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The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1485 - 1492
1 Dec 2024
Terek RM

Aims

The aim of the LightFix Trial was to evaluate the clinical outcomes for one year after the treatment of impending and completed pathological fractures of the humerus using the IlluminOss System (IS), and to analyze the performance of this device.

Methods

A total of 81 patients with an impending or completed pathological fracture were enrolled in a multicentre, open label single cohort study and treated with IS. Inclusion criteria were visual analogue scale (VAS) Pain Scores > 60 mm/100 mm and Mirels’ Score ≥ 8. VAS pain, Musculoskeletal Tumor Society (MSTS) Upper Limb Function, and The European Organization for Research and Treatment of Cancer QoL Group Bone Metastases Module (QLQ-BM22) scores were all normalized to 100, and radiographs were obtained at baseline and at 14, 30, 90, 180, and 360 days postoperatively.


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. 105-B, Issue 5 | Pages 559 - 567
1 May 2023
Aoude A Nikomarov D Perera JR Ibe IK Griffin AM Tsoi KM Ferguson PC Wunder JS

Aims

Giant cell tumour of bone (GCTB) is a locally aggressive lesion that is difficult to treat as salvaging the joint can be associated with a high rate of local recurrence (LR). We evaluated the risk factors for tumour relapse after treatment of a GCTB of the limbs.

Methods

A total of 354 consecutive patients with a GCTB underwent joint salvage by curettage and reconstruction with bone graft and/or cement or en bloc resection. Patient, tumour, and treatment factors were analyzed for their impact on LR. Patients treated with denosumab were excluded.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 715 - 722
10 Oct 2022
Matsuyama Y Nakamura T Yoshida K Hagi T Iino T Asanuma K Sudo A

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1414 - 1420
1 Aug 2021
Wellings EP Houdek MT Owen AR Bakri K Yaszemski MJ Sim FH Moran SL Rose PS

Aims

Orthopaedic and reconstructive surgeons are faced with large defects after the resection of malignant tumours of the sacrum. Spinopelvic reconstruction is advocated for resections above the level of the S1 neural foramina or involving the sacroiliac joint. Fixation may be augmented with either free vascularized fibular flaps (FVFs) or allograft fibular struts (AFSs) in a cathedral style. However, there are no studies comparing these reconstructive techniques.

Methods

We reviewed 44 patients (23 female, 21 male) with a mean age of 40 years (SD 17), who underwent en bloc sacrectomy for a malignant tumour of the sacrum with a reconstruction using a total (n = 20), subtotal (n = 2), or hemicathedral (n = 25) technique. The reconstructions were supplemented with a FVF in 25 patients (57%) and an AFS in 19 patients (43%). The mean length of the strut graft was 13 cm (SD 4). The mean follow-up was seven years (SD 5).


Bone & Joint Research
Vol. 10, Issue 5 | Pages 310 - 320
3 May 2021
Choi J Lee YS Shim DM Lee YK Seo SW

Aims

Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway.

Methods

A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses.


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

Aims

Local recurrence remains a challenging and common problem following curettage and joint-sparing surgery for giant cell tumour of bone (GCTB). We previously reported a 15% local recurrence rate at a median follow-up of 30 months in 20 patients with high-risk GCTB treated with neoadjuvant Denosumab. The aim of this study was to determine if this initial favourable outcome following the use of Denosumab was maintained with longer follow-up.

Methods

Patients with GCTB of the limb considered high-risk for unsuccessful joint salvage, due to minimal periarticular and subchondral bone, large soft tissue mass, or pathological fracture, were treated with Denosumab followed by extended intralesional curettage with the goal of preserving the joint surface. Patients were followed for local recurrence, metastasis, and secondary sarcoma.


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1743 - 1751
1 Dec 2020
Lex JR Evans S Cool P Gregory J Ashford RU Rankin KS Cosker T Kumar A Gerrand C Stevenson J

Aims

Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients.

Methods

MEDLINE (PubMed), EMBASE (Ovid), Cochrane, and CINAHL databases were searched focusing on VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, or wound complication rates.


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

Aims

Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines.

Methods

We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay.


The Bone & Joint Journal
Vol. 101-B, Issue 6 | Pages 745 - 752
1 Jun 2019
Toki S Kobayashi E Yoshida A Ogura K Wakai S Yoshimoto S Yonemori K Kawai A

Aims

The purpose of this study was to clarify the clinical behaviour, prognosis, and optimum treatment of dedifferentiated low-grade osteosarcoma (DLOS) diagnosed based on molecular pathology.

Patients and Methods

We retrospectively reviewed 13 DLOS patients (six men, seven women; median age 32 years (interquartile range (IQR) 27 to 38)) diagnosed using the following criteria: the histological coexistence of low-grade and high-grade osteosarcoma components in the lesion, and positive immunohistochemistry of mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase 4 (CDK4) associated with MDM2 amplification. These patients were then compared with 51 age-matched consecutive conventional osteosarcoma (COS) patients (33 men, 18 women; median age 25 years (IQR 20 to 38)) regarding their clinicopathological features.


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 170 - 177
1 Feb 2019
Puri A Gulia A Hegde P Verma V Rekhi B

Aims

The aims of this study were to evaluate the efficacy of preoperative denosumab in achieving prospectively decided intention of therapy in operable giant cell tumour of bone (GCTB) patients, and to document local recurrence-free survival (LRFS).

Patients and Methods

A total of 44 patients received preoperative denosumab: 22 to facilitate curettage, 16 to facilitate resection, and six with intent of converting resection to curettage. There were 26 male and 18 female patients. The mean age was 27 years (13 to 47).


The Bone & Joint Journal
Vol. 100-B, Issue 5 | Pages 667 - 674
1 May 2018
Lauthe O Soubeyrand M Babinet A Dumaine V Anract P Biau DJ

Aims

The primary aim of this study was to determine the morbidity of a tibial strut autograft and characterize the rate of bony union following its use.

Patients and Methods

We retrospectively assessed a series of 104 patients from a single centre who were treated with a tibial strut autograft of > 5 cm in length. A total of 30 had a segmental reconstruction with continuity of bone, 27 had a segmental reconstruction without continuity of bone, 29 had an arthrodesis and 18 had a nonunion. Donor-site morbidity was defined as any event that required a modification of the postoperative management. Union was assessed clinically and radiologically at a median of 36 months (IQR, 14 to 74).


Bone & Joint Research
Vol. 6, Issue 3 | Pages 186 - 193
1 Mar 2017
Choi YJ Lee YS Lee HW Shim DM Seo SW

Objectives

Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells.

Methods

To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines.


The Bone & Joint Journal
Vol. 98-B, Issue 12 | Pages 1674 - 1681
1 Dec 2016
Verdegaal SHM van Rijswijk CS Brouwers HFC Dijkstra PDS van de Sande MAJ Hogendoorn PCW Taminiau AHM

Aims

The purpose of this retrospective study was to differentiate between the MRI features of normal post-operative change and those of residual or recurrent disease after intralesional treatment of an atypical cartilage tumour (ACT)/grade I chondrosarcoma.

Patients and Methods

We reviewed the case notes, radiology and histology of 75 patients, who had been treated for an ACT/grade I chondrosarcoma by curettage, phenolisation and bone allografting between 1994 and 2005. The first post-operative Gd-enhanced MRI scan was carried out within one year of surgery. Patients had a minimum of two scans and a mean follow-up of 72 months (13 to 169). Further surgery was undertaken in cases of suspected recurrence.


Bone & Joint Research
Vol. 3, Issue 4 | Pages 101 - 107
1 Apr 2014
Edmondson MC Day R Wood D

Objectives

The most concerning infection of allografts and operative procedures is methicillin resistant Staphylococcus aureus (MRSA) and no current iontophoresed antibiotics effectively combat this microbe. It was initially hypothesised that iontophoresis of vancomycin through bone would not be effective due to its large molecular size and lack of charge. The aim of this study was to determine whether this was a viable procedure and to find the optimum conditions for its use.

Methods

An iontophoresis cell was set up with varying concentrations of Vancomycin within the medulla of a section of sheep tibia, sealed from an external saline solution. The cell was run for varying times, Vancomycin concentrations and voltages, to gain information on optimisation of conditions for impregnating the graft. Each graft was then sectioned and dust ground from the exposed surface. The dust was serially washed to extract the Vancomycin and concentrations measured and plotted for all variables tested.


The Bone & Joint Journal
Vol. 96-B, Issue 4 | Pages 555 - 561
1 Apr 2014
Igarashi K Yamamoto N Shirai T Hayashi K Nishida H Kimura H Takeuchi A Tsuchiya H

In 1999, we developed a technique for biological reconstruction after excision of a bone tumour, which involved using autografts of the bone containing the tumour treated with liquid nitrogen. We have previously reported the use of this technique in 28 patients at a mean follow up of 27 months (10 to 54).

In this study, we included 72 patients who underwent reconstruction using this technique. A total of 33 patients died and three were lost to follow-up, at a mean of 23 months (2 to 56) post-operatively, leaving 36 patients available for a assessment at a mean of 101 months 16 to 163) post-operatively. The methods of reconstruction included an osteo-articular graft in 16, an intercalary in 13 and, a composite graft with prosthesis in seven.

Post-operative function was excellent in 26 patients (72.2%), good in seven (19.4%), and fair in three (8.3%) according to the functional evaluation system of Enneking. No recurrent tumour occurred within the grafts. The autografts survived in 29 patients (80.6%), and the rates of survival at five and ten years were 86.1% and 80.6 %, respectively. Seven of 16 osteo-articular grafts (44%) failed because of fracture or infection, but all the composite and intercalary grafts survived.

The long-term outcomes of frozen autografting, particularly using composite and intercalary grafts, are satisfactory and thus represent a good method of treatment for patients with a sarcoma of bone or soft tissue.

Cite this article: Bone Joint J 2014;96-B:555–61.


The Bone & Joint Journal
Vol. 95-B, Issue 5 | Pages 683 - 688
1 May 2013
Chen Y Tai BC Nayak D Kumar N Chua KH Lim JW Goy RWL Wong HK

There is currently no consensus about the mean volume of blood lost during spinal tumour surgery and surgery for metastatic spinal disease. We conducted a systematic review of papers published in the English language between 31 January 1992 and 31 January 2012. Only papers that clearly presented blood loss data in spinal surgery for metastatic disease were included. The random effects model was used to obtain the pooled estimate of mean blood loss.

We selected 18 papers, including six case series, ten retrospective reviews and two prospective studies. Altogether, there were 760 patients who had undergone spinal tumour surgery and surgery for metastatic spinal disease. The pooled estimate of peri-operative blood loss was 2180 ml (95% confidence interval 1805 to 2554) with catastrophic blood loss as high as 5000 ml, which is rare. Aside from two studies that reported large amounts of mean blood loss (> 5500 ml), the resulting funnel plot suggested an absence of publication bias. This was confirmed by Egger’s test, which did not show any small-study effects (p = 0.119). However, there was strong evidence of heterogeneity between studies (I2 = 90%; p < 0.001).

Spinal surgery for metastatic disease is associated with significant blood loss and the possibility of catastrophic blood loss. There is a need to establish standardised methods of calculating and reporting this blood loss. Analysis should include assessment by area of the spine, primary pathology and nature of surgery so that the amount of blood loss can be predicted. Consideration should be given to autotransfusion in these patients.

Cite this article: Bone Joint J 2013;95-B:683–8.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 8 | Pages 1135 - 1142
1 Aug 2012
Derikx LC van Aken JB Janssen D Snyers A van der Linden YM Verdonschot N Tanck E

Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R2 = 0.90 and R2 = 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 8 | Pages 1078 - 1082
1 Aug 2009
Kang HG Roh YW Kim HS

We have developed a hollow perforated cannulated screw. One or more of these was implanted percutaneously in 11 patients with an osteolytic metastasis in the femoral neck and multiple metastases elsewhere. They were supplemented by one or two additional standard 6.5 mm cannulated screws in nine patients. Polymethylmethacrylate bone cement was injected through the screw into the neck of the femur using small syringes, as in vertebroplasty. The mean amount of cement injected was 23.2 ml (17 to 30). Radiotherapy was started on the fourth post-operative day and chemotherapy, on average, was resumed a day later.

Good structural stability and satisfactory relief from pain were achieved in all the patients. This technique may be useful in the palliation of metastases in the femoral neck.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 10 | Pages 1367 - 1372
1 Oct 2006
Gupta A Pollock R Cannon SR Briggs TWR Skinner J Blunn G

We used a knee-sparing distal femoral endoprosthesis in young patients with malignant bone tumours of the distal femur in whom it was possible to resect the tumour and to preserve the distal femoral condyles. The proximal shaft of the endoprosthesis had a coated hydroxyapatite collar, while the distal end had hydroxyapatite-coated extracortical plates to secure it to the small residual femoral condylar fragment. We reviewed the preliminary results of this endoprosthesis in eight patients with primary bone tumours of the distal femur. Their mean age at surgery was 17.years (14 to 21). The mean follow-up was 24 months (20 to 31). At final follow-up the mean flexion at the knee was 102° (20° to 120°) and the mean Musculoskeletal Tumour Society score was 80% (57% to 96.7%).

There was excellent osteointegration at the prosthesis-proximal bone interface with formation of new bone around the hydroxyapatite collar. The prosthesis allowed preservation of the knee and achieved a good functional result. Formation of new bone and remodelling at the interface make the implant more secure. Further follow-up is required to determine the long-term structural integrity of the prosthesis.