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Aims. This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results. We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA. Conclusion. The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. Cite this article:Bone Joint Res. 2020;9(3):90–98


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 103 - 110
1 Jul 2021
Chalmers BP Lebowitz JS Chiu Y Joseph AD Padgett DE Bostrom MPG Gonzalez Della Valle A

Aims. Due to the opioid epidemic in the USA, our service progressively decreased the number of opioid tablets prescribed at discharge after primary hip (THA) and knee (TKA) arthroplasty. The goal of this study was to analyze the effect on total morphine milligram equivalents (MMEs) prescribed and post-discharge opioid repeat prescriptions. Methods. We retrospectively reviewed 19,428 patients undergoing a primary THA or TKA between 1 February 2016 and 31 December 2019. Two reductions in the number of opioid tablets prescribed at discharge were implemented over this time; as such, we analyzed three periods (P1, P2, and P3) with different routine discharge MME (750, 520, and 320 MMEs, respectively). We investigated 90-day refill rates, refill MMEs, and whether discharge MMEs were associated with represcribing in a multivariate model. Results. A discharge prescription of < 400 MMEs was not a risk factor for opioid represcribing in the entire population (p = 0.772) or in opioid-naïve patients alone (p = 0.272). Procedure type was the most significant risk factor for narcotic represcribing, with unilateral TKA (hazard ratio (HR) = 5.62), bilateral TKA (HR = 6.32), and bilateral unicompartmental knee arthroplasty (UKA) (HR = 5.29) (all p < 0.001) being the highest risk for refills. For these three procedures, there was approximately a 5% to 6% increase in refills from P1 to P3 (p < 0.001); however, there was no significant increase in refill rates after any hip arthroplasty procedures. Total MMEs prescribed were significantly reduced from P1 to P3 (p < 0.001), leading to the equivalent of nearly 500,000 fewer oxycodone 5 mg tablets prescribed. Conclusion. Decreasing opioids prescribed at discharge led to a statistically significant reduction in total MMEs prescribed. While the represcribing rate did not increase for any hip arthroplasty procedure, the overall refill rates increased by about 5% for most knee arthroplasty procedures. As such, we are now probably prescribing an appropriate amount of opioids at discharge for knee arthroplasty procedure, but further reductions may be possible for hip arthroplasty procedures. Cite this article: Bone Joint J 2021;103-B(7 Supple B):103–110


The Bone & Joint Journal
Vol. 101-B, Issue 9 | Pages 1168 - 1176
1 Sep 2019
Calder PR McKay JE Timms AJ Roskrow T Fugazzotto S Edel P Goodier WD

Aims. The Precice intramedullary limb-lengthening system has demonstrated significant benefits over external fixation lengthening methods, leading to a paradigm shift in limb lengthening. This study compares outcomes following antegrade and retrograde femoral lengthening in both adolescent and adult patients. Patients and Methods. A retrospective review of prospectively collected data was undertaken of a consecutive series of 107 femoral lengthening operations in 92 patients. In total, 73 antegrade nails and 34 retrograde nails were inserted. Outcome was assessed by the regenerate healing index (HI), hip and knee range of movement (ROM), and the presence of any complications. Results. The mean lengthening was 4.65 cm (1.5 to 8) in the antegrade group and 4.64 cm (1.6 to 8) in the retrograde group. Of the 107 lengthenings, 100 had sufficient datapoints to calculate the mean HI. This was 31.6 days/cm (15 to 108). There was a trend toward a lower (better) HI with an antegrade nail and better outcomes in adolescent patients, but these were not statistically significant. Hip and knee ROM was maintained and/or improved following commencement of femoral lengthening in 44 patients (60%) of antegrade nails and 13 patients (38%) of retrograde nails. In female patients, loss of movement occurred both earlier and following less total length achieved. Minor implant complications included locking bolt migration and in one patient deformity of the nail, but no implant failed to lengthen and there were no deep infections. Three patients had delayed union, five patients required surgical intervention for joint contracture. Conclusion. This study confirms excellent results in femoral lengthening with antegrade and retrograde Precice nails. There is a trend for better healing and less restriction in hip and knee movement following antegrade nails. There are clinical scenarios, that mandate the use of a retrograde nail. However, when these are not present, we recommend the use of antegrade nailing. Cite this article: Bone Joint J 2019;101-B:1168–1176


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 578 - 583
1 Mar 2021
Coulin B Demarco G Spyropoulou V Juchler C Vendeuvre T Habre C Tabard-Fougère A Dayer R Steiger C Ceroni D

Aims. We aimed to describe the epidemiological, biological, and bacteriological characteristics of osteoarticular infections (OAIs) caused by Kingella kingae. Methods. The medical charts of all children presenting with OAIs to our institution over a 13-year period (January 2007 to December 2019) were reviewed. Among these patients, we extracted those which presented an OAI caused by K. kingae and their epidemiological data, biological results, and bacteriological aetiologies were assessed. Results. K. kingae was the main reported microorganism in our paediatric population, being responsible for 48.7% of OAIs confirmed bacteriologically. K. kingae affects primarily children aged between six months and 48 months. The highest prevalence of OAI caused by K. kingae was between seven months and 24 months old. After the patients were 27 months old, its incidence decreased significantly. The incidence though of infection throughout the year showed no significant differences. Three-quarters of patients with an OAI caused by K. kingae were afebrile at hospital admission, 11% had elevated WBCs, and 61.2% had abnormal CRPs, whereas the ESR was increased in 75%, constituting the most significant predictor of an OAI. On MRI, we noted 53% of arthritis affecting mostly the knee and 31% of osteomyelitis located primarily in the foot. Conclusion. K. kingae should be recognized currently as the primary pathogen causing OAI in children younger than 48 months old. Diagnosis of an OAI caused by K. kingae is not always obvious, since this infection may occur with a mild-to-moderate clinical and biological inflammatory response. Extensive use of nucleic acid amplification assays improved the detection of fastidious pathogens and has increased the observed incidence of OAI, especially in children aged between six months and 48 months. We propose the incorporation of polymerase chain reaction assays into modern diagnostic algorithms for OAIs to better identify the bacteriological aetiology of OAIs. Cite this article: Bone Joint J 2021;103-B(3):578–583


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 765 - 766
1 Jul 2022
Haddad FS Malchau H


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 184 - 191
1 Jan 2021
Perrin DL Visgauss JD Wilson DA Griffin AM Abdul Razak AR Ferguson PC Wunder JS

Aims. Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up. Methods. Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma. Results. A total of 25 patients with a mean age of 33.8 years (18 to 67) with high-risk GCTB received median six cycles of Denosumab before surgery. Tumours occurred most commonly around the knee (17/25, 68%). The median follow-up was 57 months (interquartile range (IQR) 13 to 88). The joint was salvaged in 23 patients (92%). Two required knee arthroplasty due to intra-articular fracture and arthritis. Local recurrence developed in 11 patients (44%) at a mean of 32.5 months (3 to 75) following surgery, of whom four underwent repeat curettage and joint salvage. One patient developed secondary osteosarcoma and another benign GCT lung metastases. Conclusion. The use of Denosumab for joint salvage was associated with a higher than expected rate of local recurrence at 44%. Neoadjuvant Denosumab for joint-sparing procedures should be considered with caution in light of these results. Cite this article: Bone Joint J 2021;103-B(1):184–191


Bone & Joint Research
Vol. 11, Issue 6 | Pages 362 - 370
9 Jun 2022
Zhou J He Z Cui J Liao X Cao H Shibata Y Miyazaki T Zhang J

Aims

Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA.

Methods

Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature.


The Bone & Joint Journal
Vol. 101-B, Issue 5 | Pages 552 - 558
1 May 2019
Clark D Stevens JM Tortonese D Whitehouse MR Simpson D Eldridge J

Aims. The aim of this study was to determine and compare the congruency of the articular surface contact area of the patellofemoral joint (PFJ) during both active and passive movement of the knee with the use of an MRI mapping technique in both the stable and unstable PFJ. Patients and Methods. A prospective case-control MRI imaging study of patients with a history of PFJ instability and a control group of volunteers without knee symptoms was performed. The PFJs were imaged with the use of an MRI scan during both passive and active movement from 0° through to 40° of flexion. The congruency through measurement of the contact surface area was mapped in 5-mm intervals on axial slices. In all, 40 patients were studied. The case group included 31 patients with symptomatic patellofemoral instability and the control group of nine asymptomatic volunteers. The ages were well matched between the case and control groups. The mean age was 25 years (16 to 42; . sd. 6.9) in the case group and 26 years (19 to 32; . sd. 5.1) in the control group. There were 19 female and 12 male patients in the case group. Results. The unstable PFJs were demonstrably less congruent than the stable PFJs throughout the range of knee movement. The greatest mean differences in congruency between unstable and stable PFJ’s were observed between 11° and 20° flexion (1.73 cm. 2. vs 4.00 cm. 2. ; p < 0.005). . Conclusion. The unstable PFJ is less congruent than the stable PFJ throughout the range of knee movement studied. This approach to mapping PFJ congruency produces a measurable outcome and will allow the assessment of pre- and postoperative results following surgical intervention. This may facilitate the design of new procedures for patients with PFJ instability. If a single axial series is to be obtained on MRI scan, the authors recommend 11° to 20° of tibiofemoral flexion, as this was shown to have the greatest difference in contact surface area between the case and control groups. Cite this article: Bone Joint J 2019;101-B:552–558


Bone & Joint 360
Vol. 11, Issue 3 | Pages 35 - 37
1 Jun 2022


Aims. The aim is to assess the cost-effectiveness of patellofemoral arthroplasty (PFA) in comparison with total knee arthroplasty (TKA) for the treatment of isolated patellofemoral osteoarthritis (OA) based on prospectively collected data on health outcomes and resource use from a blinded, randomized, clinical trial. Methods. A total of 100 patients with isolated patellofemoral osteoarthritis were randomized to receive either PFA or TKA by experienced knee surgeons trained in using both implants. Patients completed patient-reported outcomes including EuroQol five-dimension questionnaire (EQ-5D) and 6-Item Short-Form Health Survey questionnaire (SF-6D) before the procedure. The scores were completed again after six weeks, three, six, and nine months, and again after one- and two-year post-surgery and yearly henceforth. Time-weighted outcome measures were constructed. Cost data were obtained from clinical registrations and patient-reported questionnaires. Incremental gain in health outcomes (quality-adjusted life-years (QALYs)) and incremental costs were compared for the two groups of patients. Net monetary benefit was calculated assuming a threshold value of €10,000, €35,000, and €50,000 per QALY and used to test the statistical uncertainty and central assumptions about outcomes and costs. Results. The PFA group had an incremental 12 month EQ-5D gain of 0.056 (95% confidence interval (CI) 0.01 to 0.10) and an incremental 12 month cost of minus €328 (95% CI 836 to 180). PFA therefore dominates TKA by providing better and cheaper outcomes than TKA. The net monetary benefit of PFA was €887 (95% CI 324 to 1450) with the €10,000 threshold, and it was consistently positive when different measures of outcomes and different cost assumptions were used. Conclusion. This study provides robust evidence that PFA from a one-year hospital management perspective is cheaper and provides better outcomes than TKA when applied to patients with isolated patellofemoral osteoarthritis and performed by experienced knee surgeons. Cite this article: Bone Joint J 2020;102-B(4):449–457


Bone & Joint Open
Vol. 3, Issue 7 | Pages 582 - 588
1 Jul 2022
Hodel S Selman F Mania S Maurer SM Laux CJ Farshad M

Aims

Preprint servers allow authors to publish full-text manuscripts or interim findings prior to undergoing peer review. Several preprint servers have extended their services to biological sciences, clinical research, and medicine. The purpose of this study was to systematically identify and analyze all articles related to Trauma & Orthopaedic (T&O) surgery published in five medical preprint servers, and to investigate the factors that influence the subsequent rate of publication in a peer-reviewed journal.

Methods

All preprints covering T&O surgery were systematically searched in five medical preprint servers (medRxiv, OSF Preprints, Preprints.org, PeerJ, and Research Square) and subsequently identified after a minimum of 12 months by searching for the title, keywords, and corresponding author in Google Scholar, PubMed, Scopus, Embase, Cochrane, and the Web of Science. Subsequent publication of a work was defined as publication in a peer-reviewed indexed journal. The rate of publication and time to peer-reviewed publication were assessed. Differences in definitive publication rates of preprints according to geographical origin and level of evidence were analyzed.


The Bone & Joint Journal
Vol. 104-B, Issue 5 | Pages 613 - 619
2 May 2022
Ackerman IN Busija L Lorimer M de Steiger R Graves SE

Aims

This study aimed to describe the use of revision knee arthroplasty in Australia and examine changes in lifetime risk over a decade.

Methods

De-identified individual-level data on all revision knee arthroplasties performed in Australia from 2007 to 2017 were obtained from the Australian Orthopaedic Association National Joint Replacement Registry. Population data and life tables were obtained from the Australian Bureau of Statistics. The lifetime risk of revision surgery was calculated for each year using a standardized formula. Separate calculations were undertaken for males and females.


Bone & Joint Research
Vol. 8, Issue 5 | Pages 207 - 215
1 May 2019
Key S Scott G Stammers JG Freeman MAR Pinskerova V Field RE Skinner J Banks SA

Objectives. The medially spherical GMK Sphere (Medacta International AG, Castel San Pietro, Switzerland) total knee arthroplasty (TKA) was previously shown to accommodate lateral rollback while pivoting around a stable medial compartment, aiming to replicate native knee kinematics in which some coronal laxity, especially laterally, is also present. We assess coronal plane kinematics of the GMK Sphere and explore the occurrence and pattern of articular separation during static and dynamic activities. Methods. Using pulsed fluoroscopy and image matching, the coronal kinematics and articular surface separation of 16 well-functioning TKAs were studied during weight-bearing and non-weight-bearing, static, and dynamic activities. The closest distances between the modelled articular surfaces were examined with respect to knee position, and proportions of joint poses exhibiting separation were computed. Results. Overall, 1717 joint poses were analyzed. At a 1.0 mm detection threshold, 37 instances of surface separation were observed in the lateral compartment and four medially (p < 0.001). Separation was activity-dependent, both laterally and medially (p < 0.001), occurring more commonly during static deep flexion in the lateral compartment, and during static rotation in the medial compartment. Lateral separation occurred more frequently than medial during kneeling (7/14 lateral vs 1/14 medial; p = 0.031) and stepping (20/1022 lateral vs 0/1022 medial; p < 0.001). Separation varied significantly between individuals during dynamic activities. Conclusion. No consistent association between closest distances of the articular surfaces and knee position was found during any activity. Lift-off was infrequent and depended on the activity performed and the individual knee. Lateral separation was consistent with the design rationale. Medial lift-off was rare and mostly in non-weight-bearing activities. Cite this article: S. Key, G. Scott, J. G. Stammers, M. A. R. Freeman†, V. Pinskerova, R. E. Field, J. Skinner, S. A. Banks. Does lateral lift-off occur in static and dynamic activity in a medially spherical total knee arthroplasty? A pulsed-fluoroscopic investigation. Bone Joint Res 2019;8:207–215. DOI: 10.1302/2046-3758.85.BJR-2018-0237.R1


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 826 - 832
1 Jul 2022
Stadelmann VA Rüdiger HA Nauer S Leunig M

Aims

It is not known whether preservation of the capsule of the hip positively affects patient-reported outcome measures (PROMs) in total hip arthroplasty using the direct anterior approach (DAA-THA). A recent randomized controlled trial found no clinically significant difference at one year postoperatively. This study aimed to determine whether preservation of the anterolateral capsule and anatomical closure improve the outcome and revision rate, when compared with resection of the anterolateral capsule, at two years postoperatively.

Methods

Two consecutive groups of patients whose operations were performed by the senior author were compared. The anterolateral capsule was resected in the first group of 430 patients between January 2012 and December 2014, and preserved and anatomically closed in the second group of 450 patients between July 2015 and December 2017. There were no other technical changes between the two groups. Patient characteristics, the Charlson Comorbidity Index (CCI), and surgical data were collected from our database. PROM questionnaires, consisting of the Oxford Hip Score (OHS) and Core Outcome Measures Index (COMI-Hip), were collected two years postoperatively. Data were analyzed with generalized multiple regression analysis.


