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
Methods
The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty. A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.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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Adenosine, lidocaine, and Mg2+ (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. 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.Aims
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The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group). The study included 36 patients with T-HA stems and 30 with N-HA stems. Dual-energy X-ray absorptiometry was used to measure the change in periprosthetic BMD, one and two years postoperatively. The 3D contact between the stem and femoral cortical bone was evaluated using a density-mapping system, and clinical assessment, including patient-reported outcome measurements, was recorded.Aims
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The aim of this study was to explore parents’ experience of their child’s recovery, and their thoughts about their decision to enrol their child in a randomized controlled trial (RCT) of surgery versus non-surgical casting for a displaced distal radius fracture. A total of 20 parents of children from 13 hospitals participating in the RCT took part in an interview five to 11 months after injury. Interviews were informed by phenomenology and analyzed using thematic analysis.Aims
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The aim of this study is to evaluate the surgical treatment with the best healing rate for patients with proximal femoral unicameral bone cysts (UBCs) after initial surgery, and to determine which procedure has the lowest adverse event burden during follow-up. This multicentre retrospective study was conducted in 20 tertiary paediatric hospitals in France, Belgium, and Switzerland, and included patients aged < 16 years admitted for UBC treatment in the proximal femur from January 1995 to December 2017. UBCs were divided into seven groups based on the index treatment, which included elastic stable intramedullary nail (ESIN) insertion with or without percutaneous injection or grafting, percutaneous injection alone, curettage and grafting alone, and insertion of other orthopaedic hardware with or without curettage.Aims
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The aim of this study was to explore clinicians’ experience of a paediatric randomized controlled trial (RCT) comparing surgical reduction with non-surgical casting for displaced distal radius fractures. Overall, 22 staff from 15 hospitals who participated in the RCT took part in an interview. Interviews were informed by phenomenology and analyzed using thematic analysis.Aims
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To investigate the extent of bone development around the scaffold of custom triflange acetabular components (CTACs) over time. We performed a single-centre historical prospective cohort study, including all patients with revision THA using the aMace CTAC between January 2017 and March 2021. A total of 18 patients (18 CTACs) were included. Models of the hemipelvis and the scaffold component of the CTACs were created by segmentation of CT scans. The CT scans were performed immediately postoperatively and at least one year after surgery. The amount of bone in contact with the scaffold was analyzed at both times, and the difference was calculated.Aims
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This systematic review aims to identify 3D predictors derived from biplanar reconstruction, and to describe current methods for improving curve prediction in patients with mild adolescent idiopathic scoliosis. A comprehensive search was conducted by three independent investigators on MEDLINE, PubMed, Web of Science, and Cochrane Library. Search terms included “adolescent idiopathic scoliosis”,“3D”, and “progression”. The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool (QUIPS) and Appraisal tool for Cross-Sectional Studies (AXIS), and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. In all, 915 publications were identified, with 377 articles subjected to full-text screening; overall, 31 articles were included.Aims
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Aims. The aim of this retrospective study was to assess the incidence of early periprosthetic femoral fracture (PFF) associated with Charnley-Kerboull (CK) femoral components cemented according to the ‘French paradox’ principles through the Hueter anterior approach (HAA) in patients older than 70 years. Methods. From a prospectively collected database, all short CK femoral components implanted consecutively from January 2018 to May 2022 through the HAA in patients older than 70 years were included. Exclusion criteria were age below 70 years, use of cementless femoral component, and approaches other than the HAA. A total of 416 short CK prostheses used by 25 surgeons with various levels of experience were included. All patients had a minimum of one-year follow-up, with a mean of 2.6 years (SD 1.1). The mean age was 77.4 years (70 to 95) and the mean BMI was 25.3 kg/m. 2. (18.4 to 43). Femoral anatomy was classified according to Dorr. The measured parameters included canal flare index, morphological cortical index, canal-calcar ratio, ilium-ischial ratio, and anterior superior iliac spine to greater trochanter (GT) distance. Results. Among the 416 THAs, two PFFs (0.48% (95% confidence interval 0.13 to 1.74)) were observed, including one Vancouver type B2 fracture 24 days postoperatively and one intraoperative Vancouver type B1 fracture. Valgus malalignment and higher canal bone ratio were found to be associated with PFF. Conclusion. This study demonstrated that short CK femoral components cemented according to the French paradox were associated with a low rate of early PFF (0.48%) in patients aged over 70 years. Longer follow-up is warranted to further evaluate the rate of fracture that may occur during the
The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG. A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).Aims
Methods
This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.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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Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).Aims
