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Bone & Joint Research
Vol. 13, Issue 12 | Pages 779 - 789
16 Dec 2024
Zou H Hu F Wu X Xu B Shang G An D Qin D Zhang X Yang A

Aims

The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

Methods

Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments.


Aims

Functional alignment (FA) in total knee arthroplasty (TKA) aims to achieve balanced gaps by adjusting implant positioning while minimizing changes to constitutional joint line obliquity (JLO). Although FA uses kinematic alignment (KA) as a starting point, the final implant positions can vary significantly between these two approaches. This study used the Coronal Plane Alignment of the Knee (CPAK) classification to compare differences between KA and final FA positions.

Methods

A retrospective analysis compared pre-resection and post-implantation alignments in 2,116 robotic-assisted FA TKAs. The lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) were measured to determine the arithmetic hip-knee-ankle angle (aHKA = MPTA – LDFA), JLO (JLO = MPTA + LDFA), and CPAK type. The primary outcome was the proportion of knees that varied ≤ 2° for aHKA and ≤ 3° for JLO from their KA to FA positions, and direction and magnitude of those changes per CPAK phenotype. Secondary outcomes included proportion of knees that maintained their CPAK phenotype, and differences between sexes.


Bone & Joint 360
Vol. 13, Issue 6 | Pages 26 - 29
1 Dec 2024

The December 2024 Wrist & Hand Roundup360 looks at: Variability in thumb ulnar collateral ligament rupture management across the UK: survey insights; Identifying five distinct hand osteoarthritis pain phenotypes highlights the impact of biopsychosocial factors; Long-term outcomes of MAÏA TMC joint prosthesis for osteoarthritis: a possible alternative to trapeziectomy; Diagnostic and management strategies for malignant melanoma of the hand; Early versus delayed surgery for distal radius fractures: comparable outcomes but higher complications in delayed treatment; Perioperative anticoagulant and antiplatelet use does not increase complications in wide-awake hand surgery; Variability in treatment of metacarpal shaft fractures highlights need for standardized care; Low-intensity pulsed ultrasound ineffective in reducing time to union for scaphoid nonunion post-surgery.


Bone & Joint 360
Vol. 13, Issue 6 | Pages 45 - 47
1 Dec 2024

The December 2024 Research Roundup360 looks at: Skeletal muscle composition, power, and mitochondrial energetics in older men and women with knee osteoarthritis; Machine-learning models to predict osteonecrosis in patients with femoral neck fractures undergoing internal fixation; Aetiology of patient dissatisfaction following primary total knee arthroplasty in the era of robotic-assisted technology; Efficacy and safety of commonly used thromboprophylaxis agents following hip and knee arthroplasty; The COVID-19 effect continues; Nickel allergy in knee arthroplasty: does self-reported sensitivity affect outcomes?; Tranexamic acid use and joint infection risk in total hip and knee arthroplasty.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1363 - 1368
1 Dec 2024
Chen DB Wood JA Griffiths-Jones W Bellemans J Haddad FS MacDessi SJ

As advancements in total knee arthroplasty progress at an exciting pace, two areas are of special interest, as they directly impact implant design and surgical decision making. Knee morphometry considers the three-dimensional shape of the articulating surfaces within the knee joint, and knee phenotyping provides the ability to categorize alignment into practical groupings that can be used in both clinical and research settings. This annotation discusses the details of these concepts, and the ways in which they are helping us better understand the individual subtleties of each patient’s knee.

Cite this article: Bone Joint J 2024;106-B(12):1363–1368.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1321 - 1326
1 Nov 2024
Sanchez-Sotelo J

Periprosthetic joint infection represents a devastating complication after total elbow arthroplasty. Several measures can be implemented before, during, and after surgery to decrease infection rates, which exceed 5%. Debridement with antibiotics and implant retention has been reported to be successful in less than one-third of acute infections, but still plays a role. For elbows with well-fixed implants, staged retention seems to be equally successful as the more commonly performed two-stage reimplantation, both with a success rate of 70% to 80%. Permanent resection or even amputation are occasionally considered. Not uncommonly, a second-stage reimplantation requires complex reconstruction of the skeleton with allografts, and the extensor mechanism may also be deficient. Further developments are needed to improve our management of infection after elbow arthroplasty.

Cite this article: Bone Joint J 2024;106-B(11):1321–1326.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims

This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.

Methods

Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).


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.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 559 - 572
8 Oct 2024
Wu W Zhao Z Wang Y Liu M Zhu G Li L

Aims. This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels. Methods. A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process. Results. Mean callus volume was larger in the elastic fixation group (1,755 mm. 3. (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm. 3. (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs. Conclusion. Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN. Cite this article: Bone Joint Res 2024;13(10):559–572


Bone & Joint Research
Vol. 13, Issue 9 | Pages 474 - 484
10 Sep 2024
Liu Y Li X Jiang L Ma J

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. Methods. Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results. We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion. This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT. Cite this article: Bone Joint Res 2024;13(9):474–484


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 986 - 993
1 Sep 2024
Hatano M Sasabuchi Y Isogai T Ishikura H Tanaka T Tanaka S Yasunaga H

Aims. The aim of this study was to compare the early postoperative mortality and morbidity in older patients with a fracture of the femoral neck, between those who underwent total hip arthroplasty (THA) and those who underwent hemiarthroplasty. Methods. This nationwide, retrospective cohort study used data from the Japanese Diagnosis Procedure Combination database. We included older patients (aged ≥ 60 years) who underwent THA or hemiarthroplasty after a femoral neck fracture, between July 2010 and March 2022. A total of 165,123 patients were included. The THA group was younger (mean age 72.6 (SD 8.0) vs 80.7 years (SD 8.1)) and had fewer comorbidities than the hemiarthroplasty group. Patients with dementia or malignancy were excluded because they seldom undergo THA. The primary outcome measures were mortality and complications while in hospital, and secondary outcomes were readmission and reoperation within one and two years after discharge, and the costs of hospitalization. We conducted an instrumental variable analysis (IVA) using differential distance as a variable. Results. The IVA analysis showed that the THA group had a significantly higher rate of complications while in hospital (risk difference 6.3% (95% CI 2.0 to 10.6); p = 0.004) than the hemiarthroplasty group, but there was no significant difference in the rate of mortality while in hospital (risk difference 0.3% (95% CI -1.7 to 2.2); p = 0.774). There was no significant difference in the rate of readmission (within one year: risk difference 1.3% (95% CI -1.9 to 4.5); p = 0.443; within two years: risk difference 0.1% (95% CI -3.2 to 3.4); p = 0.950) and reoperation (within one year: risk difference 0.3% (95% CI -0.6 to 1.1); p = 0.557; within two years: risk difference 0.1% (95% CI -0.4 to 0.7); p = 0.632) after discharge. The costs of hospitalization were significantly higher in the THA group than in the hemiarthroplasty group (difference $2,634 (95% CI $2,496 to $2,772); p < 0.001). Conclusion. Among older patients undergoing surgery for a femoral neck fracture, the risk of early complications was higher after THA than after hemiarthroplasty. Our findings should aid in clinical decision-making in these patients. Cite this article: Bone Joint J 2024;106-B(9):986–993


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. Results. Signal transducer and activator of transcription 3 (STAT3) was notably expressed in both conditions. Single-cell analysis pinpointed specific cells with high STAT3 expression, and microRNA (miRNA)-125a-5p emerged as a potential regulator. Experiments confirmed the crucial role of STAT3 in osteoclast differentiation and muscle proliferation. Conclusion. STAT3 has emerged as a key gene in both POMP and sarcopenia. This insight positions STAT3 as a potential common therapeutic target, possibly improving management strategies for these age-related diseases. Cite this article: Bone Joint Res 2024;13(8):411–426


Bone & Joint Open
Vol. 5, Issue 8 | Pages 697 - 707
22 Aug 2024
Raj S Grover S Spazzapan M Russell B Jaffry Z Malde S Vig S Fleming S

Aims

The aims of this study were to describe the demographic, socioeconomic, and educational factors associated with core surgical trainees (CSTs) who apply to and receive offers for higher surgical training (ST3) posts in Trauma & Orthopaedics (T&O).

Methods

Data collected by the UK Medical Education Database (UKMED) between 1 January 2014 and 31 December 2019 were used in this retrospective longitudinal cohort study comprising 1,960 CSTs eligible for ST3. The primary outcome measures were whether CSTs applied for a T&O ST3 post and if they were subsequently offered a post. A directed acyclic graph was used for detecting confounders and adjusting logistic regression models to calculate odds ratios (ORs), which assessed the association between the primary outcomes and relevant exposures of interest, including: age, sex, ethnicity, parental socioeconomic status (SES), domiciliary status, category of medical school, Situational Judgement Test (SJT) scores at medical school, and success in postgraduate examinations. This study followed STROBE guidelines.


Bone & Joint Open
Vol. 5, Issue 8 | Pages 681 - 687
19 Aug 2024
van de Graaf VA Shen TS Wood JA Chen DB MacDessi SJ

Aims. Sagittal plane imbalance (SPI), or asymmetry between extension and flexion gaps, is an important issue in total knee arthroplasty (TKA). The purpose of this study was to compare SPI between kinematic alignment (KA), mechanical alignment (MA), and functional alignment (FA) strategies. Methods. In 137 robotic-assisted TKAs, extension and flexion stressed gap laxities and bone resections were measured. The primary outcome was the proportion and magnitude of medial and lateral SPI (gap differential > 2.0 mm) for KA, MA, and FA. Secondary outcomes were the proportion of knees with severe (> 4.0 mm) SPI, and resection thicknesses for each technique, with KA as reference. Results. FA showed significantly lower rates of medial and lateral SPI (2.9% and 2.2%) compared to KA (45.3%; p < 0.001, and 25.5%; p < 0.001) and compared to MA (52.6%; p < 0.001 and 29.9%; p < 0.001). There was no difference in medial and lateral SPI between KA and MA (p = 0.228 and p = 0.417, respectively). FA showed significantly lower rates of severe medial and lateral SPI (0 and 0%) compared to KA (8.0%; p < 0.001 and 7.3%; p = 0.001) and compared to MA (10.2%; p < 0.001 and 4.4%; p = 0.013). There was no difference in severe medial and lateral SPI between KA and MA (p = 0.527 and p = 0.307, respectively). MA resulted in thinner resections than KA in medial extension (mean difference (MD) 1.4 mm, SD 1.9; p < 0.001), medial flexion (MD 1.5 mm, SD 1.8; p < 0.001), and lateral extension (MD 1.1 mm, SD 1.9; p < 0.001). FA resulted in thinner resections than KA in medial extension (MD 1.6 mm, SD 1.4; p < 0.001) and lateral extension (MD 2.0 mm, SD 1.6; p < 0.001), but in thicker medial flexion resections (MD 0.8 mm, SD 1.4; p < 0.001). Conclusion. Mechanical and kinematic alignment (measured resection techniques) result in high rates of SPI. Pre-resection angular and translational adjustments with functional alignment, with typically smaller distal than posterior femoral resection, address this issue. Cite this article: Bone Jt Open 2024;5(8):681–687


Bone & Joint Open
Vol. 5, Issue 8 | Pages 652 - 661
8 Aug 2024
Taha R Davis T Montgomery A Karantana A

Aims

The aims of this study were to describe the epidemiology of metacarpal shaft fractures (MSFs), assess variation in treatment and complications following standard care, document hospital resource use, and explore factors associated with treatment modality.

Methods

A multicentre, cross-sectional retrospective study of MSFs at six centres in the UK. We collected and analyzed healthcare records, operative notes, and radiographs of adults presenting within ten days of a MSF affecting the second to fifth metacarpal between 1 August 2016 and 31 July 2017. Total emergency department (ED) attendances were used to estimate prevalence.


Bone & Joint 360
Vol. 13, Issue 4 | Pages 43 - 45
2 Aug 2024
Evans JT Evans JP Whitehouse MR


Bone & Joint Research
Vol. 13, Issue 7 | Pages 362 - 371
17 Jul 2024
Chang H Liu L Zhang Q Xu G Wang J Chen P Li C Guo X Yang Z Zhang F

Aims. The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 656 - 661
1 Jul 2024
Bolbocean C Hattab Z O'Neill S Costa ML

Aims

Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty – the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most.

Methods

We used causal forest analysis to compare subgroup- and individual-level treatment effects between cemented and modern uncemented hemiarthroplasty in patients aged > 60 years with an intracapsular fracture of the hip, using data from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized clinical trial. EuroQol five-dimension index scores were used to measure health-related quality of life at one, four, and 12 months postoperatively.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims. Adenosine, lidocaine, and Mg. 2+. (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. Methods. 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. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293


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.