Bone & Joint Open
Vol. 3, Issue 5 | Pages 367 - 374
5 May 2022
Sinagra ZP Davis JS Lorimer M de Steiger RN Graves SE Yates P Manning L

Aims

National joint registries under-report revisions for periprosthetic joint infection (PJI). We aimed to validate PJI reporting to the Australian Orthopaedic Association National Joint Arthroplasty Registry (AOANJRR) and the factors associated with its accuracy. We then applied these data to refine estimates of the total national burden of PJI.

Methods

A total of 561 Australian cases of confirmed PJI were captured by a large, prospective observational study, and matched to data available for the same patients through the AOANJRR.


Bone & Joint Open
Vol. 3, Issue 7 | Pages 549 - 556
1 Jul 2022
Poacher AT Bhachoo H Weston J Shergill K Poacher G Froud J

Aims

Evidence exists of a consistent decline in the value and time that medical schools place upon their undergraduate orthopaedic placements. This limited exposure to trauma and orthopaedics (T&O) during medical school will be the only experience in the speciality for the majority of doctors. This review aims to provide an overview of undergraduate orthopaedic training in the UK.

Methods

This review summarizes the relevant literature from the last 20 years in the UK. Articles were selected from database searches using MEDLINE, EMBASE, ERIC, Cochrane, and Web of Science. A total of 16 papers met the inclusion criteria.


Bone & Joint Open
Vol. 3, Issue 5 | Pages 383 - 389
1 May 2022
Motesharei A Batailler C De Massari D Vincent G Chen AF Lustig S

Aims

No predictive model has been published to forecast operating time for total knee arthroplasty (TKA). The aims of this study were to design and validate a predictive model to estimate operating time for robotic-assisted TKA based on demographic data, and evaluate the added predictive power of CT scan-based predictors and their impact on the accuracy of the predictive model.

Methods

A retrospective study was conducted on 1,061 TKAs performed from January 2016 to December 2019 with an image-based robotic-assisted system. Demographic data included age, sex, height, and weight. The femoral and tibial mechanical axis and the osteophyte volume were calculated from CT scans. These inputs were used to develop a predictive model aimed to predict operating time based on demographic data only, and demographic and 3D patient anatomy data.


Bone & Joint Research
Vol. 11, Issue 4 | Pages 214 - 225
20 Apr 2022
Hao X Zhang J Shang X Sun K Zhou J Liu J Chi R Xu T

Aims

Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

Methods

A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed.


Bone & Joint Open
Vol. 3, Issue 3 | Pages 268 - 274
21 Mar 2022
Krishnan H Eldridge JD Clark D Metcalfe AJ Stevens JM Mandalia V

Recognized anatomic variations that lead to patella instability include patella alta and trochlea dysplasia. Lateralization of the extensor mechanism relative to the trochlea is often considered to be a contributing factor; however, controversy remains as to the degree this contributes to instability and how this should be measured. As the tibial tuberosity-trochlear groove (TT-TG) is one of most common imaging measurements to assess lateralization of the extensor mechanism, it is important to understand its strengths and weaknesses. Care needs to be taken while interpreting the TT-TG value as it is affected by many factors. Medializing tibial tubercle osteotomy is sometimes used to correct the TT-TG, but may not truly address the underlying anatomical problem. This review set out to determine whether the TT-TG distance sufficiently summarizes the pathoanatomy, and if this assists with planning of surgery in patellar instability.

Cite this article: Bone Jt Open 2022;3(3):268–274.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 332 - 339
20 Apr 2022
Everett BP Sherrill G Nakonezny PA Wells JE

Aims

This study aims to answer the following questions in patients with hip osteoarthritis (OA) who underwent total hip arthroplasty (THA): are patient-reported outcome measures (PROMs) affected by the location of the maximum severity of pain?; are PROMs affected by the presence of non-groin pain?; are PROMs affected by the severity of pain?; and are PROMs affected by the number of pain locations?

Methods

We reviewed 336 hips (305 patients) treated with THA for hip OA from December 2016 to November 2019 using pain location/severity questionnaires, modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), international Hip Outcome Tool (iHOT-12) score, and radiological analysis. Descriptive statistics, analysis of covariance (ANCOVA), and Spearman partial correlation coefficients were used.