Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism. A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.Aims
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Introduction. Patients with external fixators are at risk of pin site infection. A more objective assessment of possible pin site infection is warranted, particularly for future home-based monitoring of pin sites. The aim was to determine if thermography can detect signs of inflammation around pin sites by 1) Establishing a maximum temperature cut-off value 2) Investigating the correlation between local temperature and visual signs of inflammation 3) Adjust for anatomical location and ambient room temperature. Method. This was a cross-sectional international multi-center study following STROBE guidelines. All patients with external ring-fixators scheduled for a visit in the out-patient clinic were eligible. Visual signs of inflammation were categorized using the
This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.Aims
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The Coronal Plane Alignment of the Knee (CPAK) classification has been developed to predict individual variations in inherent knee alignment. The impact of preoperative and postoperative CPAK classification phenotype on the postoperative clinical outcomes of total knee arthroplasty (TKA) remains elusive. This study aimed to examine the effect of postoperative CPAK classification phenotypes (I to IX), and their pre- to postoperative changes on patient-reported outcome measures (PROMs). A questionnaire was administered to 340 patients (422 knees) who underwent primary TKA for osteoarthritis (OA) between September 2013 and June 2019. A total of 231 patients (284 knees) responded. The Knee Society Score 2011 (KSS 2011), Knee injury and Osteoarthritis Outcome Score-12 (KOOS-12), and Forgotten Joint Score-12 (FJS-12) were used to assess clinical outcomes. Using preoperative and postoperative anteroposterior full-leg radiographs, the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated and classified based on the CPAK classification. To investigate the impact on PROMs, multivariable regression analyses using stepwise selection were conducted, considering factors such as age at surgery, time since surgery, BMI, sex, implant use, postoperative aHKA classification, JLO classification, and changes in aHKA and JLO classifications from preoperative to postoperative.Aims
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The aim of this study was to gain a consensus for best practice of the assessment and management of children with idiopathic toe walking (ITW) in order to provide a benchmark for practitioners and guide the best consistent care. An established Delphi approach with predetermined steps and degree of agreement based on a standardized protocol was used to determine consensus. The steering group members and Delphi survey participants included members from the British Society of Children’s Orthopaedic Surgery (BSCOS) and the Association of Paediatric Chartered Physiotherapists (APCP). The statements included definition, assessment, treatment indications, nonoperative and operative interventions, and outcomes. Descriptive statistics were used for analysis of the Delphi survey results. The AGREE checklist was followed for reporting the results.Aims
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The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM). Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress.Aims
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This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.Aims
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This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.Aims
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We previously reported the five to ten-year results of the Birmingham Hip Resurfacing (BHR) implant. The purpose of this study was to evaluate the survivorship, radiographic results, and clinical outcomes of the BHR at long-term follow-up. We retrospectively reviewed 250 patients from the original cohort of 324 BHRs performed from 2006 to 2013 who met contemporary BHR indications. Of these, 4 patients died and 4 withdrew. From the 242 patients, 224 patients (93%) were available for analysis.
The association between lumbar intervertebral disc degeneration (LDD) and low back pain (LBP) is modest. We have recently shown that genetic propensity to pain is an effect modifier of the LDD-LBP relationship when LDD is defined as a summary score of LDD (LSUM), suggesting the association may be driven by individuals with the greatest genetic predisposition to pain. This study examined the association between individual spine magnetic resonance imaging (MRI)-determined LDD features and LBP in subgroups defined by genetic predisposition to pain. We developed a polygenic risk score (PRS) for “genetic propensity to pain” defined as the number of non-back pain locations (head, face, neck/shoulder, stomach/abdomen, hip, and knee) with duration ≥3 months in 377,538 UK Biobank participants of European ancestry. This PRS was used to stratify TwinsUK MRI samples (n=645) into four strata of genetic propensity to pain. We examined the association between LBP and MRI features of lumbar disc height, disc signal intensity, disc bulge, and osteophytes with adjustments for age, sex, PRS strata, interaction terms for each MRI feature x PRS strata, and twin status.Background
Method
The August 2024 Wrist & Hand Roundup360 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.
Hip arthroscopy has gained prominence as a primary surgical intervention for symptomatic femoroacetabular impingement (FAI). This study aimed to identify radiological features, and their combinations, that predict the outcome of hip arthroscopy for FAI. A prognostic cross-sectional cohort study was conducted involving patients from a single centre who underwent hip arthroscopy between January 2013 and April 2021. Radiological metrics measured on conventional radiographs and magnetic resonance arthrography were systematically assessed. The study analyzed the relationship between these metrics and complication rates, revision rates, and patient-reported outcomes.Aims
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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. 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.Aims
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To investigate if preoperative CT improves detection of unstable trochanteric hip fractures. A single-centre prospective study was conducted. Patients aged 65 years or older with trochanteric hip fractures admitted to Stavanger University Hospital (Stavanger, Norway) were consecutively included from September 2020 to January 2022. Radiographs and CT images of the fractures were obtained, and surgeons made individual assessments of the fractures based on these. The assessment was conducted according to a systematic protocol including three classification systems (AO/Orthopaedic Trauma Association (OTA), Evans Jensen (EVJ), and Nakano) and questions addressing specific fracture patterns. An expert group provided a gold-standard assessment based on the CT images. Sensitivities and specificities of surgeons’ assessments were estimated and compared in regression models with correlations for the same patients. Intra- and inter-rater reliability were presented as Cohen’s kappa and Gwet’s agreement coefficient (AC1).Aims
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The treatment of chronic calcaneal osteomyelitis is a challenging and increasing problem because of the high prevalence of diabetes mellitus and operative fixation of heel fractures. In 1931, Gaenslen reported treatment of hematogenous calcaneal osteomyelitis by surgical excision through a midline, sagittal plantar incision. We have refined this approach to allow successful healing and early mobilization in a modern series of complex patients with hematogenous, diabetic, and postsurgical osteomyelitis. Twenty-eight patients (mean age 54.6 years, range 20–94) with Cierny-Mader stage IIIB chronic osteomyelitis were treated with sagittal incision and calcaneal osteotomy, excision of infected bone, and wound closure. All patients received antibiotics for at least 6 weeks, and bone defects were filled with an antibiotic carrier in 20 patients. Patients were followed for a mean of 31 months (SD 25.4). Primary outcome measures were recurrence of calcaneal osteomyelitis and below-knee amputation. Secondary outcome measures included 30-day postoperative mortality and complications, duration of postoperative inpatient stay, footwear adaptions, mobility, and use of walking aids.Background
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Acute ankle injuries are commonly seen in musculoskeletal practice. Surgical management is the gold standard for lateral ligament injury in those with failed conservative treatment for a minimum of six months. Several studies have shown good functional outcome and early rehabilitation after MBG repair with an internal brace augmentation which is a braided ultrahigh molecular weight polyethylene ligament used to enhance the repair that acts as a secondary stabiliser. Hence the aim of the study was to compare the results with and without augmentation. A single centre retrospective review conducted between November 2017 and October 2019 and this included 172 patients with symptomatic chronic lateral ligament instability with failed conservative management. The diagnosis was confirmed by MRI. All patients had an ankle arthroscopy followed by open ligament repair. Patients were grouped into isolated MBG and internal brace groups for analyses and all had dedicated rehabilitation.Introduction
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The June 2024 Foot & Ankle Roundup360 looks at: First MTPJ fusion in young versus old patients; Minimally invasive calcaneum Zadek osteotomy and the effect of sequential burr passes; Comparison between Achilles tendon reinsertion and dorsal closing wedge calcaneal osteotomy for the treatment of insertional Achilles tendinopathy; Revision ankle arthroplasty – is it worthwhile?; Tibiotalocalcaneal arthrodesis or below-knee amputation – salvage or sacrifice?; Fusion or replacement for hallux rigidus?.
Lag screw cut-out is a serious complication of dynamic hip screw fixation in trochanteric hip fractures. Lag screw position is recognised as a crucial factor influencing the occurrence of lag screw cut-out. We propose a modification of the Tip Apex Distance (TAD) and hypothesize that it could enhance the reliability of predicting lag screw cut-out in these injuries. A retrospective study of hip fracture cases was conducted from January 2018 to July 2022. A total of 109 patients were eligible for the final analysis. The modified TAD was measured in millimetres, based on the sum of the traditional TAD in the lateral view and the net value of two distances in the anteroposterior (AP) view. The first distance is from the lag screw tip to the opposite point on the femoral head along the lag screw axis, while the second distance is from that point to the femoral head apex. The first distance is a positive value, whereas the second distance is positive if the lag screw is superior and negative if it is inferior. Receiver operating characteristic (ROC) curve analysis was used to assess the reliability of various parameters for evaluating the lag screw position within the femoral head. Factors such as reduction quality, fracture pattern according to the AO/OTA classification, TAD, Calcar-Referenced TAD, Axis Blade Angle, Parker’s ratio in the AP view, Cleveland Zone 1, and modified TAD were statistically associated with lag screw cut-out. Among the tested parameters, the novel parameter exhibited 90.1% sensitivity and 90.9% specificity for predicting lag screw cut-out at a cut-off value of 25 mm, with a p-value < 0.001. The modified TAD demonstrated the highest reliability in predicting lag screw cut-out. A value of 25 mm may potentially reduce the risk of lag screw cut-out in trochanteric hip fractures.
Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.Aims
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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). 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.Aims
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