Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Aims
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Objectives. We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection. Materials and Methods. Needles were placed in the femoral condyle and proximal tibia of five anaesthetized rabbits and connected to pressure recorders. The limb was loaded with and without proximal vascular occlusion. An additional subject had simultaneous triple recordings at the femoral head, femoral condyle and proximal tibia. In a further subject, saline injections at three sites were carried out in turn. Results. Loading alone caused a rise in subchondral IOP from 11.7 mmHg (. sd. 7.1) to 17.9 mmHg (. sd. 8.1; p < 0.0002). During arterial occlusion, IOP fell to 5.3 mmHg (. sd. 4.1), then with loading there was a small rise to 7.6 mmHg (. sd. 4.5; p < 0.002). During venous occlusion, IOP rose to 20.2 mmHg (. sd. 5.8), and with loading there was a further rise to 26.3 mmHg (. sd. 6.3; p < 0.003). The effects were present at three different sites along the limb simultaneously. Saline injections showed pressure transmitted throughout the length of the femur but not across the knee joint. Conclusion. This is the first study to report changes in IOP in vivo during loading and with combinations of vascular occlusion and loading. Intraosseous pressure is not a constant. It is reduced during proximal arterial occlusion and increased with proximal venous occlusion. Whatever the perfusion state, in vivo load is transferred partly by hydraulic pressure. We propose that joints act as hydraulic pressure barriers. An understanding of subchondral physiology may be important in understanding
The primary objective of this registry-based study was to compare patient-reported outcomes of cementless and cemented medial unicompartmental knee arthroplasty (UKA) during the first postoperative year. The secondary objective was to assess one- and three-year implant survival of both fixation techniques. We analyzed 10,862 cementless and 7,917 cemented UKA cases enrolled in the Dutch Arthroplasty Registry, operated between 2017 and 2021. Pre- to postoperative change in outcomes at six and 12 months’ follow-up were compared using mixed model analyses. Kaplan-Meier and Cox regression models were applied to quantify differences in implant survival. Adjustments were made for patient-specific variables and annual hospital volume.Aims
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Patient dissatisfaction is not uncommon following primary total knee arthroplasty. One proposed method to alleviate this is by improving knee kinematics. Therefore, we aimed to answer the following research question: are there significant differences in knee kinematics based on the design of the tibial insert (cruciate-retaining (CR), ultra-congruent (UC), or medial congruent (MC))? Overall, 15 cadaveric knee joints were examined with a CR implant with three different tibial inserts (CR, UC, and MC) using an established knee joint simulator. The effects on coronal alignment, medial and lateral femoral roll back, femorotibial rotation, bony rotations (femur, tibia, and patella), and patellofemoral length ratios were determined.Aims
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This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night. In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.Aims
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Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear. A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay.Aims
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The optimal choice of management for proximal humerus fractures (PHFs) has been increasingly discussed in the literature, and this work aimed to answer the following questions: 1) what are the incidence rates of PHF in the geriatric population in the USA; 2) what is the mortality rate after PHF in the elderly population, specifically for distinct treatment procedures; and 3) what factors influence the mortality rate? PHFs occurring between 1 January 2009 and 31 December 2019 were identified from the Medicare physician service records. Incidence rates were determined, mortality rates were calculated, and semiparametric Cox regression was applied, incorporating 23 demographic, clinical, and socioeconomic covariates, to compare the mortality risk between treatments.Aims
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To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.Aims
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To assess the cost-effectiveness of a two-layer compression bandage versus a standard wool and crepe bandage following total knee arthroplasty, using patient-level data from the Knee Replacement Bandage Study (KReBS). A cost-utility analysis was undertaken alongside KReBS, a pragmatic, two-arm, open label, parallel-group, randomized controlled trial, in terms of the cost per quality-adjusted life year (QALY). Overall, 2,330 participants scheduled for total knee arthroplasty (TKA) were randomized to either a two-layer compression bandage or a standard wool and crepe bandage. Costs were estimated over a 12-month period from the UK NHS perspective, and health outcomes were reported as QALYs based on participants’ EuroQol five-dimesion five-level questionnaire responses. Multiple imputation was used to deal with missing data and sensitivity analyses included a complete case analysis and testing of costing assumptions, with a secondary analysis exploring the inclusion of productivity losses.Aims
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Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters. We used the PRISMA extension for scoping reviews for this literature search in three databases. After screening, 16 studies were included for the final analysis.Aims
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Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.Aims
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The outcomes following nonoperative management of minimally displaced greater tuberosity (GT) fractures, and the factors which influence patient experience, remain poorly defined. We assessed the early patient-derived outcomes following these injuries and examined the effect of a range of demographic- and injury-related variables on these outcomes. In total, 101 patients (53 female, 48 male) with a mean age of 50.9 years (19 to 76) with minimally displaced GT fractures were recruited to a prospective observational cohort study. During the first year after injury, patients underwent experiential assessment using the Disabilities of the Arm, Shoulder and Hand (DASH) score and assessment of associated injuries using MRI performed within two weeks of injury. The primary outcome was the one-year DASH score. Multivariate analysis was used to assess the effect of patient demographic factors, complications, and associated injuries, on outcome.Aims
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We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism. Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.Aims
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Is it feasible to conduct a definitive multicentre trial in community settings of corticosteroid injections (CSI) and hydrodilation (HD) compared to CSI for patients with frozen shoulder? An adequately powered definitive randomized controlled trial (RCT) delivered in primary care will inform clinicians and the public whether hydrodilation is a clinically and cost-effective intervention. In this study, prior to a full RCT, we propose a feasibility trial to evaluate recruitment and retention by patient and clinician willingness of randomization; rates of withdrawal, crossover and attrition; and feasibility of outcome data collection from routine primary and secondary care data. In the UK, the National Institute for Health and Care Excellence (NICE) advises that prompt early management of frozen shoulder is initiated in primary care settings with analgesia, physiotherapy, and joint injections; most people can be managed without an operation. Currently, there is variation in the type of joint injection: 1) CSI, thought to reduce the inflammation of the capsule reducing pain; and 2) HD, where a small volume of fluid is injected into the shoulder joint along with the steroid, aiming to stretch the capsule of the shoulder to improve pain, but also allowing greater movement. The creation of musculoskeletal hubs nationwide provides infrastructure for the early and effective management of frozen shoulder. This potentially reduces costs to individuals and the wider NHS perhaps negating the need for a secondary care referral.Aims
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Despite being one of the most common injuries around the elbow, the optimal treatment of olecranon fractures is far from established and stimulates debate among both general orthopaedic trauma surgeons and upper limb specialists. It is almost universally accepted that stable non-displaced fractures can be safely treated nonoperatively with minimal specialist input. Internal fixation is recommended for the vast majority of displaced fractures, with a range of techniques and implants to choose from. However, there is concern regarding the complication rates, largely related to symptomatic metalwork resulting in high rates of implant removal. As the number of elderly patients sustaining these injuries increases, we are becoming more aware of the issues associated with fixation in osteoporotic bone and the often fragile soft-tissue envelope in this group. Given this, there is evidence to support an increasing role for nonoperative management in this high-risk demographic group, even in those presenting with displaced and/or multifragmentary fracture patterns. This review summarizes the available literature to date, focusing predominantly on the management techniques and available implants for stable fractures of the olecranon. It also offers some insights into the potential avenues for future research, in the hope of addressing some of the pertinent questions that remain unanswered. Cite this article:
Studies of infant hip development to date have been limited by considering only the changes in appearance of a single ultrasound slice (Graf’s standard plane). We used 3D ultrasound (3DUS) to establish maturation curves of normal infant hip development, quantifying variation by age, sex, side, and anteroposterior location in the hip. We analyzed 3DUS scans of 519 infants (mean age 64 days (6 to 111 days)) presenting at a tertiary children’s hospital for suspicion of developmental dysplasia of the hip (DDH). Hips that did not require ultrasound follow-up or treatment were classified as ‘typically developing’. We calculated traditional DDH indices like α angle (αSP), femoral head coverage (FHCSP), and several novel indices from 3DUS like the acetabular contact angle (ACA) and osculating circle radius (OCR) using custom software.Aims
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In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.Aims
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Multiple secondary surgical procedures of the shoulder, such as soft-tissue releases, tendon transfers, and osteotomies, are described in brachial plexus birth palsy (BPBP) patients. The long-term functional outcomes of these procedures described in the literature are inconclusive. We aimed to analyze the literature looking for a consensus on treatment options. A systematic literature search in healthcare databases (PubMed, Embase, the Cochrane library, CINAHL, and Web of Science) was performed from January 2000 to July 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The quality of the included studies was assessed with the Cochrane ROBINS-I risk of bias tool. Relevant trials studying BPBP with at least five years of follow-up and describing functional outcome were included.Aims
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The aim of this study was to compare open reduction and internal fixation (ORIF) with revision surgery for the surgical management of Unified Classification System (UCS) type B periprosthetic femoral fractures around cemented polished taper-slip femoral components following primary total hip arthroplasty (THA). Data were collected for patients admitted to five UK centres. The primary outcome measure was the two-year reoperation rate. Secondary outcomes were time to surgery, transfusion requirements, critical care requirements, length of stay, two-year local complication rates, six-month systemic complication rates, and mortality rates. Comparisons were made by the form of treatment (ORIF vs revision) and UCS type (B1 vs B2/B3). Kaplan-Meier survival analysis was performed with two-year reoperation for any reason as the endpoint.Aims
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To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
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