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Bone & Joint Research
Vol. 14, Issue 3 | Pages 224 - 235
13 Mar 2025
Zhou X Ye X Yao J Lin X Weng Y Huang Y Lu Y Shang J Nong L

Aims. Osteoarthritis (OA) is a widespread chronic degenerative joint disease with an increasing global impact. The pathogenesis of OA involves complex interactions between genetic and environmental factors. Despite this, the specific genetic mechanisms underlying OA remain only partially understood, hindering the development of targeted therapeutic strategies. Methods. A transcriptome-wide association study (TWAS) was conducted for site-specific OA phenotypes using functional summary-based imputation (FUSION). High-confidence candidate genes were identified through rigorous quality control measures, including joint/conditional analysis, permutation tests, best model evaluation, and colocalization analysis. Co-expression network analysis was performed to elucidate the functional biology of these candidate genes. Druggable gene targets and their structural models were retrieved from the DrugBank and SWISS-MODEL databases. Finally, the enrichment of mitogen-activated protein kinase 3 (MAPK3) and SMAD3 in OA was validated biochemically using in vitro and in vivo OA models, as well as human histological sections. Results. Utilizing the FUSION algorithm, TWAS identified 794 candidate genes for OA. After quality control, 14 genes were classified as high-confidence genes, with seven recognized as potential drug targets including GCAT, MAPK3, MST1R, PFKM, RAD9A, SMAD3, and USAP8. Co-expression analysis revealed a strong biological association between SMAD3 and MAPK3. Both in vitro and in vivo experiments demonstrated high activity and enriched expression of these two genes in OA. Conclusion. The present study identified tissue-specific candidate genes and validated high-confidence druggable targets for OA, providing new insights into the genetic landscape and biological processes involved in OA. Further functional studies are warranted to confirm these findings. Cite this article: Bone Joint Res 2025;14(3):224–235


Bone & Joint Open
Vol. 6, Issue 3 | Pages 336 - 341
13 Mar 2025
Feng T Ablett A Scott CEH Clement ND

Aims

This study investigates the effectiveness and adequacy of the informed consent process for patients undergoing hip fracture surgery. While informed consent is a legal and ethical responsibility, factors in the trauma setting can impair patients’ understanding and retention of information. This study seeks to evaluate patients’ recall of perioperative complications and explore their perceptions of the consent process.

Methods

A mixed-methods, multicentre cohort study will be conducted in the Southeast of Scotland. Adult patients with hip fractures will be recruited via consecutive sampling. An information recall questionnaire will be administered within 36 hours of admission to assess unprompted and prompted recall of complications. A subset of participants will then undergo a semi-structured qualitative interview postoperatively to explore their experiences and perceptions of the consent process. Data will be analyzed using a social constructivist grounded theory to assess their perceptions of consent. Ethical approval has been granted by the East of England Research Ethics Committee (reference 23/EE/0233).


Bone & Joint Open
Vol. 6, Issue 3 | Pages 328 - 335
12 Mar 2025
Logishetty K Verhaegen JCF Tse S Maheswaran T Fornasiero M Subbiah Ponniah H Hutt JB Witt JD

Aims

The effectiveness of total hip arthroplasty (THA) for patients with no or minimal radiological signs of osteoarthritis (OA) is unclear. In this study, we aimed to: 1) assess the outcome of such patients; 2) identify patient comorbidities and CT or MRI findings which predicted outcome; and 3) compare their outcome to the expected outcome of THA for hip OA.

Methods

Adult patients undergoing THA for hip pain, with no or minimal radiological features of OA (Tönnis grading scale ≤ 1), were identified from a consecutive series of 1,925 THAs. Exclusion criteria were: inflammatory arthritis; osteonecrosis of the femoral head; prior trauma or infection; and patients without minimum one-year follow-up and patient-reported outcome measures (PROMs). The primary outcome measure was the Oxford Hip Score (OHS). Secondary outcome measures were EuroQol-visual analogue scale (EQ-VAS), University of California and Los Angeles (UCLA) scale, and patient satisfaction on a validated three-point ‘better’, ‘same’, or ‘worse’ scale.


Bone & Joint Open
Vol. 6, Issue 3 | Pages 298 - 311
8 Mar 2025
Alt V Szymski D Rupp M Fontalis A Vaznaisiene D Marais LC Wagner C Walter N

Aims. Periprosthetic joint infections (PJIs) pose significant challenges to patients and healthcare systems worldwide. The aim of this study was to estimate the health-economic burden of reimbursement payment in Europe for PJIs following primary hip and knee arthroplasty. Methods. The calculation was based on health-economic modelling using data on primary hip and knee arthroplasties for the year 2019 from the Statistical Office of the European Union (Eurostat) and published infection rates to estimate the total number of hip and knee PJIs in 30 European countries. Revision procedures were stratified into: 1) debridement, antibiotics, and implant retention (DAIR); 2) one-stage exchange; and 3) two-stage revision procedures. The cases were then multiplied by the respective healthcare system reimbursement payments. Payment data were acquired from a survey of 13 countries (Austria, Croatia, France, Germany, Italy, Lithuania, Netherlands, Norway, Portugal, Slovenia, Switzerland, Turkey, and the UK) and extrapolated for the remaining countries. Results. In 2019, a total of 2,048,778 primary total joint replacements were performed (total hip arthroplasty (THA) = 1,147,316 and total knee arthroplasty (TKA) = 901,462), with an estimated 20,416 cases of PJIs (11,131 hip and 9,285 knee) in Europe. This results in an estimated total reimbursement burden of €346,262,026 for European healthcare systems. The breakdown for hip PJI reimbursement was €197,230,953 (€9,751,962 for DAIR procedures, €45,135,894 for one-stage revisions, and €142,343,097 for two-stage revisions). For knee PJIs, the analysis yielded a total reimbursement of €149,031,073 (€9,335,075 for DAIR procedures, €48,058,479 for one-stage revisions, and €91,637,518 for two-stage revisions). Conclusion. This is the first study to evaluate the health-economic burden of PJIs in Europe, revealing a substantial impact on healthcare systems with an estimated case load of 20,414 cases and overall reimbursement of €346,262,026 for primary THAs and TKAs performed in 2019. Cite this article: Bone Jt Open 2025;6(3):298–311


Bone & Joint Open
Vol. 6, Issue 3 | Pages 275 - 290
6 Mar 2025
Mazarello Paes V Ting A Masters J Paes MVI Tutton E Graham SM Costa ML

Aims

Performance indicators are increasingly used to evaluate the quality of healthcare provided to patients with a hip fracture. The aim of this review was to map the variety of performance indicators used around the world and how they are defined.

Methods

We present a mixed methods systematic review of literature on the use of performance indicators in hip fracture care. Evidence was searched through 12 electronic databases and other sources. A Mixed Methods Appraisal Tool was used to assess methodological quality of studies meeting the inclusion criteria. A protocol for a suite of related systematic reviews was registered at PROSPERO (CRD42023417515).


Bone & Joint Open
Vol. 6, Issue 3 | Pages 254 - 263
4 Mar 2025
Mennen AHM Van Lieshout EMM Bloemers FW Geerlings AE Van Haeringen ME De Jong JR Verhofstad MHJ Van Vledder MG Van Embden D

Aims

Paediatric pelvic ring fractures are rare but severe injuries, presenting significant treatment challenges. This study aimed to analyze patient characteristics and explore trends in incidence, treatment methods, and mortality associated with these injuries.

Methods

This multicentre, retrospective cohort study analyzed paediatric patients (aged ≤ 18 years) with pelvic ring fractures treated between 2001 and 2021 at two level 1 trauma centres. Data on patient demographics, injury characteristics, treatment approaches, and outcomes were collected, and visual trend analysis was conducted to identify patterns.


Bone & Joint Research
Vol. 14, Issue 3 | Pages 185 - 198
4 Mar 2025
Guo Z Li H Jiang S Rahmati M Su J Yang S Wu Y Li Y Deng Z

Sarcopenia is an ageing-related disease featured by the loss of skeletal muscle quality and function. Advanced glycation end-products (AGEs) are a complex set of modified proteins or lipids by non-enzymatic glycosylation and oxidation. The formation of AGEs is irreversible, and they accumulate in tissues with increasing age. Currently, AGEs, as a biomarker of ageing, are viewed as a risk factor for sarcopenia. AGE accumulation could cause harmful effects in the human body such as elevated inflammation levels, enhanced oxidative stress, and targeted glycosylation of proteins inside and outside the cells. Several studies have illustrated the pathogenic role of AGEs in sarcopenia, which includes promoting skeletal muscle atrophy, impairing muscle regeneration, disrupting the normal structure of skeletal muscle extracellular matrix, and contributing to neuromuscular junction lesion and vascular disorders. This article reviews studies focused on the pathogenic role of AGEs in sarcopenia and the potential mechanisms of the detrimental effects, aiming to provide new insights into the pathogenesis of sarcopenia and develop novel methods for the prevention and therapy of sarcopenia.

Cite this article: Bone Joint Res 2025;14(3):185–198.


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 368 - 372
1 Mar 2025
Gazendam A Zhang L Clever D Griffin A Wunder J Ferguson P Tsoi KM

Aims. Soft-tissue sarcomas (STSs) are rare cancers with centralized care advocated to consolidate resources and expertise. However, geographical challenges, particularly in countries like Canada, can increase travel distances for patients. The impact of travel distance on sarcoma presentation and outcomes remains unclear, particularly in single-payer healthcare systems with centralized care. Methods. A retrospective cohort analysis was conducted on 1,570 patients with STS who underwent surgical resection at a Canadian tertiary referral centre between January 2010 and January 2021. Patients were divided into those living ≤ 50 km and > 50 km from the centre. Demographics, tumour characteristics, treatment methods, and survival outcomes were analyzed. A Cox regression model was constructed to evaluate predictors of overall survival. Results. Patients living > 50 km from the centre (n = 700) travelled a mean of 176 km (SD 250), while those ≤ 50 km (n = 870) travelled a mean of 24.8 km (SD 13.8). There were no significant differences in disease presentation, time to definitive treatment, use of systemic therapies, or functional outcomes between the two groups. The two-year and five-year overall survival rates were similar between the groups (83.1% (95% CI 80.1% to 86.1%) vs 83.8% (95% CI 81.8% to 85.8%) and 72.1% (95% CI 69.1% to 75.1%) vs 72.5% (95% CI 69.5% to 75.5%), respectively). The regression model demonstrated that age, higher tumour grade, depth, and lower income were predictive of worse overall survival, while distance travelled was not an independent predictor of survival. Conclusion. Contrary to previous studies, our findings suggest that travel distance did not influence disease presentation or survival outcomes in STS patients treated at a centralized sarcoma centre. This challenges previous notions regarding the impact of travel distance on cancer outcomes, and supports the effectiveness of centralized care models, even in geographically vast regions. Cite this article: Bone Joint J 2025;107-B(3):368–372


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 329 - 336
1 Mar 2025
ten Noever de Brauw GV Vossen RJM Bayoumi T Sierevelt IN Burger JA Pearle AD Kerkhoffs GMMJ Spekenbrink-Spooren A Zuiderbaan HA

Aims

The primary objective of this study was to compare short-term implant survival between cemented and cementless fixation for the mobile-bearing Oxford medial unicompartmental knee arthroplasty (UKA) across various age groups. The secondary objectives were to compare modes of failure and to evaluate patient-reported outcomes.

Methods

A total of 25,762 patients, comprising 8,022 cemented (31.1%) and 17,740 cementless (68.9%) medial UKA cases, were included from the Dutch Arthroplasty Register. Patient stratification was performed based on age: < 50 years, 50 to 59 years, 60 to 69 years, and ≥ 70 years. Survival rates and hazard ratios were calculated. Modes of failure were described and postoperative change in baseline for the Oxford Knee Score and numerical rating scale for pain at six and 12 months’ follow-up were compared.


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 283 - 290
1 Mar 2025
Al-Obaidi I Kendal A Ramasamy A

The last five years have seen notable advancements in foot and ankle surgery as a result of technical innovations and more consistent reporting of results. Much progress has been made in improving patient-reported outcome measures, in the development of basic research in this area, and in the development of personalized approaches which optimize outcomes for specific groups of patients. This review focuses on five main areas of development within foot and ankle surgery: ankle arthroplasty, osteomyelitis and the diabetic foot, sports injuries, minimally invasive surgery, and orthobiologics. The aim of this annotation is to discuss the progress made in these fields during recent years and propose avenues for further development.

Cite this article: Bone Joint J 2025;107-B(3):283–290.


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 362 - 367
1 Mar 2025
Goh EL Png ME Metcalfe D Achten J Appelbe D Griffin XL Cook JA Costa ML

Aims

The risk of mortality after a hip fracture has been extensively investigated, but there is little high-quality information available dealing with the overall risk of complications. The aim of this study was to report the risk of complications in the first 120 days after a hip fracture.

Methods

This was a multicentre, prospective cohort study of patients aged > 60 years with a hip fracture, involving 77 hospitals in England, Wales, and Northern Ireland, between January 2015 and 2022. The primary outcomes of interest were mortality and surgery-specific and general complications, at 120 days postoperatively.


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 337 - 345
1 Mar 2025
Wang D Wang Q Cui P Wang S Han D Chen X Lu S

Aims

Adult spinal deformity (ASD) surgery can reduce pain and disability. However, the actual surgical efficacy of ASD in doing so is far from desirable, with frequent complications and limited improvement in quality of life. The accurate prediction of surgical outcome is crucial to the process of clinical decision-making. Consequently, the aim of this study was to develop and validate a model for predicting an ideal surgical outcome (ISO) two years after ASD surgery.

Methods

We conducted a retrospective analysis of 458 consecutive patients who had undergone spinal fusion surgery for ASD between January 2016 and June 2022. The outcome of interest was achievement of the ISO, defined as an improvement in patient-reported outcomes exceeding the minimal clinically important difference, with no postoperative complications. Three machine-learning (ML) algorithms – LASSO, RFE, and Boruta – were used to identify key variables from the collected data. The dataset was randomly split into training (60%) and test (40%) sets. Five different ML models were trained, including logistic regression, random forest, XGBoost, LightGBM, and multilayer perceptron. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC).


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 280 - 282
1 Mar 2025
Galloway AM Nicolaou N Perry DC


Aims

To assess whether chronic knee pain (CKP) influenced health-related quality of life (HRQoL), knee-specific health, wellbeing, and use of opioid analgesia, and identify variables associated with CKP in patients awaiting knee arthroplasty.

Methods

This study included 217 patients (mean age 69.7 years (SD 8.7), 116 female (53%)) who completed questionnaires that included the EuroQol five-dimension questionnaire (EQ-5D) and EuroQol-visual analogue scale (EQ-VAS), Oxford Knee Score (OKS), and wellbeing assessments at six and 12 months after being listed for surgery. Analgesia use at 12 months was also recorded. CKP was defined using the OKS pain score (PS) of ≤ 14 points at 12 months.


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 314 - 321
1 Mar 2025
Bredgaard Jensen C Lindberg-Larsen M Kappel A Henkel C Mark-Christensen T Gromov K Troelsen A

Aims

The aim of this study was to examine the indications for further surgery and the characteristics of the patients within one year of medial unicompartmental knee arthroplasty (mUKA), providing an assessment of everyday clinical practice and outcomes in a high-volume country.

Methods

All mUKAs which were performed between 1 April 2020 and 31 March 2021 and underwent further surgery within one year, from the Danish Knee Arthroplasty Registry (DKAR), were included. For primary procedures and reoperations, we received data on the characteristics of the patients, the indications for surgery, the type of procedure, and the sizes of the components individually, from each Danish private and public arthroplasty centre. All subsequent reoperations were recorded regardless of the time since the initial procedure.


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 277 - 279
1 Mar 2025
Wignadasan W Khatoon MA Haddad FS


Bone & Joint Research
Vol. 14, Issue 2 | Pages 143 - 154
25 Feb 2025
Bühler D Hilpert M Barbero A Müller AM Müller SA Martin I Pelttari K

Aims

Our aim was to investigate occurrence of senescent cells directly in tendon tissue biopsies from patients with chronic shoulder tendinopathies, and to correlate senescence with Enhancer of zeste 2 (EZH2) expression, the functional subunit of the epigenetic master regulator polycomb repressive complex.

Methods

Human proximal long head of biceps tendons from patients with different chronic shoulder pathologies (n = 22), and controls from patients with humerus fracture (n = 6) and pathology (n = 4), were histologically scored for degeneration and analyzed for gene and protein expression of tendon specific factors, senescence markers, and EZH2. Tissues were further exposed to senotherapeutic compounds and the USA Food and Drugs Administration-approved selective EZH2 inhibitor EPZ-6438 and their senescence-associated secretory phenotype (SASP) assessed.


Bone & Joint Open
Vol. 6, Issue 2 | Pages 215 - 226
25 Feb 2025
Qu H Wang K Shi C Li H Li X Lin P Lin N Ye Z

Aims

Osseous invasion exhibited in soft-tissue sarcoma (STS) is recognized as a prognostic risk factor. Achieving a wide margin is the default surgical approach for local control. However, for STSs where the tumour is in contact with the adjacent cortex but without clear evidence of osseous invasion, such as medullary invasion, the question of whether bone resection can provide better local control or survival than more conservative sub-periosteal excision remains controversial. The aim of this study was to assess whether bone resection for thigh STS with cortical contact of the adjacent bone results in better local control and survival compared to sub-periosteal dissection, and to investigate the prognostic factors for clinical outcomes in STS.

Methods

A retrospective cohort study was conducted on 142 patients with thigh STS exhibiting cortical contact but without medullary invasion, from May 2000 to May 2020. Patients underwent either composite bone resection or sub-periosteal excision. Demographics, clinical outcomes, and functional outcomes were compared between the two groups. Additionally, Cox regression analysis was used to analyze risk factors for local recurrence.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 124 - 135
20 Feb 2025
Huang J Zheng J Yin J Lin R Wu J Xu H Zhu J Zhang H Wang G Cai D

Aims

To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism.

Methods

Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 136 - 142
20 Feb 2025
Walter N Loew T Hinterberger T Mohokum M Alt V Rupp M

Aims. Fracture-related infections (FRIs) are a major concern for patients and healthcare systems, yet their impact on mental health has been largely overlooked. This study aimed to assess the longitudinal impact of FRI on patients’ quality of life. Methods. A prospective study was conducted at a level 1 trauma centre between January 2020 and December 2022. In total, 56 patients participated, with quality of life assessed at five timepoints: one week preoperatively, and one, three, six, and 12 months postoperatively. Statistical analysis was performed using repeated measures analysis of variance (ANOVA) with adjusted post-hoc analysis. Results. The preoperative Physical Component Summary score on the 36-Item Short-Form Health Survey questionnaire (SF-36) was 26.71, increasing to 30.40 at one month, remaining stable at three months. A modest increase was observed at six months (32.45, p = 0.003), but it decreased to 29.72 at 12 months. The preoperative Mental Component Summary score (SF-36) was 46.48, decreasing to 39.89 at one month (p = 0.027) and to 36.03 at three months (p ≤ 0.001). However, it improved at six (42.74) and 12 months (44.05). Positive changes were seen in EuroQol five-dimension questionnaire (EQ-5D) subdimensions, such as mobility, self-care, usual activities, and pain/discomfort, while anxiety/depression scores decreased over time. The EQ-5D visual analogue scale (VAS) score increased to 62.79 at six months (p ≤ 0.001) and decreased to 58.2 at 12 months (p = 0.011). Conclusion. FRIs substantially affect mental health and quality of life, particularly during the initial three months of treatment. This study emphasizes the importance of addressing psychological aspects early in FRI management, advocating for holistic care encompassing both physical and psychological aspects of treatment. Cite this article: Bone Joint Res 2025;14(2):136–142