Sex Steroids and Osteoarthritis: A Mendelian Randomization Study

ObjectiveSex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method.MethodsInstrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected. We used the inverse variance weighting (IVW) approach as the main MR method to estimate causal effects based on the summary-level data for OA and joint replacement surgery from genome-wide association studies (GWAS).ResultsA positive causal association was observed between serum T level and risks of hip OA (odds ratio [OR]=1.558, 95% confidence interval [CI]: 1.193–2.034; P=0.001) and hip replacement (OR=1.013, 95% CI: 1.008–1.018; P=2.15×10−8). Serum DHT level was also positively associated with the risk of hip replacement (OR=1.011, 95% CI: 1.006–1.015; P=4.03×10−7) and had potential causality with hip OA (OR=1.398, 95% CI: 1.054–1.855; P=0.020).ConclusionsSerum T and DHT levels may play causal roles in the development of hip OA and contribute to the risk of hip replacement, although the underlying mechanisms require further investigation

Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from Stevia rebaudiana, exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression in vivo. In vitro, we found that stevioside could suppress RANKL-induced osteoclastogenesis and titanium particle-induced inflammatory response in a dose-dependent manner. Mechanistically, stevioside achieved these effects by disrupting the phosphorylation of TAK1 and subsequent activation of NF-κB/MAPKs signaling pathways. Collectively, our data suggest that stevioside effectively suppresses osteoclastogenesis and inflammatory response both in vitro and in vivo, and it might be a potential therapy for particle-induced osteolysis and other osteolytic diseases

Education in inpatient children and young people’s mental health services

<p>As a chronic disease, osteoarthritis (OA) leads to the degradation of both cartilage and subchondral bone, its development being mediated by proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of specnuezhenide (SPN) in OA and its underlying mechanism were studied in vitro and in vivo. The results showed that SPN decreases the expression of cartilage matrix-degrading enzymes and the activation of NF-κB and wnt/β-catenin signaling, and increases chondrocyte-specific gene expression in IL-1β-induced inflammation in chondrocytes. Furthermore, SPN treatment prevents the degeneration of both cartilage and subchondral bone in a rat model of OA. To the best of our knowledge, this study is the first to report that SPN decreases interleukin-1β-induced inflammation in rat chondrocytes by inhibiting the activation of the NF-κB and wnt/β-catenin pathways, and, thus, has therapeutic potential in the treatment of OA.</p

HemoglobinA1c Is a Risk Factor for Changes of Bone Mineral Density: A Mendelian Randomization Study

BackgroundAs a valuable blood glucose measurement, HemoglobinA1c (HbA1c) is of great clinical value for diabetes. However, in previous observational studies, studies on its effect on bone mineral density (BMD) have different results. This study aimed to use Mendelian randomization (MR) to assess the effect of HbA1c on bone mineral density and fracture risk, and try to further explore whether this association was achieved through glycemic or non-glycemic factors.MethodsTake HbA1c measurement as exposure, and BMD estimated from quantitative heel ultrasounds (eBMD) and bone fractures as outcomes. Two-Sample MR Analysis was conducted to assess the causal effect of HbA1C on heel BMD and risk fracture. Then, we performed the analysis using two subsets of these variants, one related to glycemic measurement and the other to erythrocyte indices.ResultsGenetically increased HbA1C was associated with the lower heel eBMD [odds ratio (OR) 0.91 (95% CI 0.87, 0.96) per %-unit, P = 3 × 10−4(IVW)]. Higher HbA1C was associated with lower heel eBMD when using only erythrocytic variants [OR 0.87 (0.82, 0.93), P=2× 10−5(IVW)]; However, when using only glycemic variants, this casual association does not hold. In further MR analysis, we test the association of erythrocytic traits with heel eBMD.ConclusionOur study revealed the significant causal effect of HbA1c on eBMD, and this causal link might achieve through non-glycemic pathways (erythrocytic indices)

Two Cases of Contact Anterior Cruciate Ligament Rupture Combined with a Posterolateral Tibial Plateau Fracture

Background. The combined occurrence of ACL rupture with a posterolateral tibial plateau fracture has not yet been reported. Two cases of such injuries have been treated in our department for the past three years. Findings. The two patients both suffered injuries from traffic accidents. The radiological examinations showed a ruptured ACL with fracture of the posterolateral tibial plateau. Reconstruction of the ACL was performed via a standard anatomical single bundle ACL reconstruction technique with autologous tendon by arthroscopy. A posterolateral tibia plateau approach was used to reduce and fix the fractured area with the aid of lag screws. After a one-year follow-up, the two patients recovered well and physical examinations showed full knee range of motion with no evidence of ACL instability. Conclusions. The cause of this type injury of ACL rupture with a posterolateral tibial plateau fracture was thought to be by a violent internal tibial rotation/anterior tibial translation without any valgus or varus knee force mechanism during the accident. Satisfactory clinical results were achieved with a standard anatomical single bundle ACL reconstruction by arthroscopy and ORIF for the posterolateral plateau fracture. Both patients reported excellent knee function and fracture healing

Gas Gangrene in Orthopaedic Patients

Clostridial myonecrosis is most often seen in settings of trauma, surgery, malignancy, and other underlying immunocompromised conditions. Since 1953 cases of gas gangrene have been reported in orthopaedic patients including open fractures, closed fractures, and orthopaedic surgeries. We present a case of 55-year-old obese woman who developed rapidly progressive gas gangrene in her right leg accompanied by tibial plateau fracture without skin lacerations. She was diagnosed with clostridial myonecrosis and above-the-knee amputation was carried out. This patient made full recovery within three weeks of the initial episode. We identified a total of 50 cases of gas gangrene in orthopaedic patients. Several factors, if available, were analyzed for each case: age, cause of injury, fracture location, pathogen, and outcome. Based on our case report and the literature review, emergency clinicians should be aware of this severe and potentially fatal infectious disease and should not delay treatment or prompt orthopedic surgery consultation

Comparison of tourniquet application only during cementation and long-duration tourniquet application in total knee arthroplasty: a meta-analysis

Abstract Background Tourniquet is widely used by orthopedic surgeons in total knee arthroplasty (TKA). However, there are still controversies on the optimal timing of tourniquet application. The aim of this meta-analysis was to compare the effect and safety of tourniquet application only during cementation with long-duration tourniquet application in TKA. Methods An electronic literature search of PubMed, the Cochrane library, Embase, and Web of Science was conducted in July 2017. All randomized controlled trials (RCTs) comparing tourniquet application only during cementation with long-duration tourniquet application in TKA were included. RevMan 5.3 software was selected to perform the meta-analysis. Results Seven studies involving 440 TKAs were included for meta-analysis. The results suggested that although significant less intraoperative and total blood loss were observed with long-duration tourniquet application, tourniquet application only during cementation would not increase the number of transfusion and operation time. Tourniquet application only during cementation results in less knee pain on post-operative day 1 (POD 1), less time needed to achieve straight-leg raise, and less minor complications following TKA. Conclusions Tourniquet application only during cementation might reduce the rate of minor complications and have faster functional recovery during the early rehabilitation period following TKA, but it could not limit intraoperative and total blood loss. No definitive conclusions can be drawn based on the current evidences. Further, large well-designed RCTs with extensive follow-up are still needed to validate this research