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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. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).Aims
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Aims. Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods. We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results. EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and
The December 2023 Children’s orthopaedics Roundup360 looks at: A comprehensive nonoperative treatment protocol for developmental dysplasia of the hip in infants; How common are refractures in childhood?; Femoral nailing for paediatric femoral shaft fracture in children aged eight to ten years; Who benefits from allowing the physis to grow in slipped capital femoral epiphysis?; Paediatric patients with an extremity bone tumour: a secondary analysis of the PARITY trial data; Split tibial tendon transfers in cerebral palsy equinovarus foot deformities; Liposomal bupivacaine nerve block: an answer to opioid use?; Correction with distal femoral transphyseal screws in hemiepiphysiodesis for coronal-plane knee deformity.
Aims. Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. Methods. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers. Results. C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes:
Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Blood and femoral bone marrow suspension Aims
Methods
Triplane ankle fractures are complex injuries typically occurring in children aged between 12 and 15 years. Classic teaching that closure of the physis dictates the overall fracture pattern, based on studies in the 1960s, has not been challenged. The aim of this paper is to analyze whether these injuries correlate with the advancing closure of the physis with age. A fracture mapping study was performed in 83 paediatric patients with a triplane ankle fracture treated in three trauma centres between January 2010 and June 2020. Patients aged younger than 18 years who had CT scans available were included. An independent Paediatric Orthopaedic Trauma Surgeon assessed all CT scans and classified the injuries as n-part triplane fractures. Qualitative analysis of the fracture pattern was performed using the modified Cole fracture mapping technique. The maps were assessed for both patterns and correlation with the closing of the physis until consensus was reached by a panel of six surgeons.Aims
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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
Methods
Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq).Aims
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Accurate skeletal age and final adult height prediction methods in paediatric orthopaedics are crucial for determining optimal timing of growth-guiding interventions and minimizing complications in treatments of various conditions. This study aimed to evaluate the accuracy of final adult height predictions using the central peak height (CPH) method with long leg X-rays and four different multiplier tables. This study included 31 patients who underwent temporary hemiepiphysiodesis for varus or valgus deformity of the leg between 2014 and 2020. The skeletal age at surgical intervention was evaluated using the CPH method with long leg radiographs. The true final adult height (FHTRUE) was determined when the growth plates were closed. The final height prediction accuracy of four different multiplier tables (1. Bayley and Pinneau; 2. Paley et al; 3. Sanders – Greulich and Pyle (SGP); and 4. Sanders – peak height velocity (PHV)) was then compared using either skeletal age or chronological age.Aims
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The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20).Aims
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Arthroscopic microfracture is a conventional form of treatment for patients with osteochondritis of the talus, involving an area of < 1.5 cm2. However, some patients have persistent pain and limitation of movement in the early postoperative period. No studies have investigated the combined treatment of microfracture and shortwave treatment in these patients. The aim of this prospective single-centre, randomized, double-blind, placebo-controlled trial was to compare the outcome in patients treated with arthroscopic microfracture combined with radial extracorporeal shockwave therapy (rESWT) and arthroscopic microfracture alone, in patients with ostechondritis of the talus. Patients were randomly enrolled into two groups. At three weeks postoperatively, the rESWT group was given shockwave treatment, once every other day, for five treatments. In the control group the head of the device which delivered the treatment had no energy output. The two groups were evaluated before surgery and at six weeks and three, six and 12 months postoperatively. The primary outcome measure was the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale. Secondary outcome measures included a visual analogue scale (VAS) score for pain and the area of bone marrow oedema of the talus as identified on sagittal fat suppression sequence MRI scans.Aims
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The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model. In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties.Aims
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Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and
The August 2023 Children’s orthopaedics Roundup360 looks at: DDH: What can patients expect after open reduction?; Femoral head deformity associated with hip displacement in non-ambulatory cerebral palsy; Bony hip reconstruction for displaced hips in patients with cerebral palsy: is postoperative immobilization indicated?; Opioid re-prescriptions after ACL reconstruction in adolescents are associated with subsequent opioid use disorder; Normative femoral and tibial lengths in a modern population of USA children; Retrospective analysis of associated anomalies in 636 patients with operatively treated congenital scoliosis; Radiological hip shape and patient-reported outcome measures in healed Perthes’ disease; Significantly displaced adolescent posterior sternoclavicular joint injuries.
Reverse total shoulder arthroplasty (rTSA) can be used in complex cases when the glenoid requires reconstruction. In this study, a baseplate with composite bone autograft and a central trabecular titanium peg was implanted, and its migration was assessed for two years postoperatively using radiostereometric analysis (RSA). A total of 14 patients who underwent a rTSA with an autograft consented to participate. Of these, 11 had a primary rTSA using humeral head autograft and three had a revision rTSA with autograft harvested from the iliac crest. The mean age of the patients was 66 years (39 to 81). Tantalum beads were implanted in the scapula around the glenoid. RSA imaging (stereographic radiographs) was undertaken immediately postoperatively and at three, six, 12, and 24 months. Analysis was completed using model-based RSA software. Outcomes were collected preoperatively and at two years postoperatively, including the Oxford Shoulder Score, the American Shoulder and Elbow Score, and a visual analogue score for pain. A Constant score was also obtained for the assessment of strength and range of motion.Aims
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Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery.Aims
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Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.
Although the Fitmore Hip Stem has been on the market for almost 15 years, it is still not well documented in randomized controlled trials. This study compares the Fitmore stem with the CementLeSs (CLS) in several different clinical and radiological aspects. The hypothesis is that there will be no difference in outcome between stems. In total, 44 patients with bilateral hip osteoarthritis were recruited from the outpatient clinic at a single tertiary orthopaedic centre. The patients were operated with bilateral one-stage total hip arthroplasty. The most painful hip was randomized to either Fitmore or CLS femoral component; the second hip was operated with the femoral component not used on the first side. Patients were evaluated at three and six months and at one, two, and five years postoperatively with patient-reported outcome measures, radiostereometric analysis, dual-energy X-ray absorptiometry, and conventional radiography. A total of 39 patients attended the follow-up visit at two years (primary outcome) and 35 patients at five years. The primary outcome was which hip the patient considered to have the best function at two years.Aims
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The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study. A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery.Aims
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Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects.Aims
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Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures.Aims
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Successful cell therapy in hip osteonecrosis (ON) may help to avoid ON progression or total hip arthroplasty (THA), but the achieved bone regeneration is unclear. The aim of this study was to evaluate amount and location of bone regeneration obtained after surgical injection of expanded autologous mesenchymal stromal cells from the bone marrow (BM-hMSCs). A total of 20 patients with small and medium-size symptomatic stage II femoral head ON treated with 140 million BM-hMSCs through percutaneous forage in the EudraCT 2012-002010-39 clinical trial were retrospectively evaluated through preoperative and postoperative (three and 12 months) MRI. Then, 3D reconstruction of the original lesion and the observed postoperative residual damage after bone regeneration were analyzed and compared per group based on treatment efficacy.Aims
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The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model.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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Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1PrαTACE’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation.Aims
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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. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed.Aims
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Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are common orthopaedic procedures requiring postoperative radiographs to confirm implant positioning and identify complications. Artificial intelligence (AI)-based image analysis has the potential to automate this postoperative surveillance. The aim of this study was to prepare a scoping review to investigate how AI is being used in the analysis of radiographs following THA and TKA, and how accurate these tools are. The Embase, MEDLINE, and PubMed libraries were systematically searched to identify relevant articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews and Arksey and O’Malley framework were followed. Study quality was assessed using a modified Methodological Index for Non-Randomized Studies tool. AI performance was reported using either the area under the curve (AUC) or accuracy.Aims
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There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining.Aims
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Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain. Cite this article:
Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks.Aims
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Aims. Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. Methods. Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature. Results. A group of 77 persistent genes that are highly relevant to extracellular matrix (ECM) biology and
Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of The human osteoblast-like Saos-2 cells infected with Aims
Methods
Perthes’ disease is an uncommon hip disorder with limited data on the long-term outcomes in adulthood. We partnered with community-based foundations and utilized web-based survey methodology to develop the Adult Perthes Survey, which includes demographics, childhood and adult Perthes’ disease history, the University of California Los Angeles (UCLA) Activity Scale item, Short Form-36, the Hip disability and Osteoarthritis Outcome Score, and a body pain diagram. Here we investigate the following questions: 1) what is the feasibility of obtaining > 1,000 survey responses from adults who had Perthes’ disease using a web-based platform?; and 2) what are the baseline characteristics and demographic composition of our sample? The survey link was available publicly for 15 months and advertised among support groups. Of 1,505 participants who attempted the Adult Perthes survey, 1,182 completed it with a median timeframe of 11 minutes (IQR 8.633 to 14.72). Participants who dropped out were similar to those who completed the survey on several fixed variables. Participants represented 45 countries including the USA (n = 570; 48%), UK (n = 295; 25%), Australia (n = 133; 11%), and Canada (n = 46; 4%). Of the 1,182 respondents, 58% were female and the mean age was 39 years (SD 12.6).Aims
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Aims. The aim of this study was to compare the mid-term patient-reported outcome,
The aim of this study was to assess the ability of morphological spinal parameters to predict the outcome of bracing in patients with adolescent idiopathic scoliosis (AIS) and to establish a novel supine correction index (SCI) for guiding bracing treatment. Patients with AIS to be treated by bracing were prospectively recruited between December 2016 and 2018, and were followed until brace removal. In all, 207 patients with a mean age at recruitment of 12.8 years (SD 1.2) were enrolled. Cobb angles, supine flexibility, and the rate of in-brace correction were measured and used to predict curve progression at the end of follow-up. The SCI was defined as the ratio between correction rate and flexibility. Receiver operating characteristic (ROC) curve analysis was carried out to assess the optimal thresholds for flexibility, correction rate, and SCI in predicting a higher risk of progression, defined by a change in Cobb angle of ≥ 5° or the need for surgery.Aims
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The aim of this study was to review the current evidence surrounding curve type and morphology on curve progression risk in adolescent idiopathic scoliosis (AIS). A comprehensive search was conducted by two independent reviewers on PubMed, Embase, Medline, and Web of Science to obtain all published information on morphological predictors of AIS progression. Search items included ‘adolescent idiopathic scoliosis’, ‘progression’, and ‘imaging’. The inclusion and exclusion criteria were carefully defined. Risk of bias of studies was assessed with the Quality in Prognostic Studies tool, and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In all, 6,286 publications were identified with 3,598 being subjected to secondary scrutiny. Ultimately, 26 publications (25 datasets) were included in this review.Aims
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Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia. In a cadaveric model, UKA and TKA procedures were performed on eight fresh-frozen knee specimens, using conventional (solid) and titanium lattice tibial implants. Stress at the bone-implant interfaces were measured and compared to the native knee.Aims
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Although the short stem concept in hip arthroplasty procedure shows acceptable clinical performance, we sometimes get unexplainable radiological findings. The aim of this retrospective study was to evaluate changes of radiological findings up to three years postoperatively, and to assess any potential contributing factors on such radiological change in a Japanese population. This is a retrospective radiological study conducted in Japan. Radiological assessment was done in accordance with predetermined radiological review protocol. A total of 241 hips were included in the study and 118 hips (49.0%) revealed radiological change from immediately after surgery to one year postoperatively; these 118 hips were eligible for further analyses. Each investigator screened whether either radiolucent lines (RLLs), cortical hypertrophy (CH), or atrophy (AT) appeared or not on the one-year radiograph. Further, three-year radiographs of eligible cases were reviewed to determine changes such as, disappeared (D), improved (I), stable (S), and progression (P). Additionally, bone condensation (BC) was assessed on the three-year radiograph.Aims
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The use and variety of stemless humeral components in anatomical total shoulder arthroplasty (TSA) have proliferated since their advent in 2004. Early outcomes are reassuring but independent mid-term results are scarce. This independent study reports a consecutive series of 143 Eclipse stemless shoulder prostheses with a minimum five-year (5 to 10) follow-up. Outcomes of 143 procedures undertaken for all indications in 131 patients were reviewed, with subset analysis of those for osteoarthritis (OA) (n = 99). The primary outcome was the Oxford Shoulder Score (OSS) at a minimum of five years. Secondary outcomes were ranges of motion and radiological analysis of humeral radiolucency, rotator cuff failure, and glenoid loosening.Aims
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Higher osteoblastic bone activity is expected in aseptic loosening and painful unicompartmental knee arthroplasty (UKA). However, insights into normal bone activity patterns after medial UKAs are lacking. The aim of this study was to identify the evolution in bone activity pattern in well-functioning medial mobile-bearing UKAs. In total, 34 patients (13 female, 21 male; mean age 62 years (41 to 79); BMI 29.7 kg/m2 (23.6 to 42.1)) with 38 medial Oxford partial UKAs (20 left, 18 right; 19 cementless, 14 cemented, and five hybrid) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively, and at one and two years postoperatively. Changes in mean osteoblastic activity were investigated using a tracer localization scheme with volumes of interest (VOIs), reported by normalized mean tracer values. A SPECT/CT registration platform additionally explored cortical tracer evolution in zones of interest identified by previous experimental research.Aims
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The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD). A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability.Aims
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Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing. A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.Aims
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Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively.Aims
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To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors.Aims
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We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants. An established allografted revision protocol was implemented bilaterally into the stifle joints of 24 canines. At revision surgery, each animal received one BMP-2 (5 µg) functionalized implant, and one raw implant. One group (12 animals) received bone graft impregnated with zoledronate (0.005 mg/ml) before impaction. The other group (12 animals) received untreated bone graft and systemic zoledronate (0.1 mg/kg) ten and 20 days after revision surgery. Animals were observed for an additional four weeks before euthanasia.Aims
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Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).Aims
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The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases until June 2020. All randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing CD alone and CD combined with other measures (CD + cell therapy, CD + bone grafting, CD + porous tantalum rod, etc.) for the treatment of ONFH were considered eligible for inclusion. The primary outcomes of interest were Harris Hip Score (HHS), ONFH stage progression, structural failure (collapse) of the femoral head, and conversion to total hip arthroplasty (THA). The pooled data were analyzed using Review Manager 5.3 software.Aims
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Aims. Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods. Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results. NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition (Pad4-/-) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion. This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury
Adverse local tissue reactions associated with abnormal wear considerably slowed down the general use of metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), now limited to a few specialized centres. In this study, we provide the clinical results of 400 consecutive MoM HRAs implanted more than 20 years ago in one such centre. A total of 355 patients (400 hips) were treated with Conserve Plus HRA between November 1996 and November 2000. There were 96 female (27%) and 259 male patients (73%). Their mean age was 48.2 years (SD 10.9). The University of California, Los Angeles (UCLA) hip scores and 12-item Short Form Survey (SF-12) quality of life scores were reported. Survivorship was assessed using Kaplan-Meier analyses.Aims
Methods
The purpose of this study was to compare clinical results, long-term survival, and complication rates of stemless shoulder prosthesis with stemmed anatomical shoulder prostheses for treatment of osteoarthritis and to analyze radiological bone changes around the implants during follow-up. A total of 161 patients treated with either a stemmed or a stemless shoulder arthroplasty for primary osteoarthritis of the shoulder were evaluated with a mean follow-up of 118 months (102 to 158). The Constant score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) score, and active range of motion (ROM) were recorded. Radiological analysis for bone adaptations was performed by plain radiographs. A Kaplan-Meier survivorship analysis was calculated and complications were noted.Aims
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The purpose of this study was to report bone adaptive changes after anatomical total shoulder arthroplasty (TSA) using a standard-length hydroxyapatite (HA)-coated humeral component, and to report on a computer-based analysis of radiographs to determine changes in peri-implant bone density objectively. A total of 44 TSAs, performed between 2011 and 2014 using a cementless standard-length humeral component proximally coated with HA, were included. There were 23 males and 21 females with a mean age of 65 years (17 to 65). All shoulders had good quality radiographs at six weeks and five years postoperatively. Three observers graded bone adaptive changes. All radiographs were uploaded into a commercially available photographic software program. The grey value density of humeral radiological areas was corrected to the grey value density of the humeral component and compared over time.Aims
Methods
Uncemented metal acetabular components show good osseointegration, but material stiffness causes stress shielding and retroacetabular bone loss. Cemented monoblock polyethylene components load more physiologically; however, the cement bone interface can suffer fibrous encapsulation and loosening. It was hypothesized that an uncemented titanium-sintered monoblock polyethylene component may offer the optimum combination of osseointegration and anatomical loading. A total of 38 patients were prospectively enrolled and received an uncemented monoblock polyethylene acetabular (pressfit) component. This single cohort was then retrospectively compared with previously reported randomized cohorts of cemented monoblock (cemented) and trabecular metal (trabecular) acetabular implants. The primary outcome measure was periprosthetic bone density using dual-energy x-ray absorptiometry over two years. Secondary outcomes included radiological and clinical analysis.Aims
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Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.Aims
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The aim of this study was to investigate whether including the stages of ulnar physeal closure in Sanders stage 7 aids in a more accurate assessment for brace weaning in patients with adolescent idiopathic scoliosis (AIS). This was a retrospective analysis of patients who were weaned from their brace and reviewed between June 2016 and December 2018. Patients who weaned from their brace at Risser stage ≥ 4, had static standing height and arm span for at least six months, and were ≥ two years post-menarche were included. Skeletal maturity at weaning was assessed using Sanders staging with stage 7 subclassified into 7a, in which all phalangeal physes are fused and only the distal radial physis is open, with narrowing of the medial physeal plate of the distal ulna, and 7b, in which fusion of > 50% of the medial growth plate of distal ulna exists, as well as the distal radius and ulna (DRU) classification, an established skeletal maturity index which assesses skeletal maturation using finer stages of the distal radial and ulnar physes, from open to complete fusion. The grade of maturity at the time of weaning and any progression of the curve were analyzed using Fisher’s exact test, with Cramer’s V, and Goodman and Kruskal’s tau.Aims
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Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma.Aims
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The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted.Aims
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Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA).Aims
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Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing. The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series.Aims
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Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone.Aims
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Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health. Cite this article:
The treatment of tibial aplasia is controversial. Amputation represents the gold standard with good functional results, but is frequently refused by the families. In these patients, treatment with reconstructive limb salvage can be considered. Due to the complexity of the deformity, this remains challenging and should be staged. The present study evaluated the role of femoro-pedal distraction using a circular external fixator in reconstructive treatment of tibial aplasia. The purpose of femoro-pedal distraction is to realign the limb and achieve soft tissue lengthening to allow subsequent reconstructive surgery. This was a retrospective study involving ten patients (12 limbs) with tibial aplasia, who underwent staged reconstruction. During the first operation a circular hexapod external fixator was applied and femoro-pedal distraction was undertaken over several months. Subsequent surgery included reconstruction of the knee joint and alignment of the foot.Aims
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The aim of this study is to determine the effects of the UK lockdown during the COVID-19 pandemic on the orthopaedic admissions, operations, training opportunities, and theatre efficiency in a large district general hospital. The number of patients referred to the orthopaedic team between 1 April 2020 and 30 April 2020 were collected. Other data collected included patient demographics, number of admissions, number and type of operations performed, and seniority of primary surgeon. Theatre time was collected consisting of anaesthetic time, surgical time, time to leave theatre, and turnaround time. Data were compared to the same period in 2019.Aims
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Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article:
A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article:
The diversity of femoral morphology renders femoral component sizing in total hip arthroplasty (THA) challenging. We aimed to determine whether femoral morphology and femoral component filling influence early clinical and radiological outcomes following THA using fully hydroxyapatite (HA)-coated femoral components. We retrospectively reviewed records of 183 primary uncemented THAs. Femoral morphology, including Dorr classification, canal bone ratio (CBR), canal flare index (CFI), and canal-calcar ratio (CCR), were calculated on preoperative radiographs. The canal fill ratio (CFR) was calculated at different levels relative to the lesser trochanter (LT) using immediate postoperative radiographs: P1, 2 cm above LT; P2, at LT; P3, 2 cm below LT; and D1, 7 cm below LT. At two years, radiological femoral component osseointegration was evaluated using the Engh score, and hip function using the Postel Merle d’Aubigné (PMA) and Oxford Hip Score (OHS).Aims
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Surgeons and most engineers believe that bone compaction improves implant primary stability without causing undue damage to the bone itself. In this study, we developed a murine distal femoral implant model and tested this dogma. Each mouse received two femoral implants, one placed into a site prepared by drilling and the other into the contralateral site prepared by drilling followed by stepwise condensation.Aims
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Although good clinical outcomes have been reported for monolithic tapered, fluted, titanium stems (TFTS), early results showed high rates of subsidence. Advances in stem design may mitigate these concerns. This study reports on the use of a current monolithic TFTS for a variety of indications. A multi-institutional retrospective study of all consecutive total hip arthroplasty (THA) and revision total hip arthroplasty (rTHA) patients who received the monolithic TFTS was conducted. Surgery was performed by eight fellowship-trained arthroplasty surgeons at four institutions. A total of 157 hips in 153 patients at a mean follow-up of 11.6 months (SD7.8) were included. Mean patient age at the time of surgery was 67.4 years (SD 13.3) and mean body mass index (BMI) was 28.9 kg/m2 (SD 6.5). Outcomes included intraoperative complications, one-year all-cause re-revisions, and subsidence at postoperative time intervals (two weeks, six weeks, six months, nine months, and one year).Aims
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The purpose of this study was to report the long-term results of extendable endoprostheses of the humerus in children after the resection of a bone sarcoma. A total of 35 consecutive patients treated with extendable endoprosthetic replacement of the humerus in children were included. There were 17 boys and 18 girls in the series with a median age at the time of initial surgery of nine years (interquartile range (IQR) 7 to 11).Aims
Methods
Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article:
MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined.Objectives
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Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34.Objectives
Methods
The osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) balance is of the utmost importance in fracture healing. The aim of this study was therefore to investigate the impact of nonosteogenic factors on OPG and RANKL levels. Serum obtained from 51 patients with long bone fractures was collected over 48 weeks. The OPG and serum sRANKL (soluble RANKL) concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Smoking habit, diabetes, and alcohol consumption were recorded.Objectives
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Shoulder arthroplasty using short humeral components is becoming increasingly popular. Some such components have been associated with relatively high rates of adverse radiological findings. The aim of this retrospective review was to evaluate the radiological humeral bone changes and mechanical failure rates with implantation of a short cementless humeral component in anatomical (TSA) and reverse shoulder arthroplasty (RSA). A total of 100 shoulder arthroplasties (35 TSA and 65 RSA) were evaluated at a mean of 3.8 years (3 to 8.3). The mean age at the time of surgery was 68 years (31 to 90). The mean body mass index was 32.7 kg/m2 (17.3 to 66.4).Aims
Patients and Methods
