Aims. To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms. Methods. Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay. Results. A total of 63 RA patients and ten controls were included. Expression of MUC1 was observed in both the synovial lining and sublining layer. The percentage of MUC1+ cells in the lining layer of synovium was significantly higher in RA than that in control, and positively correlated to joint destruction scores of RA. Meanwhile, MUC1+ cells in the sublining layer were positively correlated to the Krenn subscore of inflammatory infiltration. Knockdown of MUC1, rather than GO-203 treatment, ameliorated the expression of proinflammatory cytokines, cell migration, and invasion of rheumatoid synoviocytes. Knockdown of MUC1 decreased expression of RhoA, Cdc42, and Rac1. Treatment with LPA compromised the inhibition of migration and invasion, but not inflammation, of synoviocytes by MUC1 knockdown. Conclusion. Upregulated MUC1 promotes the aggression of rheumatoid synoviocytes via Rho guanosine triphosphatases (GTPases), thereby facilitating synovitis and joint destruction during the pathological process of RA. Cite this article: Bone Joint Res 2022;11(9):639–651

The crucial differentiation between septic arthritis and transient synovitis of the hip in children can be difficult. In 1999, Kocher et al introduced four clinical predictors which were highly predictive (99.6%) of septic arthritis. These included fever (temperature ≥ 38.5°C), inability to bear weight, white blood-cell count > 12.0 × 10. 9. cells/L and ESR ≥ 40 mm/hr; CRP ≥ 20 mg/L was later added as a fifth predictor. We retrospectively evaluated these predictors to differentiate septic arthritis from transient synovitis of the hip in children over a four-year period in a primary referral general hospital. When all five were positive, the predicted probability of septic arthritis in this study was only 59.9%, with fever being the best predictor. When applied to low-prevalence diseases, even highly specific tests yield a high number of false positives and the predictive value is thereby diminished. Clinical predictors should be applied with caution when assessing a child with an irritable hip, and a high index of suspicion, and close observation of patients at risk should be maintained

Component malalignment can be associated with pain following total knee replacement (TKR). Using MRI, we reviewed 50 patients with painful TKRs and compared them with a group of 16 asymptomatic controls to determine the feasibility of using MRI in evaluating the rotational alignment of the components. Using the additional soft-tissue detail provided by this modality, we also evaluated the extent of synovitis within these two groups. Angular measurements were based on the femoral transepicondylar axis and tibial tubercle. Between two observers, there was very high interobserver agreement in the measurements of all values. Patients with painful TKRs demonstrated statistically significant relative internal rotation of the femoral component (p = 0.030). There was relative internal rotation of the tibial to femoral component and combined excessive internal rotation of the components in symptomatic knees, although these results were significant only with one of the observers (p = 0.031). There was a statistically significant association between the presence and severity of synovitis and painful TKR (p < 0.001). MRI is an effective modality in evaluating component rotational alignment

We used ultrasonography to examine 36 children suffering from transient synovitis and 12 children with early Perthes' disease. Widening of the joint space was revealed by ultrasonography in all affected hips with either disease. In the patients with transient synovitis, capsular distension was attributed to synovial effusion, while in the patients with Perthes' disease it was produced by thickening of the synovial membrane. Neither capsular distension nor thickening of the joint cartilage was seen in the contralateral normal hip in the patients with transient synovitis, but they were common in early Perthes' disease. Ultrasonography may provide significant diagnostic clues to differentiate early Perthes' from transient synovitis

The August 2024 Wrist & Hand Roundup. 360. looks at: Methotrexate shows potential in reducing pain for hand osteoarthritis with synovitis; Circumferential casting versus plaster splinting in adult distal radius fractures: the CAST study findings; Surgery shows superior long-term success for Dupuytren contracture compared to needle fasciotomy and collagenase injection; Evolving trends in surgical management of wrist arthritis: a decade-long national analysis; Mid-term outcomes of three commonly used surgical reconstructions for scapholunate instability; SLAC and SNAC: what is the evidence for treatment?; Steroids for trapeziometacarpal osteoarthritis?; When is it safe to return to driving after distal radius fracture fixation? A prospective study

