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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 Research
Vol. 13, Issue 9 | Pages 513 - 524
19 Sep 2024
Kalsoum R Minns Lowe CJ Gilbert S McCaskie AW Snow M Wright K Bruce G Mason DJ Watt FE

Aims. To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design. Methods. Healthcare professionals, clinicians, and/or researchers (HCP/Rs) were surveyed, and the data were presented at a congress workshop. A second and related survey was then developed for people with joint damage caused by knee injury and/or osteoarthritis (PJDs), who were approached by a UK Charity newsletter or Oxford involvement registry. Anonymized data were collected and analyzed in Qualtrics. Results. Survey responses (n = 19 HCP/Rs, 39 PJDs) supported studies testing pharmacological agents preventing PTOA. All HCP/Rs and 30/31 (97%) PJDs supported the development of new treatments that improved or delayed knee symptoms and damage to knee structure. PJDs thought that improving structural knee damage was more important than knee symptoms. Both groups found studies more acceptable as expected future benefit and risk of PTOA increased. All drug delivery routes were acceptable. Workshop participants (around n = 60) reflected survey views. Discussions suggested that stratifying using molecular testing for likely drug response appeared to be more acceptable than using characteristics such as sex, age, and BMI. Conclusion. Our findings supported PTOA drug intervention studies, including situations where there is low risk of disease, no expected benefit of treatment, and frequent treatment administration. PJDs appeared less risk-averse than HCP/Rs. This work reinforces the benefits of consensus and involvement work in the co-creation of PTOA drug trial design. Involvement of key stakeholders, such as PJDs with different risks of OA and regulatory representatives, are critical for trial design success. Cite this article: Bone Joint Res 2024;13(9):513–524


Bone & Joint Open
Vol. 5, Issue 9 | Pages 785 - 792
19 Sep 2024
Clement RGE Wong SJ Hall A Howie SEM Simpson AHRW

Aims

The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms.

Methods

All microbiological samples from joint aspirations between March 2000 and December 2014 at our institution were reviewed in order to identify cases of culture-proven septic arthritis. Cases in children (aged < 16 years) and prosthetic joints were excluded. Data were abstracted on age at diagnosis, sex, joint affected (hip or knee), type of organisms isolated, cause of septic arthritis, comorbidities within the Charlson Comorbidity Index (CCI), details of treatment, and outcome.


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

Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Methods

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


Bone & Joint 360
Vol. 13, Issue 1 | Pages 32 - 35
1 Feb 2024

The February 2024 Trauma Roundup360 looks at: Posterior malleolus fractures: what about medium-sized fragments?; Acute or delayed total hip arthroplasty after acetabular fracture fixation?; Intrawound antibiotics reduce the risk of deep infections in fracture fixation; Does the VANCO trial represent real world patients?; Can a restrictive transfusion protocol be effective beyond initial resuscitation?; What risk factors result in avascular necrosis of the talus?; Pre-existing anxiety and mood disorders have a role to play in complex regional pain syndrome; Three- and four-part proximal humeral fractures at ten years.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 601 - 614
21 Sep 2023
Gu P Pu B Liu T Yue D Xin Q Li H Yang B Ke D Zheng X Zeng Z Zhang Z

Aims

Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

Methods

PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.


The Bone & Joint Journal
Vol. 105-B, Issue 9 | Pages 977 - 984
1 Sep 2023
Kamp T Gademan MGJ van Zon SKR Nelissen RGHH Vliet Vlieland TPM Stevens M Brouwer S

Aims

For the increasing number of working-age patients undergoing total hip or total knee arthroplasty (THA/TKA), return to work (RTW) after surgery is crucial. We investigated the association between occupational class and time to RTW after THA or TKA.

Methods

Data from the prospective multicentre Longitudinal Leiden Orthopaedics Outcomes of Osteoarthritis Study were used. Questionnaires were completed preoperatively and six and 12 months postoperatively. Time to RTW was defined as days from surgery until RTW (full or partial). Occupational class was preoperatively assessed and categorized into four categories according to the International Standard Classification of Occupations 2008 (blue-/white-collar, high-/low-skilled). Cox regression analyses were conducted separately for THA and TKA patients. Low-skilled blue-collar work was used as the reference category.


Bone & Joint 360
Vol. 12, Issue 4 | Pages 38 - 41
1 Aug 2023

The August 2023 Children’s orthopaedics Roundup. 360. looks at: DDH: What can patients expect after open reduction?; Femoral head deformity associated with hip displacement in non-ambulatory cerebral palsy; Bony hip reconstruction for displaced hips in patients with cerebral palsy: is postoperative immobilization indicated?; Opioid re-prescriptions after ACL reconstruction in adolescents are associated with subsequent opioid use disorder; Normative femoral and tibial lengths in a modern population of USA children; Retrospective analysis of associated anomalies in 636 patients with operatively treated congenital scoliosis; Radiological hip shape and patient-reported outcome measures in healed Perthes’ disease; Significantly displaced adolescent posterior sternoclavicular joint injuries


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 815 - 820
1 Jul 2023
Mitchell PD Abraham A Carpenter C Henman PD Mavrotas J McCaul J Sanghrajka A Theologis T

Aims

The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems.

Methods

A Delphi approach was used to determine consensus in three core aspects of care: 1) assessment, investigation, and diagnosis; 2) treatment; and 3) service, pathways, and networks. A steering group of paediatric orthopaedic surgeons created statements which were then evaluated through a two-round Delphi survey sent to all members of the British Society for Children’s Orthopaedic Surgery (BSCOS). Statements were only included (‘consensus in’) in the final agreed consensus if at least 75% of respondents scored the statement as critical for inclusion. Statements were discarded (‘consensus out’) if at least 75% of respondents scored them as not important for inclusion. Reporting these results followed the Appraisal Guidelines for Research and Evaluation.


Bone & Joint 360
Vol. 12, Issue 2 | Pages 42 - 44
1 Apr 2023

The April 2023 Research Roundup360 looks at: Ear protection for orthopaedic surgeons?; Has arthroscopic meniscectomy use changed in response to the evidence?; Time to positivity of cultures obtained for periprosthetic joint infection; Bisphosphonates for post-COVID-19 osteonecrosis of the femoral head; Missing missed fractures: is AI the answer?; Congenital insensitivity to pain and correction of the knee; YouTube and paediatric elbow injuries.


Bone & Joint Open
Vol. 4, Issue 2 | Pages 87 - 95
10 Feb 2023
Deshmukh SR Kirkham JJ Karantana A

Aims. The aim of this study was to develop a core outcome set of what to measure in all future clinical research on hand fractures and joint injuries in adults. Methods. Phase 1 consisted of steps to identify potential outcome domains through systematic review of published studies, and exploration of the patient perspective through qualitative research, consisting of 25 semi-structured interviews and five focus groups. Phase 2 involved key stakeholder groups (patients, hand surgeons, and hand therapists) prioritizing the outcome domains via a three-round international Delphi survey, with a final consensus meeting to agree the final core outcome set. Results. The systematic review of 160 studies identified 74 outcome domains based on the World Health Organization International Classification of Functioning, Disability, and Health. Overall, 35 domains were generated through thematic analysis of the patient interviews and focus groups. The domains from these elements were synthesised to develop 37 outcome domains as the basis of the Delphi survey, with a further four generated from participant suggestions in Round 1. The Delphi survey identified 20 outcome domains as ‘very important’ for the core outcome set. At the consensus meeting, 27 participants from key stakeholder groups selected seven outcomes for the core outcome set: pain/discomfort with activity, pain/discomfort with rest, fine hand use/dexterity, self-hygiene/personal care, return to usual work/job, range of motion, and patient satisfaction with outcome/result. Conclusion. This set of core outcome domains is recommended as a minimum to be reported in all clinical research on hand fractures and joint injuries in adults. While this establishes what to measure, future work will focus on determining how best to measure these outcomes. By adopting this patient-centred core outcome set, consistency and comparability of studies will be improved, aiding meta-analysis and strengthening the evidence base for management of these common and impactful injuries. Cite this article: Bone Jt Open 2023;4(2):87–95


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

Aims

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

Methods

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


Bone & Joint Research
Vol. 12, Issue 2 | Pages 121 - 132
1 Feb 2023
Mo H Wang Z He Z Wan J Lu R Wang C Chen A Cheng P

Aims

Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA.

Methods

After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.


Bone & Joint Open
Vol. 3, Issue 12 | Pages 924 - 932
23 Dec 2022
Bourget-Murray J Horton I Morris J Bureau A Garceau S Abdelbary H Grammatopoulos G

Aims

The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome.

Methods

A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined.


Aims

This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue.

Methods

The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 639 - 651
7 Sep 2022
Zou Y Zhang X Liang J Peng L Qin J Zhou F Liu T Dai L

Aims

To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms.

Methods

Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 652 - 668
7 Sep 2022
Lv G Wang B Li L Li Y Li X He H Kuang L

Aims

Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

Methods

Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 669 - 678
1 Sep 2022
Clement RGE Hall AC Wong SJ Howie SEM Simpson AHRW

Aims

Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection.

Methods

Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 514 - 517
10 Aug 2022
Little CB Zaki S Blaker CL Clarke EC

Cite this article: Bone Joint Res 2022;11(8):514–517.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K Maißner J Smolen JS Aletaha D Blüml S Redlich K

Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local joint damage, but questions the efficacy of potential combinatorial therapies of IL-1 and IL-6 in treatment of RA. In contrast, combined deficiency of IL-1/IL-6 led to an additive protective effect on TNF-driven systemic bone loss compared to single IL-1 and IL-6 deficiency. This finding clearly indicates a common contribution of both IL-1 and IL-6 in TNF-driven systemic bone loss, and points to a discrepancy of cytokine dependency in local and systemic TNF-driven mechanisms of inflammatory arthritis. Conclusion. Combinatorial treatments in RA might provide different benefits to inflammatory local arthritis and systemic comorbidities. Cite this article: Bone Joint Res 2022;11(7):484–493


Bone & Joint Research
Vol. 11, Issue 4 | Pages 214 - 225
20 Apr 2022
Hao X Zhang J Shang X Sun K Zhou J Liu J Chi R Xu T

Aims

Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

Methods

A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed.


Bone & Joint Research
Vol. 10, Issue 8 | Pages 498 - 513
3 Aug 2021
Liu Z Lu C Shen P Chou S Shih C Chen J Tien YC

Aims

Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.

Methods

Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.


Bone & Joint 360
Vol. 10, Issue 4 | Pages 42 - 45
1 Aug 2021


Bone & Joint Research
Vol. 10, Issue 7 | Pages 401 - 410
13 Jul 2021
Liu Z Wang H Wang S Gao J Niu L

Aims

Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

Methods

The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).


Bone & Joint 360
Vol. 10, Issue 2 | Pages 5 - 16
1 Apr 2021
Coco V Shivji F Thompson P Grassi A Zaffagnini S Spalding T


Bone & Joint Research
Vol. 10, Issue 4 | Pages 285 - 297
1 Apr 2021
Ji M Ryu HJ Hong JH

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA.

Cite this article: Bone Joint Res 2021;10(4):285–297.


Bone & Joint Research
Vol. 10, Issue 4 | Pages 259 - 268
1 Apr 2021
Lou A Wang L Lai W Zhu D Wu W Wang Z Cai Z Yang M

Aims

Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour.

Methods

We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation.


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 788 - 794
1 Apr 2021
Spierenburg G Lancaster ST van der Heijden L Mastboom MJL Gelderblom H Pratap S van de Sande MAJ Gibbons CLMH

Aims

Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres.

Methods

The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019.


Aims

This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA).

Methods

Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry.


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 584 - 588
1 Mar 2021
Khattak M Vellathussery Chakkalakumbil S Stevenson RA Bryson DJ Reidy MJ Talbot CL George H

Aims

The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in Kingella kingae septic arthritis when compared with those of other organisms, and whether this difference needs to be considered when assessing children in whom a diagnosis of septic arthritis is suspected.

Methods

A prospective case series was undertaken at a single UK paediatric institution between October 2012 and November 2018 of all patients referred with suspected septic arthritis. We recorded the clinical, biochemical, and microbiological findings in all patients.


Bone & Joint Open
Vol. 2, Issue 3 | Pages 150 - 163
1 Mar 2021
Flett L Adamson J Barron E Brealey S Corbacho B Costa ML Gedney G Giotakis N Hewitt C Hugill-Jones J Hukins D Keding A McDaid C Mitchell A Northgraves M O'Carroll G Parker A Scantlebury A Stobbart L Torgerson D Turner E Welch C Sharma H

Aims. A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients’ quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures. Methods. A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods. Discussion. The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open 2021;2(3):150–163


Bone & Joint 360
Vol. 10, Issue 1 | Pages 38 - 41
1 Feb 2021


Bone & Joint Research
Vol. 9, Issue 9 | Pages 623 - 632
5 Sep 2020
Jayadev C Hulley P Swales C Snelling S Collins G Taylor P Price A

Aims

The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA).

Methods

Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA.


Bone & Joint Research
Vol. 9, Issue 8 | Pages 501 - 514
1 Aug 2020
Li X Yang Y Sun G Dai W Jie X Du Y Huang R Zhang J

Aims

Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method.

Methods

We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets.


Bone & Joint Research
Vol. 9, Issue 6 | Pages 302 - 310
1 Jun 2020
Tibbo ME Limberg AK Salib CG Turner TW McLaury AR Jay AG Bettencourt JW Carter JM Bolon B Berry DJ Morrey ME Sanchez-Sotelo J van Wijnen AJ Abdel MP

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310


Bone & Joint 360
Vol. 8, Issue 2 | Pages 2 - 8
1 Apr 2019
Shivji F Bryson D Nicolaou N Ali F


Bone & Joint Research
Vol. 7, Issue 7 | Pages 494 - 500
1 Jul 2018
Jiang L Zhu X Rong J Xing B Wang S Liu A Chu M Huang G

Objectives

Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA.

Methods

We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 457 - 467
1 Jul 2018
Smith IDM Milto KM Doherty CJ Amyes SGB Simpson AHRW Hall AC

Objectives

Staphylococcus aureus (S. aureus) is the most commonly implicated organism in septic arthritis, a condition that may be highly destructive to articular cartilage. Previous studies investigating laboratory and clinical strains of S. aureus have demonstrated that potent toxins induced significant chondrocyte death, although the precise toxin or toxins that were involved was unknown. In this study, we used isogenic S. aureus mutants to assess the influence of alpha (Hla)-, beta (Hlb)-, and gamma (Hlg)-haemolysins, toxins considered important for the destruction of host tissue, on in situ bovine chondrocyte viability.

Methods

Bovine cartilage explants were cultured with isogenic S. aureus mutants and/or their culture supernatants. Chondrocyte viability was then assessed within defined regions of interest in the axial and coronal plane following live- and dead-cell imaging using the fluorescent probes 5-chloromethylfluorescein diacetate and propidium iodide, respectively, and confocal laser-scanning microscopy.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 274 - 281
1 Apr 2018
Collins KH Hart DA Seerattan RA Reimer RA Herzog W

Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 468 - 474
1 Apr 2018
Kirzner N Zotov P Goldbloom D Curry H Bedi H

Aims

The aim of this retrospective study was to compare the functional and radiological outcomes of bridge plating, screw fixation, and a combination of both methods for the treatment of Lisfranc fracture dislocations.

Patients and Methods

A total of 108 patients were treated for a Lisfranc fracture dislocation over a period of nine years. Of these, 38 underwent transarticular screw fixation, 45 dorsal bridge plating, and 25 a combination technique. Injuries were assessed preoperatively according to the Myerson classification system. The outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) score, the validated Manchester Oxford Foot Questionnaire (MOXFQ) functional tool, and the radiological Wilppula classification of anatomical reduction.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 244 - 251
1 Mar 2018
Tawonsawatruk T Sriwatananukulkit O Himakhun W Hemstapat W

Objectives

In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models.

Methods

OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score.


Bone & Joint 360
Vol. 6, Issue 5 | Pages 27 - 30
1 Oct 2017


Bone & Joint Research
Vol. 6, Issue 5 | Pages 259 - 269
1 May 2017
McKirdy A Imbuldeniya AM

Objectives

To assess the clinical and cost-effectiveness of a virtual fracture clinic (VFC) model, and supplement the literature regarding this service as recommended by The National Institute for Health and Care Excellence (NICE) and the British Orthopaedic Association (BOA).

Methods

This was a retrospective study including all patients (17 116) referred to fracture clinics in a London District General Hospital from May 2013 to April 2016, using hospital-level data. We used interrupted time series analysis with segmented regression, and direct before-and-after comparison, to study the impact of VFCs introduced in December 2014 on six clinical parameters and on local Clinical Commissioning Group (CCG) spend. Student’s t-tests were used for direct comparison, whilst segmented regression was employed for projection analysis.


The Bone & Joint Journal
Vol. 99-B, Issue 5 | Pages 623 - 631
1 May 2017
Blaney J Harty H Doran E O’Brien S Hill J Dobie I Beverland D

Aims

Our aim was to examine the clinical and radiographic outcomes in 257 consecutive Oxford unicompartmental knee arthroplasties (OUKAs) (238 patients), five years post-operatively.

Patients and Methods

A retrospective evaluation was undertaken of patients treated between April 2008 and October 2010 in a regional centre by two non-designing surgeons with no previous experience of UKAs. The Oxford Knee Scores (OKSs) were recorded and fluoroscopically aligned radiographs were assessed post-operatively at one and five years.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 57 - 65
1 Jan 2017
Gumucio JP Flood MD Bedi A Kramer HF Russell AJ Mendias CL

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

Methods

Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.


The Bone & Joint Journal
Vol. 98-B, Issue 7 | Pages 1003 - 1008
1 Jul 2016
Fenton P Al-Nammari S Blundell C Davies M

Aims

Although infrequent, a fracture of the cuboid can lead to significant disruption of the integrity of the midfoot and its function. The purpose of this study was to classify the pattern of fractures of the cuboid, relate them to the mechanism of injury and suggest methods of managing them.

Patients and Methods

We performed a retrospective review of patients with radiologically reported cuboid fractures. Fractures were grouped according to commonly occurring patterns of injury. A total of 192 fractures in 188 patients were included. They were classified into five patterns of injury.


The Bone & Joint Journal
Vol. 98-B, Issue 4 | Pages 512 - 518
1 Apr 2016
Spencer HT Hsu L Sodl J Arianjam A Yian EH

Aims. To compare radiographic failure and re-operation rates of anatomical coracoclavicular (CC) ligament reconstructional techniques with non-anatomical techniques after chronic high grade acromioclavicular (AC) joint injuries. . Patients and Methods. We reviewed chronic AC joint reconstructions within a region-wide healthcare system to identify surgical technique, complications, radiographic failure and re-operations. Procedures fell into four categories: (1) modified Weaver-Dunn, (2) allograft fixed through coracoid and clavicular tunnels, (3) allograft loop coracoclavicular fixation, and (4) combined allograft loop and synthetic cortical button fixation. Among 167 patients (mean age 38.1 years, (standard deviation (. sd. ) 14.7) treated at least a four week interval after injury, 154 had post-operative radiographs available for analysis. . Results. Radiographic failure occurred in 33/154 cases (21.4%), with the lowest rate in Technique 4 (2/42 4.8%, p = 0.001). Half the failures occurred by six weeks, and the Kaplan-Meier survivorship at 24 months was 94.4% (95% confidence interval (CI) 79.6 to 98.6) for Technique 4 and 69.9% (95% CI 59.4 to 78.3) for the other techniques when combined. In multivariable survival analysis, Technique 4 had better survival than other techniques (Hazard Ratio 0.162, 95% CI 0.039 to 0.068, p = 0.013). Among 155 patients with a minimum of six months post-operative insurance coverage, re-operation occurred in 9.7% (15 patients). However, in multivariable logistic regression, Technique 4 did not reach a statistically significant lower risk for re-operation (odds ratio 0.254, 95% CI 0.05 to 1.3, p = 0.11). Conclusion. In this retrospective series, anatomical CC ligament reconstruction using combined synthetic cortical button and allograft loop fixation had the lowest rate of radiographic failure. . Take home message: Anatomical coracoclavicular ligament reconstruction using combined synthetic cortical button and allograft loop fixation had the lowest rate of radiographic failure. Cite this article: Bone Joint J 2016;98-B:512–18


Bone & Joint Research
Vol. 5, Issue 4 | Pages 137 - 144
1 Apr 2016
Paterson SI Eltawil NM Simpson AHRW Amin AK Hall AC

Objectives

During open orthopaedic surgery, joints may be exposed to air, potentially leading to cartilage drying and chondrocyte death, however, the long-term effects of joint drying in vivo are poorly understood. We used an animal model to investigate the subsequent effects of joint drying on cartilage and chondrocytes.

Methods

The patellar groove of anaesthetised rats was exposed (sham-operated), or exposed and then subjected to laminar airflow (0.25m/s; 60 minutes) before wounds were sutured and animals recovered. Animals were monitored for up to eight weeks and then sacrificed. Cartilage and chondrocyte properties were studied by histology and confocal microscopy, respectively.


The Bone & Joint Journal
Vol. 97-B, Issue 8 | Pages 1139 - 1143
1 Aug 2015
Hutt JRB Ortega-Briones A Daurka JS Bircher MD Rickman MS

The most widely used classification system for acetabular fractures was developed by Judet, Judet and Letournel over 50 years ago primarily to aid surgical planning. As population demographics and injury mechanisms have altered over time, the fracture patterns also appear to be changing. We conducted a retrospective review of the imaging of 100 patients with a mean age of 54.9 years (19 to 94) and a male to female ratio of 69:31 seen between 2010 and 2013 with acetabular fractures in order to determine whether the current spectrum of injury patterns can be reliably classified using the original system.

Three consultant pelvic and acetabular surgeons and one senior fellow analysed anonymous imaging. Inter-observer agreement for the classification of fractures that fitted into defined categories was substantial, (κ = 0.65, 95% confidence interval (CI) 0.51 to 0.76) with improvement to near perfect on inclusion of CT imaging (κ = 0.80, 95% CI 0.69 to 0.91). However, a high proportion of injuries (46%) were felt to be unclassifiable by more than one surgeon; there was moderate agreement on which these were (κ = 0.42 95% CI 0.31 to 0.54).

Further review of the unclassifiable fractures in this cohort of 100 patients showed that they tended to occur in an older population (mean age 59.1 years; 22 to 94 vs 47.2 years; 19 to 94; p = 0.003) and within this group, there was a recurring pattern of anterior column and quadrilateral plate involvement, with or without an incomplete posterior element injury.

Cite this article: Bone Joint J 2015;97-B:1139–43.


Bone & Joint 360
Vol. 4, Issue 4 | Pages 18 - 20
1 Aug 2015

The August 2015 Foot & Ankle Roundup360 looks at: Is orthosis more important than physio in tibialis posterior deficiency?; Radiographic evaluation of ankle injury; Sciatic catheter quite enough!; A fresh look at avascular necrosis of the talus; Total ankle and VTE; Outcomes of posterior malleolar fracture; Absorbable sutures in the Achilles tendon; Lisfranc injuries under the spotlight


Bone & Joint Research
Vol. 4, Issue 7 | Pages 105 - 116
1 Jul 2015
Shea CA Rolfe RA Murphy P

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities.

Cite this article: Bone Joint Res 2015;4:105–116


Bone & Joint Research
Vol. 4, Issue 5 | Pages 84 - 92
1 May 2015
Hamamura K Nishimura A Iino T Takigawa S Sudo A Yokota H

Objectives

Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA).

Methods

OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O.


Bone & Joint 360
Vol. 4, Issue 1 | Pages 22 - 24
1 Feb 2015

The February 2015 Shoulder & Elbow Roundup360 looks at: Proximal Humerus fractures a comprehensive review, Predicting complications in shoulder ORIF, The Coronoid Revisited, Remplissage and bankart repair for Hill-Sach’s lesions, Diabetes and elbow arthroplasty, Salvage surgery for failed bankart repair, Sternoclavicular Joint Reconstruction, Steroids effective in the short-term for tennis elbow


The Bone & Joint Journal
Vol. 96-B, Issue 11 | Pages 1535 - 1539
1 Nov 2014
Tonne BM Kempton LB Lack WD Karunakar MA

The purpose of this study was to describe the radiological characteristics of a previously unreported finding: posterior iliac offset at the sacroiliac joint and to assess its association with pelvic instability as measured by initial displacement and early implant loosening or failure. Radiographs from 42 consecutive patients with a mean age of 42 years (18 to 77; 38 men, four women) and mean follow-up of 38 months (3 to 96) with Anteroposterior Compression II injuries, were retrospectively reviewed. Standardised measurements were recorded for the extent of any diastasis of the pubic symphysis, widening of the sacroiliac joint, static vertical ramus offset and a novel measurement (posterior offset of the ilium at the sacroiliac joint identified on axial CT scan). Pelvic fractures with posterior iliac offset exhibited greater levels of initial displacement of the anterior pelvis (anterior sacroiliac widening, pubic symphysis diastasis and static vertical ramus offset, p < 0.001,0.034 and 0.028, respectively). Pelvic fractures with posterior ilium offset also demonstrated higher rates of implant loosening regardless of fixation method (p = 0.05). Posterior offset of the ilium was found to be a reliable and reproducible measurement with substantial inter-observer agreement (kappa = 0.70). Posterior offset of the ilium on axial CT scan is associated with greater levels of initial pelvic displacement and early implant loosening.

Cite this article: Bone Joint J 2014;96-B:1535–9.


The Bone & Joint Journal
Vol. 95-B, Issue 12 | Pages 1595 - 1602
1 Dec 2013
Modi CS Beazley J Zywiel MG Lawrence TM Veillette CJH

The aim of this review is to address controversies in the management of dislocations of the acromioclavicular joint. Current evidence suggests that operative rather than non-operative treatment of Rockwood grade III dislocations results in better cosmetic and radiological results, similar functional outcomes and longer time off work. Early surgery results in better functional and radiological outcomes with a reduced risk of infection and loss of reduction compared with delayed surgery.

Surgical options include acromioclavicular fixation, coracoclavicular fixation and coracoclavicular ligament reconstruction. Although non-controlled studies report promising results for arthroscopic coracoclavicular fixation, there are no comparative studies with open techniques to draw conclusions about the best surgical approach. Non-rigid coracoclavicular fixation with tendon graft or synthetic materials, or rigid acromioclavicular fixation with a hook plate, is preferable to fixation with coracoclavicular screws owing to significant risks of loosening and breakage.

The evidence, although limited, also suggests that anatomical ligament reconstruction with autograft or certain synthetic grafts may have better outcomes than non-anatomical transfer of the coracoacromial ligament. It has been suggested that this is due to better restoration horizontal and vertical stability of the joint.

Despite the large number of recently published studies, there remains a lack of high-quality evidence, making it difficult to draw firm conclusions regarding these controversial issues.

Cite this article: Bone Joint J 2013;95-B:1595–1602.


Bone & Joint 360
Vol. 2, Issue 6 | Pages 26 - 28
1 Dec 2013

The December 2013 Trauma Roundup360 looks at: Re-operation for intertrochanteric hip fractures; Are twin incisions better than one round the acetabulum?; Salvage osteotomy for calcaneal fractures; Posterior dislocation; Should MRSA be covered in open fractures?; Characterising the saline load test; Has it healed: hip fractures under the spotlight; and stem cells present in atrophic non-union.


The Bone & Joint Journal
Vol. 95-B, Issue 11_Supple_A | Pages 26 - 30
1 Nov 2013
Fayad TE Khan MA Haddad FS

Young adults with hip pain secondary to femoroacetabular impingement (FAI) are rapidly being recognised as an important cohort of orthopaedic patients. Interest in FAI has intensified over the last decade since its recognition as a precursor to arthritis of the hip and the number of publications related to the topic has increased exponentially in the last decade. Although not all patients with abnormal hip morphology develop osteoarthritis (OA), those with FAI-related joint damage rapidly develop premature OA. There are no explicit diagnostic criteria or definitive indications for surgical intervention in FAI. Surgery for symptomatic FAI appears to be most effective in younger individuals who have not yet developed irreversible OA. The difficulty in predicting prognosis in FAI means that avoiding unnecessary surgery in asymptomatic individuals, while undertaking intervention in those that are likely to develop premature OA poses a considerable dilemma. FAI treatment in the past has focused on open procedures that carry a potential risk of complications. Recent developments in hip arthroscopy have facilitated a minimally invasive approach to the management of FAI with few complications in expert hands. Acetabular labral preservation and repair appears to provide superior results when compared with debridement alone. Arthroscopic correction of structural abnormalities is increasingly becoming the standard treatment for FAI, however there is a paucity of high-level evidence comparing open and arthroscopic techniques in patients with similar FAI morphology and degree of associated articular cartilage damage. Further research is needed to develop an understanding of the natural course of FAI, the definitive indications for surgery and the long-term outcomes. Cite this article: Bone Joint J 2013;95-B, Supple A:26–30



Bone & Joint Research
Vol. 2, Issue 3 | Pages 51 - 57
1 Mar 2013
Sullivan MP Torres SJ Mehta S Ahn J

Neurogenic heterotopic ossification (NHO) is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury. Ectopic bone forms around joints in characteristic patterns, causing pain and limiting movement especially around the hip and elbow. Clinical sequelae of neurogenic heterotopic ossification include urinary tract infection, pressure injuries, pneumonia and poor hygiene, making early diagnosis and treatment clinically compelling. However, diagnosis remains difficult with more investigation needed. Our pathophysiological understanding stems from mechanisms of basic bone formation enhanced by evidence of systemic influences from circulating humor factors and perhaps neurological ones. This increasing understanding guides our implementation of current prophylaxis and treatment including the use of non-steroidal anti-inflammatory drugs, bisphosphonates, radiation therapy and surgery and, importantly, should direct future, more effective ones.


Bone & Joint Research
Vol. 1, Issue 11 | Pages 297 - 309
1 Nov 2012
McIlwraith CW Frisbie DD Kawcak CE

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 3 | Pages 290 - 296
1 Mar 2012
Jayakumar P Ramachandran M Youm T Achan P

Hip arthroscopy is particularly attractive in children as it confers advantages over arthrotomy or open surgery, such as shorter recovery time and earlier return to activity. Developments in surgical technique and arthroscopic instrumentation have enabled extension of arthroscopy of the hip to this age group. Potential challenges in paediatric and adolescent hip arthroscopy include variability in size, normal developmental change from childhood to adolescence, and conditions specific to children and adolescents and their various consequences. Treatable disorders include the sequelae of traumatic and sports-related hip joint injuries, Legg–Calve–Perthes’ disease and slipped capital femoral epiphysis, and the arthritic and septic hip. Intra-articular abnormalities are rarely isolated and are often associated with underlying morphological changes. This review presents the current concepts of hip arthroscopy in the paediatric and adolescent patient, covering clinical assessment and investigation, indications and results of the experience to date, as well as technical challenges and future directions


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 6 | Pages 853 - 853
1 Jun 2011
Horan F


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 443 - 448
1 Apr 2011
Malviya A Walker LC Avery P Osborne S Weir DJ Foster HE Deehan DJ

Juvenile idiopathic arthritis (JIA) is a chronic disease of childhood; it causes joint damage which may require surgical intervention, often in the young adult. The aim of this study was to describe the long-term outcome and survival of hip replacement in a group of adult patients with JIA and to determine predictors of survival for the prosthesis. In this retrospective comparative study patients were identified from the database of a regional specialist adult JIA clinic. This documented a series of 47 hip replacements performed in 25 adult patients with JIA. Surgery was performed at a mean age of 27 years (11 to 47), with a mean follow-up of 19 years (2 to 36). The mean Western Ontario and McMaster Universities osteoarthritis index questionnaire (WOMAC) score at the last follow-up was 53 (19 to 96) and the mean Health Assessment Questionnaire score was 2.25 (0 to 3). The mean pain component of the WOMAC score (60 (20 to 100)) was significantly higher than the mean functional component score (46 (0 to 97)) (p = 0.02). Kaplan-Meier survival analysis revealed a survival probability of 46.6% (95% confidence interval 37.5 to 55.7) at 19 years, with a trend towards enhanced survival with the use of a cemented acetabular component and a cementless femoral component. This was not, however, statistically significant (acetabular component, p = 0.76, femoral component, p = 0.45). Cox’s proportional hazards regression analysis showed an implant survival rate of 54.9% at 19 years at the mean of covariates. Survival of the prosthesis was significantly poorer (p = 0.001) in patients who had been taking long-term corticosteroids and significantly better (p = 0.02) in patients on methotrexate


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 10 | Pages 1460 - 1465
1 Oct 2010
Rauh PB Clancy WG Jasper LE Curl LA Belkoff S Moorman CT

We evaluated two reconstruction techniques for a simulated posterolateral corner injury on ten pairs of cadaver knees. Specimens were mounted at 30° and 90° of knee flexion to record external rotation and varus movement. Instability was created by transversely sectioning the lateral collateral ligament at its midpoint and the popliteus tendon was released at the lateral femoral condyle. The left knee was randomly assigned for reconstruction using either a combined or fibula-based treatment with the right knee receiving the other. After sectioning, laxity increased in all the specimens. Each technique restored external rotatory and varus stability at both flexion angles to levels similar to the intact condition. For the fibula-based reconstruction method, varus laxity at 30° of knee flexion did not differ from the intact state, but was significantly less than after the combined method.

Both the fibula-based and combined posterolateral reconstruction techniques are equally effective in restoring stability following the simulated injury.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 6 | Pages 842 - 852
1 Jun 2010
Tannast M Krüger A Mack PW Powell JN Hosalkar HS Siebenrock KA

Surgical dislocation of the hip in the treatment of acetabular fractures allows the femoral head to be safely displaced from the acetabulum. This permits full intra-articular acetabular and femoral inspection for the evaluation and potential treatment of cartilage lesions of the labrum and femoral head, reduction of the fracture under direct vision and avoidance of intra-articular penetration with hardware. We report 60 patients with selected types of acetabular fracture who were treated using this approach. Six were lost to follow-up and the remaining 54 were available for clinical and radiological review at a mean follow-up of 4.4 years (2 to 9).

Substantial damage to the intra-articular cartilage was found in the anteromedial portion of the femoral head and the posterosuperior aspect of the acetabulum. Labral lesions were predominantly seen in the posterior acetabular area. Anatomical reduction was achieved in 50 hips (93%) which was considerably higher than that seen in previous reports. There were no cases of avascular necrosis. Four patients subsequently required total hip replacement. Good or excellent results were achieved in 44 hips (81.5%). The cumulative eight-year survivorship was 89.0% (95% confidence interval 84.5 to 94.1). Significant predictors of poor outcome were involvement of the acetabular dome and lesions of the femoral cartilage greater than grade 2. The functional mid-term results were better than those of previous reports.

Surgical dislocation of the hip allows accurate reduction and a predictable mid-term outcome in the management of these difficult injuries without the risk of the development of avascular necrosis.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 9 | Pages 1127 - 1133
1 Sep 2009
Kang S Sanghera T Mangwani J Paterson JMH Ramachandran M

We performed a systematic review of the optimal management of septic arthritis in children as recommended in the current English literature using MEDLINE, EMBASE, CINAHL, the Cochrane Library and reference lists of retrieved articles without date restrictions up to 31 January 2009. From 2236 citations, 227 relevant full-text articles were screened in detail; 154 papers fulfilled the inclusion criteria, from which conclusions were drawn on the management of infected joints in children.

Our review showed that no single investigation, including joint aspiration, is sufficiently reliable to diagnose conclusively joint infection. The roles of aspiration, arthrotomy and arthroscopy in treatment are not clear cut, and the ideal duration of antibiotic therapy is not yet fully defined. These issues are discussed. Further large-scale, multi-centre studies are needed to delineate the optimal management of paediatric septic arthritis.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 533 - 535
1 Apr 2009
Hamilton LC Biant LC Temple LN Field RE

Idiopathic calcium pyrophosphate deposition disease (pseudogout) has a variable presentation. Many joints are usually affected; single joint disease is uncommon. We present a case report of primary monoarticular pseudogout affecting the hip. The diagnosis was made on the appearance and analysis of specimens obtained at arthroscopy. Monoarticular pseudogout is rare, but should be considered in the differential diagnosis of any presentation of joint pain.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 12 | Pages 1620 - 1626
1 Dec 2007
Toma CD Machacek P Bitzan P Assadian O Trieb K Wanivenhaus A

We retrospectively compared wrist arthrodesis using the Mannerfelt technique in 19 or an AO-plate in 23 patients with long-standing rheumatoid arthritis. The mean follow-up was for 76 months.

Compared with the Mannerfelt fusion group, patients in the AO-plate group reported greater satisfaction with their wrist function (74% vs 37%, p = 0.015). Complications were reported in six wrists in the AO-plate group and two wrists in the Mannerfelt fusion group (p = 0.258). At final follow-up, 95% of patients (41) reported either no pain or only mild pain. There was improvement in flexion of the finger joints in both groups but no significant improvement in the extension lag in either group.

Both methods relieve pain and improve function. Overall, the activities of daily living scores and the patients’ subjective assessment of outcome tended to be higher in the AO-plate group than in the Mannerfelt fusion group, although the difference was not statistically significant. Similarly, although more postoperative complications occurred in the AO-plate group, the difference between the two groups was not statistically significant.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 10 | Pages 1388 - 1395
1 Oct 2007
Hembree WC Ward BD Furman BD Zura RD Nichols LA Guilak F Olson SA

Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments. Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after joint injury and may provide further insight into the role of chondrocyte death in post-traumatic arthritis


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 651 - 658
1 May 2007
Day AC Kinmont C Bircher MD Kumar S

Crescent fracture dislocations are a well-recognised subset of pelvic ring injuries which result from a lateral compression force. They are characterised by disruption of the sacroiliac joint and extend proximally as a fracture of the posterior iliac wing. We describe a classification with three distinct types. Type I is characterised by a large crescent fragment and the dislocation comprises no more than one-third of the sacroiliac joint, which is typically inferior. Type II fractures are associated with an intermediate-size crescent fragment and the dislocation comprises between one- and two-thirds of the joint. Type III fractures are associated with a small crescent fragment where the dislocation comprises most, but not all of the joint. The principal goals of surgical intervention are the accurate and stable reduction of the sacroiliac joint. This classification proves useful in the selection of both the surgical approach and the reduction technique. A total of 16 patients were managed according to this classification and achieved good functional results approximately two years from the time of the index injury. Confounding factors compromise the summary short-form-36 and musculoskeletal functional assessment instrument scores, which is a well-recognised phenomenon when reporting the outcome of high-energy trauma.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 4 | Pages 510 - 515
1 Apr 2007
Watts AC Morris A Robinson CM

Fractures of the distal humeral articular surface which do not involve the medial and lateral columns are often more extensive than is apparent from plain radiographs. This retrospective study describes the epidemiology of this injury using modern classification systems and compares pre-operative radiography with operative findings. The study group included 79 patients with a mean age of 47 years (13 to 91). The annual incidence was 1.5 per 100 000 population, and was highest in women over the age of 60. The majority of the fractures (59; 75%) were sustained in falls from standing height. Young males tended to sustain more high-energy injuries with more complex fracture patterns. In 24% of cases (19) there was a concomitant radial head fracture. Classification from plain radiographs often underestimates the true extent of the injury and computed tomography may be of benefit in pre-operative planning, especially in those over 60 years of age.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 2 | Pages 155 - 159
1 Feb 2007
Saudan M Saudan P Perneger T Riand N Keller A Hoffmeyer P

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 5 | Pages 699 - 699
1 May 2006
Hawken RMA


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 6 | Pages 800 - 803
1 Jun 2005
Ramesh R Von Arx O Azzopardi T Schranz PJ

We assessed hyperextension of the knee and joint laxity in 169 consecutive patients who underwent an anterior cruciate ligament reconstruction between 2000 and 2002 and correlated this with a selected number of age- and gender-matched controls. In addition, the mechanism of injury in the majority of patients was documented. Joint laxity was present in 42.6% (72 of 169) of the patients and hyperextension of the knee in 78.7% (133 of 169). All patients with joint laxity had hyperextension of their knee. In the control group only 21.5% (14 of 65) had joint laxity and 37% (24 of 65) had hyperextension of the knee. Statistical analysis showed a significant correlation for these associations. We conclude that anterior cruciate ligament injury is more common in those with joint laxity and particularly so for those with hyperextension of the knee.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 2 | Pages 309 - 309
1 Mar 2002
Eckersley R


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 2 | Pages 333 - 338
1 Mar 1998
Böstman OM

Between 1985 and 1994, 1223 patients with malleolar fractures of the ankle were treated by open reduction and internal fixation with absorbable pins and screws, of whom 74 (6.1%) had an obvious inflammatory foreign-body reaction to the implants. Of these 74, ten later developed moderate to severe osteoarthritis of the ankle despite no evidence of incongruity of the articular surface. The implants used in these patients were made from polyglycolide, polylactide or glycolidelactide copolymer. The joint damage seemed to be due to polymeric debris entering the articular cavity through an osteolytic extension of an implant track. The ten patients had a long clinical course which included a vigorous local foreign-body reaction, synovial irritation and subsequent degeneration. At a follow-up of three to nine years, ankle arthrodesis had been necessary in two patients and is being considered for another two. The incidence of these changes in the whole series was 0.8%, which is not high, but awareness of this possible late complication is essential


The Journal of Bone & Joint Surgery British Volume
Vol. 69-B, Issue 5 | Pages 730 - 733
1 Nov 1987
Walsh H McLaren C Owen R

We have reviewed 41 children under 15 years of age with a fracture of the radius and disruption of the inferior radio-ulnar joint. Despite the fact that the joint injury had not at first been recognised in 41% of cases and a variety of treatments had been used, the final results of conservative management were generally good. The more distal the radial fracture, the greater were the problems encountered


The Journal of Bone & Joint Surgery British Volume
Vol. 53-B, Issue 3 | Pages 474 - 482
1 Aug 1971
Wiley JJ

1. Twenty cases of tarso-metatarsal joint injury have been studied with regard to the mechanism of injury, and experiments have been done on cadavers to confirm clinical impressions. 2. Injuries of the tarso-metatarsal joints occur by direct and indirect mechanisms, the latter being more common. 3. Indirect injuries occur in at least two ways-namely, acute abduction of the forefoot and plantar-flexion of the forefoot. 4. Most of the indirect injuries occur when the ankle joint is in a plantar-flexed position. 5. Whereas this foot injury once gained prominence on the field of battle amongst cavalrymen, it is currently associated with the motor car, the step ladder, the toboggan, the joy-rider, and commonly the simple misguided step


The Journal of Bone & Joint Surgery British Volume
Vol. 42-B, Issue 3 | Pages 522 - 529
1 Aug 1960
Coleman HM

1 . A specific mechanism of injury can produce a tear of the articular disc of the wrist without any associated bony lesion. 2. Torn discs have been found associated with Colles's fractures and with dislocation of the inferior radio-ulnar joint. 3. The injury gives rise to clear-cut symptoms and definite physical signs. 4. Operation in fourteen cases has shown five types of tear of the disc. 5. Arthrographs of the wrist are helpful in establishing the diagnosis. 6. In isolated tears removal ofthe disc relieves the symptoms and does not prejudice function. 7. If there is other joint injury, removal of the disc cannot be expected to give as satisfactory a result