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Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1633 - 1640
1 Oct 2021
Lex JR Evans S Parry MC Jeys L Stevenson JD

Aims. Proximal femoral endoprosthetic replacements (PFEPRs) are the most common reconstruction option for osseous defects following primary and metastatic tumour resection. This study aimed to compare the rate of implant failure between PFEPRs with monopolar and bipolar hemiarthroplasties and acetabular arthroplasties, and determine the optimum articulation for revision PFEPRs. Methods. This is a retrospective review of 233 patients who underwent PFEPR. The mean age was 54.7 years (SD 18.2), and 99 (42.5%) were male. There were 90 patients with primary bone tumours (38.6%), 122 with metastatic bone disease (52.4%), and 21 with haematological malignancy (9.0%). A total of 128 patients had monopolar (54.9%), 74 had bipolar hemiarthroplasty heads (31.8%), and 31 underwent acetabular arthroplasty (13.3%). Results. At a mean 74.4 months follow-up, the overall revision rate was 15.0%. Primary malignancy (p < 0.001) and age < 50 years (p < 0.001) were risk factors for revision. The risks of death and implant failure were similar in patients with primary disease (p = 0.872), but the risk of death was significantly greater for patients who had metastatic bone disease (p < 0.001). Acetabular-related implant failures comprised 74.3% of revisions; however, no difference between hemiarthroplasty or arthroplasty groups (p = 0.209), or between monopolar or bipolar hemiarthroplasties (p = 0.307), was observed. There was greater radiological wear in patients with longer follow-up and primary bone malignancy. Re-revision rates following a revision PFEPR was 34.3%, with dual-mobility bearings having the lowest rate of instability and re-revision (15.4%). Conclusion. Hemiarthroplasty and arthroplasty PFEPRs carry the same risk of revision in the medium term, and is primarily due to acetabular complications. There is no difference in revision rates or erosion between monopolar and bipolar hemiarthroplasties. The main causes of failure were acetabular wear in the hemiarthroplasty group and instability in the arthroplasty group. These risks should be balanced and patient prognosis considered when contemplating the bearing choice. Dual-mobility, constrained bearings, or large diameter heads (> 32 mm) are recommended in all revision PFEPRs. Cite this article: Bone Joint J 2021;103-B(10):1633–1640


Bone & Joint Research
Vol. 1, Issue 10 | Pages 272 - 280
1 Oct 2012
De Mattos CBR Binitie O Dormans JP

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated


Bone & Joint Open
Vol. 5, Issue 4 | Pages 317 - 323
18 Apr 2024
Zhu X Hu J Lin J Song G Xu H Lu J Tang Q Wang J

Aims

The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours.

Methods

We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 980 - 983
1 Jul 2011
Malhas AM Grimer RJ Abudu A Carter SR Tillman RM Jeys L

We investigated the eventual diagnosis in patients referred to a tertiary centre with a possible diagnosis of a primary bone malignancy. We reviewed our database from between 1986 and 2010, during which time 5922 patients referred with a suspicious bone lesion had a confirmed diagnosis. This included bone sarcoma in 2205 patients (37%), benign bone tumour in 1309 (22%), orthopaedic conditions in 992 (17%), metastatic disease in 533 (9%), infection in 289 (5%) and haematological disease in 303 (5%). There was a similar frequency of all diagnoses at different ages except for metastatic disease. Only 0.6% of patients (17 of 2913) under the age of 35 years had metastatic disease compared with 17.1% (516 of 3009) of those over 35 years (p < 0.0001). Of the 17 patients under 35 years with metastatic disease, only four presented with an isolated lesion, had no past history of cancer and were systematically well. Patients under the age of 35 years should have suitable focal imaging (plain radiography, CT or MRI) and simple systemic studies (blood tests and chest radiography). Reduction of the time to biopsy can be achieved by avoiding an unnecessary investigation for a primary tumour to rule out metastatic disease


Bone & Joint Open
Vol. 5, Issue 11 | Pages 1020 - 1026
11 Nov 2024
Pigeolet M Sana H Askew MR Jaswal S Ortega PF Bradley SR Shah A Mita C Corlew DS Saeed A Makasa E Agarwal-Harding KJ

Aims

Lower limb fractures are common in low- and middle-income countries (LMICs) and represent a significant burden to the existing orthopaedic surgical infrastructure. In high income country (HIC) settings, internal fixation is the standard of care due to its superior outcomes. In LMICs, external fixation is often the surgical treatment of choice due to limited supplies, cost considerations, and its perceived lower complication rate. The aim of this systematic review protocol is identifying differences in rates of infection, nonunion, and malunion of extra-articular femoral and tibial shaft fractures in LMICs treated with either internal or external fixation.

Methods

This systematic review protocol describes a broad search of multiple databases to identify eligible papers. Studies must be published after 2000, include at least five patients, patients must be aged > 16 years or treated as skeletally mature, and the paper must describe a fracture of interest and at least one of our primary outcomes of interest. We did not place restrictions on language or journal. All abstracts and full texts will be screened and extracted by two independent reviewers. Risk of bias and quality of evidence will be analyzed using standardized appraisal tools. A random-effects meta-analysis followed by a subgroup analysis will be performed, given the anticipated heterogeneity among studies, if sufficient data are available.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1067 - 1073
1 Oct 2024
Lodge CJ Adlan A Nandra RS Kaur J Jeys L Stevenson JD

Aims

Periprosthetic joint infection (PJI) is a challenging complication of any arthroplasty procedure. We reviewed our use of static antibiotic-loaded cement spacers (ABLCSs) for staged management of PJI where segmental bone loss, ligamentous instability, or soft-tissue defects necessitate a static construct. We reviewed factors contributing to their failure and techniques to avoid these complications when using ABLCSs in this context.

Methods

A retrospective analysis was conducted of 94 patients undergoing first-stage revision of an infected knee prosthesis between September 2007 and January 2020 at a single institution. Radiographs and clinical records were used to assess and classify the incidence and causes of static spacer failure. Of the 94 cases, there were 19 primary total knee arthroplasties (TKAs), ten revision TKAs (varus-valgus constraint), 20 hinged TKAs, one arthrodesis (nail), one failed spacer (performed elsewhere), 21 distal femoral endoprosthetic arthroplasties, and 22 proximal tibial arthroplasties.


Bone & Joint Open
Vol. 4, Issue 6 | Pages 424 - 431
5 Jun 2023
Christ AB Piple AS Gettleman BS Duong A Chen M Wang JC Heckmann ND Menendez L

Aims

The modern prevalence of primary tumours causing metastatic bone disease is ill-defined in the oncological literature. Therefore, the purpose of this study is to identify the prevalence of primary tumours in the setting of metastatic bone disease, as well as reported rates of pathological fracture, postoperative complications, 90-day mortality, and 360-day mortality for each primary tumour subtype.

Methods

The Premier Healthcare Database was queried to identify all patients who were diagnosed with metastatic bone disease from January 2015 to December 2020. The prevalence of all primary tumour subtypes was tabulated. Rates of long bone pathological fracture, 90-day mortality, and 360-day mortality following surgical treatment of pathological fracture were assessed for each primary tumour subtype. Patient characteristics and postoperative outcomes were analyzed based upon whether patients had impending fractures treated prophylactically versus treated completed fractures.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 11_Supple_A | Pages 22 - 25
1 Nov 2012
Haidukewych GJ

Many tumors metastasise to bone, therefore, pathologic fracture and impending pathologic fractures are common reasons for orthopedic consultation. Having effective treatment strategies is important to avoid complications, and relieve pain and preserve function. Thorough pre-operative evaluation is recommended for medical optimization and to ensure that the lesion is in fact a metastasis and not a primary bone malignancy. For impending fractures, various scoring systems have been proposed to determine the risk of fracture, and therefore the need for prophylactic stabilisation. Lower score lesions can often be treated with radiation, while more problematic lesions may require internal fixation. Intramedullary fixation is generally preferred due to favorable biomechanics. Arthroplasty may be required for lesions with massive bony destruction where internal fixation attempts are likely to fail. Radiation may also be useful postoperatively to minimise construct failure due to tumor progression


Bone & Joint 360
Vol. 11, Issue 2 | Pages 41 - 43
1 Apr 2022


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 9 - 16
1 Jul 2021
Hadden WJ Ibrahim M Taha M Ure K Liu Y Paish ADM Holdsworth DW Abdelbary H

Aims

The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time.

Methods

Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces.


Bone & Joint 360
Vol. 9, Issue 4 | Pages 39 - 41
1 Aug 2020


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 285 - 292
1 Mar 2020
Tanaka A Katagiri H Murata H Wasa J Miyagi M Honda Y Takahashi M

Aims

The aim of this study is to evaluate the clinical results of operative intervention for femoral metastases which were selected based on expected survival and to discuss appropriate surgical strategies.

Methods

From 2002 to 2017, 148 consecutive patients undergoing surgery for femoral metastasis were included in this study. Prognostic risk assessments were performed according to the Katagiri and revised Katagiri scoring system. In general, the low-risk group underwent resection and reconstruction with endoprosthetic replacement (EPR), while the high-risk group underwent internal fixation (IF) and radiation therapy. For the intermediate-risk group, the operative choice depended on the patient’s condition, degree of bone destruction, and radio-sensitivity. Overall survival, local failure, walking ability, and systemic complications were evaluated.


Bone & Joint 360
Vol. 8, Issue 2 | Pages 36 - 38
1 Apr 2019


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 266 - 271
1 Mar 2019
Laitinen MK Parry MC Le Nail L Wigley CH Stevenson JD Jeys LM

Aims

The purpose of this study was to investigate the potential for achieving local and systemic control after local recurrence of a chondrosarcoma of bone

Patients and Methods

A total of 126 patients with local recurrence (LR) of chondrosarcoma (CS) of the pelvis or a limb bone were identified from a prospectively maintained database, between 1990 and 2015 at the Royal Orthopaedic Hospital, Birmingham, United Kingdom. There were 44 female patients (35%) and 82 male patients (65%) with a mean age at the time of LR of 56 years (13 to 96). The 126 patients represented 24.3% of the total number of patients with a primary CS (519) who had been treated during this period. Clinical data collected at the time of primary tumour and LR included the site (appendicular, extremity, or pelvis); primary and LR tumour size (in centimetres); type of operation at the time of primary or LR (limb-salvage or amputation); surgical margin achieved at resection of the primary tumour and the LR; grade of the primary tumour and the LR; gender; age; and oncological outcomes, including local recurrence-free survival and disease-specific survival. A minimum two years’ follow-up and complete histopathology records were available for all patients included in the study.


Bone & Joint 360
Vol. 8, Issue 1 | Pages 34 - 36
1 Feb 2019


Bone & Joint 360
Vol. 7, Issue 3 | Pages 24 - 27
1 Jun 2018


The Bone & Joint Journal
Vol. 99-B, Issue 5 | Pages 660 - 665
1 May 2017
Wouthuyzen-Bakker M Ploegmakers JJW Kampinga GA Wagenmakers-Huizenga L Jutte PC Muller Kobold AC

Aims

Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI.

Patients and Methods

In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI.

PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay.


Bone & Joint Research
Vol. 6, Issue 3 | Pages 137 - 143
1 Mar 2017
Cho HS Park YK Gupta S Yoon C Han I Kim H Choi H Hong J

Objectives

We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model.

Methods

We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice.


Bone & Joint Research
Vol. 4, Issue 9 | Pages 154 - 162
1 Sep 2015

Objective

Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours.

Methods

We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens.