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Bone & Joint Research
Vol. 12, Issue 4 | Pages 256 - 258
3 Apr 2023
Farrow L Evans J

Cite this article: Bone Joint Res 2023;12(4):256–258.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1060 - 1066
1 Sep 2022
Jin X Gallego Luxan B Hanly M Pratt NL Harris I de Steiger R Graves SE Jorm L

Aims. The aim of this study was to estimate the 90-day periprosthetic joint infection (PJI) rates following total knee arthroplasty (TKA) and total hip arthroplasty (THA) for osteoarthritis (OA). Methods. This was a data linkage study using the New South Wales (NSW) Admitted Patient Data Collection (APDC) and the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), which collect data from all public and private hospitals in NSW, Australia. Patients who underwent a TKA or THA for OA between 1 January 2002 and 31 December 2017 were included. The main outcome measures were 90-day incidence rates of hospital readmission for: revision arthroplasty for PJI as recorded in the AOANJRR; conservative definition of PJI, defined by T84.5, the PJI diagnosis code in the APDC; and extended definition of PJI, defined by the presence of either T84.5, or combinations of diagnosis and procedure code groups derived from recursive binary partitioning in the APDC. Results. The mean 90-day revision rate for infection was 0.1% (0.1% to 0.2%) for TKA and 0.3% (0.1% to 0.5%) for THA. The mean 90-day PJI rates defined by T84.5 were 1.3% (1.1% to 1.7%) for TKA and 1.1% (0.8% to 1.3%) for THA. The mean 90-day PJI rates using the extended definition were 1.9% (1.5% to 2.2%) and 1.5% (1.3% to 1.7%) following TKA and THA, respectively. Conclusion. When reporting the revision arthroplasty for infection, the AOANJRR substantially underestimates the rate of PJI at 90 days. Using combinations of infection codes and PJI-related surgical procedure codes in linked hospital administrative databases could be an alternative way to monitor PJI rates. Cite this article: Bone Joint J 2022;104-B(9):1060–1066


Bone & Joint Open
Vol. 5, Issue 1 | Pages 69 - 77
25 Jan 2024
Achten J Appelbe D Spoors L Peckham N Kandiyali R Mason J Ferguson D Wright J Wilson N Preston J Moscrop A Costa M Perry DC

Aims. The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial. Methods. Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale, and quality of life (QoL) assessed with the EuroQol five-dimension questionnaire for younger patients (EQ-5D-Y) will be collected. Each patient will be randomly allocated (1:1, stratified using a minimization algorithm by centre and initial elbow dislocation status (i.e. dislocated or not-dislocated at presentation to the emergency department)) to either a regimen of the operative fixation or non-surgical treatment. Outcomes. At six weeks, and three, six, and 12 months, data on function, pain, sports/music participation, QoL, immobilization, and analgesia will be collected. These will also be repeated annually until the child reaches the age of 16 years. Four weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the PROMIS upper limb score at 12 months post-randomization. All data will be obtained through electronic questionnaires completed by the participants and/or parents/guardians. The NHS number of participants will be stored to enable future data linkage to sources of routinely collected data (i.e. Hospital Episode Statistics). Cite this article: Bone Jt Open 2024;5(1):69–77


Bone & Joint Research
Vol. 11, Issue 2 | Pages 134 - 142
23 Feb 2022
Luo P Cheng S Zhang F Feng R Xu K Jing W Xu P

Aims. The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Methods. Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls. Results. We found that seven kinds of plasma proteins had genetic correlations with RA, such as Soluble Receptor for Advanced Glycation End Products (sRAGE) (correlation coefficient = 0.2582, p = 0.049), vesicle transport protein USE1 (correlation coefficient = 0.1337, p = 0.018), and spermatogenesis-associated protein 20 (correlation coefficient = 0.3706, p = 0.018). There was a significant causal relationship between sRAGE and RA. By comparing the genes encoding seven plasma proteins, we found that only USE1 was a DEG associated with RA. Conclusion. Our study identified a set of candidate plasma proteins that showed signals correlated with RA. Since the results of this study need further experimental verification, they should be interpreted with caution. However, we hope that this paper will provide new insights for the discovery of pathogenic genes and RA pathogenesis in the future. Cite this article: Bone Joint Res 2022;11(2):134–142


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1312 - 1320
1 Nov 2024
Hamoodi Z Sayers A Whitehouse MR Rangan A Kearsley-Fleet L Sergeant J Watts AC

Aims. The aim of this study was to review the provision of total elbow arthroplasties (TEAs) in England, including the incidence, the characteristics of the patients and the service providers, the types of implant, and the outcomes. Methods. We analyzed the primary TEAs recorded in the National Joint Registry (NJR) between April 2012 and December 2022, with mortality data from the Civil Registration of Deaths dataset. Linkage with Hospital Episode Statistics-Admitted Patient Care (HES-APC) data provided further information not collected by the NJR. The incidences were calculated using estimations of the populations from the Office for National Statistics. The annual number of TEAs performed by surgeons and hospitals was analyzed on a national and regional basis. Results. A total of 3,891 primary TEAs were included. The annual incidence of TEA was between 0.72 and 0.82 per 100,000 persons before 2020 and declined to 0.4 due to a decrease in elective TEAs during the COVID-19 pandemic, with a slight recovery in 2022. Older patients, those of white ethnicity and females, were more likely to undergo TEA. Those who underwent elective TEA had a median wait of between 89 (IQR 41 to 221) and 122 days (IQR 74 to 189) in the years before 2021, and this increased to 183 days (IQR 66 to 350) in 2021. The number of TEAs performed by surgeons per annum remained unchanged, with a median of two (IQR 1 to 3). The median annual number of TEAs per region was three to six times higher than the median annual case load of the highest volume hospital in a region. Patients in the lowest socioeconomic group had a higher rate of serious adverse events and mortality (11%) when undergoing TEA for acute trauma. Conclusion. In England, TEA is more common in older age groups, those of white ethnicity, and females. The COVID-19 pandemic affected the incidence of elective TEA and waiting times, and the provision of TEA has not yet recovered. The Getting it Right First Time recommendation of centralizing services to one centre per region could result in up to a six-fold increase in the number of TEAs being performed in some centres. Cite this article: Bone Joint J 2024;106-B(11):1312–1320


Bone & Joint Research
Vol. 11, Issue 1 | Pages 12 - 22
13 Jan 2022
Zhang F Rao S Baranova A

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 77 - 85
1 Jan 2024
Foster AL Warren J Vallmuur K Jaiprakash A Crawford R Tetsworth K Schuetz MA

Aims. The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). Methods. This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. Results. There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. Conclusion. The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies. Cite this article: Bone Joint J 2024;106-B(1):77–85


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 20 - 27
1 Jan 2018
Sabah SA Moon JC Jenkins-Jones S Morgan CL Currie CJ Wilkinson JM Porter M Captur G Henckel J Chaturvedi N Kay P Skinner JA Hart AH Manisty C

Aims. The aim of this study was to determine whether patients with metal-on-metal (MoM) arthroplasties of the hip have an increased risk of cardiac failure compared with those with alternative types of arthroplasties (non-MoM). Patients and Methods. A linkage study between the National Joint Registry, Hospital Episodes Statistics and records of the Office for National Statistics on deaths was undertaken. Patients who underwent elective total hip arthroplasty between January 2003 and December 2014 with no past history of cardiac failure were included and stratified as having either a MoM (n = 53 529) or a non-MoM (n = 482 247) arthroplasty. The primary outcome measure was the time to an admission to hospital for cardiac failure or death. Analysis was carried out using data from all patients and from those matched by propensity score. Results. The risk of cardiac failure was lower in the MoM cohort compared with the non-MoM cohort (adjusted hazard ratio (aHR) 0.901; 95% confidence interval (CI) 0.853 to 0.953). The risk of cardiac failure was similar following matching (aHR 0.909; 95% CI 0.838 to 0.987) and the findings were consistent in subgroup analysis. Conclusion. The risk of cardiac failure following total hip arthroplasty was not increased in those in whom MoM implants were used, compared with those in whom other types of prostheses were used, in the first seven years after surgery. Cite this article: Bone Joint J 2018;100-B:20–7


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 10 - 18
1 Jan 2015
Sabah SA Henckel J Cook E Whittaker R Hothi H Pappas Y Blunn G Skinner JA Hart AJ

Arthroplasty registries are important for the surveillance of joint replacements and the evaluation of outcome. Independent validation of registry data ensures high quality. The ability for orthopaedic implant retrieval centres to validate registry data is not known. We analysed data from the National Joint Registry for England, Wales and Northern Ireland (NJR) for primary metal-on-metal hip arthroplasties performed between 2003 and 2013. Records were linked to the London Implant Retrieval Centre (RC) for validation. A total of 67 045 procedures on the NJR and 782 revised pairs of components from the RC were included. We were able to link 476 procedures (60.9%) recorded with the RC to the NJR successfully. However, 306 procedures (39.1%) could not be linked. The outcome recorded by the NJR (as either revised, unrevised or death) for a primary procedure was incorrect in 79 linked cases (16.6%). The rate of registry-retrieval linkage and correct assignment of outcome code improved over time. The rates of error for component reference numbers on the NJR were as follows: femoral head category number 14/229 (5.0%); femoral head batch number 13/232 (5.3%); acetabular component category number 2/293 (0.7%) and acetabular component batch number 24/347 (6.5%). . Registry-retrieval linkage provided a novel means for the validation of data, particularly for component fields. This study suggests that NJR reports may underestimate rates of revision for many types of metal-on-metal hip replacement. This is topical given the increasing scope for NJR data. We recommend a system for continuous independent evaluation of the quality and validity of NJR data. Cite this article: Bone Joint J 2015;97-B:10–18


Bone & Joint 360
Vol. 3, Issue 3 | Pages 23 - 25
1 Jun 2014

The June 2014 Wrist & Hand Roundup360 looks at: aart throwing not quite as we thought; two-gear, four-bar linkage in the wrist?; assessing outcomes in distal radial fractures; gold standard Swanson’s?; multistrand repairs of unclear benefit in flexor tendon release; for goodness’ sake, leave the thumb alone in scaphoid fractures; horizons in carpal tunnel surgery; treading the Essex-Lopresti tightrope; wrist replacement in trauma? and radial shortening reliable in the long term for Kienbock’s disease


Bone & Joint Open
Vol. 5, Issue 3 | Pages 184 - 201
7 Mar 2024
Achten J Marques EMR Pinedo-Villanueva R Whitehouse MR Eardley WGP Costa ML Kearney RS Keene DJ Griffin XL

Aims

Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care.

Methods

This trial is a pragmatic, multicentre, randomized non-inferiority clinical trial with an embedded pilot, and with 12 months clinical follow-up and parallel economic analysis. A surveillance study using routinely collected data will be performed annually to five years post-treatment. Adult patients, aged 60 years and younger, with unstable ankle fractures will be identified in daily trauma meetings and fracture clinics and approached for recruitment prior to their treatment. Treatments will be performed in trauma units across the UK by a wide range of surgeons. Details of the surgical treatment, including how the operation is done, implant choice, and the recovery programme afterwards, will be at the discretion of the treating surgeon. The non-surgical treatment will be close-contact casting performed under anaesthetic, a technique which has gained in popularity since the publication of the Ankle Injury Management (AIM) trial. In all, 890 participants (445 per group) will be randomly allocated to surgical or non-surgical treatment. Data regarding ankle function, QoL, complications, and healthcare-related costs will be collected at eight weeks, four and 12 months, and then annually for five years following treatment. The primary outcome measure is patient-reported ankle function at four months from treatment.


Bone & Joint Open
Vol. 5, Issue 1 | Pages 60 - 68
24 Jan 2024
Shawon MSR Jin X Hanly M de Steiger R Harris I Jorm L

Aims

It is unclear whether mortality outcomes differ for patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery who are readmitted to the index hospital where their surgery was performed, or to another hospital.

Methods

We analyzed linked hospital and death records for residents of New South Wales, Australia, aged ≥ 18 years who had an emergency readmission within 90 days following THA or TKA surgery between 2003 and 2022. Multivariable modelling was used to identify factors associated with non-index readmission and to evaluate associations of readmission destination (non-index vs index) with 90-day and one-year mortality.


Bone & Joint Open
Vol. 5, Issue 3 | Pages 162 - 173
4 Mar 2024
Di Mascio L Hamborg T Mihaylova B Kassam J Shah B Stuart B Griffin XL

Aims

Is it feasible to conduct a definitive multicentre trial in community settings of corticosteroid injections (CSI) and hydrodilation (HD) compared to CSI for patients with frozen shoulder? An adequately powered definitive randomized controlled trial (RCT) delivered in primary care will inform clinicians and the public whether hydrodilation is a clinically and cost-effective intervention. In this study, prior to a full RCT, we propose a feasibility trial to evaluate recruitment and retention by patient and clinician willingness of randomization; rates of withdrawal, crossover and attrition; and feasibility of outcome data collection from routine primary and secondary care data.

Methods

In the UK, the National Institute for Health and Care Excellence (NICE) advises that prompt early management of frozen shoulder is initiated in primary care settings with analgesia, physiotherapy, and joint injections; most people can be managed without an operation. Currently, there is variation in the type of joint injection: 1) CSI, thought to reduce the inflammation of the capsule reducing pain; and 2) HD, where a small volume of fluid is injected into the shoulder joint along with the steroid, aiming to stretch the capsule of the shoulder to improve pain, but also allowing greater movement. The creation of musculoskeletal hubs nationwide provides infrastructure for the early and effective management of frozen shoulder. This potentially reduces costs to individuals and the wider NHS perhaps negating the need for a secondary care referral.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 198 - 204
16 Mar 2023
Ramsay N Close JCT Harris IA Harvey LA

Aims

Cementing in arthroplasty for hip fracture is associated with improved postoperative function, but may have an increased risk of early mortality compared to uncemented fixation. Quantifying this mortality risk is important in providing safe patient care. This study investigated the association between cement use in arthroplasty and mortality at 30 days and one year in patients aged 50 years and over with hip fracture.

Methods

This retrospective cohort study used linked data from the Australian Hip Fracture Registry and the National Death Index. Descriptive analysis and Kaplan-Meier survival curves tested the unadjusted association of mortality between cemented and uncemented procedures. Multilevel logistic regression, adjusted for covariates, tested the association between cement use and 30-day mortality following arthroplasty. Given the known institutional variation in preference for cemented fixation, an instrumental variable analysis was also performed to minimize the effect of unknown confounders. Adjusted Cox modelling analyzed the association between cement use and mortality at 30 days and one year following surgery.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

Methods

We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 474 - 484
10 Sep 2024
Liu Y Li X Jiang L Ma J

Aims

Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

Methods

Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 843 - 850
8 Oct 2024
Greve K Ek S Bartha E Modig K Hedström M

Aims

The primary aim of this study was to compare surgical methods (sliding hip screw (SHS) vs intramedullary nailing (IMN)) for trochanteric hip fracture in relation to death within 120 days after surgery and return to independent living. The secondary aim was to assess whether the associations between surgical method and death or ability to return to independent living varied depending on fracture subtype or other patient characteristics.

Methods

A total of 27,530 individuals from the Swedish Hip Fracture Register RIKSHÖFT (SHR) aged ≥ 70 years, admitted to hospital between 1 January 2014 and 31 December 2019 with trochanteric hip fracture, were included. Within this cohort, 12,041 individuals lived independently at baseline, had follow-up information in the SHR, and were thus investigated for return to independent living. Death within 120 days after surgery was analyzed using Cox regression with SHS as reference and adjusted for age and fracture type. Return to independent living was analyzed using logistic regression adjusted for age and fracture type. Analyses were repeated after stratification by fracture type, age, and sex.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1050 - 1058
1 Oct 2024
Holleyman RJ Jameson SS Meek RMD Khanduja V Reed MR Judge A Board TN

Aims

This study evaluates the association between consultant and hospital volume and the risk of re-revision and 90-day mortality following first-time revision of primary hip arthroplasty for aseptic loosening.

Methods

We conducted a cohort study of first-time, single-stage revision hip arthroplasties (RHAs) performed for aseptic loosening and recorded in the National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man between 2003 and 2019. Patient identifiers were used to link records to national mortality data, and to NJR data to identify subsequent re-revision procedures. Multivariable Cox proportional hazard models with restricted cubic splines were used to define associations between volume and outcome.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 321 - 330
9 May 2023
Lenguerrand E Whitehouse MR Beswick AD Kunutsor SK Webb JCJ Mehendale S Porter M Blom AW

Aims

We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty.

Methods

Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.


Aims

Delirium is associated with adverse outcomes following hip fracture, but the prevalence and significance of delirium for the prognosis and ongoing rehabilitation needs of patients admitted from home is less well studied. Here, we analyzed relationships between delirium in patients admitted from home with 1) mortality; 2) total length of hospital stay; 3) need for post-acute inpatient rehabilitation; and 4) hospital readmission within 180 days.

Methods

This observational study used routine clinical data in a consecutive sample of hip fracture patients aged ≥ 50 years admitted to a single large trauma centre during the COVID-19 pandemic between 1 March 2020 and 30 November 2021. Delirium was prospectively assessed as part of routine care by the 4 A’s Test (4AT), with most assessments performed in the emergency department. Associations were determined using logistic regression adjusted for age, sex, Scottish Index of Multiple Deprivation quintile, COVID-19 infection within 30 days, and American Society of Anesthesiologists grade.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 601 - 614
21 Sep 2023
Gu P Pu B Liu T Yue D Xin Q Li H Yang B Ke D Zheng X Zeng Z Zhang Z

Aims

Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies.

Methods

PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 624 - 635
4 Oct 2023
Harrison CJ Plessen CY Liegl G Rodrigues JN Sabah SA Beard DJ Fischer F

Aims

To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health.

Methods

Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale.


Bone & Joint Open
Vol. 3, Issue 11 | Pages 898 - 906
15 Nov 2022
Dakin H Rombach I Dritsaki M Gray A Ball C Lamb SE Nanchahal J

Aims

To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren’s disease (DD) and the value of further research from an NHS perspective.

Methods

We used data from the Repurposing anti-TNF for Dupuytren’s disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded.


Aims

To systematically review the efficacy of split tendon transfer surgery on gait-related outcomes for children and adolescents with cerebral palsy (CP) and spastic equinovarus foot deformity.

Methods

Five databases (CENTRAL, CINAHL, PubMed, Embase, Web of Science) were systematically screened for studies investigating split tibialis anterior or split tibialis posterior tendon transfer for spastic equinovarus foot deformity, with gait-related outcomes (published pre-September 2022). Study quality and evidence were assessed using the Methodological Index for Non-Randomized Studies, the Risk of Bias In Non-Randomized Studies of Interventions, and the Grading of Recommendations Assessment, Development and Evaluation.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 690 - 699
4 Oct 2022
Lenguerrand E Whitehouse MR Kunutsor SK Beswick AD Baker RP Rolfson O Reed MR Blom AW

Aims

We compared the risks of re-revision and mortality between two-stage revision surgery and single-stage revision surgery among patients with infected primary knee arthroplasty.

Methods

Patients with a periprosthetic joint infection (PJI) of their primary knee arthroplasty, initially revised with a single-stage or a two-stage procedure in England and Wales between 2003 and 2014, were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HR) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.


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 Research
Vol. 11, Issue 9 | Pages 652 - 668
7 Sep 2022
Lv G Wang B Li L Li Y Li X He H Kuang L

Aims

Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

Methods

Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 811 - 819
1 Jul 2022
Galvain T Mantel J Kakade O Board TN

Aims

The aim of this study was to estimate the clinical and economic burden of dislocation following primary total hip arthroplasty (THA) in England.

Methods

This retrospective evaluation used data from the UK Clinical Practice Research Datalink database. Patients were eligible if they underwent a primary THA (index date) and had medical records available 90 days pre-index and 180 days post-index. Bilateral THAs were excluded. Healthcare costs and resource use were evaluated over two years. Changes (pre- vs post-THA) in generic quality of life (QoL) and joint-specific disability were evaluated. Propensity score matching controlled for baseline differences between patients with and without THA dislocation.


Bone & Joint Open
Vol. 3, Issue 7 | Pages 515 - 528
1 Jul 2022
van der Heijden L Bindt S Scorianz M Ng C Gibbons MCLH van de Sande MAJ Campanacci DA

Aims

Giant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review.

Methods

We included 76 patients with distal radius GCTB in three sarcoma centres (1990 to 2019). Median follow-up was 8.8 years (2 to 23). Seven patients underwent curettage, 38 curettage with adjuvants, and 31 resection; 20 had denosumab.


Bone & Joint Open
Vol. 3, Issue 5 | Pages 390 - 397
1 May 2022
Hiranaka T Suda Y Saitoh A Tanaka A Arimoto A Koide M Fujishiro T Okamoto K

The kinematic alignment (KA) approach to total knee arthroplasty (TKA) has recently increased in popularity. Accordingly, a number of derivatives have arisen and have caused confusion. Clarification is therefore needed for a better understanding of KA-TKA. Calipered (or true, pure) KA is performed by cutting the bone parallel to the articular surface, compensating for cartilage wear. In soft-tissue respecting KA, the tibial cutting surface is decided parallel to the femoral cutting surface (or trial component) with in-line traction. These approaches are categorized as unrestricted KA because there is no consideration of leg alignment or component orientation. Restricted KA is an approach where the periarthritic joint surface is replicated within a safe range, due to concerns about extreme alignments that have been considered ‘alignment outliers’ in the neutral mechanical alignment approach. More recently, functional alignment and inverse kinematic alignment have been advocated, where bone cuts are made following intraoperative planning, using intraoperative measurements acquired with computer assistance to fulfill good coordination of soft-tissue balance and alignment. The KA-TKA approach aims to restore the patients’ own harmony of three knee elements (morphology, soft-tissue balance, and alignment) and eventually the patients’ own kinematics. The respective approaches start from different points corresponding to one of the elements, yet each aim for the same goal, although the existing implants and techniques have not yet perfectly fulfilled that goal.


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.


The Bone & Joint Journal
Vol. 103-B, Issue 12 | Pages 1821 - 1830
1 Dec 2021
Marson BA Manning JC James M Craxford S Deshmukh SR Perry DC Ollivere BJ

Aims

The aim of this study is to develop a core set of outcome domains that should be considered and reported in all future trials of childhood limb fractures.

Methods

A four-phase study was conducted to agree a set of core outcome domains. Identification of candidate outcome domains were identified through systematic review of trials, and outcome domains relevant to families were identified through semi-structured interviews with 20 families (parent-child pairing or group). Outcome domains were prioritized using an international three-round Delphi survey with 205 panellists and then condensed into a core outcome set through a consensus workshop with 30 stakeholders.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 734 - 741
1 Nov 2021
Cheng B Wen Y Yang X Cheng S Liu L Chu X Ye J Liang C Yao Y Jia Y Zhang F

Aims

Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

Methods

A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 348 - 350
1 Jun 2021
Skinner JA Sabah SA Hart AJ


Bone & Joint Open
Vol. 2, Issue 6 | Pages 371 - 379
15 Jun 2021
Davies B Kaila R Andritsos L Gray Stephens C Blunn GW Gerrand C Gikas P Johnston A

Aims

Hydroxyapatite (HA)-coated collars have been shown to reduce aseptic loosening of massive endoprostheses following primary surgery. Limited information exists about their effectiveness in revision surgery. The aim of this study was to radiologically assess osteointegration to HA-coated collars of cemented massive endoprostheses following revision surgery.

Methods

Retrospective review of osseointegration frequency, pattern, and timing to a specific HA-coated collar on massive endoprostheses used in revision surgery at our tertiary referral centre between 2010 to 2017 was undertaken. Osseointegration was radiologically classified on cases with a minimum follow-up of six months.


The Bone & Joint Journal
Vol. 103-B, Issue 7 | Pages 1317 - 1324
1 Jul 2021
Goubar A Martin FC Potter C Jones GD Sackley C Ayis S Sheehan KJ

Aims

The aim of this study to compare 30-day survival and recovery of mobility between patients mobilized early (on the day of, or day after surgery for a hip fracture) and patients mobilized late (two days or more after surgery), and to determine whether the presence of dementia influences the association between the timing of mobilization, 30-day survival, and recovery.

Methods

Analysis of the National Hip Fracture Database and hospital records for 126,897 patients aged ≥ 60 years who underwent surgery for a hip fracture in England and Wales between 2014 and 2016. Using logistic regression, we adjusted for covariates with a propensity score to estimate the association between the timing of mobilization, survival, and recovery of walking ability.


Bone & Joint Open
Vol. 2, Issue 6 | Pages 414 - 421
1 Jun 2021
Kim SK Nguyen C Avins AL Abrams GD

Aims

The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury.

Methods

Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies.


Bone & Joint Research
Vol. 10, Issue 6 | Pages 340 - 347
1 Jun 2021
Jenkinson MRJ Meek RMD Tate R MacMillan S Grant MH Currie S

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy.

Cite this article: Bone Joint Res 2021;10(6):340–347.


The Bone & Joint Journal
Vol. 102-B, Issue 2 | Pages 145 - 147
1 Feb 2020
Ollivere B Metcalfe D Perry DC Haddad FS


Bone & Joint Open
Vol. 2, Issue 3 | Pages 203 - 210
19 Mar 2021
Yapp LZ Clarke JV Moran M Simpson AHRW Scott CEH

Aims

The COVID-19 pandemic led to a national suspension of “non-urgent” elective hip and knee arthroplasty. The study aims to measure the effect of the COVID-19 pandemic on total hip arthroplasty (THA) and total knee arthroplasty (TKA) volume in Scotland. Secondary objectives are to measure the success of restarting elective services and model the time required to bridge the gap left by the first period of suspension.

Methods

A retrospective observational study using the Scottish Arthroplasty Project dataset. All patients undergoing elective THAs and TKAs during the period 1 January 2008 to 31 December 2020 were included. A negative binomial regression model using historical case-volume and mid-year population estimates was built to project the future case-volume of THA and TKA in Scotland. The median monthly case volume was calculated for the period 2008 to 2019 (baseline) and compared to the actual monthly case volume for 2020. The time taken to eliminate the deficit was calculated based upon the projected monthly workload and with a potential workload between 100% to 120% of baseline.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 689 - 700
7 Oct 2020
Zhang A Ma S Yuan L Wu S Liu S Wei X Chen L Ma C Zhao H

Aims

The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5).

Methods

TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR.


Aims

Slipped capital femoral epiphysis (SCFE) is one of the most common hip diseases of adolescence that can cause marked disability, yet there is little robust evidence to guide treatment. Fundamental aspects of the disease, such as frequency, are unknown and consequently the desire of clinicians to undertake robust intervention studies is somewhat prohibited by a lack of fundamental knowledge.

Methods

The study is an anonymized nationwide comprehensive cohort study with nested consented within the mechanism of the British Orthopaedic Surgery Surveillance (BOSS) Study. All relevant hospitals treating SCFE in England, Scotland, and Wales will contribute anonymized case details. Potential missing cases will be cross-checked against two independent external sources of data (the national administrative data and independent trainee data). Patients will be invited to enrich the data collected by supplementing anonymized case data with patient-reported outcome measures. In line with recommendations of the IDEAL Collaboration, the study will primarily seek to determine incidence, describe case mix and variations in surgical interventions, and explore the relationships between baseline factors (patients and types of interventions) and two-year outcomes.


Bone & Joint Open
Vol. 1, Issue 3 | Pages 41 - 46
18 Mar 2020
Perry DC Arch B Appelbe D Francis P Spowart C Knight M

Introduction

There is widespread variation in the management of rare orthopaedic disease, in a large part owing to uncertainty. No individual surgeon or hospital is typically equipped to amass sufficient numbers of cases to draw robust conclusions from the information available to them. The programme of research will establish the British Orthopaedic Surgery Surveillance (BOSS) Study; a nationwide reporting structure for rare disease in orthopaedic surgery.

Methods

The BOSS Study is a series of nationwide observational cohort studies of pre-specified orthopaedic disease. All relevant hospitals treating the disease are invited to contribute anonymised case details. Data will be collected digitally through REDCap, with an additional bespoke software solution used to regularly confirm case ascertainment, prompt follow-up reminders and identify potential missing cases from external sources of information (i.e. national administrative data). With their consent, patients will be invited to enrich the data collected by supplementing anonymised case data with patient reported outcomes.

The study will primarily seek to calculate the incidence of the rare diseases under investigation, with 95% confidence intervals. Descriptive statistics will be used to describe the case mix, treatment variations and outcomes. Inferential statistical analysis may be used to analyze associations between presentation factors and outcomes. Types of analyses will be contingent on the disease under investigation.


Bone & Joint Research
Vol. 9, Issue 8 | Pages 501 - 514
1 Aug 2020
Li X Yang Y Sun G Dai W Jie X Du Y Huang R Zhang J

Aims

Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method.

Methods

We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets.


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.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 635 - 644
1 Oct 2020
Lemaignen A Grammatico-Guillon L Astagneau P Marmor S Ferry T Jolivet-Gougeon A Senneville E Bernard L

Aims

The French registry for complex bone and joint infections (C-BJIs) was created in 2012 in order to facilitate a homogeneous management of patients presented for multidisciplinary advice in referral centres for C-BJI, to monitor their activity and to produce epidemiological data. We aimed here to present the genesis and characteristics of this national registry and provide the analysis of its data quality.

Methods

A centralized online secured database gathering the electronic case report forms (eCRFs) was filled for every patient presented in multidisciplinary meetings (MM) among the 24 French referral centres. Metrics of this registry were described between 2012 and 2016. Data quality was assessed by comparing essential items from the registry with a controlled dataset extracted from medical charts of a random sample of patients from each centre. Internal completeness and consistency were calculated.


Bone & Joint Research
Vol. 8, Issue 11 | Pages 544 - 549
1 Nov 2019
Zheng W Liu C Lei M Han Y Zhou X Li C Sun S Ma X

Objectives

The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility.

Methods

Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software (http://analysis.bio-x.cn/) was employed.


Aims

To investigate the effect of polyethylene manufacturing characteristics and irradiation dose on the survival of cemented and reverse hybrid total hip arthroplasties (THAs).

Methods

In this registry study, data from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man (NJR) were linked with manufacturing data supplied by manufacturers. The primary endpoint was revision of any component. Cox proportional hazard regression was a primary analytic approach adjusting for competing risk of death, patient characteristics, head composition, and stem fixation.


Bone & Joint Research
Vol. 9, Issue 7 | Pages 351 - 359
1 Jul 2020
Fitzgerald J

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 130 - 138
1 Mar 2020
Qi X Yu F Wen Y Li P Cheng B Ma M Cheng S Zhang L Liang C Liu L Zhang F

Aims

Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear.

Methods

Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools.


Bone & Joint Research
Vol. 8, Issue 11 | Pages 570 - 572
1 Nov 2019
Ahmed SS Haddad FS


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 90 - 101
1 Jan 2020
Davis ET Pagkalos J Kopjar B

Aims

The aim of this study was to identify the effect of the manufacturing characteristics of polyethylene acetabular liners on the survival of cementless and hybrid total hip arthroplasty (THA).

Methods

Prospective cohort study using linked National Joint Registry (NJR) and manufacturer data. The primary endpoint was revision for aseptic loosening. Cox proportional hazard regression was the primary analytical approach. Manufacturing variables included resin type, crosslinking radiation dose, terminal sterilization method, terminal sterilization radiation dose, stabilization treatment, total radiation dose, packaging, and face asymmetry. Total radiation dose was further divided into G1 (no radiation), G2 (> 0 Mrad to < 5 Mrad), G3 (≥ 5 Mrad to < 10 Mrad), and G4 (≥ 10 Mrad).


Bone & Joint Research
Vol. 9, Issue 1 | Pages 1 - 14
1 Jan 2020
Stewart S Darwood A Masouros S Higgins C Ramasamy A

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.


Bone & Joint 360
Vol. 8, Issue 5 | Pages 14 - 16
1 Oct 2019


Bone & Joint 360
Vol. 8, Issue 3 | Pages 40 - 42
1 Jun 2019


Bone & Joint 360
Vol. 6, Issue 4 | Pages 38 - 39
1 Aug 2017
Khan T


The Bone & Joint Journal
Vol. 101-B, Issue 8 | Pages 1015 - 1023
1 Aug 2019
Metcalfe D Zogg CK Judge A Perry DC Gabbe B Willett K Costa ML

Aims

Hip fractures are associated with high morbidity, mortality, and costs. One strategy for improving outcomes is to incentivize hospitals to provide better quality of care. We aimed to determine whether a pay-for-performance initiative affected hip fracture outcomes in England by using Scotland, which did not participate in the scheme, as a control.

Materials and Methods

We undertook an interrupted time series study with data from all patients aged more than 60 years with a hip fracture in England (2000 to 2018) using the Hospital Episode Statistics Admitted Patient Care (HES APC) data set linked to national death registrations. Difference-in-differences (DID) analysis incorporating equivalent data from the Scottish Morbidity Record was used to control for secular trends. The outcomes were 30-day and 365-day mortality, 30-day re-admission, time to operation, and acute length of stay.


Bone & Joint Research
Vol. 7, Issue 7 | Pages 494 - 500
1 Jul 2018
Jiang L Zhu X Rong J Xing B Wang S Liu A Chu M Huang G

Objectives

Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA.

Methods

We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.


Bone & Joint 360
Vol. 7, Issue 2 | Pages 23 - 25
1 Apr 2018


Bone & Joint 360
Vol. 7, Issue 2 | Pages 30 - 33
1 Apr 2018


Bone & Joint Research
Vol. 6, Issue 6 | Pages 391 - 398
1 Jun 2017
Lenguerrand E Whitehouse MR Beswick AD Jones SA Porter ML Blom* AW

Objectives

We used the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) to investigate the risk of revision due to prosthetic joint infection (PJI) for patients undergoing primary and revision hip arthroplasty, the changes in risk over time, and the overall burden created by PJI.

Methods

We analysed revision total hip arthroplasties (THAs) performed due to a diagnosis of PJI and the linked index procedures recorded in the NJR between 2003 and 2014. The cohort analysed consisted of 623 253 index primary hip arthroplasties, 63 222 index revision hip arthroplasties and 7585 revision THAs performed due to a diagnosis of PJI. The prevalence, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression.


Bone & Joint Research
Vol. 6, Issue 10 | Pages 572 - 576
1 Oct 2017
Wang W Huang S Hou W Liu Y Fan Q He A Wen Y Hao J Guo X Zhang F

Objectives

Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data

Method

We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05.


Bone & Joint 360
Vol. 6, Issue 5 | Pages 12 - 16
1 Oct 2017


Bone & Joint 360
Vol. 6, Issue 3 | Pages 10 - 12
1 Jun 2017


Bone & Joint 360
Vol. 6, Issue 3 | Pages 16 - 19
1 Jun 2017


Bone & Joint Research
Vol. 5, Issue 3 | Pages 80 - 86
1 Mar 2016
Scott G Imam MA Eifert A Freeman MAR Pinskerova V Field RE Skinner J Banks SA

Objectives

Throughout the 20th Century, it has been postulated that the knee moves on the basis of a four-bar link mechanism composed of the cruciate ligaments, the femur and the tibia. As a consequence, the femur has been thought to roll back with flexion, and total knee arthroplasty (TKA) prostheses have been designed on this basis. Recent work, however, has proposed that at a position of between 0° and 120° the medial femoral condyle does not move anteroposteriorly whereas the lateral femoral condyle tends, but is not obliged, to roll back – a combination of movements which equates to tibial internal/ femoral external rotation with flexion. The aim of this paper was to assess if the articular geometry of the GMK Sphere TKA could recreate the natural knee movements in situ/in vivo.

Methods

The pattern of knee movement was studied in 15 patients (six male: nine female; one male with bilateral TKAs) with 16 GMK Sphere implants, at a mean age of 66 years (53 to 76) with a mean BMI of 30 kg/m2 (20 to 35). The motions of all 16 knees were observed using pulsed fluoroscopy during a number of weight-bearing and non-weight-bearing static and dynamic activities.


The Bone & Joint Journal
Vol. 99-B, Issue 8 | Pages 1020 - 1027
1 Aug 2017
Matharu GS Judge A Pandit HG Murray DW

Aims

To determine the outcomes following revision surgery of metal-on-metal hip arthroplasties (MoMHA) performed for adverse reactions to metal debris (ARMD), and to identify factors predictive of re-revision.

Patients and Methods

We performed a retrospective observational study using National Joint Registry (NJR) data on 2535 MoMHAs undergoing revision surgery for ARMD between 2008 and 2014. The outcomes studied following revision were intra-operative complications, mortality and re-revision surgery. Predictors of re-revision were identified using competing-risk regression modelling.


Bone & Joint Research
Vol. 6, Issue 7 | Pages 405 - 413
1 Jul 2017
Matharu GS Judge A Murray DW Pandit HG

Objectives

Few studies have assessed outcomes following non-metal-on-metal hip arthroplasty (non-MoMHA) revision surgery performed for adverse reactions to metal debris (ARMD). We assessed outcomes following non-MoMHA revision surgery performed for ARMD, and identified predictors of re-revision.

Methods

We performed a retrospective observational study using data from the National Joint Registry for England and Wales. All non-MoMHAs undergoing revision surgery for ARMD between 2008 and 2014 were included (185 hips in 185 patients). Outcome measures following ARMD revision were intra-operative complications, mortality and re-revision surgery. Predictors of re-revision were identified using Cox regression.


Bone & Joint 360
Vol. 5, Issue 3 | Pages 10 - 12
1 Jun 2016


Bone & Joint Research
Vol. 5, Issue 5 | Pages 169 - 174
1 May 2016
Wang Y Chu M Rong J Xing B Zhu L Zhao Y Zhuang X Jiang L

Objectives

Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations.

Methods

We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.


Bone & Joint 360
Vol. 5, Issue 1 | Pages 32 - 33
1 Feb 2016


Bone & Joint 360
Vol. 3, Issue 1 | Pages 14 - 17
1 Feb 2014

The February 2014 Hip & Pelvis Roundup360 looks at: length of stay; cementless metaphyseal fixation; mortality trends in over 400,000 total hip replacements; antibiotics in hip fracture surgery; blood supply to the femoral head after dislocation; resurfacing and THR in metal-on-metal replacement; diabetes and hip replacement; bone remodelling over two decades following hip replacement; and whether bisphosphonates affect acetabular fixation.


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 360
Vol. 4, Issue 2 | Pages 10 - 12
1 Apr 2015

The April 2015 Hip & Pelvis Roundup360 looks at: Goal-directed fluid therapy in hip fracture; Liberal blood transfusion no benefit in the longer term; Repeated measures: increased accuracy or compounded errors?; Peri-acetabular osteotomy safer than perhaps thought?; Obesity and peri-acetabular osteotomy: poor bedfellows; Stress fracture in peri-acetabular osteotomy; Infection and tantalum implants; Highly crosslinked polyethylene really does work


Bone & Joint Research
Vol. 4, Issue 4 | Pages 50 - 55
1 Apr 2015
Sekimoto T Kurogi S Funamoto T Ota T Watanabe S Sakamoto T Hamada H Chosa E

Objectives

Excessive acetabular coverage is the most common cause of pincer-type femoroacetabular impingement. To date, an association between acetabular over-coverage and genetic variations has not been studied. In this study we investigated the association between single nucleotide polymorphisms (SNPs) of paralogous Homeobox (HOX)9 genes and acetabular coverage in Japanese individuals to identify a possible genetic variation associated with acetabular over-coverage.

Methods

We investigated 19 total SNPs in the four HOX9 paralogs, then focused in detail on seven of those located in the 3’ untranslated region of HOXB9 (rs8844, rs3826541, rs3826540, rs7405887, rs2303485, rs2303486, rs79931349) using a case-control association study. The seven HOXB9 SNPs were genotyped in 316 subjects who had all undergone radiological examination. The association study was performed by both single-locus and haplotype-based analyses.


Bone & Joint 360
Vol. 3, Issue 5 | Pages 10 - 12
1 Oct 2014

The October 2014 Hip & Pelvis Roundup360 looks at: functional acetabular orientation; predicting re-admission following THR; metal ions and resurfacing; lipped liners increase stability; all anaesthetics equal in hip fracture surgery; revision hip surgery in very young patients; and uncemented hips.


Bone & Joint 360
Vol. 3, Issue 3 | Pages 2 - 8
1 Jun 2014
Phillips JRA Waterson HB Searle DJ Mandalia VI Toms AD

This is the second of a series of reviews of registries. This review looks specifically at worldwide registry data that have been collected on knee arthroplasty, what we have learned from their reports, and what the limitations are as to what we currently know.


Bone & Joint 360
Vol. 2, Issue 1 | Pages 30 - 32
1 Feb 2013

The February 2013 Trauma Roundup360 looks at: the risk of ankle fractures; absorbable implants; minimally invasive heel fracture fixation; pertrochanteric fractures; arthroplasty and intracapsular hip fractures; and extensor mechanism disruption.


Bone & Joint 360
Vol. 1, Issue 5 | Pages 30 - 32
1 Oct 2012

The October 2012 Research Roundup360 looks at: whether you can escape your genes; oral prophylaxis for DVT; non-responders and the internet; metal-on-metal, mice and damaged livers; sleeping on the job; cartilage contact stress in the normal human hip; and a perfect reason to subscribe to 360.