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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.


Bone & Joint Research
Vol. 14, Issue 3 | Pages 209 - 222
10 Mar 2025
Xiao Y Yue Z Zijing H Yao Z Sui M Xuemin Z Qiang Z Xiao Y Dapeng R

Aims

Excessive chondrocyte hypertrophy is a common feature in cartilage degeneration which is susceptible to joint overloading, but the relationship between mechanical overloading and chondrocyte hypertrophy still remains elusive. The aim of our study was to explore the mechanism of mechanical compression-induced chondrocyte hypertrophy.

Methods

In this study, the temporomandibular joint (TMJ) degeneration model was built through forced mandibular retrusion (FMR)-induced compression in TMJ. Chondrocytes were also mechanically compressed in vitro. The role of O-GlcNAcylation in mechanical compression-induced chondrocyte hypertrophy manifested through specific activator Thiamet G and inhibitor OSMI-1.


Bone & Joint Research
Vol. 14, Issue 3 | Pages 199 - 207
5 Mar 2025
Largo R Mediero A Villa-Gomez C Bermejo-Alvarez I Herrero-Beaumont G

Osteoarthritis (OA) is a highly prevalent and disabling disease with an unmet therapeutic need. The characteristic cartilage loss and alteration of other joint structures result from a complex interaction of multiple risk factors, with mechanical overload consistently playing a central role. This overload generates an inflammatory response in the cartilage due to the activation of the innate immune response in chondrocytes, which occurs through various cellular mechanisms. Moreover, risk factors associated with obesity, being overweight, and metabolic syndrome enhance the inflammatory response both locally and systemically. OA chondrocytes, the only cells present in articular cartilage, are therefore inflamed and initiate an anabolic process in an attempt to repair the damaged tissue, which ultimately results in an aberrant and dysfunctional process. Under these circumstances, where the cartilage continues to be subjected to chronic mechanical stress, proposing a treatment that stimulates the chondrocytes’ anabolic response to restore tissue structure does not appear to be a therapeutic target with a high likelihood of success. In fact, anabolic drugs proposed for the treatment of OA have yet to demonstrate efficacy. By contrast, multiple therapeutic strategies focused on pharmacologically managing the inflammatory component, both at the joint and systemic levels, have shown promise. Therefore, prioritizing the control of chronic innate pro-inflammatory pathways presents the most viable and promising therapeutic strategy for the effective management of OA. As research continues, this approach may offer the best opportunity to alleviate the burden of this incapacitating disease. Cite this article: Bone Joint Res 2025;14(3):199–207


The Bone & Joint Journal
Vol. 107-B, Issue 3 | Pages 322 - 328
1 Mar 2025
Walker T Freericks J Mick P Trefzer R Lunz A Koch K Renkawitz T Hariri M

Aims

Unicompartmental knee arthroplasty (UKA) is one option in the treatment of isolated unicompartmental advanced osteoarthritis (OA). While long-term results exist for medial mobile-bearing (MB) UKA, evidence regarding lateral MB-UKA is still limited. The Oxford Domed Lateral (ODL) implant aims to reduce the bearing dislocation rate in lateral MB-UKA through enhanced bearing entrapment. However, the long-term performance of this implant remains unclear. This study evaluated the long-term survival and clinical outcomes of the ODL in a non-designer centre.

Methods

This single-centre retrospective analysis included 115 lateral MB-UKAs using the ODL performed between January 2006 and December 2014. The primary endpoint of the study was implant survival, defined as the time until a revision procedure was required for any reason. Secondary outcomes included Oxford Knee Score (OKS), Forgotten Joint Score (FJS), pain, satisfaction, and Tegner Activity Scale (TAS). Survival was assessed using Kaplan-Meier analysis.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 155 - 165
27 Feb 2025
Guo Y Peng X Cao B Liu Q Li S Chen F Zhi D Zhang S Chen Z

Aims. A large number of surgical operations are available to treat osteochondral defects of the knee. However, the knee joint arthroplasty materials cannot completely mimic the articular cartilage and subchondral bone, which may bring some obvious side effects. Thus, this study proposed a biocompatible osteochondral repair material prepared from a double-layer scaffold of collagen and nanohydroxyapatite (CHA), consisting of collagen hydrogel as the upper layer of the scaffold, and the composite of CHA as the lower layer of the scaffold. Methods. The CHA scaffold was prepared, and properties including morphology, internal structure, and mechanical strength of the CHA scaffold were measured by scanning electron microscopy (SEM) and a MTS electronic universal testing machine. Then, biocompatibility and repair capability of the CHA scaffold were further evaluated using a rabbit knee cartilage defect model. Results. The CHA scaffold was well suited for the repair of articular cartilage and subchondral bone; the in vitro results showed that the CHA scaffold had good cytocompatibility. In vivo experiments demonstrated that the material had high biocompatibility and effectively induced cartilage and subchondral bone regeneration. Conclusion. The CHA scaffold has a high potential for commercialization and could be used as an effective knee repair material in clinical applications. Cite this article: Bone Joint Res 2025;14(2):155–165


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 360
Vol. 14, Issue 1 | Pages 39 - 42
1 Feb 2025

The February 2025 Oncology Roundup360 looks at:The role of bone grafting versus bone cement in the treatment of giant cell tumour of bone: a systematic review and meta-analysis on the risk of recurrence in 1,454 patients; Tumour necrosis drives prognosis in osteosarcoma; Correlation between post-chemotherapy MRI and histopathology of malignant bone tumours treated with extra-articular resection; Real-world referral pattern of unplanned excision in patients with soft-tissue sarcoma; Assessment of artificial intelligence chatbot responses to common patient questions on bone sarcoma; Chondrosarcoma of the pelvis and limbs at ten years; Chest wall resection and reconstruction for primary chest wall sarcomas: analysis of survival, predictors of outcome, and long-term functional status; Ewing’s sarcoma in the paediatric population: predictors of survival within the USA; Pulmonary metastasectomy for sarcoma: insights from a referral centre cohort.


Bone & Joint Research
Vol. 14, Issue 1 | Pages 20 - 32
17 Jan 2025
Chen Z Zhou T Yin Z Duan P Zhang Y Feng Y Shi R Xu Y Pang R Tan H

Aims

Magnesium ions (Mg2+) play an important role in promoting cartilage repair in cartilage lesions. However, no research has focused on the role of Mg2+ combined with microfracture (MFX) in hyaline-like cartilage repair mediated by cartilage injury. This study aimed to investigate the beneficial effects of the combination of MFX and Mg2+ in cartilage repair.

Methods

A total of 60 rabbits were classified into five groups (n = 12 each): sham, MFX, and three different doses of Mg2+ treatment groups (0.05, 0.5, and 5 mol/L). Bone cartilage defects were created in the trochlear groove cartilage of rabbits. MFX surgery was performed after osteochondral defects. Mg2+ was injected into knee joints immediately and two and four weeks after surgery. At six and 12 weeks after surgery, the rabbits were killed. Cartilage damage was detected by gross observation, micro-CT, and histological analysis. The expression levels of related genes were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).


Bone & Joint Research
Vol. 13, Issue 12 | Pages 764 - 778
12 Dec 2024
Huang Q Zhuo Y Duan Z Long Y Wang J Zhang Z Fan S Huang Y Deng K Xin H

Aims

Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.

Methods

In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 725 - 740
5 Dec 2024
Xing J Liu S

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1399 - 1407
1 Dec 2024
Fujii M Tanaka S Kawano S Ueno M Nagamine S Mawatari M

Aims

This study aimed to determine clinical outcomes; relationships between postoperative anterior, lateral, and posterior acetabular coverage and joint survival; and prognostic factors for joint survival after transposition osteotomy of the acetabulum (TOA).

Methods

Data from 616 patients (800 hips) with hip dysplasia who underwent TOA between November 1998 and December 2019 were reviewed. The median follow-up period was 8.9 years (IQR 5 to 14). A medical notes review was conducted to collect demographic data, complications, and modified Harris Hip Score (mHHS). Radiological indicators of acetabular coverage included lateral centre-edge angle (LCEA), anterior wall index (AWI), and posterior wall index (PWI). The cumulative probability of TOA failure (progression to Tönnis grade 3 or conversion to total hip arthroplasty) was estimated using the Kaplan-Meier product-limited method. A multivariate Cox proportional hazards model was used to identify predictors for failure.


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1431 - 1442
1 Dec 2024
Poutoglidou F van Groningen B McMenemy L Elliot R Marsland D

Lisfranc injuries were previously described as fracture-dislocations of the tarsometatarsal joints. With advancements in modern imaging, subtle Lisfranc injuries are now more frequently recognized, revealing that their true incidence is much higher than previously thought. Injury patterns can vary widely in severity and anatomy. Early diagnosis and treatment are essential to achieve good outcomes. The original classification systems were anatomy-based, and limited as tools for guiding treatment. The current review, using the best available evidence, instead introduces a stability-based classification system, with weightbearing radiographs and CT serving as key diagnostic tools. Stable injuries generally have good outcomes with nonoperative management, most reliably treated with immobilization and non-weightbearing for six weeks. Displaced or comminuted injuries require surgical intervention, with open reduction and internal fixation (ORIF) being the most common approach, with a consensus towards bridge plating. While ORIF generally achieves satisfactory results, its effectiveness can vary, particularly in high-energy injuries. Primary arthrodesis remains niche for the treatment of acute injuries, but may offer benefits such as lower rates of post-traumatic arthritis and hardware removal. Novel fixation techniques, including suture button fixation, aim to provide flexible stabilization, which theoretically could improve midfoot biomechanics and reduce complications. Early findings suggest promising functional outcomes, but further studies are required to validate this method compared with established techniques. Future research should focus on refining stability-based classification systems, validation of weightbearing CT, improving rehabilitation protocols, and optimizing surgical techniques for various injury patterns to ultimately enhance patient outcomes.

Cite this article: Bone Joint J 2024;106-B(12):1431–1442.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 659 - 672
20 Nov 2024
Mo H Sun K Hou Y Ruan Z He Z Liu H Li L Wang Z Guo F

Aims

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Methods

A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1273 - 1283
1 Nov 2024
Mahmud H Wang D Topan-Rat A Bull AMJ Heinrichs CH Reilly P Emery R Amis AA Hansen UN

Aims. The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids. Methods. Intact right cadaveric shoulders from donors aged between 50 and 65 years were assigned to a ceramic group (n = 8, four male cadavers) and a metal group (n = 9, four male cadavers). A dedicated shoulder wear simulator was used to simulate daily activity by replicating the relevant joint motion and loading profiles. During testing, the joint was kept lubricated with diluted calf serum at room temperature. Each test of wear was performed for 500,000 cycles at 1.2 Hz. At intervals of 125,000 cycles, micro-CT scans of each glenoid were taken to characterize and quantify glenoid wear by calculating the change in the thickness of its articular cartilage. Results. At the completion of the wear test, the total thickness of the cartilage had significantly decreased in both the ceramic and metal groups, by 27% (p = 0.019) and 29% (p = 0.008), respectively. However, the differences between the two were not significant (p = 0.606) and the patterns of wear in the specimens were unpredictable. No significant correlation was found between cartilage wear and various factors, including age, sex, the size of the humeral head, joint mismatch, the thickness of the native cartilage, and the surface roughness (all p > 0.05). Conclusion. Although ceramic has better tribological properties than metal, we did not find evidence that its use in hemiarthroplasty of the shoulder in patients with healthy cartilage is a better alternative than conventional metal humeral heads. Cite this article: Bone Joint J 2024;106-B(11):1273–1283


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%).


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1231 - 1239
1 Nov 2024
Tzanetis P Fluit R de Souza K Robertson S Koopman B Verdonschot N

Aims

The surgical target for optimal implant positioning in robotic-assisted total knee arthroplasty remains the subject of ongoing discussion. One of the proposed targets is to recreate the knee’s functional behaviour as per its pre-diseased state. The aim of this study was to optimize implant positioning, starting from mechanical alignment (MA), toward restoring the pre-diseased status, including ligament strain and kinematic patterns, in a patient population.

Methods

We used an active appearance model-based approach to segment the preoperative CT of 21 osteoarthritic patients, which identified the osteophyte-free surfaces and estimated cartilage from the segmented bones; these geometries were used to construct patient-specific musculoskeletal models of the pre-diseased knee. Subsequently, implantations were simulated using the MA method, and a previously developed optimization technique was employed to find the optimal implant position that minimized the root mean square deviation between pre-diseased and postoperative ligament strains and kinematics.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 944 - 952
25 Oct 2024
Deveza L El Amine MA Becker AS Nolan J Hwang S Hameed M Vaynrub M

Aims

Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension.

Methods

We performed a retrospective case-control study of patients who underwent extra-articular excision for sarcoma of the knee, hip, or shoulder from 1 June 2000 to 1 November 2020. Radiologists blinded to the pathology results evaluated preoperative MRI for three direct signs of joint invasion (capsular disruption, cortical breach, cartilage invasion) and indirect signs (e.g. joint effusion, synovial thickening). The discriminatory ability of MRI to detect intra-articular tumour extension was determined by receiver operating characteristic analysis.


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).


Bone & Joint 360
Vol. 13, Issue 5 | Pages 24 - 26
1 Oct 2024

The October 2024 Knee Roundup360 looks at: Managing the unexpected: treatment of intraoperative medial collateral ligament injuries; Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: secondary analysis of data from a randomized controlled trial; Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial; Cartilage regeneration and long-term survival in medial knee osteoarthritis patients treated with high tibial osteotomy and osteochondral autologous transfer system; Treatment of chronic and complex meniscal tears with arthroscopic meniscus repair augmented with collagen matrix wrapping: failure rate and functional outcomes; Long-term outcomes of multiligament knee injuries in American football players.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1100 - 1110
1 Oct 2024
Arenas-Miquelez A Barco R Cabo Cabo FJ Hachem A

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available.

Cite this article: Bone Joint J 2024;106-B(10):1100–1110.