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Aims. The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders. Methods. Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 10. 3. or 1 × 10. 6. colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 10. 3. or 1 × 10. 6. CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash. Results. The first part of the study showed that low-grade infection was more significant in 400 µm cylinders than cylinders with larger pore sizes (p < 0.05). The second part of the study showed that saline wash alone was ineffective in eradicating both low- and high-grade infections. Saline plus PVA-VAN/TOB-P eradicated the titanium cylinder-associated infections, as manifested by negative cultures of the washouts and supported by scanning electron microscopy and histology. Conclusion. Porous titanium cylinders were vulnerable to bacterial infection and biofilm formation that could not be treated by saline irrigation alone. Application of PVA-VAN/TOB-P directly into the surgical site alone or after saline wash represents a feasible approach for prevention and/or treatment of porous implant-related infections. Cite this article: Bone Joint Res 2024;13(11):622–631


Bone & Joint Research
Vol. 13, Issue 10 | Pages 559 - 572
8 Oct 2024
Wu W Zhao Z Wang Y Liu M Zhu G Li L

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

Methods

A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 837 - 843
7 Oct 2024
Zalikha AK Waheed MA Twal C Keeley J El-Othmani MM Hajj Hussein I

Aims

This study aims to evaluate the impact of metabolic syndrome in the setting of obesity on in-hospital outcomes and resource use after total joint replacement (TJR).

Methods

A retrospective analysis was conducted using the National Inpatient Sample from 2006 to the third quarter of 2015. Discharges representing patients aged 40 years and older with obesity (BMI > 30 kg/m2) who underwent primary TJR were included. Patients were stratified into two groups with and without metabolic syndrome. The inverse probability of treatment weighting (IPTW) method was used to balance covariates.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 799 - 805
24 Sep 2024
Fletcher WR Collins T Fox A Pillai A

Aims

The Cartiva synthetic cartilage implant (SCI) entered mainstream use in the management of first metatarsophalangeal joint (MTPJ) arthritis following the positive results of large trials in 2016. Limited information is available on the longer-term outcomes of this implant within the literature, particularly when independent from the originator. This single-centre cohort study investigates the efficacy of the Cartiva SCI at up to five years.

Methods

First MTPJ arthritis was radiologically graded according to the Hattrup and Johnson (HJ) classification. Preoperative and sequential postoperative patient-reported outcome measures (PROMs) were evaluated using the Manchester-Oxford Foot Questionnaire (MOXFQ), and the activities of daily living (ADL) sub-section of the Foot and Ankle Ability Measure (FAAM).


Bone & Joint Open
Vol. 5, Issue 9 | Pages 768 - 775
18 Sep 2024
Chen K Dong X Lu Y Zhang J Liu X Jia L Guo Y Chen X

Aims

Surgical approaches to cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. The purpose of the present study was to analyze and compare the long-term neurological recovery following anterior decompression with fusion (ADF) and posterior laminectomy and fusion with bone graft and internal fixation (PLF) based on > ten-year follow-up outcomes in a single centre.

Methods

Included in this retrospective cohort study were 48 patients (12 females; mean age 55.79 years (SD 8.94)) who were diagnosed with cervical OPLL, received treatment in our centre, and were followed up for 10.22 to 15.25 years. Of them, 24 patients (six females; mean age 52.88 years (SD 8.79)) received ADF, and the other 24 patients (five females; mean age 56.25 years (SD 9.44)) received PLF. Clinical data including age, sex, and the OPLL canal-occupying ratio were analyzed and compared. The primary outcome was Japanese Orthopaedic Association (JOA) score, and the secondary outcome was visual analogue scale neck pain.


Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims

Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).

Methods

A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 656 - 661
1 Jul 2024
Bolbocean C Hattab Z O'Neill S Costa ML

Aims. Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty – the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most. Methods. We used causal forest analysis to compare subgroup- and individual-level treatment effects between cemented and modern uncemented hemiarthroplasty in patients aged > 60 years with an intracapsular fracture of the hip, using data from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized clinical trial. EuroQol five-dimension index scores were used to measure health-related quality of life at one, four, and 12 months postoperatively. Results. Our analysis revealed a complex landscape of responses to the use of a cemented hemiarthroplasty in the 12 months after surgery. There was heterogeneity of effects with regard to baseline characteristics, including age, pre-injury health status, and lifestyle factors such as alcohol consumption. This heterogeneity was greater at the one-month mark than at subsequent follow-up timepoints, with particular regard to subgroups based on age. However, for all subgroups, the effect estimates for quality of life lay within the confidence intervals derived from the analysis of all patients. Conclusion. The use of a cemented hemiarthroplasty is expected to increase health-related quality of life compared with modern uncemented hemiarthroplasty for all subgroups of patients aged > 60 years with a displaced intracapsular fracture of the hip. Cite this article: Bone Joint J 2024;106-B(7):656–661


Bone & Joint Open
Vol. 5, Issue 6 | Pages 499 - 513
20 Jun 2024
Keene DJ Achten J Forde C Png ME Grant R Draper K Appelbe D Tutton E Peckham N Dutton SJ Lamb SE Costa ML

Aims

Ankle fractures are common, mainly affecting adults aged 50 years and over. To aid recovery, some patients are referred to physiotherapy, but referral patterns vary, likely due to uncertainty about the effectiveness of this supervised rehabilitation approach. To inform clinical practice, this study will evaluate the effectiveness of supervised versus self-directed rehabilitation in improving ankle function for older adults with ankle fractures.

Methods

This will be a multicentre, parallel-group, individually randomized controlled superiority trial. We aim to recruit 344 participants aged 50 years and older with an ankle fracture treated surgically or non-surgically from at least 20 NHS hospitals. Participants will be randomized 1:1 using a web-based service to supervised rehabilitation (four to six one-to-one physiotherapy sessions of tailored advice and prescribed home exercise over three months), or self-directed rehabilitation (provision of advice and exercise materials that participants will use to manage their recovery independently). The primary outcome is participant-reported ankle-related symptoms and function six months after randomization, measured by the Olerud and Molander Ankle Score. Secondary outcomes at two, four, and six months measure health-related quality of life, pain, physical function, self-efficacy, exercise adherence, complications, and resource use. Due to the nature of the interventions, participants and intervention providers will be unblinded to treatment allocation.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 452 - 456
1 Jun 2024
Kennedy JW Rooney EJ Ryan PJ Siva S Kennedy MJ Wheelwright B Young D Meek RMD

Aims

Femoral periprosthetic fractures are rising in incidence. Their management is complex and carries a high associated mortality. Unlike native hip fractures, there are no guidelines advising on time to theatre in this group. We aim to determine whether delaying surgical intervention influences morbidity or mortality in femoral periprosthetic fractures.

Methods

We identified all periprosthetic fractures around a hip or knee arthroplasty from our prospectively collated database between 2012 and 2021. Patients were categorized into early or delayed intervention based on time from admission to surgery (early = ≤ 36 hours, delayed > 36 hours). Patient demographics, existing implants, Unified Classification System fracture subtype, acute medical issues on admission, preoperative haemoglobin, blood transfusion requirement, and length of hospital stay were identified for all patients. Complication and mortality rates were compared between groups.


Bone & Joint Open
Vol. 5, Issue 5 | Pages 444 - 451
24 May 2024
Gallagher N Cassidy R Karayiannis P Scott CEH Beverland D

Aims

The overall aim of this study was to determine the impact of deprivation with regard to quality of life, demographics, joint-specific function, attendances for unscheduled care, opioid and antidepressant use, having surgery elsewhere, and waiting times for surgery on patients awaiting total hip arthroplasty (THA) and total knee arthroplasty (TKA).

Methods

Postal surveys were sent to 1,001 patients on the waiting list for THA or TKA in a single Northern Ireland NHS Trust, which consisted of the EuroQol five-dimension five-level questionnaire (EQ-5D-5L), visual analogue scores (EQ-VAS), and Oxford Hip and Knee Scores. Electronic records determined prescriptions since addition to the waiting list and out-of-hour GP and emergency department attendances. Deprivation quintiles were determined by the Northern Ireland Multiple Deprivation Measure 2017 using postcodes of home addresses.


Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Methods

An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 184 - 192
18 Apr 2024
Morita A Iida Y Inaba Y Tezuka T Kobayashi N Choe H Ike H Kawakami E

Aims

This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model.

Methods

The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate.


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 412 - 418
1 Apr 2024
Alqarni AG Nightingale J Norrish A Gladman JRF Ollivere B

Aims

Frailty greatly increases the risk of adverse outcome of trauma in older people. Frailty detection tools appear to be unsuitable for use in traumatically injured older patients. We therefore aimed to develop a method for detecting frailty in older people sustaining trauma using routinely collected clinical data.

Methods

We analyzed prospectively collected registry data from 2,108 patients aged ≥ 65 years who were admitted to a single major trauma centre over five years (1 October 2015 to 31 July 2020). We divided the sample equally into two, creating derivation and validation samples. In the derivation sample, we performed univariate analyses followed by multivariate regression, starting with 27 clinical variables in the registry to predict Clinical Frailty Scale (CFS; range 1 to 9) scores. Bland-Altman analyses were performed in the validation cohort to evaluate any biases between the Nottingham Trauma Frailty Index (NTFI) and the CFS.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 83 - 90
19 Feb 2024
Amri R Chelly A Ayedi M Rebaii MA Aifa S Masmoudi S Keskes H

Aims

The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.

Methods

A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).


Bone & Joint Open
Vol. 5, Issue 2 | Pages 87 - 93
2 Feb 2024
Wolf O Ghukasyan Lakic T Ljungdahl J Sundkvist J Möller M Rogmark C Mukka S Hailer NP

Aims

Our primary aim was to assess reoperation-free survival at one year after the index injury in patients aged ≥ 75 years treated with internal fixation (IF) or arthroplasty for undisplaced femoral neck fractures (uFNFs). Secondary outcomes were reoperations and mortality analyzed separately.

Methods

We retrieved data on all patients aged ≥ 75 years with an uFNF registered in the Swedish Fracture Register from 2011 to 2018. The database was linked to the Swedish Arthroplasty Register and the National Patient Register to obtain information on comorbidity, mortality, and reoperations. Our primary outcome, reoperation, or death at one year was analyzed using restricted mean survival time, which gives the mean time to either event for each group separately.


Bone & Joint Open
Vol. 4, Issue 12 | Pages 957 - 963
18 Dec 2023
van den Heuvel S Penning D Sanders F van Veen R Sosef N van Dijkman B Schepers T

Aims

The primary aim of this study was to present the mid-term follow-up of a multicentre randomized controlled trial (RCT) which compared the functional outcome following routine removal (RR) to the outcome following on-demand removal (ODR) of the syndesmotic screw (SS).

Methods

All patients included in the ‘ROutine vs on DEmand removal Of the syndesmotic screw’ (RODEO) trial received the Olerud-Molander Ankle Score (OMAS), American Orthopaedic Foot and Ankle Hindfoot Score (AOFAS), Foot and Ankle Outcome Score (FAOS), and EuroQol five-dimension questionnaire (EQ-5D). Out of the 152 patients, 109 (71.7%) completed the mid-term follow-up questionnaire and were included in this study (53 treated with RR and 56 with ODR). Median follow-up was 50 months (interquartile range 43.0 to 56.0) since the initial surgical treatment of the acute syndesmotic injury. The primary outcome of this study consisted of the OMAS scores of the two groups.


Bone & Joint Research
Vol. 12, Issue 12 | Pages 722 - 733
6 Dec 2023
Fu T Chen W Wang Y Chang C Lin T Wong C

Aims

Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration.

Methods

A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses.


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. Results. A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves’ disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion. Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA. Cite this article: Bone Joint Res 2023;12(9):601–614


Bone & Joint Research
Vol. 12, Issue 9 | Pages 580 - 589
20 Sep 2023
Dai X Liu B Hou Q Dai Q Wang D Xie B Sun Y Wang B

Aims

The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

Methods

In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties.