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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.


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 404 - 412
1 Mar 2018
Parker JD Lim KS Kieser DC Woodfield TBF Hooper GJ

Aims

The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage.

Materials and Methods

The cellular morphology, adhesion, metabolic activity, and viability of human chondrocytes when increasing the concentration (0 mg/ml to 40 mg/ml) and length of exposure to TXA (0 to 12 hours) were analyzed in a 2D model. This was then repeated, excluding cellular adhesion, in a 3D model and confirmed in viable samples of articular cartilage.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 263 - 273
1 Apr 2018
Ferreira E Porter RM

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation.

Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006.


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 296 - 302
1 Mar 2018
Sprowson† AP Jensen C Parsons N Partington P Emmerson K Carluke I Asaad S Pratt R Muller S Ahmed I Reed MR

Aims

Surgical site infection (SSI) is a common complication of surgery with an incidence of about 1% in the United Kingdom. Sutures can lead to the development of a SSI, as micro-organisms can colonize the suture as it is implanted. Triclosan-coated sutures, being antimicrobical, were developed to reduce the rate of SSI. Our aim was to assess whether triclosan-coated sutures cause a reduction in SSIs following arthroplasty of the hip and knee.

Patients and Methods

This two-arm, parallel, double-blinded study involved 2546 patients undergoing elective total hip (THA) and total knee arthroplasty (TKA) at three hospitals. A total of 1323 were quasi-randomized to a standard suture group, and 1223 being quasi-randomized to the triclosan-coated suture group. The primary endpoint was the rate of SSI at 30 days postoperatively.


Bone & Joint Research
Vol. 5, Issue 12 | Pages 610 - 618
1 Dec 2016
Abubakar AA Noordin MM Azmi TI Kaka U Loqman MY

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine.

Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2.


Aims

It is well established that there is a strong association between Perthes’ disease and worsening socioeconomic deprivation. It has been suggested that the primary determinant driving this association is exposure to tobacco smoke. This study aimed to examine this hypothesis.

Patients and Methods

A hospital case-control study (n = 149/146) examined the association between tobacco smoke exposure and Perthes’ disease, adjusting for area-level socioeconomic deprivation. Tobacco smoke exposure was assessed by parental questionnaire of smoking habits during pregnancy, and by quantitative assay of current exposure using the urinary cotinine-creatinine ratio, which is a widely used and validated measure of tobacco smoke exposure.


Bone & Joint Research
Vol. 7, Issue 3 | Pages 205 - 212
1 Mar 2018
Lin Y Hall AC Simpson AHRW

Objectives

The purpose of this study was to create a novel ex vivo organ culture model for evaluating the effects of static and dynamic load on cartilage.

Methods

The metatarsophalangeal joints of 12 fresh cadaveric bovine feet were skinned and dissected aseptically, and cultured for up to four weeks. Dynamic movement was applied using a custom-made machine on six joints, with the others cultured under static conditions. Chondrocyte viability and matrix glycosaminoglycan (GAG) content were evaluated by the cell viability probes, 5-chloromethylfluorescein diacetate (CMFDA) and propidium iodide (PI), and dimethylmethylene blue (DMMB) assay, respectively.


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 360
Vol. 6, Issue 3 | Pages 19 - 21
1 Jun 2017


Bone & Joint Research
Vol. 7, Issue 2 | Pages 131 - 138
1 Feb 2018
Bennett PM Stevenson T Sargeant ID Mountain A Penn-Barwell JG

Objectives

The surgical challenge with severe hindfoot injuries is one of technical feasibility, and whether the limb can be salvaged. There is an additional question of whether these injuries should be managed with limb salvage, or whether patients would achieve a greater quality of life with a transtibial amputation. This study aims to measure functional outcomes in military patients sustaining hindfoot fractures, and identify injury features associated with poor function.

Methods

Follow-up was attempted in all United Kingdom military casualties sustaining hindfoot fractures. All respondents underwent short-form (SF)-12 scoring; those retaining their limb also completed the American Academy of Orthopaedic Surgeons Foot and Ankle (AAOS F&A) outcomes questionnaire. A multivariate regression analysis identified injury features associated with poor functional recovery.


The Bone & Joint Journal
Vol. 100-B, Issue 2 | Pages 143 - 151
1 Feb 2018
Bovonratwet P Malpani R Ottesen TD Tyagi V Ondeck NT Rubin LE Grauer JN

Aims

The aim of this study was to compare the rate of perioperative complications following aseptic revision total hip arthroplasty (THA) in patients aged ≥ 80 years with that in those aged < 80 years, and to identify risk factors for the incidence of serious adverse events in those aged ≥ 80 years using a large validated national database.

Patients and Methods

Patients who underwent aseptic revision THA were identified in the 2005 to 2015 National Surgical Quality Improvement Program (NSQIP) database and stratified into two age groups: those aged < 80 years and those aged ≥ 80 years. Preoperative and procedural characteristics were compared. Multivariate regression analysis was used to compare the risk of postoperative complications and readmission. Risk factors for the development of a serious adverse event in those aged ≥ 80 years were characterized.


The Bone & Joint Journal
Vol. 100-B, Issue 1_Supple_A | Pages 55 - 61
1 Jan 2018
Kim K Elbuluk A Yu S Iorio R

Aims

The aim of this study was to determine the optimal regimen for the management of pain following total knee arthroplasty (TKA) by comparing the outcomes and cost-effectiveness of different protocols implemented at a large, urban, academic medical centre.

Patients and Methods

Between September 2013 and September 2015, we used a series of modifications to our standard regimen for the management of pain after TKA. In May 2014, there was a department-wide transition from protocols focused on femoral nerve blocks (FNB) to periarticular injections of liposomal bupivacaine. In February 2015, patient-controlled analgesia (PCA) was removed from the protocol while continuing liposomal bupivacaine injections. Quality measures and hospital costs were compared between the three protocols.


The Bone & Joint Journal
Vol. 99-B, Issue 12 | Pages 1677 - 1680
1 Dec 2017
Herron J Hutchinson R Lecky F Bouamra O Edwards A Woodford M Eardley WGP

Aims

To compare the early management and mortality of older patients sustaining major orthopaedic trauma with that of a younger population with similar injuries.

Patients and Methods

The Trauma Audit Research Network database was reviewed to identify eligible patients admitted between April 2012 and June 2015. Distribution and severity of injury, interventions, comorbidity, critical care episodes and mortality were recorded. The population was divided into young (64 years or younger) and older (65 years and older) patients.


Bone & Joint 360
Vol. 6, Issue 6 | Pages 28 - 31
1 Dec 2017


Bone & Joint Research
Vol. 7, Issue 1 | Pages 94 - 102
1 Jan 2018
Hopper N Singer E Henson F

Objectives

The exact aetiology and pathogenesis of microdamage-induced long bone fractures remain unknown. These fractures are likely to be the result of inadequate bone remodelling in response to damage. This study aims to identify an association of osteocyte apoptosis, the presence of osteocytic osteolysis, and any alterations in sclerostin expression with a fracture of the third metacarpal (Mc-III) bone of Thoroughbred racehorses.

Methods

A total of 30 Mc-III bones were obtained; ten bones were fractured during racing, ten were from the contralateral limb, and ten were from control horses. Each Mc-III bone was divided into a fracture site, condyle, condylar groove, and sagittal ridge. Microcracks and diffuse microdamage were quantified. Apoptotic osteocytes were measured using TUNEL staining. Cathepsin K, matrix metalloproteinase-13 (MMP-13), HtrA1, and sclerostin expression were analyzed.


Bone & Joint 360
Vol. 5, Issue 6 | Pages 8 - 12
1 Dec 2016
Kumar KHS Lawrence JE Khanduja V


The Bone & Joint Journal
Vol. 99-B, Issue 10 | Pages 1265 - 1266
1 Oct 2017
Jacofsky DJ Haddad FS


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 12 | Pages 640 - 648
1 Dec 2017
Xia B Li Y Zhou J Tian B Feng L

Objectives

Osteoporosis is a chronic disease. The aim of this study was to identify key genes in osteoporosis.

Methods

Microarray data sets GSE56815 and GSE56814, comprising 67 osteoporosis blood samples and 62 control blood samples, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in osteoporosis using Limma package (3.2.1) and Meta-MA packages. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify biological functions. Furthermore, the transcriptional regulatory network was established between the top 20 DEGs and transcriptional factors using the UCSC ENCODE Genome Browser. Receiver operating characteristic (ROC) analysis was applied to investigate the diagnostic value of several DEGs.


Bone & Joint Research
Vol. 6, Issue 12 | Pages 656 - 664
1 Dec 2017
Morita W Dakin SG Snelling SJB Carr AJ

Objectives

Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified.

Methods

We performed a systematic review of the literature using MEDLINE (U.S. National Library of Medicine, Bethesda, Maryland) in March 2017. Studies reporting the expression of interleukins (ILs), tumour necrosis factor alpha (TNF-α) and interferon gamma in diseased human tendon tissues, and animal models of tendon injury or exercise in comparison with healthy control tissues were included.