Periprosthetic osteolysis resulting in aseptic loosening is a leading cause for total hip arthroplasty (THA) failure. Individuals vary in their susceptibility to osteolysis, and it is thought that heritable factors contribute to this variation. We conducted two genome-wide association studies to identify genetic risk loci associated with osteolysis and genetic risk loci associated with time to prosthesis failure due to osteolysis. The Norway cohort comprised 2,624 subjects after THA recruited from the Norwegian Arthroplasty Registry, 779 with revision surgery for osteolysis. The UK cohort comprised 890 subjects recruited from hospitals in the north of England, 317 with radiographic evidence or revision surgery for osteolysis. All subjects had received a fully cemented or hybrid THA using small-diameter metal or ceramic-on-conventional polyethylene bearing. Osteolysis susceptibility case-control analyses and quantitative trait analyses for time to prosthesis failure were undertaken after genome-wide genotyping. Finally, a meta-analysis of the discovery datasets was undertaken.Introduction
Patients/Materials & Methods
The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies.Aims
Methods
This is the largest reported natural history study of frozen shoulder. 500 patients were identified from a specialist shoulder clinic register with a diagnosis of frozen shoulder based on Codman’s criteria. 273 patients with primary frozen shoulder replied to a detailed postal questionnaire regarding their condition. Mean follow up from symptom onset was 52 months (range 12–240months), with 89% of shoulders followed up for a minimum of 3 years. A positive family history was identified in 20% (n=45) of 1st degree relatives. The relative risk to siblings compared with a control population was 4:1. Patients with mild to moderate symptoms recovered more quickly than those with severe or unbearable symptoms. The mean age of onset was 53 years (range27–85yrs). The female to male ratio was 1.6:1. The condition was bilateral in 20%, with no incidence of ipsilateral recurrence. 22% of patients reported a history of minor trauma to the upper limb prior to the onset of symptoms. 16% were diabetic and 4% reported a history of Dupuytren’s contracture. Right and left arms were affected equally with no relationship to hand dominance. 61% reported slow, and 39% reported sudden onset of symptoms. Generally pain and stiffness improved with time but at 3 and 4 years after onset 13% and 9% respectively still had symptoms. Frozen shoulder affects people mainly in their 6th decade. Genetic factors play an important role in the aetiology. The natural history is for improvement with time, with the less severe symptoms at onset improving most quickly. 9% of patients were still symptomatic at 4 year follow up.
From the many human studies that attempt to identify genes for adolescent idiopathic scoliosis (AIS), the view emerging is that AIS is a complex genetic disorder with many predisposing genes exhibiting complex phenotypes through environmental interactions. Although advancements in genomic technology are transforming how we undertake genetic and genomic studies, only some success has been reached in deciphering complex diseases such as AIS. Moreover, the present challenge in AIS research is to understand the causative and correlative effects of discovered genetic perturbations. An important limitation to such investigations has been the absence of a method that can easily stratify patients with AIS. To overcome these challenges, we have developed a functional test that allows us to stratify patients with AIS into three functional subgroups, representing specific endophenotypes. Interestingly, in families with multiple cases of AIS, a specific endophenotype is shared among the affected family members, indicating that such a transmission is inherited. Moreover, increased vulnerability to AIS could be attributable to sustained exposure to osteopontin (OPN), a multifunctional cytokine that appears to be at the origin of the Gi-coupled receptor signalling dysfunction discovered in AIS. We examined the molecular expression profiles of patients with AIS and their response to OPN. Osteoblasts isolated from patients with AIS were selected for each functional subgroup and compared with osteoblasts obtained from healthy matched controls. We used the latest gene chip human genome array Affymetrix (HuU133 Plus 2.0 array) that allows for the analysis of the expression level of 38 000 well characterised human genes. Raw data were normalised with robust multiarray analysis method. Statistical analysis was done by the EB method with FlexArray software. Selection criteria for in-depth analysis include the magnitude of change in expression (at least □} 3-fold) and 5% false discovery rate as stringency selection. Validation of selected candidate genes was done by qPCR and at the protein level by Western blot and ELISA methods. Plasma OPN concentrations were measured by ELISA on a group of 683 consecutive patients with AIS and were compared with 262 healthy controls and 178 asymptomatic offspring, born from at least one scoliotic parent, and thus considered at risk of developing the disorder. The regulation of OPN signalling pathway in normal and AIS cells were validated in vitro by cellular dielectric spectroscopy (CDS).Introduction
Methods
Research project supported by La Fondation Yves Cotrel de l’Institut de France
Medical
Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and
Dupuytren's disease (DD) is a fibroproliferative soft tissue disease affecting the palmar fascia of the hand causing permanent and irreversible flexion contracture. Aberrant fibrosis is likely to manifest through a combination of extrinsic, intrinsic, and environmental factors, including
Aims. The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones. Methods. Three groups (seven per group) of 12-week-old mice were: 1) ovariectomized and 20 weeks thereafter treated weekly for 24 weeks with 100 μm/kg subcutaneous ibandronate (OVX+IBN); 2) ovariectomized (OVX); or 3) sham-operated (SHAM). Quantitative fracture analysis generated biomechanical properties for the femoral neck. Tibiae were microCT scanned and trabecular (proximal metaphysis) and cortical parameters along almost its whole length measured. Results. Fracture analyses revealed that OVX+IBN significantly reduced yield displacement (vs SHAM/OVX) and resilience, and increased stiffness (vs SHAM). OVX+IBN elevated tibial trabecular parameters and also increased cortical cross-sectional area and second moment of area around minor axis, and diminished ellipticity proximally. Conclusion. These data indicate that combined ovariectomy and bisphosphonate generates cortical changes linked with greater bone brittleness and modified fracture characteristics, which may provide a basis in mice for interrogating the mechanisms and
Abstract. Objectives. Despite overwhelming need, with about 9 million osteoarthritis (OA) sufferers in UK alone, little progress has been made towards pathogenesis-based categorising of patients and subsequent intervention. Experimental studies relied heavily on animal models, which is inefficient and expensive, and has often produced drugs failing in phase I/II clinical trials due to off-target side effects or failure to predict human disease in animal models. This project aims to address this challenge by developing a scalable in vitro human organotypic tissue model. The model can be used to simulate OA processes and ultimately, exploited to seek biomarkers for early diagnosis or screen potential drugs for efficacy. Methods. We have previously shown that a stratified 3D-tissue akin of articular cartilage can be generated over a 35-day period using a tissue engineering approach with primary human chondrocyte progenitor cells. The engineered tissue mimics native cartilage both in structural organization and biochemical composition. Here, we explore the influence of the nature and homogeneity of initial cell population on cartilage development and maturation. Results. Cell commitment to chondrogenic lineage was found to be a pre-requisite for induction of appropriate appositional growth and stratification of cartilage. Fully differentiated chondrocytes failed to produce a zonated, cartilage-like matrix. Immortalized clonal cell lines were generated, and these were capable of reproducing an appropriate tissue architecture, showing that tissue formation depends on a single progenitor. Conclusion. These findings not only enable generation of human tissue at scale in a highly controlled way, but open up the possibility to consider developmental positional information or
The presentation of musculoskeletal disease differs in men and women, and recognition of the differences between men and women's burden of disease and response to treatment is critical to optimizing care. In this presentation, I will discuss the expanding evidence in the literature that examine the role of sex and gender in musculoskeletal disease, including how its examination increases the innovations and contributions, as well as expands the knowledge about musculoskeletal disease, conditions, and injury in a broad sense. We will discuss the role that structural anatomy differences, hormones, and
Modifiable factors contributing to stiffness include alignment, implant size, implant position and rotation, and soft tissue tightness or laxity. Less modifiable factors include
Aim. Toxin-antitoxin (TA) systems are small
Background. The cartilaginous growth plate (GP) is a zonal structure, in which chondrocytes are organized into columns and drive the longitudinal elongation of the endochondral bones. In the proliferative zone (PZ), cells exhibit high mitotic activity, are flattened and oriented along the mediolateral (ML) axis of the GP. Mitotic figures in the elongated chondrocytes lie perpendicular to the proximo-distal (PD) direction of growth, while cell divisions occur parallel to the columns followed by a gliding movement of the daughter cells. The mechanisms responsible for the geometrical anisotropy and columnar arrangement of PZ chondrocytes are poorly understood. Here, we assessed the function of the adhesive receptor β1 integrins on spindle and division geometry in chondrocytes using mouse
Systemic concentrations of metal ions (cobalt and chromium) are persistently elevated in patients with metal-on-metal hip resurfacing (MOMHR) compared to conventional total hip arthroplasty (THA). Several studies by us and others have described the detrimental effects of metal exposure on survival and function of various cell types in-vitro, but the mechanisms for these effects remain unclear. Epigenetic modifications following chronic metal exposure is a possible mechanism that could mediate these effects. Here we test the methylation status in genomic DNA from MOMHR (“cases”) and THA (“controls”) patient-groups, and its correlation with circulating metal levels. The cohort consisted of 34 patients with a well-functioning MOMHR at a median follow-up of 9.75 years. These were individually matched for gender, age and time-since-surgery to a non-exposure group consisting of patients with THA. Genomic DNA was isolated from blood samples and cell composition estimated using the ‘estimateCellCounts’ function in ‘minfi R-package’. Methylation was assessed using the Illumina 450k BeadChip array analysing 426,225 probes. Logit model was fitted at each probe with case/control status as independent variable and covariates of gender, age, time-since-surgery, smoking, non-arthroplasty metal exposure, and cell composition. DNA methylation age was assessed using an online calculator (. https://dnamage.
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
Purpose and Background. Low birth weight is related to decreased lumbar spine vertebral canal size and bone mineral content later in life, suggesting that antenatal factors affect spine development. The purpose of this study was to explore associations between antenatal factors and lumbar spine morphology in childhood. Methods. Antenatal data and supine MR images of the lumbar spine were available for 161 children. Shape modelling, using principle components analysis, was performed on mid-sagittal images to quantify different modes of variation in lumbar spine shape. Previously collected measures of spine canal dimensions were analysed. Results. Almost 75 % of all of the variation in lumbar spine shape was explained by just three modes. Modes 1 and 3 described the total amount and the distribution of curvature along the spine, respectively. Mode 2 (M2) captured variation in vertebral shape and size; increasing mode scores represented flatter vertebral bodies with increasing anterior-posterior dimensions. We saw no significant associations between mode scores and birth weight z-scores, placental weight, gestation length and no effect of maternal smoking (P>0.05). Controlling for gestation length revealed a positive correlation between birth weight and M2 (P=0.02). Males, longer babies and those from heavier mothers had higher M2 scores (P<0.05). This sex difference remained even when controlling for the other factors (P<0.001). Modes 1 and 2 correlated with spine canal dimensions (P<0.05). Conclusions. Our results suggest that antenatal factors have some effect on vertebral body morphology but not overall lumbar spinal shape. Perhaps environmental factors during growth and
Scoliosis Clinic and the Department of Human
Networks of Excellence (NoE’s) are an instrument to overcome the fragmentation of the European research landscape with the objective to strengthen European excellence in a given area. Their purpose is to reach a durable restructuring/shaping and integration of efforts and institutions or parts of institutions in areas where this is necessary. The success of a NoE is not measured in terms of scientific results but by the extent to which the social fabric for researchers and research institutions in a given field has changed due to the project and the extent to which the existing capacities become more competitive as a result of this change. With that background a “European Network to promote research into uncommon cancers in adults and childrens: Pathology, Biology and
We have observed congenital hypophosphataemic rickets in two sons of a marriage between first cousins, their mother being clinically and biochemically normal. Both patients are now approaching middle age. In addition to severe childhood rickets and lifelong hypophosphataemia, their disease is characterised by gross osteosclerosis with extraskeletal ossification, clinically persistent osteomalacia in one and spinal cord compression in the other. The
The purpose of this study was to investigate the role that
While classically bone tumors were classified according to the differentiation and cellular morphology at the light microscopical level, it has become clear that over the past decade the array of knowledge which became available on the cytogenetic and molecular genetic level should influence tumor classification. This lead to an integrated approach in drafting the 2002 WHO nomenclature for bone tumors in which morphology was combined with the evolving genetic information. With regard to bone tumorigenesis distinct patterns can be recognized with regard to underlying
Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size.Aims
Methods
This is a case series of 25 patients with Multiple Epiphyseal Dysplasia (MED), a genetically determined disorder characterised by abnormal ossification of multiple epiphyses. The Nottingham Skeletal Dysplasia Clinic has run since 1966. In 1994 it combined with the Clinical
This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures.Aims
Methods
Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.Aims
Methods
The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI). This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm2, who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain.Aims
Methods
1. We have described here various forms of rickets and osteomalacia that we have studied ourselves and have come to recognise as comprising definite syndromes. We have included only diseases in which hereditary factors have been proved or might be suspected to play a part. 2. There are more of these syndromes than previously defined. 3. All these hereditary diseases can be treated, usually very satisfactorily, using the same general principles and with only very few simple medicines such as vitamin D and sodium bicarbonate. Careful control and long follow-up, however, may be required to achieve best results and to avoid accidents. 4. A study of the
This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.Aims
Methods
Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify English studies, including ≥ 18-year-old participants, without evidence of hip or spine pathology or a history of previous surgery or interventional treatment, documenting lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). From a total of 2,543 articles retrieved after the initial database search, 61 articles were eventually selected for data extraction.Aims
Methods
Multiple Hereditary Exostoses is a rare skeletal chondrodysplasia characterized by the presence of a variable number of osteochondromas, usually mostly affecting the long bones but possibly located anywhere. Appearance and growth of exostoses is parallel to the patient’s growth, essentially ending when skeletal maturity is reached. Its clinical expression is well known and may vary from asymptomatic to severe deformities and is rarely complicated by trasformation to secondary chondrosarcoma (0.5–2%). Research in the field of
It has been known for well over a century that the corresponding ossification centres of the hand tend to appear before those of the foot (Mall 1906), although even now the range of variability remains poorly defined. Presumably a similar asynchrony also obtains for chondrification, although precise timing is more difficult here than for ossification. Accordingly, it is tempting with respect to this syndrome to relate fusions restricted to the phalanges of the hand and to the tarsal bones to the action of a gene which during a very limited period of development exerts an effect on those small bones of the hand and foot which are in a very specific stage of development. But since there are other inherited abnormalities of the skeleton, such as brachydactyly, where homologous bones are involved, it is clear that at the descriptive level gene action can either appear to be "stage-specific" or "homologue-specific." There are also mutations affecting the axial skeleton such as the type of polydactyly of the foot described by Neel and Rusk (1963) which appear to be neither "stage" nor "homologue" specific, involving only the foot. Finally then, there are syndromes, such as Lawrence-Moon-Biedl-Bardot, in which involvement of the hands and feet (polydactyly) is associated with such other apparently completely unrelated defects as retinitis pigmentosa and hypogonadism. While it is tempting to try to construct theoretical patterns and systems of developmental processes on the basis of results such as these, it is clear that the ultimate understanding of how genes can appear to act in so many ways almost certainly depends on the identification of a genetically controlled, qualitative or quantitative biochemical lesion. With the current parallel developments in biochemical and developmental
Aims: The aim of the study is to present patients, to who uncemented conic, polyethylene acetabular components of total hip endoprosthesis (EP) Endler model, were implanted. The study tries to establish whether the cause of aseptic loosening of polyethylene acetabular components is the particle disease itself, as a reaction on polyethylene, or the causes may be found in other factors as well. Materials and methods: In the period from 1985 to 1991, 100 patients (59 females and 41 males) were operated and 110 EP were implanted. The patients were followed from 10 to 16 years (median time – 12.47 years). In these study 72 patients with 80-implanted EP were evaluated (radiological, clinical and subjective evaluation). Results: In 42 (52.50%) implanted Endler acetabular components subjective, radiological and clinical findings were very good or excellent. In 38 (47.40%) implanted acetabular components reacetabuloplasty was performed due to aseptic loosening; in 22 of those components follow-up was 10 years and other 16 had follow-up of 11 to 16 years after the primary implantation. Conclusion: The results confirmed that aseptic loosening developed in one group of the patients (38 EP), but did not develop in the other group (42 EP) after long period. The comparison of postoperative biomechanic conditions which has not shown any statistically significant differences, led to conclusion that beside the main role of polyethylene and mechanic factors, immunological cell reaction and
The aim of this study is to define a core outcome set (COS) to allow consistency in outcome reporting amongst studies investigating the management of orthopaedic treatment in children with spinal dysraphism (SD). Relevant outcomes will be identified in a four-stage process from both the literature and key stakeholders (patients, their families, and clinical professionals). Previous outcomes used in clinical studies will be identified through a systematic review of the literature, and each outcome will be assigned to one of the five core areas, defined by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT). Additional possible outcomes will be identified through consultation with patients affected by SD and their families.Aims
Methods