Our experience of five children with chronic thorn synovitis indicates that removal of free thorn fragments and all the macroscopically abnormal synovium is required in order to achieve a complete cure. Four children required total synovectomy for diffuse proliferative synovitis and one needed partial synovectomy of the area immediately around the embedded thorn. Joint washouts and partial synovectomy were unsuccessful in children with diffuse synovitis. Careful review is required following removal of a thorn as fragments may be retained within the joint

Aims. The purpose of this study was to assess mid-term survivorship following primary total knee arthroplasty (TKA) with Optetrak Logic components and identify the most common revision indications at a single institution. Methods. We identified a retrospective cohort of 7,941 Optetrak primary TKAs performed from January 2010 to December 2018. We reviewed the intraoperative findings of 369 TKAs that required revision TKA from January 2010 to December 2021 and the details of the revision implants used. Kaplan-Meier analysis was used to determine survivorship. Cox regression analysis was used to examine the impact of patient variables and year of implantation on survival time. Results. The estimated survivorship free of all-cause revision was 98% (95% confidence interval (CI) 97% to 98%), 95% (95% CI 95% to 96%), and 86% (95% CI 83% to 88%) at two, five, and ten years, respectively. In 209/369 revisions there was a consistent constellation of findings with varying severity that included polyethylene wear and associated synovitis, osteolysis, and component loosening. This failure mode, which we refer to as aseptic mechanical failure, was the most common revision indication. The mean time from primary TKA to revision for aseptic mechanical failure was five years (5 months to 11 years). Conclusion. In this series of nearly 8,000 primary TKAs performed with a specific implant, we identified a lower-than-expected mid-term survivorship and a high number of revisions with a unique presentation. This study, along with the recent recall of the implant, confirms the need for frequent monitoring of patients with Optetrak TKAs given the incidence of polyethylene failure, osteolysis, and component loosening. Cite this article: Bone Joint J 2023;105-B(3):277–283

Aims. Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. Results. In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. Conclusion. Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA. Cite this article: Bone Joint Res 2023;12(2):121–132

A prospective study was made of 119 children with transient synovitis or any other cause for synovial effusion and elevated intra-articular pressure. During a follow-up of one year not one case of Perthes' disease was diagnosed and the late clinical and radiographic changes were minimal with moderate overgrowth of the femoral head in 33% and widening of the joint space in 14.2%. Our results do not support the widely accepted concept that Perthes' disease develops as a result of the period of elevated intra-articular pressure found in transient synovitis. Further research into this and Perthes' disease should follow the premise that they are two different diseases without any aetiological connection

Aims. To analyze the short-term outcome of two types of total wrist arthroplasty (TWA) in terms of wrist function, migration, and periprosthetic bone behaviour. Methods. A total of 40 patients suffering from non-rheumatoid wrist arthritis were enrolled in a randomized controlled trial comparing the ReMotion and Motec TWAs. Patient-rated and functional outcomes, radiological changes, blood metal ion levels, migration measured by model-based radiostereometric analysis (RSA), bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), complications, loosening, and revision rates at two years were compared. Results. Patient-Rated Wrist and Hand Evaluation (PRWHE) scores, abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) scores, and pain improved similarly and significantly in both groups. Wrist motion improved significantly in the Motec group only, and forearm rotation in the ReMotion group only. Cobalt (Co) and chromium (Cr) blood ion levels were significantly higher in the metal-on-metal (MoM) Motec group than in the metal-on-polyethylene (MoP) ReMotion group. Mean total translation was 0.65 mm (95% confidence interval (CI) 0.26 to 1.12) and 0.27 mm (95% CI 0.14 to 0.47) for the ReMotion carpal and radial components, and 0.32 mm (95% CI 0.22 to 0.45) and 0.26 mm (95% CI 0.20 to 0.34) for the Motec metacarpal and radial components, respectively. Apart from dorsal and volar tilts, which were significantly higher for the radial ReMotion than for the Motec component, no significant differences in absolute migration occurred. BMD around the radial components never returned to baseline. Almost one-third of patients required reoperation due to complications. Two ReMotion implants were revised to Motec TWAs due to carpal component loosening, and three Motec MoM articulations were revised to metal-on-polyether ether ketone due to painful synovitis. Conclusion. Both implants provided matched function and were stable at short-term follow-up, but with a high complication rate. This procedure should be restricted to specialist centres undertaking prospective analysis until its role is clarified. Cite this article: Bone Joint J 2022;104-B(10):1132–1141

