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Bone & Joint Research
Vol. 9, Issue 1 | Pages 1 - 14
1 Jan 2020
Stewart S Darwood A Masouros S Higgins C Ramasamy A

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion. Cite this article: Bone Joint Res 2019;9(1):1–14


Bone & Joint Research
Vol. 3, Issue 4 | Pages 123 - 129
1 Apr 2014
Perry DC Griffin XL Parsons N Costa ML

The surgical community is plagued with a reputation for both failing to engage and to deliver on clinical research. This is in part due to the absence of a strong research culture, however it is also due to a multitude of barriers encountered in clinical research; particularly those involving surgical interventions. ‘Trauma’ amplifies these barriers, owing to the unplanned nature of care, unpredictable work patterns, the emergent nature of treatment and complexities in the consent process. This review discusses the barriers to clinical research in surgery, with a particular emphasis on trauma. It considers how barriers may be overcome, with the aim to facilitate future successful clinical research. Cite this article: Bone Joint Res 2014;3:123–9


Bone & Joint Research
Vol. 8, Issue 8 | Pages 387 - 396
1 Aug 2019
Alt V Rupp M Lemberger K Bechert T Konradt T Steinrücke P Schnettler R Söder S Ascherl R

Objectives. Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. Methods. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3. Results. In total, 11 of the 12 patients completed the study. No argyria or considerable differences in laboratory parameters were detected. Silver blood concentrations were below or around the detection limit of 1 ppb in ten of the 11 patients. A maximum of 5.6 ppb at 48 hours after implantation of the silver spacer, which is below the recommended maximum level of 10 ppb, was found in one patient. No silver was detected in the urine. Drainage fluids showed concentrations between 16.1 ppb and 23.3 ppb at 12 hours after implantation of the silver spacers, and between 16.8 ppb to 25.1 ppb at 48 hours after implantation. Pathohistological assessment of the periprosthetic membrane did not reveal any differences between the two groups. Conclusion. Microsilver-loaded gentamicin-PMMA spacers showed good biocompatibility and the broad antimicrobial activity warrants further clinical research to assess its effectivity in reducing infection rates in prosthetic joint infection. Cite this article: V. Alt, M. Rupp, K. Lemberger, T. Bechert, T. Konradt, P. Steinrücke, R. Schnettler, S. Söder, R. Ascherl. Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study. Bone Joint Res 2019;8:387–396. DOI: 10.1302/2046-3758.88.BJR-2018-0270.R1


Bone & Joint Research
Vol. 12, Issue 4 | Pages 294 - 305
20 Apr 2023
Aquilina AL Claireaux H Aquilina CO Tutton E Fitzpatrick R Costa ML Griffin XL

Aims

Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture.

Methods

Candidate outcomes were identified from a previously published systematic review and a secondary thematic analysis of 25 patient interviews exploring the lived experience of recovery from open lower limb fracture. Outcomes were categorized and sequentially refined using healthcare professional and patient structured discussion groups. Consensus methods included a multi-stakeholder two-round online Delphi survey and a consensus meeting attended by a purposive sample of stakeholders, facilitated discussion, and voting using a nominal group technique.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 352 - 361
1 Jun 2023
Aquilina AL Claireaux H Aquilina CO Tutton E Fitzpatrick R Costa ML Griffin XL

Aims

A core outcome set for adult, open lower limb fracture has been established consisting of ‘Walking, gait and mobility’, ‘Being able to return to life roles’, ‘Pain or discomfort’, and ‘Quality of life’. This study aims to identify which outcome measurement instruments (OMIs) should be recommended to measure each core outcome.

Methods

A systematic review and quality assessment were conducted to identify existing instruments with evidence of good measurement properties in the open lower limb fracture population for each core outcome. Additionally, shortlisting criteria were developed to identify suitable instruments not validated in the target population. Candidate instruments were presented, discussed, and voted on at a consensus meeting of key stakeholders.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 294 - 305
17 Jun 2024
Yang P He W Yang W Jiang L Lin T Sun W Zhang Q Bai X Sun W Guo D

Aims

In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method.

Methods

We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis.


Cite this article: Bone Joint Res 2023;12(9):598–600.


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.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 467 - 475
2 Aug 2023
Wu H Sun D Wang S Jia C Shen J Wang X Hou C Xie Z Luo F

Aims

This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis.

Methods

We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 546 - 558
4 Oct 2024
Li Y Wuermanbieke S Wang F Mu W Ji B Guo X Zou C Chen Y Zhang X Cao L

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Methods

A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.


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.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 647 - 658
12 Nov 2024
Li K Zhang Q

Aims

The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.

Methods

A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively.


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

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Methods

A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Methods

Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 423 - 432
6 Jul 2023
Xie H Wang N He H Yang Z Wu J Yang T Wang Y

Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

Methods

PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 28 - 39
10 Jan 2024
Toya M Kushioka J Shen H Utsunomiya T Hirata H Tsubosaka M Gao Q Chow SK Zhang N Goodman SB

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Methods

We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).


Bone & Joint Research
Vol. 11, Issue 8 | Pages 585 - 593
1 Aug 2022
Graham SM Jalal MMK Lalloo DG Hamish R. W. Simpson A

Aims

A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

Methods

A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 239 - 250
20 Apr 2022
Stewart CC O’Hara NN Bzovsky S Bahney CS Sprague S Slobogean GP

Aims

Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

Methods

A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 189 - 199
13 Apr 2022
Yang Y Li Y Pan Q Bai S Wang H Pan X Ling K Li G

Aims

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model.

Methods

A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.


Bone & Joint Research
Vol. 10, Issue 9 | Pages 591 - 593
7 Sep 2021
Thompson JW Simpson AHRW Haddad FS


Bone & Joint Research
Vol. 10, Issue 9 | Pages 619 - 628
27 Sep 2021
Maestro-Paramio L García-Rey E Bensiamar F Saldaña L

Aims

To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities.

Methods

We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 36 - 45
1 Jan 2018
Kleinlugtenbelt YV Krol RG Bhandari M Goslings JC Poolman RW Scholtes VAB

Objectives. The patient-rated wrist evaluation (PRWE) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire are patient-reported outcome measures (PROMs) used for clinical and research purposes. Methodological high-quality clinimetric studies that determine the measurement properties of these PROMs when used in patients with a distal radial fracture are lacking. This study aimed to validate the PRWE and DASH in Dutch patients with a displaced distal radial fracture (DRF). Methods. The intraclass correlation coefficient (ICC) was used for test-retest reliability, between PROMs completed twice with a two-week interval at six to eight months after DRF. Internal consistency was determined using Cronbach’s α for the dimensions found in the factor analysis. The measurement error was expressed by the smallest detectable change (SDC). A semi-structured interview was conducted between eight and 12 weeks after DRF to assess the content validity. Results. A total of 119 patients (mean age 58 years (. sd. 15)), 74% female, completed PROMs at a mean time of six months (. sd. 1) post-fracture. One overall meaningful dimension was found for the PRWE and the DASH. Internal consistency was excellent for both PROMs (Cronbach’s α 0.96 (PRWE) and 0.97 (DASH)). Test-retest reliability was good for the PRWE (ICC 0.87) and excellent for the DASH (ICC 0.91). The SDC was 20 for the PRWE and 14 for the DASH. No floor or ceiling effects were found. The content validity was good for both questionnaires. Conclusion. The PRWE and DASH are valid and reliable PROMs in assessing function and disability in Dutch patients with a displaced DRF. However, due to the high SDC, the PRWE and DASH are less useful for individual patients with a distal radial fracture in clinical practice. Cite this article: Y. V. Kleinlugtenbelt, R. G. Krol, M. Bhandari, J. C. Goslings, R. W. Poolman, V. A. B. Scholtes. Are the patient-rated wrist evaluation (PRWE) and the disabilities of the arm, shoulder and hand (DASH) questionnaire used in distal radial fractures truly valid and reliable? Bone Joint Res 2018;7:36–45. DOI: 10.1302/2046-3758.71.BJR-2017-0081.R1


Bone & Joint Research
Vol. 10, Issue 1 | Pages 10 - 21
1 Jan 2021
Zong Z Zhang X Yang Z Yuan W Huang J Lin W Chen T Yu J Chen J Cui L Li G Wei B Lin S

Aims

Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model.

Methods

Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone.


Bone & Joint Research
Vol. 9, Issue 12 | Pages 873 - 883
8 Dec 2020
Clement ND Ng N Simpson CJ Patton RFL Hall AJ Simpson AHRW Duckworth AD

Aims

The aims of this meta-analysis were to assess: 1) the prevalence of coronavirus disease 2019 (COVID-19) in hip fracture patients; 2) the associated mortality rate and risk associated with COVID-19; 3) the patient demographics associated with COVID-19; 4) time of diagnosis; and 5) length of follow-up after diagnosis of COVID-19.

Methods

Searches of PubMed, Medline, and Google Scholar were performed in October 2020 in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Search terms included “hip”, “fracture”, and “COVID-19”. The criteria for inclusion were published clinical articles reporting the mortality rate associated with COVID-19 in hip fracture patients. In total, 53 articles were identified and following full text screening 28 articles satisfied the inclusion criteria.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 635 - 644
1 Oct 2020
Lemaignen A Grammatico-Guillon L Astagneau P Marmor S Ferry T Jolivet-Gougeon A Senneville E Bernard L

Aims

The French registry for complex bone and joint infections (C-BJIs) was created in 2012 in order to facilitate a homogeneous management of patients presented for multidisciplinary advice in referral centres for C-BJI, to monitor their activity and to produce epidemiological data. We aimed here to present the genesis and characteristics of this national registry and provide the analysis of its data quality.

Methods

A centralized online secured database gathering the electronic case report forms (eCRFs) was filled for every patient presented in multidisciplinary meetings (MM) among the 24 French referral centres. Metrics of this registry were described between 2012 and 2016. Data quality was assessed by comparing essential items from the registry with a controlled dataset extracted from medical charts of a random sample of patients from each centre. Internal completeness and consistency were calculated.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 543 - 553
1 Sep 2020
Bakirci E Tschan K May RD Ahmad SS Kleer B Gantenbein B

Aims

The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL.

Methods

The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF).


Bone & Joint Research
Vol. 9, Issue 8 | Pages 531 - 533
1 Aug 2020
Magan AA Plastow R Haddad FS


Bone & Joint Research
Vol. 9, Issue 7 | Pages 351 - 359
1 Jul 2020
Fitzgerald J

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 414 - 421
1 Jun 2018
Yu CD Miao WH Zhang YY Zou MJ Yan XF

Objectives

The aim of this study was to investigate the role of miR-126 in the development of osteoarthritis, as well as the potential molecular mechanisms involved, in order to provide a theoretical basis for osteoarthritis treatment and a novel perspective for clinical therapy.

Methods

Human chondrocyte cell line CHON-001 was administrated by different doses of interleukin (IL)-1β to simulate inflammation. Cell viability, migration, apoptosis, IL-6, IL-8, and tumour necrosis factor (TNF)-α expression, as well as expression of apoptosis-related factors, were measured to assess inflammation. miR-126 expression was measured by quantitative polymerase chain reaction (qPCR). Cells were then transfected with miR-126 inhibitor to assess the effect of miR-126 on IL-1β-injured CHON-001 cells. Expression of B-cell lymphoma 2 (Bcl-2) and the activity of mitogen-activated protein kinase (MAPK) / Jun N-terminal kinase (JNK) signaling pathway were measured by Western blot to explore the underlying mechanism through which miR-126 affects IL-1β-induced inflammation.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 58 - 68
1 Jan 2018
Portal-Núñez S Ardura JA Lozano D Martínez de Toda I De la Fuente M Herrero-Beaumont G Largo R Esbrit P

Objectives

Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain.

Methods

We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 307 - 314
1 May 2017
Rendon JS Swinton M Bernthal N Boffano M Damron T Evaniew N Ferguson P Galli Serra M Hettwer W McKay P Miller B Nystrom L Parizzia W Schneider P Spiguel A Vélez R Weiss K Zumárraga JP Ghert M

Objectives

As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration.

