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Aims

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.

Methods

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.


The Bone & Joint Journal
Vol. 105-B, Issue 1 | Pages 1 - 2
1 Jan 2023
Haddad FS


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 1 - 2
1 Jan 2024
Haddad FS


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 341 - 342
15 Mar 2023
Haddad FS


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1199 - 1202
1 Nov 2024
Watts AC Tennent TD Haddad FS


The Bone & Joint Journal
Vol. 105-B, Issue 3 | Pages 227 - 229
1 Mar 2023
Theologis T Brady MA Hartshorn S Faust SN Offiah AC

Acute bone and joint infections in children are serious, and misdiagnosis can threaten limb and life. Most young children who present acutely with pain, limping, and/or loss of function have transient synovitis, which will resolve spontaneously within a few days. A minority will have a bone or joint infection. Clinicians are faced with a diagnostic challenge: children with transient synovitis can safely be sent home, but children with bone and joint infection require urgent treatment to avoid complications. Clinicians often respond to this challenge by using a series of rudimentary decision support tools, based on clinical, haematological, and biochemical parameters, to differentiate childhood osteoarticular infection from other diagnoses. However, these tools were developed without methodological expertise in diagnostic accuracy and do not consider the importance of imaging (ultrasound scan and MRI). There is wide variation in clinical practice with regard to the indications, choice, sequence, and timing of imaging. This variation is most likely due to the lack of evidence concerning the role of imaging in acute bone and joint infection in children. We describe the first steps of a large UK multicentre study, funded by the National Institute for Health Research, which seeks to integrate definitively the role of imaging into a decision support tool, developed with the assistance of individuals with expertise in the development of clinical prediction tools.

Cite this article: Bone Joint J 2023;105-B(3):227–229.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1039 - 1043
1 Oct 2024
Luo TD Kayani B Magan A Haddad FS

The subject of noise in the operating theatre was recognized as early as 1972 and has been compared to noise levels on a busy highway. While noise-induced hearing loss in orthopaedic surgery specifically has been recognized as early as the 1990s, it remains poorly studied. As a result, there has been renewed focus in this occupational hazard. Noise level is typically measured in decibels (dB), whereas noise adjusted for human perception uses A-weighted sound levels and is expressed in dBA. Mean operating theatre noise levels range between 51 and 75 dBA, with peak levels between 80 and 119 dBA. The greatest sources of noise emanate from powered surgical instruments, which can exceed levels as high as 140 dBA. Newer technology, such as robotic-assisted systems, contribute a potential new source of noise. This article is a narrative review of the deleterious effects of prolonged noise exposure, including noise-induced hearing loss in the operating theatre team and the patient, intraoperative miscommunication, and increased cognitive load and stress, all of which impact the surgical team’s overall performance. Interventions to mitigate the effects of noise exposure include the use of quieter surgical equipment, the implementation of sound-absorbing personal protective equipment, or changes in communication protocols. Future research endeavours should use advanced research methods and embrace technological innovations to proactively mitigate the effects of operating theatre noise.

Cite this article: Bone Joint J 2024;106-B(10):1039–1043.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 548 - 560
17 Aug 2022
Yuan W Yang M Zhu Y

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Methods

Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 580 - 589
20 Sep 2023
Dai X Liu B Hou Q Dai Q Wang D Xie B Sun Y Wang B

Aims

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.

Methods

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.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 657 - 666
17 Oct 2023
Sung J Barratt KR Pederson SM Chenu C Reichert I Atkins GJ Anderson PH Smitham PJ

Aims

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.

Methods

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).


Bone & Joint Open
Vol. 5, Issue 6 | Pages 479 - 488
6 Jun 2024
Paksoy A Meller S Schwotzer F Moroder P Trampuz A Imiolczyk J Perka C Hackl M Plachel F Akgün D

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

Methods

This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 447 - 454
10 Jul 2023
Lisacek-Kiosoglous AB Powling AS Fontalis A Gabr A Mazomenos E Haddad FS

The use of artificial intelligence (AI) is rapidly growing across many domains, of which the medical field is no exception. AI is an umbrella term defining the practical application of algorithms to generate useful output, without the need of human cognition. Owing to the expanding volume of patient information collected, known as ‘big data’, AI is showing promise as a useful tool in healthcare research and across all aspects of patient care pathways. Practical applications in orthopaedic surgery include: diagnostics, such as fracture recognition and tumour detection; predictive models of clinical and patient-reported outcome measures, such as calculating mortality rates and length of hospital stay; and real-time rehabilitation monitoring and surgical training. However, clinicians should remain cognizant of AI’s limitations, as the development of robust reporting and validation frameworks is of paramount importance to prevent avoidable errors and biases. The aim of this review article is to provide a comprehensive understanding of AI and its subfields, as well as to delineate its existing clinical applications in trauma and orthopaedic surgery. Furthermore, this narrative review expands upon the limitations of AI and future direction.

Cite this article: Bone Joint Res 2023;12(7):447–454.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 590 - 597
20 Sep 2023
Uemura K Otake Y Takashima K Hamada H Imagama T Takao M Sakai T Sato Y Okada S Sugano N

Aims

This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images.

Methods

The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm3). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis.


Bone & Joint Research
Vol. 13, Issue 5 | Pages 237 - 246
17 May 2024
Cheng B Wu C Wei W Niu H Wen Y Li C Chen P Chang H Yang Z Zhang F

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.

Methods

Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 91 - 102
1 Feb 2023
Li Z Chen M Wang Z Fan Q Lin Z Tao X Wu J Liu Z Lin R Zhao C

Aims

Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis.

Methods

Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology.


Bone & Joint Research
Vol. 11, Issue 12 | Pages 843 - 853
1 Dec 2022
Cai Y Huang C Chen X Chen Y Huang Z Zhang C Zhang W Fang X

Aims

This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI).

Methods

A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR).


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

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.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1292 - 1303
1 Dec 2022
Polisetty TS Jain S Pang M Karnuta JM Vigdorchik JM Nawabi DH Wyles CC Ramkumar PN

Literature surrounding artificial intelligence (AI)-related applications for hip and knee arthroplasty has proliferated. However, meaningful advances that fundamentally transform the practice and delivery of joint arthroplasty are yet to be realized, despite the broad range of applications as we continue to search for meaningful and appropriate use of AI. AI literature in hip and knee arthroplasty between 2018 and 2021 regarding image-based analyses, value-based care, remote patient monitoring, and augmented reality was reviewed. Concerns surrounding meaningful use and appropriate methodological approaches of AI in joint arthroplasty research are summarized. Of the 233 AI-related orthopaedics articles published, 178 (76%) constituted original research, while the rest consisted of editorials or reviews. A total of 52% of original AI-related research concerns hip and knee arthroplasty (n = 92), and a narrative review is described. Three studies were externally validated. Pitfalls surrounding present-day research include conflating vernacular (“AI/machine learning”), repackaging limited registry data, prematurely releasing internally validated prediction models, appraising model architecture instead of inputted data, withholding code, and evaluating studies using antiquated regression-based guidelines. While AI has been applied to a variety of hip and knee arthroplasty applications with limited clinical impact, the future remains promising if the question is meaningful, the methodology is rigorous and transparent, the data are rich, and the model is externally validated. Simple checkpoints for meaningful AI adoption include ensuring applications focus on: administrative support over clinical evaluation and management; necessity of the advanced model; and the novelty of the question being answered.

Cite this article: Bone Joint J 2022;104-B(12):1292–1303.


Bone & Joint Open
Vol. 3, Issue 10 | Pages 841 - 849
27 Oct 2022
Knight R Keene DJ Dutton SJ Handley R Willett K

Aims

The rationale for exacting restoration of skeletal anatomy after unstable ankle fracture is to improve outcomes by reducing complications from malunion; however, current definitions of malunion lack confirmatory clinical evidence.

Methods

Radiological (absolute radiological measurements aided by computer software) and clinical (clinical interpretation of radiographs) definitions of malunion were compared within the Ankle Injury Management (AIM) trial cohort, including people aged ≥ 60 years with an unstable ankle fracture. Linear regressions were used to explore the relationship between radiological malunion (RM) at six months and changes in function at three years. Function was assessed with the Olerud-Molander Ankle Score (OMAS), with a minimal clinically important difference set as six points, as per the AIM trial. Piecewise linear models were used to investigate new radiological thresholds which better explain symptom impact on ankle function.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1348 - 1360
1 Nov 2024
Spek RWA Smith WJ Sverdlov M Broos S Zhao Y Liao Z Verjans JW Prijs J To M Åberg H Chiri W IJpma FFA Jadav B White J Bain GI Jutte PC van den Bekerom MPJ Jaarsma RL Doornberg JN

Aims

The purpose of this study was to develop a convolutional neural network (CNN) for fracture detection, classification, and identification of greater tuberosity displacement ≥ 1 cm, neck-shaft angle (NSA) ≤ 100°, shaft translation, and articular fracture involvement, on plain radiographs.

Methods

The CNN was trained and tested on radiographs sourced from 11 hospitals in Australia and externally validated on radiographs from the Netherlands. Each radiograph was paired with corresponding CT scans to serve as the reference standard based on dual independent evaluation by trained researchers and attending orthopaedic surgeons. Presence of a fracture, classification (non- to minimally displaced; two-part, multipart, and glenohumeral dislocation), and four characteristics were determined on 2D and 3D CT scans and subsequently allocated to each series of radiographs. Fracture characteristics included greater tuberosity displacement ≥ 1 cm, NSA ≤ 100°, shaft translation (0% to < 75%, 75% to 95%, > 95%), and the extent of articular involvement (0% to < 15%, 15% to 35%, or > 35%).