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Bone & Joint 360
Vol. 4, Issue 2 | Pages 12 - 14
1 Apr 2015

The April 2015 Knee Roundup360 looks at: Genetic determinants of ACL strength; TKA outcomes influenced by prosthesis; Single- or two-stage revision for infected TKA?; Arthroscopic meniscectomy: a problem that just won’t go away!; Failure in arthroscopic ACL reconstruction; ACL reconstruction in the over 50s?; Knee arthroplasty for early osteoarthritis; All inside meniscal repair; Steroids, thrombogenic markers and TKA


Bone & Joint Research
Vol. 5, Issue 7 | Pages 301 - 306
1 Jul 2016
Madhuri V Santhanam M Rajagopal K Sugumar LK Balaji V

Objectives

To determine the pattern of mutations of the WISP3 gene in clinically identified progressive pseudorheumatoid dysplasia (PPD) in an Indian population.

Patients and Methods

A total of 15 patients with clinical features of PPD were enrolled in this study. Genomic DNA was isolated and polymerase chain reaction performed to amplify the WISP3 gene. Screening for mutations was done by conformation-sensitive gel electrophoresis, beginning with the fifth exon and subsequently proceeding to the remaining exons. Sanger sequencing was performed for both forward and reverse strands to confirm the mutations.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 560 - 568
1 Nov 2016
Peeters M Huang CL Vonk LA Lu ZF Bank RA Helder MN Doulabi BZ

Objectives

Studies which consider the molecular mechanisms of degeneration and regeneration of cartilaginous tissues are seriously hampered by problematic ribonucleic acid (RNA) isolations due to low cell density and the dense, proteoglycan-rich extracellular matrix of cartilage. Proteoglycans tend to co-purify with RNA, they can absorb the full spectrum of UV light and they are potent inhibitors of polymerase chain reaction (PCR). Therefore, the objective of the present study is to compare and optimise different homogenisation methods and RNA isolation kits for an array of cartilaginous tissues.

Materials and Methods

Tissue samples such as the nucleus pulposus (NP), annulus fibrosus (AF), articular cartilage (AC) and meniscus, were collected from goats and homogenised by either the MagNA Lyser or Freezer Mill. RNA of duplicate samples was subsequently isolated by either TRIzol (benchmark), or the RNeasy Lipid Tissue, RNeasy Fibrous Tissue, or Aurum Total RNA Fatty and Fibrous Tissue kits. RNA yield, purity, and integrity were determined and gene expression levels of type II collagen and aggrecan were measured by real-time PCR.


Bone & Joint Research
Vol. 3, Issue 9 | Pages 262 - 272
1 Sep 2014
Gumucio J Flood M Harning J Phan A Roche S Lynch E Bedi A Mendias C

Objectives

Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.

Methods

A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation.


Bone & Joint 360
Vol. 2, Issue 6 | Pages 2 - 8
1 Dec 2013
Jones R Wood D

This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.


Bone & Joint Research
Vol. 5, Issue 6 | Pages 218 - 224
1 Jun 2016
Cheng N Guo A Cui Y

Objectives

Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA.

Methods

Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 287 - 293
1 Jul 2016
Ismail H Phedy P Kholinne E Djaja YP Kusnadi Y Merlina M Yulisa ND

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.

Methods

Ten patients with an atrophic nonunion of a long bone fracture were selectively divided into two groups. Five subjects in the treatment group were treated with the combination of 15 million autologous BM-MSCs, 5g/cm3 (HA) granules and internal fixation. Control subjects were treated with iliac crest autograft, 5g/cm3 HA granules and internal fixation. The outcomes measured were post-operative pain (visual analogue scale), level of functionality (LEFS and DASH), and radiograph assessment.


The Bone & Joint Journal
Vol. 98-B, Issue 3 | Pages 298 - 300
1 Mar 2016
Fullilove S Gozzard C

The results of the DRAFFT (distal radius acute fracture fixation trial) study, which compared volar plating with Kirschner (K-) wire fixation for dorsally displaced fractures of the distal radius, were published in August 2014. The use of K-wires to treat these fractures is now increasing, with a concomitant decline in the use of volar locking plates.

We provide a critical appraisal of the DRAFFT study and question whether surgeons have been unduly influenced by its headline conclusions.

Cite this article: Bone Joint J 2016;98-B:298–300.


Bone & Joint 360
Vol. 5, Issue 1 | Pages 12 - 14
1 Feb 2016


Bone & Joint 360
Vol. 3, Issue 6 | Pages 2 - 7
1 Dec 2014
Lewis C Mauffrey C Lewis AC Whiting F

There are significant differences in the methods and styles of orthopaedic surgical training between continents, all with the aim to produce competent consultant surgeons, but the differences in training content and pathway are vast. We review and contrast the key differences between three continents.


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.


Bone & Joint Research
Vol. 3, Issue 7 | Pages 236 - 240
1 Jul 2014
Robubi A Berger C Schmid M Huber KR Engel A Krugluger W

Objectives

Effects of insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 2 (BMP2) on the expression of genes involved in the proliferation and differentiation of osteoblasts in culture were analysed. The best sequence of growth factor addition that induces expansion of cells before their differentiation was sought.

Methods

Primary human osteoblasts in in vitro culture were treated with IGF1, BMP2 or FGF2 (10 ng/ml) for 24 hours (IGF1) or 48 hours (BMP2 and FGF2). Experiments were performed during the exponential growth phase with approximately 1e7 cells per 75 cm2 flask. mRNA was reverse transcribed directly and analysed using RT-PCR Taqman assays. Expression levels of key genes involved in cell growth and differentiation (CDH11, TNFRSF11B, RUNX2, POSTN, ALP, WNT5A, LEF1, HSPA5, FOS, p21) were monitored using RT-PCR with gene-specific Taqman probes.


Bone & Joint Research
Vol. 5, Issue 1 | Pages 11 - 17
1 Jan 2016
Barlow JD Morrey ME Hartzler RU Arsoy D Riester S van Wijnen AJ Morrey BF Sanchez-Sotelo J Abdel MP

Aims

Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone.

Methods

A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis.


The Bone & Joint Journal
Vol. 96-B, Issue 8 | Pages 1133 - 1138
1 Aug 2014
van Vendeloo SN Brand PLP Verheyen CCPM

We aimed to determine quality of life and burnout among Dutch orthopaedic trainees following a modern orthopaedic curriculum, with strict compliance to a 48-hour working week. We also evaluated the effect of the clinical climate of learning on their emotional well-being.

We assessed burnout, quality of life and the clinical climate of learning in 105 orthopaedic trainees using the Maslach Burnout Inventory, linear analogue scale self-assessments, and Dutch Residency Educational Climate Test (D-RECT), respectively.

A total of 19 trainees (18%) had poor quality of life and 49 (47%) were dissatisfied with the balance between their personal and professional life. Some symptoms of burnout were found in 29 trainees (28%). Higher D-RECT scores (indicating a better climate of learning) were associated with a better quality of life (r = 0.31, p = 0.001), more work-life balance satisfaction (r = 0.31, p = 0.002), fewer symptoms of emotional exhaustion (r = -0.21, p = 0.028) and depersonalisation (r = -0,28, p = 0.04).

A reduced quality of life with evidence of burnout were still seen in a significant proportion of orthopaedic trainees despite following a modern curriculum with strict compliance to a 48-hour working week. It is vital that further work is undertaken to improve the quality of life and reduce burnout in this cohort.

Cite this article: Bone Joint J 2014;96-B:1133–8.


The Bone & Joint Journal
Vol. 97-B, Issue 10 | Pages 1423 - 1427
1 Oct 2015
Rand BCC Penn-Barwell JG Wenke JC

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery.

An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified.

Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62).

These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role.

Cite this article: Bone Joint J 2015;97-B:1423–7.


Bone & Joint 360
Vol. 2, Issue 1 | Pages 37 - 39
1 Feb 2013

The February 2013 Children’s orthopaedics Roundup360 looks at: the human genome; new RNA; cells, matrix and gene enhancement; the histology of x-rays; THR and VTE in the Danish population; potential therapeutic targets for GCT; optimising vancomycin elution from cement; and how much sleep is enough.


Bone & Joint Research
Vol. 5, Issue 1 | Pages 18 - 25
1 Jan 2016
Sims AL Parsons N Achten J Griffin XL Costa ML Reed MR

Background

Approximately half of all hip fractures are displaced intracapsular fractures. The standard treatment for these fractures is either hemiarthroplasty or total hip arthroplasty. The recent National Institute for Health and Care Excellence (NICE) guidance on hip fracture management recommends the use of ‘proven’ cemented stem arthroplasty with an Orthopaedic Device Evaluation Panel (ODEP) rating of at least 3B (97% survival at three years). The Thompsons prosthesis is currently lacking an ODEP rating despite over 50 years of clinical use, likely due to the paucity of implant survival data. Nationally, adherence to these guidelines is varied as there is debate as to which prosthesis optimises patient outcomes.

Design

This study design is a multi-centre, multi-surgeon, parallel, two arm, standard-of-care pragmatic randomised controlled trial. It will be embedded within the WHiTE Comprehensive Cohort Study (ISRCTN63982700). The main analysis is a two-way equivalence comparison between Hemi-Thompson and Hemi-Exeter polished taper with Unitrax head. Secondary outcomes will include radiological leg length discrepancy measured as per Bidwai and Willett, mortality, re-operation rate and indication for re-operation, length of index hospital stay and revision at four months. This study will be supplemented by the NHFD (National Hip Fracture Database) dataset.


Bone & Joint Research
Vol. 3, Issue 6 | Pages 193 - 202
1 Jun 2014
Hast MW Zuskov A Soslowsky LJ

Tendinopathy is a debilitating musculoskeletal condition which can cause significant pain and lead to complete rupture of the tendon, which often requires surgical repair. Due in part to the large spectrum of tendon pathologies, these disorders continue to be a clinical challenge. Animal models are often used in this field of research as they offer an attractive framework to examine the cascade of processes that occur throughout both tendon pathology and repair. This review discusses the structural, mechanical, and biological changes that occur throughout tendon pathology in animal models, as well as strategies for the improvement of tendon healing.

Cite this article: Bone Joint Res 2014;3:193–202.


The Bone & Joint Journal
Vol. 95-B, Issue 5 | Pages 583 - 597
1 May 2013
Kurien T Pearson RG Scammell BE

We reviewed 59 bone graft substitutes marketed by 17 companies currently available for implantation in the United Kingdom, with the aim of assessing the peer-reviewed literature to facilitate informed decision-making regarding their use in clinical practice. After critical analysis of the literature, only 22 products (37%) had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita), Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question the need for so many different products, especially with limited published clinical evidence for their efficacy, and conclude that there is a considerable need for further prospective randomised trials to facilitate informed decision-making with regard to the use of current and future bone graft substitutes in clinical practice.

Cite this article: Bone Joint J 2013;95-B:583–97.


The Bone & Joint Journal
Vol. 95-B, Issue 4 | Pages 568 - 573
1 Apr 2013
Pichler K Herbert V Schmidt B Fischerauer EE Leithner A Weinberg A

Matrix metalloproteinases (MMPs), responsible for extracellular matrix remodelling and angiogenesis, might play a major role in the response of the growth plate to detrimental loads that lead to overuse injuries in young athletes. In order to test this hypothesis, human growth plate chondrocytes were subjected to mechanical forces equal to either physiological loads, near detrimental or detrimental loads for two hours. In addition, these cells were exposed to physiological loads for up to 24 hours. Changes in the expression of MMPs -2, -3 and -13 were investigated.

We found that expression of MMPs in cultured human growth plate chondrocytes increases in a linear manner with increased duration and intensity of loading. We also showed for the first time that physiological loads have the same effect on growth plate chondrocytes over a long period of time as detrimental loads applied for a short period.

These findings confirm the involvement of MMPs in overuse injuries in children. We suggest that training programmes for immature athletes should be reconsidered in order to avoid detrimental stresses and over-expression of MMPs in the growth plate, and especially to avoid physiological loads becoming detrimental.

Cite this article: Bone Joint J 2013;95-B:568–73.