Methods

All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 544 - 551
1 Nov 2016
Kim Y Bok DH Chang H Kim SW Park MS Oh JK Kim J Kim T

Objectives

Although vertebroplasty is very effective for relieving acute pain from an osteoporotic vertebral compression fracture, not all patients who undergo vertebroplasty receive the same degree of benefit from the procedure. In order to identify the ideal candidate for vertebroplasty, pre-operative prognostic demographic or clinico-radiological factors need to be identified. The objective of this study was to identify the pre-operative prognostic factors related to the effect of vertebroplasty on acute pain control using a cohort of surgically and non-surgically managed patients.

Patients and Methods

Patients with single-level acute osteoporotic vertebral compression fracture at thoracolumbar junction (T10 to L2) were followed. If the patients were not satisfied with acute pain reduction after a three-week conservative treatment, vertebroplasty was recommended. Pain assessment was carried out at the time of diagnosis, as well as three, four, six, and 12 weeks after the diagnosis. The effect of vertebroplasty, compared with conservative treatment, on back pain (visual analogue score, VAS) was analysed with the use of analysis-of-covariance models that adjusted for pre-operative VAS scores.


Bone & Joint Research
Vol. 6, Issue 2 | Pages 73 - 81
1 Feb 2017
Ishihara K Okazaki K Akiyama T Akasaki Y Nakashima Y

Objectives

Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts.

Methods

Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation. Conditioned media were prepared using osteophytes and cancellous bone, and growth factor concentration and effects of each graft on proliferation, differentiation and migration of osteoblastic cells were assessed using enzyme-linked immunosorbent assays, MTS ((3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) assays, quantitative real-time polymerase chain reaction, and migration assays.


Bone & Joint Research
Vol. 5, Issue 4 | Pages 130 - 136
1 Apr 2016
Thornley P de SA D Evaniew N Farrokhyar F Bhandari M Ghert M

Objectives

Evidence -based medicine (EBM) is designed to inform clinical decision-making within all medical specialties, including orthopaedic surgery. We recently published a pilot survey of the Canadian Orthopaedic Association (COA) membership and demonstrated that the adoption of EBM principles is variable among Canadian orthopaedic surgeons. The objective of this study was to conduct a broader international survey of orthopaedic surgeons to identify characteristics of research studies perceived as being most influential in informing clinical decision-making.

Materials and Methods

A 29-question electronic survey was distributed to the readership of an established orthopaedic journal with international readership. The survey aimed to analyse the influence of both extrinsic (journal quality, investigator profiles, etc.) and intrinsic characteristics (study design, sample size, etc.) of research studies in relation to their influence on practice patterns.


Objectives

The annual incidence of hip fracture is 620 000 in the European Union. The cost of this clinical problem has been estimated at 1.75 million disability-adjusted life years lost, equating to 1.4% of the total healthcare burden in established market economies. Recent guidance from The National Institute for Health and Clinical Excellence (NICE) states that research into the clinical and cost effectiveness of total hip arthroplasty (THA) as a treatment for hip fracture is a priority. We asked the question: can a trial investigating THA for hip fracture currently be delivered in the NHS?

Methods

We performed a contemporaneous process evaluation that provides a context for the interpretation of the findings of WHiTE Two – a randomised study of THA for hip fracture. We developed a mixed methods approach to situate the trial centre within the context of wider United Kingdom clinical practice. We focused on fidelity, implementation, acceptability and feasibility of both the trial processes and interventions to stakeholder groups, such as healthcare providers and patients.


Bone & Joint Research
Vol. 5, Issue 8 | Pages 347 - 352
1 Aug 2016
Nuttall J Evaniew N Thornley P Griffin A Deheshi B O’Shea T Wunder J Ferguson P Randall RL Turcotte R Schneider P McKay P Bhandari M Ghert M

Objectives

The diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial.

Materials and Methods

The Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 586 - 593
1 Nov 2016
Rakhra KS Bonura AA Nairn R Schweitzer ME Kolanko NM Beaule PE

Objectives

The purpose of this study was to compare the thickness of the hip capsule in patients with surgical hip disease, either with cam-femoroacetabular impingement (FAI) or non-FAI hip pathology, with that of asymptomatic control hips.

