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The Bone & Joint Journal
Vol. 100-B, Issue 10 | Pages 1280 - 1288
1 Oct 2018
Grammatopoulos G Gofton W Cochran M Dobransky J Carli A Abdelbary H Gill HS Beaulé PE

Aims. This study aims to: determine the difference in pelvic position that occurs between surgery and radiographic, supine, postoperative assessment; examine how the difference in pelvic position influences subsequent component orientation; and establish whether differences in pelvic position, and thereafter component orientation, exist between total hip arthroplasties (THAs) performed in the supine versus the lateral decubitus positions. Patients and Methods. The intra- and postoperative anteroposterior pelvic radiographs of 321 THAs were included; 167 were performed with the patient supine using the anterior approach and 154 were performed with the patient in the lateral decubitus using the posterior approach. The inclination and anteversion of the acetabular component was measured and the difference (Δ) between the intra- and postoperative radiographs was determined. The target zone was inclination/anteversion of 40°/20° (± 10°). Changes in the tilt, rotation, and obliquity of the pelvis on the intra- and postoperative radiographs were calculated from Δinclination/anteversion using the Levenberg–Marquardt algorithm. Results. The mean postoperative inclination/anteversion was 40° (± 8°)/23° (± 9°) with Δinclination and/or Δanteversion > ± 10° in 74 (21%). Intraoperatively, the pelvis was anteriorly tilted by a mean of 4° (± 10°), internally rotated by a mean of 1° (± 10°) and adducted by a mean of 1° (± 5°). Having Δinclination and/or Δanteversion > ± 10° was associated with a 3.5 odds ratio of having the acetabular component outside the target zone. A greater proportion of THAs that were undertaken with the patient in the lateral decubitus position had Δinclination and/or Δanteversion > ± 10° (35.3%, 54/153) compared with those in the supine position (4.8%, 8/167; p < 0.001). A greater number of acetabular components were within the target zone in THAs undertaken with the patient in the supine position (72%, 120/167), compared with those in the lateral decubitus position (44%, 67/153; p < 0.001). Intraoperatively, the pelvis was more anteriorly tilted (p < 0.001) and more internally rotated (p = 0.04) when the patient was in the lateral decubitus position. Conclusion. The pelvic position is more reliable when the patient is in the supine position, leading to more consistent orientation of the acetabular component. Significant differences in pelvic tilt and rotation are seen with the patient in the lateral decubitus position. Cite this article: Bone Joint J 2018;100-B:1280–8


Bone & Joint Research
Vol. 10, Issue 2 | Pages 122 - 133
1 Feb 2021
He CP Jiang XC Chen C Zhang HB Cao WD Wu Q Ma C

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122–133


Bone & Joint Research
Vol. 10, Issue 4 | Pages 237 - 249
1 Apr 2021
Chen X Chen W Aung ZM Han W Zhang Y Chai G

Aims. LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling. Methods. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action. Results. LY3023414 attenuated PI3K/protein kinase B (Akt)/GSK3-dependent activation of β-catenin and nuclear factor-activated T cell 1 (NFATc1) during osteogenesis and osteoclastogenesis, respectively. LY3023414 mainly inhibited osteoclast formation instead of mature osteoclast function. Moreover, it suppressed osteogenesis both in the early stage of differentiation and late stage of calcification. Similarly, gene knockdown of Akt isoforms by siRNA downregulated osteogenic and osteoclastogenic processes, indicating that Akt1 and Akt2 acted synergistically. Conclusion. LY3023414 can suppress osteogenesis and osteoclastogenesis through inhibition of the PI3K/Akt/GSK3 signalling pathway, which highlights the potential benefits and side effects of LY3023414 for future clinical applications. Cite this article: Bone Joint Res 2021;10(4):237–249


Bone & Joint Research
Vol. 8, Issue 7 | Pages 290 - 303
1 Jul 2019
Li H Yang HH Sun ZG Tang HB Min JK

Objectives. The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods. The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results. In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion. This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients. Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290–303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1


Bone & Joint Research
Vol. 8, Issue 8 | Pages 367 - 377
1 Aug 2019
Chen M Chang C Chiang-Ni C Hsieh P Shih H Ueng SWN Chang Y

