Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05.Objectives
Method
The aim of this study was to identify key pathological genes in osteoarthritis (OA). We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis.Objectives
Methods
In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs.Objectives
Methods
Diabetes mellitus (DM) is known to impair fracture healing. Increasing evidence suggests that some microRNA (miRNA) is involved in the pathophysiology of diabetes and its complications. We hypothesized that the functions of miRNA and changes to their patterns of expression may be implicated in the pathogenesis of impaired fracture healing in DM. Closed transverse fractures were created in the femurs of 116 rats, with half assigned to the DM group and half assigned to the control group. Rats with DM were induced by a single intraperitoneal injection of streptozotocin. At post-fracture days five, seven, 11, 14, 21, and 28, miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture days five and 11. For further analysis, real-time polymerase chain reaction (PCR) analysis was performed at each timepoint.Objectives
Methods
The posterior malleolus component of a fracture
of the ankle is important, yet often overlooked. Pre-operative CT scans
to identify and classify the pattern of the fracture are not used
enough. Posterior malleolus fractures are not difficult to fix.
After reduction and fixation of the posterior malleolus, the articular
surface of the tibia is restored; the fibula is out to length; the
syndesmosis is more stable and the patient can rehabilitate faster.
There is therefore considerable merit in fixing most posterior malleolus
fractures. An early post-operative CT scan to ensure that accurate
reduction has been achieved should also be considered. Cite this article:
Stable fractures of the ankle can be safely treated
non-operatively. It is also gradually being recognised that the integrity
of the ‘medial column’ is essential for the stability of the fracture.
It is generally thought that bi- and tri-malleolar fractures are
unstable, as are pronation external rotation injuries resulting
in an isolated high fibular fracture (Weber type-C), where the deltoid
ligament is damaged or the medial malleolus fractured. However,
how best to identify unstable, isolated, trans-syndesmotic Weber
type-B supination external rotation (SER) fractures of the lateral
malleolus remains controversial. We provide a rationale as to how to classify SER distal fibular
fractures using weight-bearing radiographs, and how this can help
guide the management of these common injuries. Cite this article:
Accurate, reproducible outcome measures are essential
for the evaluation of any orthopaedic procedure, in both clinical
practice and research. Commonly used patient-reported outcome measures (PROMs) have
drawbacks such as ‘floor’ and ‘ceiling’ effects, limitations of
worldwide adaptability and an inability to distinguish pain from
function. They are also unable to measure the true outcome of an
intervention rather than a patient’s perception of that outcome. Performance-based functional outcome tools may address these
problems. It is important that both clinicians and researchers are
aware of these measures when dealing with high-demand patients,
using a new intervention or implant, or testing a new rehabilitation
protocol. This article provides an overview of some of the clinically-validated
performance-based functional outcome tools used in the assessment
of patients undergoing hip and knee surgery. Cite this article:
Wear of polyethylene inserts plays an important role in failure
of total knee replacement and can be monitored Before revision, the minimum joint space width values and their
locations on the insert were measured in 15 fully weight-bearing
radiographs. These measurements were compared with the actual minimum
thickness values and locations of the retrieved tibial inserts after
revision. Introduction
Method
The routine administration of prophylactic antibiotics for dental interventions to prevent haematogenous spread of infections to prosthetic joints is a contentious issue. In this editorial we discuss the potentially harmful effects of this practice and propose an alternative solution.
Fractures of the proximal femur are one of the
greatest challenges facing the medical community, constituting a
heavy socioeconomic burden worldwide. Controversy exists regarding
the optimal treatment for independent patients with displaced intracapsular fractures
of the proximal femur. The recognised alternatives are hemiarthroplasty
and total hip replacement. At present there is no established standard
of care, with both types of arthroplasty being used in many centres.
The principal advantages of total hip replacement are a functional
benefit over hemiarthroplasty and a reduced risk of revision surgery.
The principal criticism is the increased risk of dislocation. We
believe that an alternative acetabular component may reduce the
risk of dislocation but still provide the functional benefit of
total hip replacement in these patients. We therefore propose to
investigate the dislocation risk of a dual-mobility acetabular component
compared with standard polyethylene component in total hip replacement
for independent patients with displaced intracapsular fractures
of the proximal femur within the framework of the larger WHiTE (Warwick
Hip Trauma Evaluation) Comprehensive Cohort Study. Cite this article:
This paper describes how we came to understand the pathophysiology of Volkmann’s ischaemic contracture with references to relevant papers in this Journal, and the investigation and management of acute compartment syndrome is briefly discussed.
Guidelines for the management of patients with metastatic bone
disease (MBD) have been available to the orthopaedic community for
more than a decade, with little improvement in service provision
to this increasingly large patient group. Improvements in adjuvant
and neo-adjuvant treatments have increased both the number and overall
survival of patients living with MBD. As a consequence the incidence
of complications of MBD presenting to surgeons has increased and
is set to increase further. The British Orthopaedic Oncology Society
(BOOS) are to publish more revised detailed guidelines on what represents
‘best practice’ in managing patients with MBD. This article is designed
to coincide with and publicise new BOOS guidelines and once again
champion the cause of patients with MBD. A series of short cases highlight common errors frequently being
made in managing patients with MBD despite the availability of guidelines.Objectives
Methods
This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.
