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Bone & Joint Research
Vol. 10, Issue 5 | Pages 328 - 339
31 May 2021
Jia X Huang G Wang S Long M Tang X Feng D Zhou Q

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Methods

In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.


Bone & Joint 360
Vol. 10, Issue 5 | Pages 24 - 28
1 Oct 2021


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1571 - 1577
1 Oct 2021
Schelde AB Petersen J Jensen TB Gromov K Overgaard S Olesen JB Jimenez-Solem E

Aims

The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA).

Methods

Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis.


Bone & Joint 360
Vol. 10, Issue 4 | Pages 27 - 30
1 Aug 2021


Bone & Joint Research
Vol. 5, Issue 12 | Pages 594 - 601
1 Dec 2016
Li JJ Wang BQ Fei Q Yang Y Li D

Objectives. In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 231 - 236
1 Feb 2012
Clement ND Aitken S Duckworth AD McQueen MM Court-Brown CM

We present the prevalence of multiple fractures in the elderly in a single catchment population of 780 000 treated over a 12-month period and describe the mechanisms of injury, common patterns of occurrence, management, and the associated mortality rate. A total of 2335 patients, aged ≥ 65 years of age, were prospectively assessed and of these 119 patients (5.1%) presented with multiple fractures. Distal radial (odds ratio (OR) 5.1, p <  0.0001), proximal humeral (OR 2.2, p < 0.0001) and pelvic (OR 4.9, p < 0.0001) fractures were associated with an increased risk of sustaining associated fractures. Only 4.5% of patients sustained multiple fractures after a simple fall, but due to the frequency of falls in the elderly this mechanism resulted in 80.7% of all multiple fractures. Most patients required admission (> 80%), of whom 42% did not need an operation but more than half needed an increased level of care before discharge (54%). The standardised mortality rate at one year was significantly greater after sustaining multiple fractures that included fractures of the pelvis, proximal humerus or proximal femur (p < 0.001). This mortality risk increased further if patients were < 80 years of age, indicating that the existence of multiple fractures after low-energy trauma is a marker of mortality


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1373 - 1379
1 Aug 2021
Matar HE Bloch BV Snape SE James PJ

Aims

Single-stage revision total knee arthroplasty (rTKA) is gaining popularity in treating chronic periprosthetic joint infections (PJIs). We have introduced this approach to our clinical practice and sought to evaluate rates of reinfection and re-revision, along with predictors of failure of both single- and two-stage rTKA for chronic PJI.

Methods

A retrospective comparative cohort study of all rTKAs for chronic PJI between 1 April 2003 and 31 December 2018 was undertaken using prospective databases. Patients with acute infections were excluded; rTKAs were classified as single-stage, stage 1, or stage 2 of two-stage revision. The primary outcome measure was failure to eradicate or recurrent infection. Variables evaluated for failure by regression analysis included age, BMI, American Society of Anesthesiologists grade, infecting organisms, and the presence of a sinus. Patient survivorship was also compared between the groups.


Bone & Joint Open
Vol. 2, Issue 10 | Pages 785 - 795
1 Oct 2021
Matar HE Porter PJ Porter ML

Aims

Metal allergy in knee arthroplasty patients is a controversial topic. We aimed to conduct a scoping review to clarify the management of metal allergy in primary and revision total knee arthroplasty (TKA).

Methods

Studies were identified by searching electronic databases: Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Embase, from their inception to November 2020, for studies evaluating TKA patients with metal hypersensitivity/allergy. All studies reporting on diagnosing or managing metal hypersensitivity in TKA were included. Data were extracted and summarized based on study design, study population, interventions and outcomes. A practical guide is then formulated based on the available evidence.


Bone & Joint Research
Vol. 10, Issue 10 | Pages 677 - 689
1 Oct 2021
Tamaddon M Blunn G Xu W Alemán Domínguez ME Monzón M Donaldson J Skinner J Arnett TR Wang L Liu C

Aims

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Methods

The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 523 - 530
1 Oct 2016
Yuan Y Zhang GQ Chai W Ni M Xu C Chen JY

Objectives. Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Materials and Methods. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1. Results. MiR-138-5p was significantly increased in OA cartilage and in chondrocytes in response to IL-1β-stimulation. Overexpression of miR-138-5p significantly increased the IL-1β-induced downregulation of COL2A1, ACAN, and GAGs, and increased the IL-1β-induced over expression of MMP-13.We found that FOXC1 is directly regulated by miR-138-5p. Additionally, co-transfection with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 resulted in higher levels of COL2A1, ACAN, and GAGs, but lower levels of MMP-13. Conclusion. miR-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes, possibly by targeting FOXC1. Cite this article: Y. Yuan, G. Q. Zhang, W. Chai,M. Ni, C. Xu, J. Y. Chen. Silencing of microRNA-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation. Bone Joint Res 2016;5:523–530. DOI: 10.1302/2046-3758.510.BJR-2016-0074.R2


Bone & Joint Research
Vol. 10, Issue 9 | Pages 571 - 573
2 Sep 2021
Beverly MC Murray DW


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 2 | Pages 166 - 171
1 Feb 2008
Lundblad H Kreicbergs A Jansson K

We suggest that different mechanisms underlie joint pain at rest and on movement in osteoarthritis and that separate assessment of these two features with a visual analogue scale (VAS) offers better information about the likely effect of a total knee replacement (TKR) on pain. The risk of persistent pain after TKR may relate to the degree of central sensitisation before surgery, which might be assessed by determining the pain threshold to an electrical stimulus created by a special tool, the Pain Matcher. Assessments were performed in 69 patients scheduled for TKR. At 18 months after operation, separate assessment of pain at rest and with movement was again carried out using a VAS in order to enable comparison of pre- and post-operative measurements. A less favourable outcome in terms of pain relief was observed for patients with a high pre-operative VAS score for pain at rest and a low pain threshold, both features which may reflect a central sensitisation mechanism


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1405 - 1413
1 Aug 2021
Ogura K Fujiwara T Morris CD Boland PJ Healey JH

Aims

Rotating-hinge knee prostheses are commonly used to reconstruct the distal femur after resection of a tumour, despite the projected long-term burden of reoperation due to complications. Few studies have examined the factors that influence their failure and none, to our knowledge, have used competing risk models to do so. The purpose of this study was to determine the risk factors for failure of a rotating-hinge knee distal femoral arthroplasty using the Fine-Gray competing risk model.

Methods

We retrospectively reviewed 209 consecutive patients who, between 1991 and 2016, had undergone resection of the distal femur for tumour and reconstruction using a rotating-hinge knee prosthesis. The study endpoint was failure of the prosthesis, defined as removal of the femoral component, the tibial component, or the bone-implant fixation; major revision (exchange of the femoral component, tibial component, or the bone-implant fixation); or amputation.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 1012 - 1018
1 Jul 2005
Beck M Kalhor M Leunig M Ganz R

Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification. Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1361 - 1363
1 Oct 2005
Hardy JRW Chimutengwende-Gordon M Bakar I

We reviewed the records of 107 consecutive patients who had undergone surgery for disruption of the knee extensor mechanism to test whether an association existed between rupture of the quadriceps tendon and the presence of a patellar spur. The available standard pre-operative lateral radiographs were examined to see if a patellar spur was an indicator for rupture of the quadriceps tendon in this group of patients. Of the 107 patients, 12 underwent repair of a ruptured patellar tendon, 59 had an open reduction and internal fixation of a patellar fracture and 36 repair of a ruptured quadriceps tendon. In the 88 available lateral radiographs, patellar spurs were present significantly more commonly (p < 0.0005) in patients operated on for rupture of the quadriceps tendon (79%) than in patients with rupture of the patellar tendon (27%) or fracture of the patella (15%). In patients presenting with failure of the extensor mechanism of the knee in the presence of a patellar spur, rupture of the quadriceps tendon should be considered as a possible diagnosis


The Bone & Joint Journal
Vol. 103-B, Issue 6 Supple A | Pages 94 - 101
1 Jun 2021
Roy ME Whiteside LA Ly KK Gauvain MJ

Aims

The aims of this study were to evaluate wear on the surface of cobalt-chromium (CoCr) femoral components used in total knee arthroplasty (TKA) and compare the wear of these components with that of ceramic femoral components.

Methods

Optical profilometry was used to evaluate surface roughness and to examine the features created by the wear process in a knee wear simulator. We developed a method of measuring surface changes on five CoCr femoral components and quantifying the loss of material from the articular surface during the wear process. We also examined the articular surface of three ceramic femoral components from a previous test for evidence of surface damage, and compared it with that of CoCr components.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 307 - 309
3 May 2021
Eitner A Wildemann B


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 4 | Pages 557 - 564
1 Apr 2009
Rumian AP Draper ERC Wallace AL Goodship AE

An understanding of the remodelling of tendon is crucial for the development of scientific methods of treatment and rehabilitation. This study tested the hypothesis that tendon adapts structurally in response to changes in functional loading. A novel model allowed manipulation of the mechanical environment of the patellar tendon in the presence of normal joint movement via the application of an adjustable external fixator mechanism between the patella and the tibia in sheep, while avoiding exposure of the patellar tendon itself. Stress shielding caused a significant reduction in the structural and material properties of stiffness (79%), ultimate load (69%), energy absorbed (61%), elastic modulus (76%) and ultimate stress (72%) of the tendon compared with controls. Compared with the material properties the structural properties exhibited better recovery after re-stressing with stiffness 97%, ultimate load 92%, energy absorbed 96%, elastic modulus 79% and ultimate stress 80%. The cross-sectional area of the re-stressed tendons was significantly greater than that of stress-shielded tendons. The remodelling phenomena exhibited in this study are consistent with a putative feedback mechanism under strain control. This study provides a basis from which to explore the interactions of tendon remodelling and mechanical environment


The Bone & Joint Journal
Vol. 99-B, Issue 4 | Pages 522 - 530
1 Apr 2017
Bus MPA van de Sande MAJ Taminiau AHM Dijkstra PDS

Aims. To assess complications and failure mechanisms of osteoarticular allograft reconstructions for primary bone tumours. Patients and Methods. We retrospectively evaluated 38 patients (28 men, 74%) who were treated at our institution with osteoarticular allograft reconstruction between 1989 and 2010. Median age was 19 years (interquartile range 14 to 32). Median follow-up was 19.5 years (95% confidence interval (CI) 13.0 to 26.1) when 26 patients (68%) were alive. In addition, we systematically searched the literature for clinical studies on osteoarticular allografts, finding 31 studies suitable for analysis. Results of papers that reported on one site exclusively were pooled for comparison. Results. A total of 20 patients (53%) experienced graft failure, including 15 due to mechanical complications (39%) and three (9%) due to infection. In the systematic review, 514 reconstructions were analysed (distal femur, n = 184, 36%; proximal tibia, n = 136, 26%; distal radius, n = 99, 19%; proximal humerus, n = 95, 18%). Overall rates of failure, fracture and infection were 27%, 20%, and 10% respectively. With the distal femur as the reference, fractures were more common in the humerus (odds ratio (OR) 4.1, 95% CI 2.2 to 7.7) and tibia (OR 2.2, 95% CI 1.3 to 4.4); infections occurred more often in the tibia (OR 2.2, 95% CI 1.3 to 4.4) and less often in the radius (OR 0.1, 95% CI 0.0 to 0.8). Conclusion. Osteoarticular allograft reconstructions are associated with high rates of mechanical complications. Although comparative studies with alternative techniques are scarce, the risk of mechanical failure in our opinion does not justify routine employment of osteoarticular allografts for reconstruction of large joints after tumour resection. Cite this article: Bone Joint J 2017;99-B:522–30


Bone & Joint Open
Vol. 2, Issue 7 | Pages 522 - 529
13 Jul 2021
Nicholson JA Clement ND Clelland AD MacDonald DJ Simpson AHRW Robinson CM

Aims

It is unclear whether acute plate fixation facilitates earlier return of normal shoulder function following a displaced mid-shaft clavicular fracture compared with nonoperative management when union occurs. The primary aim of this study was to establish whether acute plate fixation was associated with a greater return of normal shoulder function when compared with nonoperative management in patients who unite their fractures. The secondary aim was to investigate whether there were identifiable predictors associated with return of normal shoulder function in patients who achieve union with nonoperative management.

Methods

Patient data from a randomized controlled trial were used to compare acute plate fixation with nonoperative management of united fractures. Return of shoulder function was based on the age- and sex-matched Disabilities of the Arm, Shoulder and Hand (DASH) scores for the cohort. Independent predictors of an early recovery of normal shoulder function were investigated using a separate prospective series of consecutive nonoperative displaced mid-shaft clavicular fractures recruited over a two-year period (aged ≥ 16 years). Patient demographics and functional recovery were assessed over the six months post-injury using a standardized protocol.