Introduction: Diminished adult stature is a key feature of Hereditary Multiple Exostoses (HME). Current debate on the pathogenesis of skeletal abnormalities in HME centres on whether there are ‘field-change’ effects which might retard bone-growth, or whether exostoses themselves distort normal bone development locally. The latter theory allows for surgical excision of exostoses to improve prospects for local normal bone development whereas the former does not. No study has previously investigated patterns of height disturbance in HME. Such an analysis in a cohort of children and adults with HME may provide evidence for or against either pathogenesis theory, and throw light on the chance of success of lower limb surgery in improving final height. Methods: Between 1996 and 2000, 172 individuals from 78 families with HME had clinical measurement of standing height and leg length (anterior superior iliac spine to medial malleolus. 71 were skeletally immature (1st and 2nd decades). Surgical intervention in anatomical areas affecting stature (lower limb, pelvis and spine) were recorded. Centile heights were calculated from Tanner Whitehouse charts. Results: 25/172 (15%) exhibited severe short stature (<
3rd centile height). Overall, Statural retardation was not apparent up to age 10; thereafter progressive diminution in centile height was recorded (figure 1). Before age 10, 25/37 (68%) were over the 50th centile. Beyond this age, 98/35 (73%) were less than the 50th centile (X2=22.42, p<
0.001). 101 patients who had surgery did not achieve a greater stature than those who had not. In the normal population lower limb contribution to height increases with age, whereas in HME it remains static suggesting that the retardation of stature seen between ages 10 and 20 in HME is mainly due to lower limb, not spinal growth retardation. Leg length discrepancy of >
1% of centile height was seen in 35/167 (21%), encompassing all age groups without significant difference. Discussion: The pattern of height retardation observed in this study is consistent with a progressive linear disturbance which is not apparent in early childhood, but progresses significantly in the second decade. Overt spinal exostoses are rare; and the spine’s contribution to growth retardation in HME appears be far less than that due to the lower limb. Although the
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
Methods
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.Aims
Methods
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:
The aticularis genu (AG) is the least substantial and deepest muscle of the anterior compartment of the thigh and of uncertain significance. The aim of the study was to describe the anatomy of AG in cadaveric specimens, to characterize the relevance of AG in pathological distal femur specimens, and to correlate the anatomy and pathology with preoperative magnetic resonance imaging (MRI) of AG. In 24 cadaveric specimens, AG was identified, photographed, measured, and dissected including neurovascular supply. In all, 35 resected distal femur specimens were examined. AG was photographed and measured and its utility as a surgical margin examined. Preoperative MRIs of these cases were retrospectively analyzed and assessed and its utility assessed as an anterior soft tissue margin in surgery. In all cadaveric specimens, AG was identified as a substantial structure, deep and separate to vastus itermedius (VI) and separated by a clear fascial plane with a discrete neurovascular supply. Mean length of AG was 16.1 cm ( ± 1.6 cm) origin anterior aspect distal third femur and insertion into suprapatellar bursa. In 32 of 35 pathological specimens, AG was identified (mean length 12.8 cm ( ± 0.6 cm)). Where AG was used as anterior cover in pathological specimens all surgical margins were clear of disease. Of these cases, preoperative MRI identified AG in 34 of 35 cases (mean length 8.8 cm ( ± 0.4 cm)).Aims
Methods
The aim of this study is to report the 30 day COVID-19 related morbidity and mortality of patients assessed as SARS-CoV-2 negative who underwent emergency or urgent orthopaedic surgery in the NHS during the peak of the COVID-19 pandemic. A retrospective, single centre, observational cohort study of all patients undergoing surgery between 17 March 2020 and 3May 2020 was performed. Outcomes were stratified by British Orthopaedic Association COVID-19 Patient Risk Assessment Tool. Patients who were SARS-CoV-2 positive at the time of surgery were excluded.Introduction
Method
The purpose of this study was to use pharmacogenetics to determine the frequency of genetic variants in our total knee arthroplasty (TKA) patients that could affect postoperative pain medications. Pharmacogenetic testing evaluates patient DNA to determine if a drug is expected to have a normal clinical effect, heightened effect, or no effect at all on the patient. It also predicts whether patients are likely to experience side effects from medicine. We further sought to determine if changing the multimodal programme based on these results would improve pain control or reduce side effects. In this pilot study, buccal samples were collected from 31 primary TKA patients. Pharmacogenetics testing examined genetic variants in genes Aims
Methods