Objectives. Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI. Methods. We analyzed the bacterial composition of 22 SF samples collected from 11 patients with PJIs (first- and second-stage surgery). The V3 and V4 region of bacteria was assessed by comparing the taxonomic distribution of the 16S rDNA amplicons with microbiome sequencing analysis. We also compared the results of bacterial detection from different methods including 16S metagenomics, traditional cultures, and targeted Sanger sequencing. Results. Polymicrobial infections were not only detected, but also characterized at different timepoints corresponding to first- and second-stage exchange arthroplasty. Similar taxonomic distributions were obtained by matching sequence data against SILVA, Greengenes, and The National Center for Biotechnology Information (NCBI). All bacteria isolated from the traditional culture could be further identified by 16S metagenomics and targeted Sanger sequencing. Conclusion. The data highlight 16S rRNA metagenomics as a suitable and promising method to detect and identify infecting bacteria, most of which may be uncultivable. Importantly, the method dramatically reduces turnaround time to two days rather than approximately one week for conventional cultures. Cite this article: M-F. Chen, C-H. Chang, C. Chiang-Ni, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Rapid analysis of bacterial composition in prosthetic joint infection by 16S rRNA metagenomic sequencing. Bone Joint Res 2019;8:367–377. DOI: 10.1302/2046-3758.88.BJR-2019-0003.R2


Bone & Joint Open
Vol. 2, Issue 8 | Pages 679 - 684
2 Aug 2021
Seddigh S Lethbridge L Theriault P Matwin S Dunbar MJ

Aims. In countries with social healthcare systems, such as Canada, patients may experience long wait times and a decline in their health status prior to their operation. The aim of this study is to explore the association between long preoperative wait times (WT) and acute hospital length of stay (LoS) for primary arthroplasty of the knee and hip. Methods. The study population was obtained from the provincial Patient Access Registry Nova Scotia (PARNS) and the Canadian national hospital Discharge Access Database (DAD). We included primary total knee and hip arthroplasties (TKA, THA) between 2011 and 2017. Patients waiting longer than the recommended 180 days Canadian national standard were compared to patients waiting equal or less than the standard WT. The primary outcome measure was acute LoS postoperatively. Secondarily, patient demographics, comorbidities, and perioperative parameters were correlated with LoS with multivariate regression. Results. A total of 11,833 TKAs and 6,627 THAs were included in the study. Mean WT for TKA was 348 days (1 to 3,605) with mean LoS of 3.6 days (1 to 98). Mean WT for THA was 267 days (1 to 2,015) with mean LoS of 4.0 days (1 to 143). There was a significant increase in mean LoS for TKA waiting longer than 180 days (2.5% (SE 1.1); p = 0.028). There was no significant association for THA. Age, sex, surgical year, admittance from home, rural residence, household income, hospital facility, the need for blood transfusion, and comorbidities were all found to influence LoS. Conclusion. Surgical WT longer than 180 days resulted in increased acute LoS for primary TKA. Meeting a shorter WT target may be cost-saving in a social healthcare system by having shorter LoS. Cite this article: Bone Jt Open 2021;2(8):679–684


Bone & Joint Research
Vol. 9, Issue 11 | Pages 821 - 826
1 Nov 2020
Hagi T Nakamura T Kita K Iino T Asanuma K Sudo A

Aims. Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. Methods. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay. Results. The OS cell lines 143B, HOS, and Saos-2 expressed IL-6R. Recombinant human IL-6 treatment increased proliferation of 143B and HOS cells. Tocilizumab treatment decreased proliferation and invasion of 143B, HOS, and Saos-2. Conclusion. In conclusion, we confirmed the production of IL-6 and the expression of IL-6R in OS cells and demonstrated that tocilizumab inhibits proliferation and invasion in OS cells. Cite this article: Bone Joint Res 2020;9(11):821–826


The Bone & Joint Journal
Vol. 103-B, Issue 6 | Pages 1047 - 1054
1 Jun 2021
Keene DJ Knight R Bruce J Dutton SJ Tutton E Achten J Costa ML

Aims. To identify the prevalence of neuropathic pain after lower limb fracture surgery, assess associations with pain severity, quality of life and disability, and determine baseline predictors of chronic neuropathic pain at three and at six months post-injury. Methods. Secondary analysis of a UK multicentre randomized controlled trial (Wound Healing in Surgery for Trauma; WHiST) dataset including adults aged 16 years or over following surgery for lower limb major trauma. The trial recruited 1,547 participants from 24 trauma centres. Neuropathic pain was measured at three and six months using the Doleur Neuropathique Questionnaire (DN4); 701 participants provided a DN4 score at three months and 781 at six months. Overall, 933 participants provided DN4 for at least one time point. Physical disability (Disability Rating Index (DRI) 0 to 100) and health-related quality-of-life (EuroQol five-dimension five-level; EQ-5D-5L) were measured. Candidate predictors of neuropathic pain included sex, age, BMI, injury mechanism, concurrent injury, diabetes, smoking, alcohol, analgaesia use pre-injury, index surgery location, fixation type, Injury Severity Score, open injury, and wound care. Results. The median age of the participants was 51 years (interquartile range 35 to 64). At three and six months post-injury respectively, 32% (222/702) and 30% (234/787) had neuropathic pain, 56% (396/702) and 53% (413/787) had chronic pain without neuropathic characteristics, and the remainder were pain-free. Pain severity was higher among those with neuropathic pain. Linear regression analyses found that those with neuropathic pain at six months post-injury had more physical disability (DRI adjusted mean difference 11.49 (95% confidence interval (CI) 7.84 to 15.14; p < 0.001) and poorer quality of life (EQ-5D utility -0.15 (95% CI -0.19 to -0.11); p < 0.001) compared to those without neuropathic characteristics. Logistic regression identified that prognostic factors of younger age, current smoker, below knee fracture, concurrent injuries, and regular analgaesia pre-injury were associated with higher odds of post-injury neuropathic pain. Conclusion. Pain with neuropathic characteristics is common after lower limb fracture surgery and persists to six months post-injury. Persistent neuropathic pain is associated with substantially poorer recovery. Further attention to identify neuropathic pain post-lower limb injury, predicting patients at risk, and targeting interventions, is indicated. Cite this article: Bone Joint J 2021;103-B(6):1047–1054


The Bone & Joint Journal
Vol. 103-B, Issue 6 | Pages 1070 - 1077
1 Jun 2021
Hipfl C Mooij W Perka C Hardt S Wassilew GI

Aims. The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision. Methods. A total of 274 THA revisions performed for presumed aseptic loosening from 2012 to 2016 were reviewed. In addition to obtaining intraoperative tissue cultures from all patients, synovial and sonication fluid samples of the removed implant were obtained in 215 cases (79%) and 101 cases (37%), respectively. Histopathological analysis was performed in 250 cases (91%). Patients were classified as having low-grade infections according to institutional criteria and Musculoskeletal Infection Society (MSIS) International Consensus Meeting (ICM) 2013 criteria. Low-grade infections according to institutional criteria were treated with targeted antibiotics for six weeks postoperatively. Implant failure was defined as the need for re-revision resulting from periprosthetic joint infection (PJI) and aseptic reasons. The mean follow-up was 68 months (26 to 95). Results. Unexpected positive intraoperative samples were found in 77 revisions (28%). Low-grade infection was diagnosed in 36 cases (13%) using institutional criteria and in nine cases (3%) using MSIS ICM 2013 criteria. In all, 41 patients (15%) had single specimen growth of a low-virulent pathogen and were deemed contaminated. Coagulase-negative Staphylococcus and anaerobes were the most commonly isolated bacteria. Implant failure for PJI was higher in revisions with presumed contaminants (5/41, 12%) compared to those with low-grade infections (2/36, 6%) and those with negative samples (5/197, 3%) (p = 0.021). The rate of all-cause re-revision was similar in patients diagnosed with low-grade infections (5/36, 14%) and those with presumed contaminants (6/41, 15%) and negative samples (21/197, 11%) (p = 0.699). Conclusion. Our findings suggest that the presumption of culture contamination in aseptic revision hip arthroplasty may increase the detection of PJI. In this cohort, the presence of low-grade infection did not increase the risk of re-revision. Further studies are needed to assess the relevance of single specimen growth and the benefits of specific postoperative antibiotic regimens. Cite this article: Bone Joint J 2021;103-B(6):1070–1077


The Bone & Joint Journal
Vol. 103-B, Issue 11 | Pages 1725 - 1730
1 Nov 2021
Baumber R Gerrand C Cooper M Aston W

Aims. The incidence of bone metastases is between 20% to 75% depending on the type of cancer. As treatment improves, the number of patients who need surgical intervention is increasing. Identifying patients with a shorter life expectancy would allow surgical intervention with more durable reconstructions to be targeted to those most likely to benefit. While previous scoring systems have focused on surgical and oncological factors, there is a need to consider comorbidities and the physiological state of the patient, as these will also affect outcome. The primary aim of this study was to create a scoring system to estimate survival time in patients with bony metastases and to determine which factors may adversely affect this. Methods. This was a retrospective study which included all patients who had presented for surgery with metastatic bone disease. The data collected included patient, surgical, and oncological variables. Univariable and multivariable analysis identified which factors were associated with a survival time of less than six months and less than one year. A model to predict survival based on these factors was developed using Cox regression. Results. A total of 164 patients were included with a median survival time of 1.6 years (interquartile range 0.5 to 3.1) after surgery. On multivariable analysis, a higher American Society of Anesthesiologists grade (p < 0.001), a high white cell count (p = 0.002), hyponatraemia (p = 0.001), a preoperative resting heart rate of > 100 bpm (p = 0.052), and the type of primary cancer (p = 0.026) remained significant predictors of reduced survival time. The predictive model developed showed good discrimination and calibration to predict both six- and 12-month survival in patients with metastatic bone disease. Conclusion. In addition to surgical and oncological factors, the level of comorbidity and physiological state of the patient has a significant impact on survival in patients with metastatic bone disease. These factors should be considered when assessing the appropriateness of surgical intervention. This is the first study to examine other patient factors alongside surgical and oncological data to identify a relationship between these and survival. Cite this article: Bone Joint J 2021;103-B(11):1725–1730


Bone & Joint Research
Vol. 6, Issue 4 | Pages 196 - 203
1 Apr 2017
Jin Y Chen X Gao ZY Liu K Hou Y Zheng J

Objectives. This study aimed to explore the role of miR-320a in the pathogenesis of osteoarthritis (OA). Methods. Human cartilage cells (C28/I2) were transfected with miR-320a or antisense oligonucleotides (ASO)-miR-320a, and treated with IL-1β. Subsequently the expression of collagen type II alpha 1 (Col2α1) and aggrecan (ACAN), and the concentrations of sulfated glycosaminoglycans (sGAG) and matrix metallopeptidase 13 (MMP-13), were assessed. Luciferase reporter assay, qRT-PCR, and Western blot were performed to explore whether pre-B-cell leukemia Homeobox 3 (PBX3) was a target of miR-320a. Furthermore, cells were co-transfected with miR-320a and PBX3 expressing vector, or cells were transfected with miR-320a and treated with a nuclear factor kappa B (NF-κB) antagonist MG132. The changes in Col2α1 and ACAN expression, and in sGAG and MMP-13 concentrations, were measured again. Statistical comparisons were made between two groups by using the two-tailed paired t-test. Results. Expression of miR-320a was elevated in OA cartilage tissues and chondrocytes, and in IL-1β-stimulated C28/I2 cells (p < 0.05 or p < 0.01). MiR-320a overexpression enhanced IL-1β-induced down-regulation of Col2α1 and ACAN and sGAG, and increased the IL-1β-induced overexpression of MMP-13 (p < 0.01). PBX3 was a direct target of miR-320a. PBX3 and MG132 co-transfection attenuated the effects of miR-320a on the expression of Col2α1, ACAN, sGAG and MMP-13(p < 0.01). Conclusion. Overexpression of miR-320a might enhance IL-1β-induced cartilage degradation factors. These effects might be via targeting PBX3 and regulating NF-κB. Cite this article: Y. Jin, X. Chen, Z. Y. Gao, K. Liu, Y. Hou, J. Zheng. The role of miR-320a and IL-1β in human chondrocyte degradation. Bone Joint Res 2017;6:–203. DOI: 10.1302/2046-3758.64.BJR-2016-0224.R1


The Bone & Joint Journal
Vol. 103-B, Issue 6 Supple A | Pages 23 - 31
1 Jun 2021
Burnett III RA Yang J Courtney PM Terhune EB Hannon CP Della Valle CJ

Aims. The aim of this study was to compare ten-year longitudinal healthcare costs and revision rates for patients undergoing unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA). Methods. The Humana database was used to compare 2,383 patients undergoing UKA between 2007 and 2009, who were matched 1:1 from a cohort of 63,036 patients undergoing primary TKA based on age, sex, and Elixhauser Comorbidity Index. Medical and surgical complications were tracked longitudinally for one year following surgery. Rates of revision surgery and cumulative mean healthcare costs were recorded for this period of time and compared between the cohorts. Results. Patients undergoing TKA had significantly higher rates of manipulation under anaesthesia (3.9% vs 0.9%; p < 0.001), deep vein thrombosis (5.0% vs 3.1%; p < 0.001), pulmonary embolism (1.5% vs 0.8%; p = 0.001), and renal failure (4.2% vs 2.2%; p < 0.001). Revision rates, however, were significantly higher for UKA at five years (6.0% vs 4.2%; p = 0.007) and ten years postoperatively (6.5% vs 4.4%; p = 0.002). Longitudinal-related healthcare costs for patients undergoing TKA were greater than for those undergoing UKA at one year ($24,771 vs $22,071; p < 0.001) and five years following surgery ($26,549 vs $25,730; p < 0.001); however, the mean costs of TKA were comparable to UKA at ten years ($26,877 vs $26,891; p = 0.425). Conclusion. Despite higher revision rates, patients undergoing UKA had lower mean healthcare costs than those undergoing TKA up to ten years following the procedure, at which time costs were comparable. In the era of value-based care, surgeons and policymakers should be aware of the costs involved with these procedures. UKA was associated with fewer complications at one year postoperatively but higher revision rates at five and ten years. While UKA was significantly less costly than TKA at one and five years, costs at ten years were comparable with a mean difference of only $14. Lowering the risk of revision surgery should be targeted as a source of cost savings for both UKA and TKA as the mean related healthcare costs were 2.5-fold higher in patients requiring revision surgery. Cite this article: Bone Joint J 2021;103-B(6 Supple A):23–31


Bone & Joint Research
Vol. 6, Issue 5 | Pages 323 - 330
1 May 2017
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Objectives. Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?. Methods. Titanium alloy cylinders (Ti6Al4V) were exposed to PEMF from an induction heater with maximum 2000 watts at 27 kHz after being contaminated with five different types of micro-organisms: Staphylococcus epidermidis; Staphylococcus aureus; Pseudomonas aeruginosa; spore-forming Bacillus cereus; and yeast Candida albicans. The cylinders were exposed to incremental target temperatures (35°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C) for up to 3.5 minutes. Results. There was an average linear heating rate of 0.39°C per second up to the target temperature, and thereafter the target temperature was maintained until the end of the experiment. At 60°C and higher (duration 3.5 minutes), there was a 6-log reduction or higher for every micro-organism tested. At 60°C, we found that the shortest duration of effective induction heating was 1.5 minutes. This resulted in a 5-log reduction or higher for every micro-organism tested. Conclusion. Non-contact induction heating of a titanium disk is effective in reducing bacterial load in vitro. These promising results can be further explored as a new treatment modality for infections of metal orthopaedic implants. Cite this article: B. G. Pijls, I. M. J. G. Sanders, E. J. Kuijper, R. G. H. H. Nelissen. Non-contact electromagnetic induction heating for eradicating bacteria and yeasts on biomaterials and possible relevance to orthopaedic implant infections: In vitro findings. Bone Joint Res 2017;6:323–330. DOI: 10.1302/2046-3758.65.BJR-2016-0308.R1


The Bone & Joint Journal
Vol. 100-B, Issue 7 | Pages 891 - 897
1 Jul 2018
Teeter MG Lanting BA Naudie DD McCalden RW Howard JL MacDonald SJ

Aims. The aim of this study was to determine whether there is a difference in the rate of wear between acetabular components positioned within and outside the ‘safe zones’ of anteversion and inclination angle. Patients and Methods. We reviewed 100 hips in 94 patients who had undergone primary total hip arthroplasty (THA) at least ten years previously. Patients all had the same type of acetabular component with a bearing couple which consisted of a 28 mm cobalt-chromium head on a highly crosslinked polyethylene (HXLPE) liner. A supine radiostereometric analysis (RSA) examination was carried out which acquired anteroposterior (AP) and lateral paired images. Acetabular component anteversion and inclination angles were measured as well as total femoral head penetration, which was divided by the length of implantation to determine the rate of polyethylene wear. Results. The mean anteversion angle was 19.4° (-15.2° to 48°, . sd. 11.4°), the mean inclination angle 43.4° (27.3° to 60.5°, . sd. 6.6°), and the mean wear rate 0.055 mm/year (. sd. 0.060). Exactly half of the hips were positioned inside the ‘safe zone’. There was no difference (median difference, 0.012 mm/year; p = 0.091) in the rate of wear between acetabular components located within or outside the ‘safe zone’. When compared to acetabular components located inside the ‘safe zone’, the wear rate was no different for acetabular components that only achieved the target anteversion angle (median difference, 0.012 mm/year; p = 0.138), target inclination angle (median difference, 0.013 mm/year; p = 0.354), or neither target (median difference, 0.012 mm/year; p = 0.322). Conclusion. Placing the acetabular component within or outside the ‘safe zone’ did not alter the wear rate of HXLPE at long-term follow-up to a level that risked osteolysis. HXLPE appears to be a forgiving bearing material in terms of articular surface wear, but care must still be taken to position the acetabular component correctly so that the implant is stable. Cite this article: Bone Joint J 2018;100-B:891-7


Bone & Joint Open
Vol. 1, Issue 9 | Pages 530 - 540
4 Sep 2020
Arafa M Nesar S Abu-Jabeh H Jayme MOR Kalairajah Y

Aims. The coronavirus disease (COVID)-19 pandemic forced an unprecedented period of challenge to the NHS in the UK where hip fractures in the elderly population are a major public health concern. There are approximately 76,000 hip fractures in the UK each year which make up a substantial proportion of the trauma workload of an average orthopaedic unit. This study aims to assess the impact of the COVID-19 pandemic on hip fracture care service and the emerging lessons to withstand any future outbreaks. Methods. Data were collected retrospectively on 157 hip fractures admitted from March to May 2019 and 2020. The 2020 group was further subdivided into COVID-positive and COVID-negative. Data including the four-hour target, timing to imaging, hours to operation, anaesthetic and operative details, intraoperative complications, postoperative reviews, COVID status, Key Performance Indicators (KPIs), length of stay, postoperative complications, and the 30-day mortality were compiled from computer records and our local National Hip Fracture Database (NHFD) export data. Results. Hip fractures and inpatient falls significantly increased by 61.7% and 7.2% respectively in the 2020 group. A significant difference was found among the three groups regarding anaesthetic preparation time, anaesthetic time, and recovery time. The mortality rate in the 2020 COVID-positive group (36.8%) was significantly higher than both the 2020 COVID-negative and 2019 groups (11.5% and 11.7% respectively). The hospital stay was significantly higher in the COVID-positive group (mean of 24.21 days (SD 19.29)). Conclusion. COVID-19 has had notable effects on the hip fracture care service: hip fracture rates increased significantly. There were inefficiencies in theatre processes for which we have recommended the use of alternate theatres. COVID-19 infection increased the 30-day mortality and hospital stay in hip fractures. More research needs to be done to reduce this risk. Cite this article: Bone Joint Open 2020;1-9:530–540


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. 102-B, Issue 6 Supple A | Pages 19 - 23
1 Jun 2020
Yayac M Schiller N Austin MS Courtney PM

Aims. The purpose of this study was to determine the impact of the removal of total knee arthroplasty (TKA) from the Medicare Inpatient Only (IPO) list on our Bundled Payments for Care Improvement (BPCI) Initiative in 2018. Methods. We examined our institutional database to identify all Medicare patients who underwent primary TKA from 2017 to 2018. Hospital inpatient or outpatient status was cross-referenced with Centers for Medicare & Medicaid Services (CMS) claims data. Demographics, comorbidities, and outcomes were compared between patients classified as ‘outpatient’ and ‘inpatient’ TKA. Episode-of-care BPCI costs were then compared from 2017 to 2018. Results. Of the 2,135 primary TKA patients in 2018, 908 (43%) were classified as an outpatient and were excluded from BPCI. Inpatient classified patients had longer mean length of stay (1.9 (SD 1.4) vs 1.4 (SD 1.7) days, p < 0.001) and higher rates of discharge to rehabilitation (17% vs 3%, p < 0.001). Post-acute care costs increased when comparing the BPCI patients from 2017 to 2018, ($5,037 (SD $7,792) vs $5793 (SD $8,311), p = 0.010). The removal of TKA from the IPO list turned a net savings of $53,805 in 2017 into a loss of $219,747 in 2018 for our BPCI programme. Conclusions. Following the removal of TKA from the IPO list, nearly half of the patients at our institution were inappropriately classified as an outpatient. Our target price was increased and our institution realized a substantial loss in 2018 BPCI despite strong quality metrics. CMS should address its negative implications on bundled payment programmes. Cite this article: Bone Joint J 2020;102-B(6 Supple A):19–23


Objectives. MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Methods. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. Results. MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. Conclusion. In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture. Cite this article: Bone Joint Res 2019;8:550–562


Bone & Joint Research
Vol. 9, Issue 4 | Pages 173 - 181
1 Apr 2020
Schon J Chahla J Paudel S Manandhar L Feltham T Huard J Philippon M Zhang Z

Aims. Femoroacetabular impingement (FAI) is a potential cause of hip osteoarthritis (OA). The purpose of this study was to investigate the expression profile of matrix metalloproteinases (MMPs) in the labral tissue with FAI pathology. Methods. In this study, labral tissues were collected from four FAI patients arthroscopically and from three normal hips of deceased donors. Proteins extracted from the FAI and normal labrums were separately applied for MMP array to screen the expression of seven MMPs and three tissue inhibitors of metalloproteinases (TIMPs). The expression of individual MMPs and TIMPs was quantified by densitometry and compared between the FAI and normal labral groups. The expression of selected MMPs and TIMPs was validated and localized in the labrum with immunohistochemistry. Results. On MMP arrays, most of the targeted MMPs and TIMPs were detected in the FAI and normal labral proteins. After data normalization, in comparison with the normal labral proteins, expression of MMP-1 and MMP-2 in the FAI group was increased and expression of TIMP-1 reduced. The histology of the FAI labrum showed disorderly cell distribution and altered composition of thick and thin collagen fibres. The labral cells expressing MMP-1 and MMP-2 were localized and their percentages were increased in the FAI labrum. Immunohistochemistry confirmed that the percentage of TIMP-1 positive cells was reduced in the FAI labrum. Conclusion. This study established an expression profile of MMPs and TIMPs in the FAI labrum. The increased expression of MMP-1 and MMP-2 and reduced expression of TIMP-1 in the FAI labrum are indicative of a pathogenic role of FAI in hip OA development. Cite this article:Bone Joint Res. 2020;9(4):173–181


Bone & Joint Open
Vol. 1, Issue 2 | Pages 8 - 12
18 Feb 2020
Bhimani SJ Bhimani R Smith A Eccles C Smith L Malkani A

Aims. Robotic-assisted total knee arthroplasty (RA-TKA) has been introduced to provide accurate bone cuts and help achieve the target knee alignment, along with symmetric gap balancing. The purpose of this study was to determine if any early clinical benefits could be realized following TKA using robotic-assisted technology. Methods. In all, 140 consecutive patients undergoing RA-TKA and 127 consecutive patients undergoing conventional TKA with minimum six-week follow-up were reviewed. Differences in visual analogue scores (VAS) for pain at rest and with activity, postoperative opiate usage, and length of stay (LOS) between the RA-TKA and conventional TKA groups were compared. Results. Patients undergoing RA-TKA had lower average VAS pain scores at rest (p = 0.001) and with activity (p = 0.03) at two weeks following the index procedure. At the six-week interval, the RA-TKA group had lower VAS pain scores with rest (p = 0.03) and with activity (p = 0.02), and required 3.2 mg less morphine equivalents per day relative to the conventional group (p < 0.001). At six weeks, a significantly greater number of patients in the RA-TKA group were free of opioid use compared to the conventional TKA group; 70.7% vs 57.0% (p = 0.02). Patients in the RA-TKA group had a shorter LOS; 1.9 days versus 2.3 days (p < 0.001), and also had a greater percentage of patient discharged on postoperative day one; 41.3% vs 20.5% (p < 0.001). Conclusion. Patients undergoing RA-TKA had lower pain levels at both rest and with activity, required less opioid medication, and had a shorter LOS