We previously reported the long-term results of the cementless Duraloc-Profile total hip arthroplasty (THA) system in a 12- to 15-year follow-up study. In this paper, we provide an update on the clinical and radiological results of a previously reported cohort of patients at 23 to 26 years´ follow-up. Of the 99 original patients (111 hips), 73 patients (82 hips) with a mean age of 56.8 years (21 to 70) were available for clinical and radiological study at a minimum follow-up of 23 years. There were 40 female patients (44 hips) and 33 male patients (38 hips).Aims
Patients and Methods
Long bone defects often require surgical intervention for functional restoration. The ‘gold standard’ treatment is autologous bone graft (ABG), usually from the patient’s iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done. We compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses.Objectives
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The aim of this study was to investigate the effects of preoperative bisphosphonate treatment on the intra- and postoperative outcomes of arthroplasty of the shoulder. The hypothesis was that previous bisphosphonate treatment would adversely affect both intra- and postoperative outcomes. A retrospective cohort study was conducted involving patients undergoing arthroplasty of the shoulder, at a single institution. Two patients with no previous bisphosphonate treatment were matched to each patient who had received this treatment preoperatively by gender, age, race, ethnicity, body mass index (BMI), and type of arthroplasty. Previous bisphosphonate treatment was defined as treatment occurring during the three-year period before the arthroplasty. The primary outcome measure was the incidence of intraoperative complications and those occurring at one and two years postoperatively. A total of 87 patients were included: 29 in the bisphosphonates-exposed (BP+) group and 58 in the non-exposed (BP-) group. In the BP+ group, there were 26 female and three male patients, with a mean age of 71.4 years (51 to 87). In the BP- group, there were 52 female and six male patients, with a mean age of 72.1 years (53 to 88).Aims
Patients and Methods
Elevated proximal tibial bone strain may cause unexplained pain, an important cause of unicompartmental knee arthroplasty (UKA) revision. This study investigates the effect of tibial component alignment in metal-backed (MB) and all-polyethylene (AP) fixed-bearing medial UKAs on bone strain, using an experimentally validated finite element model (FEM). A previously experimentally validated FEM of a composite tibia implanted with a cemented fixed-bearing UKA (MB and AP) was used. Standard alignment (medial proximal tibial angle 90°, 6° posterior slope), coronal malalignment (3°, 5°, 10° varus; 3°, 5° valgus), and sagittal malalignment (0°, 3°, 6°, 9°, 12°) were analyzed. The primary outcome measure was the volume of compressively overstrained cancellous bone (VOCB) < -3000 µε. The secondary outcome measure was maximum von Mises stress in cortical bone (MSCB) over a medial region of interest.Objectives
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Objectives. Many in vitro studies have investigated the mechanism by which mechanical signals are transduced into biological signals that regulate bone homeostasis via periodontal ligament fibroblasts during orthodontic treatment, but the results have not been systematically reviewed. This review aims to do this, considering the parameters of various in vitro mechanical loading approaches and their effects on osteogenic and osteoclastogenic properties of periodontal ligament fibroblasts. Methods. Specific keywords were used to search electronic databases (EMBASE, PubMed, and Web of Science) for English-language literature published between 1995 and 2017. Results. A total of 26 studies from the 555 articles obtained via the database search were ultimately included, and four main types of biomechanical approach were identified. Compressive force is characterized by static and continuous application, whereas tensile force is mainly cyclic. Only nine studies investigated the mechanisms by which periodontal ligament fibroblasts transduce mechanical stimulus. The studies provided evidence from in vitro mechanical loading regimens that periodontal ligament fibroblasts play a unique and dominant role in the regulation of
The aim of this study was to evaluate the outcomes of a salvage procedure using a 95° angled blade plate for failed osteosynthesis of atypical subtrochanteric femoral fractures associated with the long-term use of bisphosphonates. These were compared with those for failed osteosynthesis of subtrochanteric fractures not associated with bisphosphonate treatment. Between October 2008 and July 2016, 14 patients with failed osteosynthesis of an atypical subtrochanteric femoral fracture were treated with a blade plate (atypical group). Their mean age was 67.8 years (60 to 74); all were female. During the same period, 21 patients with failed osteosynthesis of a typical subtrochanteric fracture underwent restabilization using a blade plate (typical group). Outcome variables included the time of union, postoperative complications, Harris Hip Score, and Sanders functional rating scale.Aims
Patients and Methods
The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours.Objectives
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