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The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 880 - 887
1 Aug 2023
Onodera T Momma D Matsuoka M Kondo E Suzuki K Inoue M Higano M Iwasaki N

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Methods

A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations.


Bone & Joint Open
Vol. 5, Issue 7 | Pages 534 - 542
1 Jul 2024
Woods A Howard A Peckham N Rombach I Saleh A Achten J Appelbe D Thamattore P Gwilym SE

Aims

The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions’ safety and efficacy.

Methods

Participants were recruited from two community musculoskeletal treatment centres in the UK. Patients were eligible if aged 18 years or older, and had a clinical diagnosis of subacromial impingement syndrome which the treating clinician thought was suitable for treatment with a subacromial injection. Consenting patients were randomly allocated 1:1 to a patient-blinded subacromial injection of CSI (standard care) or APS. The primary outcome measures of this study relate to rates of recruitment, retention, and compliance with intervention and follow-up to determine feasibility. Secondary outcome measures relate to the safety and efficacy of the interventions.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 83 - 90
19 Feb 2024
Amri R Chelly A Ayedi M Rebaii MA Aifa S Masmoudi S Keskes H

Aims

The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

Methods

A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 526 - 533
1 May 2023
Harmer JR Wyles CC Duong SQ Morgan III RJ Maradit-Kremers H Abdel MP

Aims

The aim of this study was to determine the prevalence of depressive and anxiety disorders prior to total hip (THA) and total knee arthroplasty (TKA) and to assess their impact on the rates of any infection, revision, or reoperation.

Methods

Between January 2000 and March 2019, 21,469 primary and revision arthroplasties (10,011 THAs; 11,458 TKAs), which were undertaken in 15,504 patients at a single academic medical centre, were identified from a 27-county linked electronic medical record (EMR) system. Depressive and anxiety disorders were identified by diagnoses in the EMR or by using a natural language processing program with subsequent validation from review of the medical records. Patients with mental health diagnoses other than anxiety or depression were excluded.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 202 - 211
7 Mar 2023
Bai Z Shou Z Hu K Yu J Meng H Chen C

Aims

This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

Methods

This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

Methods

We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.


Bone & Joint Research
Vol. 5, Issue 3 | Pages 95 - 100
1 Mar 2016
Pilge H Fröbel J Prodinger PM Mrotzek SJ Fischer JC Zilkens C Bittersohl B Krauspe R

Objectives. Venous thromboembolism (VTE) is a major potential complication following orthopaedic surgery. Subcutaneously administered enoxaparin has been used as the benchmark to reduce the incidence of VTE. However, concerns have been raised regarding the long-term administration of enoxaparin and its possible negative effects on bone healing and bone density with an increase of the risk of osteoporotic fractures. New oral anticoagulants such as rivaroxaban have recently been introduced, however, there is a lack of information regarding how these drugs affect bone metabolism and post-operative bone healing. Methods. We measured the migration and proliferation capacity of mesenchymal stem cells (MSCs) under enoxaparin or rivaroxaban treatment for three consecutive weeks, and evaluated effects on MSC mRNA expression of markers for stress and osteogenic differentiation. Results. We demonstrate that enoxaparin, but not rivaroxaban, increases the migration potential of MSCs and increases their cell count in line with elevated mRNA expression of C-X-C chemokine receptor type 4 (CXCR4), tumor necrosis factor alpha (TNFα), and alpha-B-crystallin (CryaB). However, a decrease in early osteogenic markers (insulin-like growth factors 1 and 2 (IGF1, IGF2), bone morphogenetic protein2 (BMP2)) indicated inhibitory effects on MSC differentiation into osteoblasts caused by enoxaparin, but not by rivaroxaban. Conclusions. Our findings may explain the adverse effects of enoxaparin treatment on bone healing. Rivaroxaban has no significant impact on MSC metabolism or capacity for osteogenic differentiation in vitro. Cite this article: Dr H. Pilge. Enoxaparin and rivaroxaban have different effects on human mesenchymal stromal cells in the early stages of bone healing. Bone Joint Res 2016;5:95–100. DOI: 10.1302/2046-3758.53.2000595


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 1 | Pages 144 - 147
1 Jan 2001
Mayr-Wohlfart U Kessler S Puhl W Günther KP Knöchel W

Since bone morphogenetic proteins (BMPs) are highly homologous, we investigated the hypothesis that recombinant BMP-4 of the genome of Xenopus laevis (rxBMP-4) may influence the proliferation or differentiation of human primary osteoblast-like cells (HPOC), as occurs with recombinant human BMP (rhBMP-2). HPOC were incubated in the presence of either rxBMP-4, rhBMP-2 or basic fibroblast growth factor (rh-bFGF). The last two were used as positive controls and are known to induce differentiation or proliferation of HPOC, respectively. rxBMP-4 (50 ng/ml and 100 ng/ml) induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied in the same concentration, failed to have any influence on cell differentiation. rh-bFGF however, provoked an increase in cell proliferation of up to 150% when compared with non-stimulated HPOC, while rhBMP-2 and rxBMP-4 had no such effect. Our results indicate an equipotent effect of rhBMP-2 and rxBMP-4 obtained from Xenopus laevis on the differentiation and proliferation of human primary osteoblast-like cells


Bone & Joint Open
Vol. 4, Issue 2 | Pages 72 - 78
9 Feb 2023
Kingsbury SR Smith LKK Pinedo-Villanueva R Judge A West R Wright JM Stone MH Conaghan PG

Aims

To review the evidence and reach consensus on recommendations for follow-up after total hip and knee arthroplasty.

Methods

A programme of work was conducted, including: a systematic review of the clinical and cost-effectiveness literature; analysis of routine national datasets to identify pre-, peri-, and postoperative predictors of mid-to-late term revision; prospective data analyses from 560 patients to understand how patients present for revision surgery; qualitative interviews with NHS managers and orthopaedic surgeons; and health economic modelling. Finally, a consensus meeting considered all the work and agreed the final recommendations and research areas.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 536 - 545
8 Sep 2023
Luo P Yuan Q Yang M Wan X Xu P

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 540 - 547
1 Jun 2024
Nandra RS Elnahal WA Mayne A Brash L McBryde CW Treacy RBC

Aims

The Birmingham Hip Resurfacing (BHR) was introduced in 1997 to address the needs of young active patients using a historically proven large-diameter metal-on-metal (MoM) bearing. A single designer surgeon’s consecutive series of 130 patients (144 hips) was previously reported at five and ten years, reporting three and ten failures, respectively. The aim of this study was to extend the follow-up of this original cohort at 25 years.

Methods

The study extends the reporting on the first consecutive 144 resurfacing procedures in 130 patients for all indications. All operations were undertaken between August 1997 and May 1998. The mean age at operation was 52.1 years (SD 9.93; 17 to 76), and included 37 female patients (28.5%). Failure was defined as revision of either component for any reason. Kaplan-Meier survival analysis was performed. Routine follow-up with serum metal ion levels, radiographs, and Oxford Hip Scores (OHSs) was undertaken.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 486 - 493
4 Aug 2023
Yamanaka Y Tajima T Tsujimura Y Naito T Mano Y Tsukamoto M Zenke Y Sakai A

Aims

Dupuytren’s contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis.

Methods

We compared the expression of the adipocytokines adiponectin and leptin in the adipose tissue surrounding the palmar aponeurosis of male patients with Dupuytren’s contracture, and of male patients with carpal tunnel syndrome (CTS) as the control group. We also examined the effects of adiponectin on fibrosis-related genes and proteins expressed by fibroblasts in the palmar aponeurosis of patients with Dupuytren’s contracture.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 978 - 985
1 Sep 2024
Savoie III FH Delvadia BP Tate JP Winter JE Williams GH Sherman WF O’Brien MJ

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 158 - 167
10 Mar 2023
Landers S Hely R Hely A Harrison B Page RS Maister N Gwini SM Gill SD

Aims

This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure.

Methods

A total of 59 participants with symptomatic Kellgren-Lawrence grade 2 knee OA were randomly allocated to TAE or a sham procedure. The intervention group underwent TAE of one or more genicular arteries. The control group received a blinded sham procedure. The primary outcome was knee pain at 12 months according to the Knee injury and Osteoarthritis Outcome Score (KOOS) pain scale. Secondary outcomes included self-reported function and quality of life (KOOS, EuroQol five-dimension five-level questionnaire (EQ-5D-5L)), self-reported Global Change, six-minute walk test, 30-second chair stand test, and adverse events. Subgroup analyses compared participants who received complete embolization of all genicular arteries (as distinct from embolization of some arteries) (n = 17) with the control group (n = 29) for KOOS and Global Change scores at 12 months. Continuous variables were analyzed with quantile regression, adjusting for baseline scores. Dichotomized variables were analyzed with chi-squared tests.


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 99 - 106
1 Jan 2024
Khal AA Aiba H Righi A Gambarotti M Atherley O'Meally AO Manfrini M Donati DM Errani C

Aims

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

Methods

We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome.


The Bone & Joint Journal
Vol. 105-B, Issue 6 | Pages 679 - 687
1 Jun 2023
Lou Y Zhao C Cao H Yan B Chen D Jia Q Li L Xiao J

Aims

The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS).

Methods

We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 667 - 676
19 Oct 2023
Forteza-Genestra MA Antich-Rosselló M Ramis-Munar G Calvo J Gayà A Monjo M Ramis JM

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Methods

pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 439 - 452
13 Jul 2022
Sun Q Li G Liu D Xie W Xiao W Li Y Cai M

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.


Bone & Joint Research
Vol. 6, Issue 2 | Pages 98 - 107
1 Feb 2017
Kazemi D Shams Asenjan K Dehdilani N Parsa H

Objectives. Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Methods. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (. sd. ) and compared at different time points between the two groups using the Mann-Whitney U test, with a value < 0.05 considered statistically significant. Results. Higher cumulative macroscopic and histological scores were observed in stem cell treated defects throughout the study period with significant differences noted at four and 24 weeks (9.25, . sd. 0.5 vs 7.25, . sd. 0.95, and 10, . sd. 0.81 vs 7.5, . sd. 0.57; p < 0.05) and 16 weeks (16.5, . sd. 4.04 vs 11, . sd. 1.15; p < 0.05), respectively. Superior gross and histological characteristics were also observed in stem cell treated defects. Conclusion. The use of autologous culture expanded bone marrow derived mesenchymal stem cells on platelet rich fibrin is a novel method for articular cartilage regeneration. It is postulated that platelet rich fibrin creates a suitable environment for proliferation and differentiation of stem cells by releasing endogenous growth factors resulting in creation of a hyaline-like reparative tissue. Cite this article: D. Kazemi, K. Shams Asenjan, N. Dehdilani, H. Parsa. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin: Macroscopic and histological assessments. Bone Joint Res 2017;6:98–107. DOI: 10.1302/2046-3758.62.BJR-2016-0188.R1