Methods

A total of 56 hips in 55 patients underwent a 3Tesla MRI of the hip. These included 40 patients with 41 hips with arthroscopically proven hip disease (16 with cam-FAI; nine men, seven women; mean age 39 years, 22 to 58) and 25 with non-FAI chondrolabral pathology (four men, 21 women; mean age 40 years, 18 to 63) as well as 15 asymptomatic volunteers, whose hips served as controls (ten men, five women; mean age 62 years, 33 to 77). The maximal capsule thickness was measured anteriorly and superiorly, and compared within and between the three groups with a gender subanalysis using student’s t-test. The correlation between alpha angle and capsule thickness was determined using Pearson’s correlation coefficient.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 512 - 519
1 Oct 2016
Mills L Tsang J Hopper G Keenan G Simpson AHRW

Objectives

A successful outcome following treatment of nonunion requires the correct identification of all of the underlying cause(s) and addressing them appropriately. The aim of this study was to assess the distribution and frequency of causative factors in a consecutive cohort of nonunion patients in order to optimise the management strategy for individual patients presenting with nonunion.

Methods

Causes of the nonunion were divided into four categories: mechanical; infection; dead bone with a gap; and host. Prospective and retrospective data of 100 consecutive patients who had undergone surgery for long bone fracture nonunion were analysed.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 253 - 262
1 Jun 2016
Liu H Li W Liu YS Zhou YS

Objectives

This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats.

Methods

The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 198 - 205
1 May 2016
Wang WJ Liu F Zhu Y Sun M Qiu Y Weng WJ

Objectives

Normal sagittal spine-pelvis-lower extremity alignment is crucial in humans for maintaining an ergonomic upright standing posture, and pathogenesis in any segment leads to poor balance. The present study aimed to investigate how this sagittal alignment can be affected by severe knee osteoarthritis (KOA), and whether associated changes corresponded with symptoms of lower back pain (LBP) in this patient population.

Methods

Lateral radiograph films in an upright standing position were obtained from 59 patients with severe KOA and 58 asymptomatic controls free from KOA. Sagittal alignment of the spine, pelvis, hip and proximal femur was quantified by measuring several radiographic parameters. Global balance was accessed according to the relative position of the C7 plumb line to the sacrum and femoral heads. The presence of chronic LBP was documented. Comparisons between the two groups were carried by independent samples t-tests or chi-squared test.


Bone & Joint Research
Vol. 5, Issue 4 | Pages 116 - 121
1 Apr 2016
Leow JM Clement ND Tawonsawatruk T Simpson CJ Simpson AHRW

Objectives

The radiographic union score for tibial (RUST) fractures was developed by Whelan et al to assess the healing of tibial fractures following intramedullary nailing. In the current study, the repeatability and reliability of the RUST score was evaluated in an independent centre (a) using the original description, (b) after further interpretation of the description of the score, and (c) with the immediate post-operative radiograph available for comparison.

Methods

A total of 15 radiographs of tibial shaft fractures treated by intramedullary nailing (IM) were scored by three observers using the RUST system. Following discussion on how the criteria of the RUST system should be implemented, 45 sets (i.e. AP and lateral) of radiographs of IM nailed tibial fractures were scored by five observers. Finally, these 45 sets of radiographs were rescored with the baseline post-operative radiograph available for comparison.


Bone & Joint Research
Vol. 4, Issue 8 | Pages 134 - 136
1 Aug 2015
Ghert M


Bone & Joint Research
Vol. 5, Issue 3 | Pages 73 - 79
1 Mar 2016
Anwander H Cron GO Rakhra K Beaule PE

Objectives

Hips with metal-on-metal total hip arthroplasty (MoM THA) have a high rate of adverse local tissue reactions (ALTR), often associated with hypersensitivity reactions. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) measures tissue perfusion with the parameter Ktrans (volume transfer constant of contrast agent). Our purpose was 1) to evaluate the feasibility of DCE-MRI in patients with THA and 2) to compare DCE-MRI in patients with MoM bearings with metal-on-polyethylene (MoP) bearings, hypothesising that the perfusion index Ktrans in hips with MoM THA is higher than in hips with MoP THA.

Methods

In this pilot study, 16 patients with primary THA were recruited (eight MoM, eight MoP). DCE-MRI of the hip was performed at 1.5 Tesla (T). For each patient, Ktrans was computed voxel-by-voxel in all tissue lateral to the bladder. The mean Ktrans for all voxels was then calculated. These values were compared with respect to implant type and gender, and further correlated with clinical parameters.


Bone & Joint Research
Vol. 4, Issue 6 | Pages 93 - 98
1 Jun 2015
Smith NA Achten J Parsons N Wright D Parkinson B Thompson P Hutchinson CE Spalding T Costa ML

Objectives

Subtotal or total meniscectomy in the medial or lateral compartment of the knee results in a high risk of future osteoarthritis. Meniscal allograft transplantation has been performed for over thirty years with the scientifically plausible hypothesis that it functions in a similar way to a native meniscus. It is thought that a meniscal allograft transplant has a chondroprotective effect, reducing symptoms and the long-term risk of osteoarthritis. However, this hypothesis has never been tested in a high-quality study on human participants. This study aims to address this shortfall by performing a pilot randomised controlled trial within the context of a comprehensive cohort study design.

Methods

Patients will be randomised to receive either meniscal transplant or a non-operative, personalised knee therapy program. MRIs will be performed every four months for one year. The primary endpoint is the mean change in cartilage volume in the weight-bearing area of the knee at one year post intervention. Secondary outcome measures include the mean change in cartilage thickness, T2 maps, patient-reported outcome measures, health economics assessment and complications.


Bone & Joint Research
Vol. 3, Issue 5 | Pages 161 - 168
1 May 2014
Mundi R Chaudhry H Mundi S Godin K Bhandari M

High-quality randomised controlled trials (RCTs) evaluating surgical therapies are fundamental to the delivery of evidence-based orthopaedics. Orthopaedic clinical trials have unique challenges; however, when these challenges are overcome, evidence from trials can be definitive in its impact on surgical practice. In this review, we highlight several issues that pose potential challenges to orthopaedic investigators aiming to perform surgical randomised controlled trials. We begin with a discussion on trial design issues, including the ethics of sham surgery, the importance of sample size, the need for patient-important outcomes, and overcoming expertise bias. We then explore features surrounding the execution of surgical randomised trials, including ethics review boards, the importance of organisational frameworks, and obtaining adequate funding.

Cite this article: Bone Joint Res 2014;3:161–8.


Bone & Joint Research
Vol. 3, Issue 5 | Pages 169 - 174
1 May 2014
Rangan A Jefferson L Baker P Cook L

The aim of this study was to review the role of clinical trial networks in orthopaedic surgery. A total of two electronic databases (MEDLINE and EMBASE) were searched from inception to September 2013 with no language restrictions. Articles related to randomised controlled trials (RCTs), research networks and orthopaedic research, were identified and reviewed. The usefulness of trainee-led research collaborations is reported and our knowledge of current clinical trial infrastructure further supplements the review. Searching yielded 818 titles and abstracts, of which 12 were suitable for this review. Results are summarised and presented narratively under the following headings: 1) identifying clinically relevant research questions; 2) education and training; 3) conduct of multicentre RCTs and 4) dissemination and adoption of trial results. This review confirms growing international awareness of the important role research networks play in supporting trials in orthopaedic surgery. Multidisciplinary collaboration and adequate investment in trial infrastructure are crucial for successful delivery of RCTs.

Cite this article: Bone Joint Res 2014;3:169–74.


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. 3, Issue 3 | Pages 48 - 50
1 Mar 2014
Lidgren L Gomez-Barrena E N. Duda G Puhl W Carr A


Bone & Joint Research
Vol. 4, Issue 2 | Pages 17 - 22
1 Feb 2015
Vo A Beaule PE Sampaio ML Rotaru C Rakhra KS

Objectives

The purpose of this study was to investigate whether the femoral head–neck contour, characterised by the alpha angle, varies with the stage of physeal maturation using MRI evaluation of an asymptomatic paediatric population.

Methods

Paediatric volunteers with asymptomatic hips were recruited to undergo MRI of both hips. Femoral head physes were graded from 1 (completely open) to 6 (completely fused). The femoral head–neck contour was evaluated using the alpha angle, measured at the 3:00 (anterior) and 1:30 (anterosuperior) positions and correlated with physeal grade, with gender sub-analysis performed.


Bone & Joint Research
Vol. 2, Issue 1 | Pages 9 - 17
1 Jan 2013
Xia Y

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T1, T2 and T) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative.