option for patients with medial knee OA: load reduction without load transfer, durability, preservation of downstream treatment options, safety, and early-term efficacy

Treatment of OA of the shoulder in young and active patients remains a problem. Present treatment options are debridement, microfracturing, arthrodesis or shoulder replacement. We report the preliminary results of soft-tissue interposition arthroplasty with an acellular allograft skin-derived collagen matrix (Graft Jacket®, Wright Medical). Between July and December 2003 five men and one woman with severe glenohumeral OA had a soft-tissue interposition arthroplasty of the shoulder. The mean age of the patients was 47 years (34 to 58). In four patients the procedure was done arthroscopically. The Graft Jacket® was sutured to the labrum with a minimum of five sutures. The mean postoperative follow-up was 6.2 months. Four patients experienced notable pain relief after the operation. Preoperatively the mean visual analogue pain score was 7.2 and postoperatively it was 2.6. One patient had no improvement and elected to wait before having further treatment. One patient needed a hemi-arthroplasty. The range of motion improved in only one patient. The mean Constant score improved 14 points, from 45 to 59. There were no complications peroperatively or postoperatively. While the long-term results are still unknown, soft-tissue interposition arthroplasty with the Graft Jacket® shows promising results

Introduction and aim: In a prospective comparative study we were interested in the question, wether the total ankle arthroplasty in the midterm FU, especially in patients with RA, is a successful and correctly indicated surgical procedure. We compared our clinical and radiological results with a cohort of patients with OA. Furthermore we analysed especially the rheuma patients for their known periarticular osteopenia and the cementless fixation as a possible contraindication for the ankle arthroplasty. Material and methods: With a mean FU of 4,4 years and a total number of 153 total ankle arthroplasties from 07/1997 to 12/2003 we assessed 92 patients with 94 S.T.A.R total ankle arthroplasties. Indication for this surgical procedure was the rheumatoid arthritis in 26 patients (27.7%) and an idiopathic osteoarthritis of the upper ankle joint in 29 cases (30.8%), furthermore a posttraumatic osteoarthritis in 39 patients (41.5%). Results: The functional increase in their range of motion (ROM) and the significant decrease of pain are the most important and impressing facts for the patients. The increase of ROM in all patients is 17.9 (RA: 18.7 /OA: 16.6). Significant pain relief is described by 92.4% of patients, here all the groups showed no significant differences. An increase in the clinical outcome measured by the Kofoeds Ankle Score is seen from < 70 pts. preoperatively (100% of patients) to > 75 pts. postoperatively (82.3% of patients). The most frequent complication especially in patients with RA is a delayed wound healing (19%), but the revision rate is higher in patients with traumatic and idiopathic osteoarthritis (17% OA /13% RA). A secondary arthrodesis has to be performed only in 2 OA cases. Conclusion: Rheumatoid arthritis in the LDE stage IV and V is the adequate indication for the S.T.A.R. prosthesis. The functional benefit and the clinical outcome is satisfying, the results for the rheumatoid arthritis patients are comparable to other indications. Periarticular osteopenia is not considered as a contraindication

Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589

The management of disabling osteoarthritis of the knee following ipsilateral femoral fracture malunion can be difficult. This study presents the results of seven such patients treated by femoral shaft osteotomy in the fracture region and with locked intramedullary nail fixation. Seven patients with malunited femoral shaft fractures presenting with knee symptoms between 1992 and 1999 were treated by femoral shaft osteotomy. The presenting knee symptoms and function were graded from 0–4. All patients underwent open femoral shaft osteotomy at the apex of the deformity and fixation was by locked intramedullary nailing. The patients were followed up until osteotomy union and reviewed clinically and radiologically with particular emphasis on knee symptoms and function. There were six males and one female. The mean age at presentation was 48 years and the mean time from fracture 28 years. (Range 13–37 years). The mean knee alignment angle preoperatively was 5 degrees varus (range 0–12). The mean time to osteotomy union was 28 months. The mean knee alignment angle postoperatively was 2 degrees valgus. (range 5 degrees varus-5 degrees valgus). Five of the seven patients reported excellent pain relief and functional improvement. One patient had serious vascular complication and now has a stiff but pain free knee. One patient who presented with very advanced OA has since undergone an uncomplicated total knee arthroplasty after osteotomy union and nail removal. These patients presenting with severe disability at an age that would be too young for total knee replacement are difficult to manage. Five out seven patients in these series are symptomatically improved to return to their old occupation. The knee replacement has been delayed in these by a mean of five years. Their eventual knee replacement is likely to have been made less difficult as a result of alignment correction

Introduction. Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair. Methods. In this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining. Results. Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks. Conclusions. Bone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome. Cite this article: Bone Joint Res 2014;3:32–7

There are a variety of potential causes of shoulder arthritis in young patients including osteoarthritis, inflammatory arthritis, post-traumatic arthritis, and avascular necrosis. However, the primary etiology in my practice is related to complications of instability surgery or labral repair: thermal or anchor/suture related chondrolysis. The outcomes of arthroscopic debridement have been disappointing in patients with shoulder arthritis with worse results with increasing severity of articular cartilage changes.

Among all joint arthroplasty procedures, patients who undergo shoulder arthroplasty have the youngest average age. Results of hemiarthroplasty (HA) have been approximately 75% to 80% compared to 90% with total shoulder arthroplasty (TSA).

The largest series in the literature on shoulder arthroplasty in young patients is Schoch et al. They reviewed the results of 56 hemiarthroplasties and 19 TSA performed in patients less than 50 years old with a minimum 20-year follow-up or follow-up until reoperation. Both HA and TSA resulted in significant improvements in pain scores (p<0.001), abduction (p<0.01), and external rotation (p=0.02). Eighty-one percent of shoulders were rated much better or better than pre-operatively. Unsatisfactory ratings in HA were due to reoperations in 25 (glenoid arthrosis in 16) and limited motion, pain, or dissatisfaction in 11. Unsatisfactory ratings in TSA were due to reoperations in 6 (component loosening in 4) and limited motion in 5. Estimated 20-year survival was 75.6% (confidence interval, 65.9–86.5) for HAs and 83.2% (confidence interval, 70.5–97.8) for TSAs.

Aims

Reverse total shoulder arthroplasty (rTSA) can be used in complex cases when the glenoid requires reconstruction. In this study, a baseplate with composite bone autograft and a central trabecular titanium peg was implanted, and its migration was assessed for two years postoperatively using radiostereometric analysis (RSA).

Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition. Cite this article: Bone Joint J 2013;95-B:738–46

The recommended surgical treatment of osteoarthritis (OA) of the shoulder remains controversial.

Recent published and presented trials evaluating hemiarthroplasty (HA) vs total shoulder arthroplasty (TSA) have been underpowered to detect a clinically relevant difference between the treatments.

A meta-analysis was carried out using methodology as described by the Cochrane Collaboration. Comprehensive search strategy was used including Medline, Science Citation Index, a review of references of relevant papers and abstracts of recent orthopaedic meetings. All articles were reviewed in a blinded fashion to select qualified articles based on population, intervention, outcome and methodological rigor. 4 RCT’s were identified. One was excluded due to selection bias introduced by the timing of randomization. The data of the 3 remaining trials was combined for analysis.

In each trial multiple tools were used to assess patient outcome however, the UCLA score was the only one consistent to all 3 studies.

The results demonstrated a statistically significant difference in change scores from baseline to 1 year (TSA 15.6; HA 11.2, p=0.012) in favour of the total shoulder arthroplasty group. This meta analysis demonstrated that in this selected group of patients, (primary osteoarthritis with intact rotator cuff and without excessive glenoid erosion), total shoulder arthroplasty provided a more predictable improvement in pain and function than hemiarthroplasty at 2 years.

Introduction: The medial tibial plateau is composed of two relatively flat facets. An anterior upward sloping “extension facet” (EF) articulates with the medial femoral condyle from 0 to 20–the stance phase of gait (in Man but not in other mammals). Anatomical variation in this area might be responsible for antero-medial osteoarthritis (AMOA).

This paper reports the angle between the EF and the horizontal (the extension facet angle- EFA) in normal knees and in knees with early AMOA.

Method: MRI reports were searched to identify patients with acute rupture of the ACL on the assumption that they had anatomically normal tibiae (46 males and 18 females) and patients with MRI evidence of early AMOA without bone loss (11 males and 9 females).

A sagittal image at the midpoint of the femoral condyle was used to determine the EFA.

Results: The EFA in normal tibiae is 14 +/− 5 (range 3–25). The angle is unrelated to age. The EFA in individuals with early AMOA is 19 +/− 4 (range 13–26). The difference is significant (p< 0.001).

Discussion: There is a wide variation in the EFA in normal knees which is unrelated to age.

There is an association between an increased EFA (ie a steeper EF) and MRI evidence of AMOA. Although a causal link is not proven, we speculate that a steeper angle increases the duration of loading on the EF in stance and tibio-femoral interface shear. This may initiate cartilage breakdown.

Introduction: The medial tibial plateau is composed of two relatively flat facets. An anterior upward sloping “extension facet” (EF) articulates with the medial femoral condyle from 0 to 20° – the stance phase of gait (in Man but not in other mammals). A horizontal “flexion facet” contacts the femur from 20° to full flexion. Anatomical variation in this area might be responsible for the initiation of antero-medial osteoarthritis (AMOA).

This paper reports the angle between the EF and the horizontal (the extension facet angle - EFA) in normal knees and in knees with early AMOA.

Method: MRI reports were searched to identify patients with acute rupture of the ACL on the assumption that they had anatomically normal tibiae (46 males and 18 females) and patients with MRI evidence of early AMOA without bone loss (11 males and 9 females).

A sagittal image at the midpoint of the femoral condyle was used to determine the EFA. Repeat measurements were taken by two observers.

Results: The EFA in normal tibiae is 14 +/− 5° (range 3 – 25°). The angle is unrelated to age. The EFA in individuals with early AMOA is 19 +/− 4° (range 13 – 26°). The difference is highly significant (p< 0.001).

Discussion: There is a wide variation in the EFA in normal knees that is unrelated to age.

There is an association between an increased EFA (ie a steeper EF) and MRI evidence of AMOA. Although a causal link is not proven, we speculate that a steeper angle increases the duration of loading on the EF in stance and tibio-femoral interface shear. This may initiate cartilage breakdown.

Osteoarthritis of the knee is a global scourge. Treatment ranges from cumbersome conservative measures with too many drugs with undesirable side effects, to aggressive knee replacements which still remain elusive to an average Indian. Can we provide hope to these patients and offer them a dignified existence?

In a study conducted over 100 patients in my hospital since 1998, I have devised a very effective treatment option, a new integrated therapy incorporating Yoga and a few alternative systems. Apart from offering to combat associated problems like diabetes, hypertension, obesity, osteoporosis etc it has lessened the amount of medications used for their treatment.

Opening wedge high tibial osteotomy (OWHTO) is a treatment option for medial compartment osteoarthritis of the knee in the young active adult. Limited evidence exists in the literature regarding return to activities following OWHTO.

We performed a retrospective study of local patients who underwent OWHTO from 2005 – 2012 assessing post-operative return to sporting function. Patients with additional knee pathology, surgery or alternative issues affecting activity were excluded.

110 patients met inclusion criteria, 75 were successfully contacted.

Mean improvement in pain score = 4.8/10 (95%CI 4.2 to 5.4, p<0.01). Mean pre-operative KOS-SAS score = 0.5/2, mean post-operative KOS-SAS score = 1.1/2, mean change in KOS-SAS score following OWHTO = 0.6 (95% CI 0.5 to 0.7, p<0.01). Mean pre-morbid Tegner score = 5.9/10, pre-operative = 2.7/10, post-operative = 4.2/10. Mean change in Tegner score following OWHTO = 1.5 (95% CI 1 to 1.9, p<0.01). Following OWHTO 25% of patients achieved pre-morbid Tegner scores. Patient BMI, age, type of implant or graft used had no significant effect on outcome.

OWHTO can temporarily improve pain, activity and sporting levels in young patients with isolated medial compartment knee OA. Return to pre-morbid activity levels and even high level sports function is possible although not the norm.

Purpose: The management of disabling knee osteoarthritis of the knee following malunion of an ipsilateral femoral shaft fracture is difficult and controversial. The purpose of this study is to analyse the results of femoral shaft osteotomy at the level of the old fracture in seven such patients.

Materials and Methods: Seven patients with old malunited femoral shaft fractures presented with disabling knee osteoarthritis between 1992 and 1999. Knee symptoms and function were graded at presentation. All underwent open femoral shaft osteotomy at the apex of the deformity, with locked intramedullary nail fixation. The patients were followed up regularly until osteotomy union and reviewed clinically and radiologically with particular emphasis on knee symptoms and function.

Results: There were six males and one female. The mean age at presentation was 55 years and mean time from the fracture was 28 years (range 13–35 years). The mean preoperative knee alignment angle was 5.60 varus (range O′12′). The mean time to osteotomy union was 28 months. The mean postoperative knee alignment angle was 20 valgus (range 50 valgus -50 varus). All patients reported significant improvement in knee symptoms and function. One osteotomy was followed by a serious vascular complication and the patient now has a stiff but pain free knee. One patient with very advanced osteoarthritis underwent an uncomplicated total knee replacement after osteotomy union and nail removal.

Conclusion: These patients presenting with severe disability at an age which is worryingly young for total knee arthroplasty present a difficult management problem. Five out seven patients had excellent symptomatic and functional improvement following the femoral shaft osteotomy. The possible need for knee replacement was delayed by at least 5 years and the eventual arthroplasty is likely to have been made less technically difficult and more functionally satisfactory as a result of the alignment correction.

Given the growing prevalence of obesity around the world and its association with osteoarthritis of the knee, orthopaedic surgeons need to be familiar with the management of the obese patient with degenerative knee pain. The precise mechanism by which obesity leads to osteoarthritis remains unknown, but is likely to be due to a combination of mechanical, humoral and genetic factors.

Weight loss has clear medical benefits for the obese patient and seems to be a logical way of relieving joint pain associated with degenerative arthritis. There are a variety of ways in which this may be done including diet and exercise, and treatment with drugs and bariatric surgery. Whether substantial weight loss can delay or even reverse the symptoms associated with osteoarthritis remains to be seen.

Surgery for osteoarthritis in the obese patient can be technically more challenging and carries a risk of additional complications. Substantial weight loss before undertaking total knee replacement is advisable. More prospective studies that evaluate the effect of significant weight loss on the evolution of symptomatic osteoarthritis of the knee are needed so that orthopaedic surgeons can treat this patient group appropriately.

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA. Cite this article: Bone Joint Res 2023;12(9):536–545

Aims. 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. Methods. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSW. L. ) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. Results. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSW. L. was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m. 2. had a smaller JSW. L. than those with a ‘normal’ BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). Conclusion. This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good. Cite this article: Bone Jt Open 2023;4(3):210–218

Aims. 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. Methods. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy. Cite this article: Bone Joint Res 2022;11(12):862–872

Aims. The aim of this study was to estimate time to arthroplasty among patients with hip and knee osteoarthritis (OA), and to identify factors at enrolment to first-line intervention that are prognostic for progression to surgery. Methods. In this longitudinal register-based observational study, we identified 72,069 patients with hip and knee OA in the Better Management of Patients with Osteoarthritis Register (BOA), who were referred for first-line OA intervention, between May 2008 and December 2016. Patients were followed until the first primary arthroplasty surgery before 31 December 2016, stratified into a hip and a knee OA cohort. Data were analyzed with Kaplan-Meier and multivariable-adjusted Cox regression. Results. At five years, Kaplan-Meier estimates showed that 46% (95% confidence interval (CI) 44.6 to 46.9) of those with hip OA, and 20% (95% CI 19.7 to 21.0) of those with knee OA, had progressed to arthroplasty. The strongest prognostic factors were desire for surgery (hazard ratio (HR) hip 3.12 (95% CI 2.95 to 3.31), HR knee 2.72 (95% CI 2.55 to 2.90)), walking difficulties (HR hip 2.20 (95% CI 1.97 to 2.46), HR knee 1.95 (95% CI 1.73 to 2.20)), and frequent pain (HR hip 1.56 (95% CI 1.40 to 1.73), HR knee 1.77 (95% CI 1.58 to 2.00)). In hip OA, the probability of progression to surgery was lower among those with comorbidities (e.g. ≥ four conditions; HR 0.64 (95% CI 0.59 to 0.69)), with no detectable effects in the knee OA cohort. Instead, being overweight or obese increased the probability of OA progress in the knee cohort (HR 1.25 (95% CI 1.15 to 1.37)), but not among those with hip OA. Conclusion. Patients with hip OA progressed faster and to a greater extent to arthroplasty than patients with knee OA. Progression was strongly influenced by patients’ desire for surgery and by factors related to severity of OA symptoms, but factors not directly related to OA symptoms are also of importance. However, a large proportion of patients with OA do not seem to require surgery within five years, especially among those with knee OA. Cite this article: Bone Joint J 2022;104-B(7):792–800

Aims. Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA. Methods. Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro. Results. IL-38 was highly expressed in lentivirus vector-mediated OA mice. Meanwhile, injection of exogenous IL-38 to OA mice alleviated the cartilage damage, and reduced the levels of proinflammatory factors and chondrocyte apoptosis. TP53 was responsible for lncRNA H19-mediated upregulation of IL-38. Furthermore, it was found that the anti-inflammatory effects of IL-38 were achieved by its binding with the IL-36 receptor (IL-36R). Overexpression of H19 reduced the expression of inflammatory factors and chondrocyte apoptosis, which was abrogated by knockdown of IL-38 or TP53. Conclusion. Collectively, our findings evidenced that upregulation of lncRNA H19 attenuates inflammation and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating TP53, IL-38, and by activating IL-36R. Cite this article: Bone Joint Res 2022;11(8):594–607

Aims. The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371

Aims. Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis. Methods. Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression. Results. Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. Conclusion. Taken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA. Cite this article: Bone Joint Res 2023;12(1):33–45

Aims. 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. Methods. In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results. The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion. Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA. Cite this article: Bone Joint Res 2024;13(3):110–123

Aims. This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. Methods. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed. Results. A total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018). Conclusion. ATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression. Cite this article: Bone Joint Res 2022;11(9):679–689

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain. Cite this article: Bone Joint Res 2022;11(7):439–452

Aims. Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. Methods. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers. Results. C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes: bone remodelling subtype (C1), immune metabolism subtype (C2), and cartilage degradation subtype (C3). The number of macrophage M0 and activated mast cells of C2 subtype was significantly higher than those of the other two subtypes. COL2A1 has significant differences in different subtypes. The expression of COL2A1 is related to age, and trafficking protein particle complex subunit 2 is related to the sex of OA patients. Conclusion. This study linked different tissues with gene expression profiles, revealing different molecular subtypes of patients with knee OA. The relationship between clinical characteristics and OA-related genes was also studied, which provides a new concept for the diagnosis and treatment of OA. Cite this article: Bone Joint Res 2023;12(12):702–711

Aims. Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods. We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results. EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of β1 and β3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate β1 and β3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1β-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/β) and phospholipase C gamma 1 (PLC-γ1). Conclusion. EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA. Cite this article: Bone Joint Res 2023;12(12):734–746

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22

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. Methods. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot. Results. DC-exo inhibited macrophage autophagy (p = 0.002) and promoted M1 macrophage polarization (p = 0.002). DC-exo at 20 μg/ml induced collagen degradation (p < 0.001) and inflammatory cell infiltration (p = 0.023) in rats. OANCT was elevated in DC (p < 0.001) and in cartilage tissues of OA patients (p < 0.001), and positively correlated with patients’ Kellgren-Lawrence grade (p < 0.001). PIK3R5 was increased in DC-exo-treated cartilage tissues (p < 0.001), and OANCT bound to fat mass and obesity-associated protein (FTO) (p < 0.001). FTO bound to PIK3R5 (p < 0.001) to inhibit the stability of PIK3R5 messenger RNA (mRNA) (p < 0.001) and disrupt the PI3K/AKT/mTOR pathway (p < 0.001). Conclusion. Exosomal OANCT from DC could bind to FTO protein, thereby maintaining the mRNA stability of PIK3R5, further activating the PI3K/AKT/mTOR pathway to exacerbate OA. Cite this article: Bone Joint Res 2022;11(9):652–668

Aims. The objective of this study was to present the outcomes of rotational acetabular osteotomy (RAO) over a 30-year period for osteoarthritis (OA) secondary to dysplasia of the hip in pre- or early-stage OA. Methods. Between September 1987 and December 1994, we provided treatment to 47 patients (55 hips) with RAO for the management of pre- or early-stage OA due to developmental hip dysplasia. Of those, eight patients (11 hips) with pre-OA (follow-up rate 79%) and 27 patients (32 hips) with early-stage OA (follow-up rate 78%), totalling 35 patients (43 hips) (follow-up rate 78%), were available at a minimum of 28 years after surgery. Results. In the pre-OA group, the mean Merle d'Aubigné score improved significantly from 14.5 points (SD 0.7) preoperatively to 17.4 points at final follow-up (SD 1.2; p = 0.004) and in the early-stage group, the mean score did not improve significantly from 14.0 (SD 0.3) to 14.6 (SD 2.4; p = 0.280). Radiologically, the centre-edge angle, acetabular roof angle, and head lateralization index were significantly improved postoperatively in both groups. Radiological progression of OA was observed in two patients (two hips) in the pre-OA group and 17 patients (18 hips) in the early-stage group. Kaplan-Meier survival analysis, with radiological progression of OA as the primary outcome, projected a 30-year survival rate of 81.8% (95% confidence interval (CI) 0.59 to 1.00) for the pre-OA group and 42.2% (95% CI 0.244 to 0.600) for the early-stage group. In all cases, the overall survival rate stood at 51.5% (95% CI 0.365 to 0.674) over a 30-year period, and when the endpoint was conversion to total hip arthroplasty, the survival rate was 74.0% (95% CI 0.608 to 0.873). Conclusion. For younger patients with pre-OA, joint preservation of over 30 years can be expected after RAO. Cite this article: Bone Joint J 2024;106-B(5 Supple B):25–31

Aims. This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future

Aims. Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. Methods. Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature. Results. A group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and bone remodelling signalling were identified in OA subchondral lesions. A loading responsive gene set, including 446 principal genes, was highly enriched in OA medial tibial plateaus compared to lateral tibial plateaus. Of this gene set, a total of 223 genes were identified as the main contributors that were strongly associated with osteocyte functions and signalling pathways, such as ECM modelling, axon guidance, Hippo, Wnt, and transforming growth factor beta (TGF-β) signalling pathways. We limited the loading-responsive genes obtained via the osteocyte transcriptome signature to identify a subgroup of genes that are highly relevant to osteocytes, as the mechanics-responsive osteocyte signature in OA. Based on WGCNA, we found that this signature was highly co-expressed and identified three clusters, including early, late, and persistently responsive genes. Conclusion. In this study, we identified the mechanics-responsive osteocyte signature in OA-lesioned subchondral bone. Cite this article: Bone Joint Res 2022;11(6):362–370

Osteoarthritis (OA) is a degenerative disease resulting from progressive joint destruction caused by many factors. Its pathogenesis is complex and has not been elucidated to date. Advanced glycation end products (AGEs) are a series of irreversible and stable macromolecular complexes formed by reducing sugar with protein, lipid, and nucleic acid through a non-enzymatic glycosylation reaction (Maillard reaction). They are an important indicator of the degree of ageing. Currently, it is considered that AGEs accumulation in vivo is a molecular basis of age-induced OA, and AGEs production and accumulation in vivo is one of the important reasons for the induction and acceleration of the pathological changes of OA. In recent years, it has been found that AGEs are involved in a variety of pathological processes of OA, including extracellular matrix degradation, chondrocyte apoptosis, and autophagy. Clearly, AGEs play an important role in regulating the expression of OA-related genes and maintaining the chondrocyte phenotype and the stability of the intra-articular environment. This article reviews the latest research results of AGEs in a variety of pathological processes of OA, to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2022;11(5):292–300