We have reviewed seven cases of synovitis caused by date palm thorns, six involving the knee and one the ankle. Five were satisfactorily treated by thorough irrigation of the joint with normal saline, but two required arthrotomy and synovectomy. All made a full recovery

The appearance and the biochemical, cytological and bacteriological findings were studied in synovial fluid obtained from the knees of 72 patients from south-west India. We report a group of 12 patients with 'eosinophilic synovitis'. In these patients, all below the age of 20 years with an acute onset of severe pain in the knee, there was a large effusion with painful limitation of movement. Their blood leucocyte count averaged 11,200 per mm3 with a mild eosinophilia of 6%. Biochemical examination of synovial fluid was normal, but cytology showed an increase in leucocytes ranging from 1200 to 20,500 (mean 9525) with between 75% and 90% of eosinophils in eight patients and 60% to 75% in four. All the patients responded well to a course of diethylcarbamazine

In a prospective five-year study, 294 episodes of acute transient synovitis of the hip were diagnosed in 275 children. The average annual incidence was 0.2% and the accumulated risk of suffering at least one episode was 3%. The risk of recurrence was 20 times greater than the risk of having a single episode. Perthes' disease was diagnosed from one to five months after the acute attack of synovitis in 10 cases (3.4%). Review of the initial radiographs revealed signs of avascular necrosis in three of the 10 cases, and an increased joint space in five. Only two cases had had completely normal radiographs. The value of routine radiographs taken after three months was minimal. Factors associated with the incidence of Perthes' disease included prolonged time in traction before the range of hip movement became normal, increase in joint space on the initial radiographs and the recurrence of hip symptoms after initial relief

We reviewed 15 children with transient synovitis of the hip who had aspiration of an effusion under local anaesthesia with ultrasound guidance. There were no significant complications; aspiration was useful for diagnosis and gave considerable symptomatic relief. We discuss the role of ultrasound in diagnosis and treatment

Sonography was successfully used to diagnose an effusion in the hips of three adults with septic arthritis and four with aseptic synovitis. The effusions were confirmed by aspiration. All the patients had markedly increased intracapsular pressure which, in the extended position, exceeded the systolic blood pressure and could well compromise the blood supply to the head of femur. Aspiration reduced pain and intracapsular pressure, as did flexion of the hip to 45 degrees

The pathogenesis of Perthes' disease has been related to increased intra-articular pressure secondary to a joint effusion. The pressure within the hip in different positions was measured in eight children with transient synovitis and four with the synovial stage of Perthes' disease. In the position of comfort for the hip this pressure was always less than the arteriolar blood pressure and in a supine position it did not exceed the systolic blood pressure. However, in extension with medial rotation the intra-articular pressure always became several times the systolic blood pressure. This high pressure was also recorded in the stable lateral position which occurs normally during sleep. It is concluded that in the presence of a synovial effusion in the hip, a position of extension and medial rotation causes an increase in intra-articular pressure which may compromise the blood supply to the capital epiphysis of the femur

