Local recurrence along the biopsy track is a known complication of percutaneous needle biopsy of malignant musculoskeletal tumours. In order to completely excise the track with the tumour its identification is essential, but this becomes increasingly difficult over time. In an initial prospective study, 22 of 45 patients (48.8%) identified over a three-month period, treated by resection of a musculoskeletal tumour, had an unidentifiable biopsy site at operation, with identification statistically more difficult after 50 days. We therefore introduced the practice of marking the biopsy site with India ink. In all 55 patients undergoing this procedure, the biopsy track was identified pre-operatively (100%); this difference was statistically significant. We recommend this technique as a safe, easy and accurate means of ensuring adequate excision of the biopsy track. Cite this article: Bone Joint J 2013;95-B:250–3

Objectives. Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis. Methods. Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs. Results. A total of 1320 DEGs were obtained, of which 855 were up-regulated and 465 were down-regulated. These differentially expressed genes were enriched in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways, mainly associated with gene expression and osteoclast differentiation. In the transcriptional regulatory network, there were 6038 interactions pairs involving 88 transcriptional factors. In addition, the quantitative reverse transcriptase-polymerase chain reaction result validated the expression of several genes (VPS35, FCGR2A, TBCA, HIRA, TYROBP, and JUND). Finally, ROC analyses showed that VPS35, HIRA, PHF20 and NFKB2 had a significant diagnostic value for osteoporosis. Conclusion. Genes such as VPS35, FCGR2A, TBCA, HIRA, TYROBP, JUND, PHF20, NFKB2, RPL35A and BICD2 may be considered to be potential pathogenic genes of osteoporosis and may be useful for further study of the mechanisms underlying osteoporosis. Cite this article: B. Xia, Y. Li, J. Zhou, B. Tian, L. Feng. Identification of potential pathogenic genes associated with osteoporosis. Bone Joint Res 2017;6:640–648. DOI: 10.1302/2046-3758.612.BJR-2017-0102.R1

Aims

Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

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.

We have investigated the errors in the identification of the transepicondylar axis and the anteroposterior axis between a minimally-invasive and a conventional approach in four fresh-frozen cadaver knees. The errors in aligning the femoral prosthesis were compared with the reference transepicondylar axis as established by CT. The error in the identification of the transepicondylar axis was significantly higher in the minimal approach (4.5° of internal rotation, . sd. 4) than in the conventional approach (3° of internal rotation, . sd. 4; p < 0.001). The errors in identifying the anteroposterior axis in the two approaches were 0° (. sd. 5) and 1.8° (. sd. 5) of internal rotation, respectively (p < 0.001)

Objectives. 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. Methods. 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. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Aims

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.

Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

The purpose of this study was to devise a simple but reliable radiological method of identifying a lumbosacral transitional vertebra (LSTV) with a solid bony bridge on sagittal MRI, which could then be applied to a lateral radiograph.

The vertical mid-vertebral angle (VMVA) and the vertical anterior vertebral angle (VAVA) of the three most caudal segments of the lumbar spine were measured on MRI and/or on a lateral radiograph in 92 patients with a LSTV and 94 controls, and the differences per segment (Diff-VMVA and Diff-VAVA) were calculated. The Diff-VMVA of the two most caudal vertebrae was significantly higher in the control group (25° (sd 8) than in patients with a LSTV (type 2a+b: 16° (sd 9), type 3a+b: -9° (sd 10), type 4: -5° (sd 7); p < 0.001). A Diff-VMVA of ≤ +10° identified a LSTV with a solid bony bridge (type 3+4) with a sensitivity of 100% and a specificity of 89% on MRI and a sensitivity of 94% and a specificity of 74% on a lateral radiograph. A sensitivity of 100% could be achieved with a cut-off value of 28° for the Diff-VAVA, but with a lower specificity (76%) on MRI than with Diff-VMVA.

Using this simple method (Diff-VMVA ≤ +10°), solid bony bridging of the posterior elements of a LSTV, and therefore the first adjacent mobile segment, can be easily identified without the need for additional imaging.

Cite this article: Bone Joint J 2013;95-B:1533–7.

Caveolae, specialised regions of the cell membrane which have been detected in a wide range of mammalian cells, have not been described in bone cells. They are plasmalemmal invaginations, 50 to 100 nm in size, characterised by the presence of the structural protein, caveolin, which exists as three subtypes. Caveolin-1 and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is thought to be a muscle-specific subtype. There is little information on the precise function of caveolae, but it has been proposed that they play an important role in signal transduction. As the principal bone-producing cell, the osteoblast has been widely studied in an effort to understand the signalling pathways by which it responds to extracellular stimuli. Our aim in this study was to identify caveolae and their structural protein caveolin in normal human osteoblasts, and to determine which subtypes of caveolin were present. Confocal microscopy showed staining which was associated with the plasma membrane. Transmission electron microscopy revealed the presence of membrane invaginations of 50 to 100 nm, consistent with the appearance of caveolae. Finally, we isolated protein from these osteoblasts, and performed Western blotting using anti-caveolin primary antibodies. This revealed the presence of caveolin-1 and -2, while caveolin-3 was absent. The identification of these structures and their associated protein may provide a significant contribution to our further understanding of signal transduction pathways in osteoblasts

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.

Instability is the reason for revision of a primary total knee replacement (TKR) in 20% of patients. To date, the diagnosis of instability has been based on the patient’s symptoms and a subjective clinical assessment. We assessed whether a measured standardised forced leg extension could be used to quantify instability.

A total of 25 patients (11 male/14 female, mean age 70 years; 49 to 85) who were to undergo a revision TKR for instability of a primary implant were assessed with a Nottingham rig pre-operatively and then at six and 26 weeks post-operatively. Output was quantified (in revolutions per minute (rpm)) by accelerating a stationary flywheel. A control group of 183 patients (71 male/112 female, mean age 69 years) who had undergone primary TKR were evaluated for comparison.

Pre-operatively, all 25 patients with instability exhibited a distinctive pattern of reduction in ‘mid-push’ speed. The mean reduction was 55 rpm (sd 33.2). Post-operatively, no patient exhibited this pattern and the reduction in ‘mid-push’ speed was 0 rpm. The change between pre- and post-operative assessment was significant (p < 0.001). No patients in the control group exhibited this pattern at any of the intervals assessed. The between-groups difference was also significant (p < 0.001). This suggests that a quantitative diagnostic test to assess the unstable primary TKR could be developed.

Cite this article: Bone Joint J 2014;96-B:1339–43.

We describe a lateral approach to the distal humerus based on initial location of the superficial branches of the radial nerve, the inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm. In 18 upper limbs the superficial branches of the radial nerve were located in the subcutaneous tissue between the triceps and brachioradialis muscles and dissected proximally to their origin from the radial nerve, exposing the shaft of the humerus. The inferior lateral cutaneous nerve of the arm arose from the radial nerve at the lower part of the spiral groove, at a mean of 14.2 cm proximal to the lateral epicondyle. The posterior cutaneous nerve of the forearm arose from the inferior lateral cutaneous nerve at a mean of 6.9 cm (6.0 to 8.1) proximal to the lateral epicondyle and descended vertically along the dorsal aspect of the forearm. The size and constant site of emergence between the triceps and brachioradialis muscles constitute a readily identifiable landmark to explore the radial nerve and expose the humeral shaft.

The Nottingham Hip Fracture Score (NHFS) was developed to assess the risk of death following a fracture of the hip, based on pre-operative patient characteristics. We performed an independent validation of the NHFS, assessed the degree of geographical variation that exists between different units within the United Kingdom and attempted to define a NHFS level that is associated with high risk of mortality.

The NHFS was calculated retrospectively for consecutive patients presenting with a fracture of the hip to two hospitals in England. The observed 30-day mortality for each NHFS cohort was compared with that predicted by the NHFS using the Hosmer–Lemeshow test. The distribution of NHFS in the observed group was compared with data from other hospitals in the United Kingdom. The proportion of patients identified as high risk and the mortality within the high risk group were assessed for groups defined using different thresholds for the NHFS.

In all 1079 hip fractures were included in the analysis, with a mean age of 83 years (60 to 105), 284 (26%) male. Overall 30-day mortality was 7.3%. The NHFS was a significant predictor of 30-day mortality. Statistically significant differences in the distribution of the NHFS were present between different units in England (p < 0.001). A NHFS ≥ 6 appears to be an appropriate cut-point to identify patients at high risk of mortality following a fracture of the hip.

Cite this article: Bone Joint J 2015;96-B:100–3.

A retrospective review of 72 cases of Charnley low friction arthroplasty revised for stem loosening, has identified a number of "at risk" factors. These were: previous hip surgery and, in radiographs taken at one year, demarcation of the distal cement and fracture of the cement near the tip of the stem. Separation of the back of the stem from the cement, as an isolated feature, was not considered significant. Endosteal cavitation of the femoral shaft, rare in the first year, indicated loosening of some duration. Patients whose radiographs show the "at risk" changes, should be followed-up indefinitely in order to plan timely revision and avoid gross loss of the femoral bone stock.

Nanometre-sized particles of ultra-high molecular weight polyethylene have been identified in the lubricants retrieved from hip simulators. Tissue samples were taken from seven failed Charnley total hip replacements, digested using strong alkali and analysed using high-resolution field emission gun-scanning electron microscopy to determine whether nanometre-sized particles of polyethylene debris were generated in vivo. A randomised method of analysis was used to quantify and characterise all the polyethylene particles isolated.

We isolated nanometre-sized particles from the retrieved tissue samples. The smallest identified was 30 nm and the majority were in the 0.1 μm to 0.99 μm size range. Particles in the 1.0 μm to 9.99 μm size range represented the highest proportion of the wear volume of the tissue samples, with 35% to 98% of the total wear volume comprised of particles of this size. The number of nanometre-sized particles isolated from the tissues accounted for only a small proportion of the total wear volume. Further work is required to assess the biological response to nanometre-sized polyethylene particles.

Aims. Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre. Methods. A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes. Results. All patients had comorbidities and/or non-spinal procedures within the previous year. Most infections affected lumbar segments (20/32), with Escherichia coli the commonest organism (17/32). Causative organisms were identified by blood culture (23/32), biopsy/aspiration (7/32), or intraoperative samples (2/32). There were 56 different antibiotic regimes, with oral (PO) ciprofloxacin being the most prevalent (13/56; 17.6%). Multilevel, contiguous infections were common (8/32; 25%), usually resulting in bone destruction and collapse. Epidural collections were seen in 13/32 (40.6%). In total, five patients required surgery, three for neurological deterioration. Overall, 24 patients improved or recovered with a mean halving of CRP at 8.5 days (SD 6). At the time of review (two to six years post-diagnosis), 16 patients (50%) were deceased. Conclusion. This is the largest published cohort of gram-negative spinal infections. In older patients with comorbidities and/or previous interventions in the last year, a high level of suspicion must be given to gram-negative infection with blood cultures and biopsy essential. Early organism identification permits targeted treatment and good initial clinical outcomes; however, mortality is 50% in this cohort at a mean of 4.2 years (2 to 6) after diagnosis. Cite this article: Bone Jt Open 2024;5(5):435–443

Aims. 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. Methods. 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. Results. Of the 455 studies identified, only 12 were suitable for inclusion. Nine reported implant identification and three described predicting risk of implant failure. Of the 12, three studies compared AI performance with orthopaedic surgeons. AI-based implant identification achieved AUC 0.992 to 1, and most algorithms reported an accuracy > 90%, using 550 to 320,000 training radiographs. AI prediction of dislocation risk post-THA, determined after five-year follow-up, was satisfactory (AUC 76.67; 8,500 training radiographs). Diagnosis of hip implant loosening was good (accuracy 88.3%; 420 training radiographs) and measurement of postoperative acetabular angles was comparable to humans (mean absolute difference 1.35° to 1.39°). However, 11 of the 12 studies had several methodological limitations introducing a high risk of bias. None of the studies were externally validated. Conclusion. These studies show that AI is promising. While it already has the ability to analyze images with significant precision, there is currently insufficient high-level evidence to support its widespread clinical use. Further research to design robust studies that follow standard reporting guidelines should be encouraged to develop AI models that could be easily translated into real-world conditions. Cite this article: Bone Joint J 2022;104-B(8):929–937