We evaluated histologically samples of synovial tissue from the knees of 50 patients with rheumatoid arthritis (RA). The samples were taken during revision for aseptic loosening. The findings were compared with those in 64 knees with osteoarthritis (OA) and aseptic loosening and in 18 knees with RA without loosening. The last group had been revised because of failure of the inlay or the coupling system of a constrained prosthesis. All the patients had had a total ventral synovectomy before implantation of the primary prosthesis. In all three groups a foreign-body reaction and lymphocellular infiltration were seen in more than 80% of the tissue samples. Deposits of fibrin were observed in about one-third to one-half of the knees in all groups. Typical signs of the reactivation of RA such as rheumatoid necrosis and/or proliferation of synovial stromal cells were found in 26% of knees with RA and loosening, but not in those with OA and loosening and in those with RA without loosening. Our findings show that reactivation of rheumatoid synovitis occurs after total knee replacement and may be a cofactor in aseptic loosening in patients with RA

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

Pigmented villonodular synovitis (PVNS) is a rare benign neoplastic proliferation of synovial tissue which is typically localised and usually responds well to surgery and/or radiotherapy. We present a case of unusually aggressive of PVNS of the hip in a 73-year-old woman.

Pigmented villonodular synovitis (PVNS) is a rare benign disease of the synovium of joints and tendon sheaths, which may be locally aggressive. We present 18 patients with diffuse-type PVNS of the foot and ankle followed for a mean of 5.1 years (2 to 11.8). There were seven men and 11 women, with a mean age of 42 years (18 to 73). A total of 13 patients underwent open or arthroscopic synovectomy, without post-operative radiotherapy. One had surgery at the referring unit before presentation with residual tibiotalar PVNS. The four patients who were managed non-operatively remain symptomatically controlled and under clinical and radiological surveillance. At final follow-up the mean Musculoskeletal Tumour Society score was 93.8% (95% confidence interval (CI) 85 to 100), the mean Toronto Extremity Salvage Score was 92 (95% CI 82 to 100) and the mean American Academy of Orthopaedic Surgeons foot and ankle score was 89 (95% CI 79 to 100). The lesion in the patient with residual PVNS resolved radiologically without further intervention six years after surgery. Targeted synovectomy without adjuvant radiotherapy can result in excellent outcomes, without recurrence. Asymptomatic patients can be successfully managed non-operatively. This is the first series to report clinical outcome scores for patients with diffuse-type PVNS of the foot and ankle.

Cite this article: Bone Joint J 2013;95-B:384–90.

Pigmented villonodular synovitis (PVNS) is a rare proliferative process of the synovium which most commonly affects the knee and occurs in either a localised (LPVNS) or a diffuse form (DPVNS). The effect of different methods of surgical synovectomy and adjuvant radiotherapy on the rate of recurrence is unclear. We conducted a systematic review and identified 35 observational studies in English which reported the use of surgical synovectomy to treat PVNS of the knee.

A meta-analysis included 630 patients, 137 (21.8%) of whom had a recurrence after synovectomy. For patients with DPVNS, low-quality evidence found that the rate of recurrence was reduced by both open synovectomy (odds ration (OR) = 0.47; 95% CI 0.25 to 0.90; p = 0.024) and combined open and arthroscopic synovectomy (OR = 0.19, 95% CI = 0.06 to 0.58; p = 0.003) compared with arthroscopic surgery. Very low-quality evidence found that the rate of recurrence of DPVNS was reduced by peri-operative radiotherapy (OR = 0.31, 95% CI 0.14 to 0.70; p = 0.01). Very low-quality evidence suggested that the rate of recurrence of LPVNS was not related to the surgical approach.

This meta-analysis suggests that open synovectomy or synovectomy combined with peri-operative radiotherapy for DPVNS is associated with a reduced rate of recurrence. Large long-term prospective multicentre observational studies, with a focus on both rate of recurrence and function, are required to confirm these findings.

Cite this article: Bone Joint J 2015;97-B:550–7.

Torsion and subsequent ischaemia is a well-recognised cause of symptoms and morbidity in general surgery. We present three cases of solitary pigmented villonodular tumours of the knee which were found to have undergone torsion. We believe these to be the first intra-articular tumours in which torsion has been reported.

Aims. This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Methods. Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model. Results. We discovered for the first time that MCL was substantially enriched in the synovial fluid of OA patients and promoted the release of inflammatory cytokines from FLSs through MCL phagocytosis. Through LC‒MS, ANT3 was identified and determined to be significantly upregulated in MCL and OA-FLSs, corresponding to impaired mitochondrial function and cell viability in OA-FLSs. Mitochondrial homeostasis was restored by ANT3 suppression, thereby alleviating synovial inflammation. Furthermore, elevated ANT3 levels inhibited ERK phosphorylation. Specifically, silencing ANT3 prevented inhibition of ERK phosphorylation and significantly reduced the elevation of reactive oxygen species (ROS) and JC1 membrane potential in MCL-induced synovial inflammation. Conclusion. This study revealed the important roles of MCL and ANT3 in FLS mitochondria. Silencing ANT3 rescued ERK phosphorylation, thereby restoring mitochondrial homeostasis in FLSs and alleviating synovitis and OA development, offering a potential target for treating synovitis and preventing early-stage OA. Cite this article: Bone Joint Res 2023;12(4):274–284

Acute bone and joint infections in children are serious, and misdiagnosis can threaten limb and life. Most young children who present acutely with pain, limping, and/or loss of function have transient synovitis, which will resolve spontaneously within a few days. A minority will have a bone or joint infection. Clinicians are faced with a diagnostic challenge: children with transient synovitis can safely be sent home, but children with bone and joint infection require urgent treatment to avoid complications. Clinicians often respond to this challenge by using a series of rudimentary decision support tools, based on clinical, haematological, and biochemical parameters, to differentiate childhood osteoarticular infection from other diagnoses. However, these tools were developed without methodological expertise in diagnostic accuracy and do not consider the importance of imaging (ultrasound scan and MRI). There is wide variation in clinical practice with regard to the indications, choice, sequence, and timing of imaging. This variation is most likely due to the lack of evidence concerning the role of imaging in acute bone and joint infection in children. We describe the first steps of a large UK multicentre study, funded by the National Institute for Health Research, which seeks to integrate definitively the role of imaging into a decision support tool, developed with the assistance of individuals with expertise in the development of clinical prediction tools. Cite this article: Bone Joint J 2023;105-B(3):227–229

Aims. The aim of this prospective study was to assess the long-term clinical, radiological, functional, and quality of life (QoL)-related outcome of patients treated with the synthetic Ligament Advanced Reinforcement System (LARS) device for anterior cruciate ligament (ACL) rupture. Methods. A total of 41 patients who underwent ACL reconstruction with the LARS device (mean age 39.8 years (SD 12.1 ); 32% females (n = 13)) were prospectively included between August 2001 and March 2005. MRI scans and radiographs were performed at a median follow-up of 2.0 years (interquartile range (IQR) 1.3 to 3.0; n = 40) and 12.8 years (IQR 12.1 to 13.8; n = 22). Functional and QoL-related outcome was assessed in 29 patients at a median follow-up of 12.8 years (IQR 12.0 to 14.0) and clinically reconfirmed at latest median follow-up of 16.5 years (IQR 15.5 to 17.9). International Knee Documentation Committee (IKDC) and Tegner scores were obtained pre- and postoperatively, and Lysholm score postoperatively only. At latest follow-up, range of motion, knee stability tests, 36-Item Short Form Health Survey (SF-36), and IKDC scores were ascertained. Complications and reoperations during follow-up were documented. Results. Cumulative complication rate was 66% (n = 27), with 11 developing within one year from surgery and 16 after one year (including five patients with both early and late complications). Ten graft failures (24%) and eight cases of reactive synovitis were observed (20%). All 11 patients with early complications and ten with late complications underwent reoperation (including five with another surgical procedure for early complications), amounting to a cumulative reoperation rate of 51% (n = 21). Revision ACL reconstruction was performed in one patient (2.4%). Median IKDC at latest follow-up was 89.7 (IQR 78.2 to 93.1), being significantly worse in the event of previous complications. Lachman test was positive in 56% (n = 15) of reconstructed knees. All norm-based SF-36 items were at or above median at latest follow-up, and did not differ depending on development of complications. Conclusion. Despite good functional and QoL-related results in the long term, the cumulative complication rate of 66%, including graft failures and reactive synovitis, has to be viewed with great concern. Cite this article: Bone Joint J 2022;104-B(2):242–248

Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

Clinical prediction algorithms are used to differentiate transient synovitis from septic arthritis. These algorithms typically include the erythrocyte sedimentation rate (ESR), although in clinical practice measurement of the C-reactive protein (CRP) has largely replaced the ESR. We evaluated the use of CRP in a predictive algorithm. The records of 311 children with an effusion of the hip, which was confirmed on ultrasound, were reviewed (mean age 5.3 years (0.2 to 15.1)). Of these, 269 resolved without intervention and without long-term sequelae and were considered to have had transient synovitis. The remaining 42 underwent arthrotomy because of suspicion of septic arthritis. Infection was confirmed in 29 (18 had micro-organisms isolated and 11 had a high synovial fluid white cell count). In the remaining 13 no evidence of infection was found and they were also considered to have had transient synovitis. In total 29 hips were categorised as septic arthritis and 282 as transient synovitis. The temperature, weight-bearing status, peripheral white blood cell count and CRP was reviewed in each patient. A CRP > 20 mg/l was the strongest independent risk factor for septic arthritis (odds ratio 81.9, p < 0.001). A multivariable prediction model revealed that only two determinants (weight-bearing status and CRP > 20 mg/l) were independent in differentiating septic arthritis from transient synovitis. Individuals with neither predictor had a < 1% probability of septic arthritis, but those with both had a 74% probability of septic arthritis. A two-variable algorithm can therefore quantify the risk of septic arthritis, and is an excellent negative predictor.

We investigated the clinical response to arthroscopic synovectomy in patients with undifferentiated chronic monoarthritis (UCMA) of the wrist. Arthroscopic synovectomy was performed on 20 wrists in 20 patients with UCMA of the wrist who had not responded to non-steroidal anti-inflammatory drugs. The mean duration of symptoms at the time of surgery was 4.3 months (3 to 7) and the mean follow-up was 51.8 months (24 to 94). Inflamed synovium was completely removed from the radiocarpal, midcarpal and distal radioulnar joints using more portals than normal. After surgery, nine patients had early remission of synovitis and 11 with uncontrolled synovitis received antirheumatic medication. Overall, there was significant improvement in terms of pain relief, range of movement and Mayo score. Radiological deterioration was seen in five patients who were diagnosed as having rheumatoid arthritis during the follow-up period. Lymphoid follicles and severe lymphocyte infiltration were seen more often in synovial biopsies from patients with uncontrolled synovitis. These results suggest that arthroscopic synovectomy provides pain relief and functional improvement, and allows rapid resolution of synovitis in about half of patients with UCMA of the wrist

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

Objectives. This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model. Methods. Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR). Results. The OARSI score was significantly lower in mice treated with SRT1720 than in control mice at eight and 12 weeks associated with the decreased size of osteophytes at four and eight weeks. The delayed OA progression in the mice treated with SRT1720 was also associated with increased SIRT1-positive chondrocytes and decreased MMP-13-, ADAMTS-5-, cleaved caspase-3-, PARP p85-, and acetylated NF-κB p65-positive chondrocytes and decreased synovitis at four and eight weeks. SRT1720 treatment partially rescued the decreases in collagen type II alpha 1 (COL2A1) and aggrecan caused by IL-1β, while also reducing the induction of MMP-13 by IL-1β in vitro. Conclusion. The intraperitoneal injection of SRT1720 attenuated experimental OA progression in mice, indicating that SRT1720 could be a new therapeutic approach for OA. Cite this article: K. Nishida, T. Matsushita, K. Takayama, T. Tanaka, N. Miyaji, K. Ibaraki, D. Araki, N. Kanzaki, T. Matsumoto, R. Kuroda. Intraperitoneal injection of the SIRT1 activator SRT1720 attenuates the progression of experimental osteoarthritis in mice. Bone Joint Res 2018;7:252–262. DOI: 10.1302/2046-3758.73.BJR-2017-0227.R1

We carried out a prospective study of 71 patients who had undergone reconstruction of the anterior cruciate ligament with the ABC scaffold. Their mean age was 28 years (18 to 50). All had either sub-acute or chronic traumatic deficiency of the ligament. The mean period of follow-up was five years (four to seven). Assessment included the use of the International Knee Documentation Committee score, the modified Lysholm score, the Tegner Activity score, the Knee Injury and Osteoarthritis Outcome score and measurement with the KT-1000 arthrometer. Two patients had mild recurrent synovitis. There were no infections and no failures of the ligament. During the period of study, two patients sustained a traumatic fracture of a femoral condyle. The implants retained their integrity in both cases. All patients returned to their previous or enhanced levels of daily activity by three months after operation and 56 (79%) achieved their pre-injury level of sporting activity by six months. The patients who were competing in National level sports returned to play at one level less after operation than before. The Lysholm score showed that 58% of the patients (41) were excellent, 34% (24) good, and 8% (6) fair, with a mean post-operative score of 93. According to the International Knee Documentation Committee score, 35% of knees (25) were ‘normal’, 52% (37) ‘nearly normal’ and 13% (9) ‘abnormal’. Complete satisfaction was noted in 90% of patients (64). The development of osteoarthritis and the management of anterior cruciate deficiency associated with laxity of the medial collateral ligament remains uncertain. Our results indicate that in the medium-term, the ABC ligament scaffold is suitable and effective when early and safe return to unrestricted activities is demanded. We acknowledge the current general hostility towards reconstruction of the anterior cruciate ligament with artificial materials following reports of early failure and chronic synovitis associatiated with the production of particulate debris. We did not encounter these problems

1. A systematic collection of the clinical findings in fifty patients with pyrophosphate synovitis,among some 300 patients with obscure disorder of the knee, has been made over a period of eighteen months. The numbers of men and women were equal, the mean age being seventy years (range thirty-seven to ninety), and the mean age at the onset of symptoms fifty-nine years. 2. A difference in the clinical picture between the sexes was found. In men an acute synovitis predominated, in women chronic joint complaints. 3. A high incidence of accompanying disease was found, but none had a significant relationship to the arthropathy, although the high frequency (20 per cent) of synovitis following an acute severe illness of some other kind was striking. 4. No specific radiological sign except for calcifications in articular cartilage and menisci was found in these patients, and no relationship to osteoarthrosis could be established. 5. The great variability of symptoms and the surprisingly high incidence attracts attention to pyrophosphate synovitis as a cause of joint symptoms, especially in elderly patients

Aims. To report our experience with trunnion corrosion following metal-on-polyethylene total hip arthroplasty, in particular to report the spectrum of presentation and determine the mean time to presentation. Patients and Methods. We report the presenting symptoms and signs, intraoperative findings, and early results and complications of operative treatment in nine patients with a mean age of 74 years (60 to 86). The onset of symptoms was at a mean of seven years (3 to 18) after index surgery. Results. Patients presented with a variety of symptoms including pain, limp and rash. The preoperative mean serum cobalt level was 7.1 ppb (2.2 to 12.8) and mean serum chromium level was 2.2 ppb (0.5 to 5.2). Metal artifact reduction sequence (MARS) MRI showed fluid collection and possible pseudotumour formation in five hips, fluid collection in two hips, and synovitis/debris in one hip, with no MRI in one patient. Acetabular revision was performed in three patients, six patients underwent liner and head exchange only. The postoperative metal levels decreased in all patients: mean cobalt 0.5 ppb (0 to 1.8) and mean chromium 0.9 ppb (0 to 2.6) at a mean of five months (3 to 8) postoperatively. Seven patients had good pain relief and no complications at one year. There were two major complications requiring reoperation: acute infection at six weeks, for which the patient required two-stage reimplantation; and recurrent dislocation, for which the patient was revised to a dual mobility component. Conclusion. Trunnion corrosion in metal-on-polyethylene THA has a range of presenting symptoms, and may present later than previously described. A high index of suspicion is warranted, and serum cobalt and chromium levels are recommended for diagnosis. Patients should be counselled about possible postoperative complications. Cite this article: Bone Joint J 2018;100-B:898–902

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This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients.

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

Four patients who developed malignant synovial tumours are described; one with chondromatosis developed a synovial chondrosarcoma and three with pigmented villonodular synovitis developed malignant change. The relevant literature is discussed

Injury to the triangular fibrocartilage complex (TFCC) may result in ulnar wrist pain with or without instability. One component of the TFCC, the radioulnar ligaments, serve as the primary soft-tissue stabilizer of the distal radioulnar joint (DRUJ). Tears or avulsions of its proximal, foveal attachment are thought to be associated with instability of the DRUJ, most noticed during loaded pronosupination. In the absence of detectable instability, injury of the foveal insertion of the radioulnar ligaments may be overlooked. While advanced imaging techniques such as MRI and radiocarpal arthroscopy are well-suited for diagnosing central and distal TFCC tears, partial and complete foveal tears without instability may be missed without a high degree of suspicion. While technically challenging, DRUJ arthroscopy provides the most accurate method of detecting foveal abnormalities. In this annotation the spectrum of foveal injuries is discussed and a modified classification scheme is proposed.

Cite this article: Bone Joint J 2023;105-B(1):5–10.

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

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps.

Cite this article: Bone Joint Res 2022;11(7):426–438.

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The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

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Unicompartmental knee arthroplasty (UKA) has higher revision rates than total knee arthroplasty (TKA). As revision of UKA may be less technically demanding than revision TKA, UKA patients with poor functional outcomes may be more likely to be offered revision than TKA patients with similar outcomes. The aim of this study was to compare clinical thresholds for revisions between TKA and UKA using revision incidence and patient-reported outcomes, in a large, matched cohort at early, mid-, and late-term follow-up.

The June 2014 Knee Roundup. 360 . looks at: acute repair preferable in hamstring ruptures; osteoarthritis a given in ACL injury, even with reconstruction?; chicken and egg: patellofemoral dysfunction and hip weakness; meniscal root tears as bad as we thought; outcomes in the meniscus; topical NSAIDs have a measurable effect on synovitis; nailing for tibial peri-prosthetic fracture

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cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

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To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA).

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To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope.

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Arthroplasties of the elbow, including total elbow arthroplasty, radial head arthroplasty, distal humeral hemiarthroplasty, and radiocapitellar arthroplasty, are rarely undertaken. This scoping review aims to outline the current research in this area to inform the development of future research.

The June 2024 Oncology Roundup³⁶⁰ looks at: Chondrosarcoma of the femur: is local recurrence influenced by the presence of an extraosseous component?; Diagnostic challenges in low-grade central osteosarcoma; Single osteotomy technique for frozen autograft (pedicled freezing) in patients with malignant bone tumours; Unplanned resection for small superficial soft-tissue sarcomas: disastrous or simply bad?; Inactivation and replantation of the knee joint: an infeasible surgical method; Active surveillance of diffuse-type tenosynovial giant cell tumours: a retrospective, multicentre cohort study.