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Bone & Joint Open
Vol. 5, Issue 10 | Pages 868 - 878
14 Oct 2024
Sekita T Asano N Kobayashi H Yonemoto T Kobayashi E Ishii T Kawai A Nakayama R

Aims. Surgical limb sparing for knee-bearing paediatric bone sarcoma is considered to have a clinically significant influence on postoperative function due to complications and leg-length discrepancies. However, researchers have not fully evaluated the long-term postoperative functional outcomes. Therefore, in this study, we aimed to elucidate the risk factors and long-term functional prognosis associated with paediatric limb-sparing surgery. Methods. We reviewed 40 patients aged under 14 years who underwent limb-sparing surgery for knee bone sarcoma (15 cases in the proximal tibia and 25 in the distal femur) between January 2000 and December 2013, and were followed up for a minimum of five years. A total of 35 patients underwent reconstruction using artificial materials, and five underwent biological reconstruction. We evaluated the patients’ postoperative complications, survival rate of reconstruction material, and limb, limb function, and leg-length discrepancy at the final follow-up, as well as the risk factors for each. Results. Complications were observed in 55% (22/40) of patients. The limb survival and reconstruction material rates at five and ten years were 95% and 91%, and 88% and 66%, respectively. Infection was the only risk factor in both survivals (p < 0.001, p = 0.019). In the 35 patients with limb preservation, the median International Society of Limb Salvage (ISOLS) score at the final follow-up was 80 (47% to 97%). Younger age (p = 0.027) and complications (p = 0.005) were poor prognostic factors. A negative correlation was found between age and leg-length discrepancy (R = −0.426; p = 0.011). The ISOLS scores were significantly lower in patients with a leg-length discrepancy of more than 5 cm (p = 0.005). Conclusion. Young age and complications were linked to an unfavourable functional prognosis. Leg-length correction was insufficient, especially in very young children, resulting in decreased function of the affected limb. Limb-sparing surgery for these children remains a considerable challenge. Cite this article: Bone Jt Open 2024;5(10):868–878


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). Results. We found that RANKL and RUNX2 gene expression was upregulated more in recurrent than in non-recurrent GCTB tissues, while OPG gene expression was downregulated more in recurrent than in non-recurrent GCTB tissues. Additionally, we proved that changes in DNA methylation contribute to upregulating the expression of RANKL and downregulating the expression of OPG, which are critical for bone homeostasis and GCTB development. Conclusion. Our results suggest that the overexpression of RANKL/RUNX2 and the lower expression of OPG are associated with recurrence in GCTB patients. Cite this article: Bone Joint Res 2024;13(2):84–91


Bone & Joint Research
Vol. 11, Issue 5 | Pages 278 - 291
12 May 2022
Hu X Fujiwara T Houdek MT Chen L Huang W Sun Z Sun Y Yan W

Aims. Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. Methods. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). Results. Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). Conclusion. In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278–291


Bone & Joint Research
Vol. 13, Issue 9 | Pages 497 - 506
16 Sep 2024
Hsieh H Yen H Hsieh W Lin C Pan Y Jaw F Janssen SJ Lin W Hu M Groot O

Aims. Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments. Methods. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve. Results. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians’ experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs. Cite this article: Bone Joint Res 2024;13(9):497–506


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. Results. In all, 17 patients with locally aggressive bone tumours (Enneking stage IIB) located in the femoral shaft underwent JSLSS and reconstruction with 3D-printed modular prostheses between January 2020 and June 2022. The median surgical time was 153 minutes (interquartile range (IQR) 117 to 248), and the median estimated blood loss was 200ml (IQR 125 to 400). Osteosarcoma was the most common pathological type (n = 12; 70.6%). The mean osteotomy length was 197.53 mm (SD 12.34), and the median follow-up was 25 months (IQR 19 to 38). Two patients experienced local recurrence and three developed distant metastases. Postoperative complications included wound infection in one patient and screw loosening in another, both of which were treated successfully with revision surgery. The median Musculoskeletal Tumor Society score at the final follow-up was 28 (IQR 27 to 28). Conclusion. The 3D-printed modular prosthesis is a reliable and feasible reconstruction option for patients with malignant femoral diaphyseal tumours. It helps to improve the limb salvage rate, restore limb function, and achieve better short-term effectiveness. Cite this article: Bone Jt Open 2024;5(4):317–323


Bone & Joint Research
Vol. 10, Issue 9 | Pages 602 - 610
24 Sep 2021
Tsoi KM Gokgoz N Darville-O'Quinn P Prochazka P Malekoltojari A Griffin AM Ferguson PC Wunder JS Andrulis IL

Aims. Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Methods. Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR). Results. Cell-free was present in 69 of 70 samples above 0.5 ng/ml. Improved disease-free survival was found for patients with lower cfDNA levels (90% vs 48% at one-year for ≤ 6 ng/ml and > 6 ng/ml, respectively; p = 0.005). Digital droplet PCR was performed as a pilot study and mutant alleles were detectable at 0.5% to 2.5% of the wild type genome, and at a level of 0.25 ng tumour DNA. Tumour-specific alterations (ctDNA) were found in five of six cases. Conclusion. This work demonstrates the feasibility and potential utility of cfDNA and ctDNA as biomarkers for bone and soft-tissue sarcomas, despite the lack of recurrent genomic alterations. A larger study is required to validate these findings. Cite this article: Bone Joint Res 2021;10(9):602–610


Bone & Joint Open
Vol. 2, Issue 2 | Pages 125 - 133
1 Feb 2021
Bavan L Wijendra A Kothari A

Aims. Aneurysmal bone cysts (ABCs) are locally aggressive lesions typically found in the long bones of children and adolescents. A variety of management strategies have been reported to be effective in the treatment of these lesions. The purpose of this review was to assess the effectiveness of current strategies for the management of primary ABCs of the long bones. Methods. A systematic review of the published literature was performed to identify all articles relating to the management of primary ABCs. Studies required a minimum 12-month follow-up and case series reporting on under ten participants were not included. Results. A total of 28 articles meeting the eligibility criteria were included in this review, and all but one were retrospective in design. Due to heterogeneity in study design, treatment, and outcome reporting, data synthesis and group comparison was not possible. The most common treatment option reported on was surgical curettage with or without a form of adjuvant therapy, followed by injection-based therapies. Of the 594 patients treated with curettage across 17 studies, 86 (14.4%) failed to heal or experienced a recurrence. Similar outcomes were reported for 57 (14.70%) of the 387 patients treated with injection therapy across 12 studies. Only one study directly compared curettage with injection therapy (polidocanol), randomizing 94 patients into both treatment groups. This study was at risk of bias and provided low-quality evidence of a lack of difference between the two interventions, reporting success rates of 93.3% and 84.8% for injection and surgical treatment groups, respectively. Conclusion. While both surgery and sclerotherapy are widely implemented for treatment of ABCs, there is currently no good quality evidence to support the use of one option over the other. There is a need for prospective multicentre randomized controlled trials (RCTs) on interventions for the treatment of ABCs. Cite this article: Bone Jt Open 2021;2(2):125–133


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. Results. Vancomycin was successfully delivered and impregnated to the graft using the iontophoresis technique. The first order fit to the whole data set gave a significant result (p = 0.0233), with a significant concentration (p = 0.02774) component. The time component was the next most significant (p = 0.0597), but did not exceed the 95% confidence level. Conclusions. Iontophoresis is an effective method for delivering Vancomycin to allograft bone. The concentrations of the vancomycin solution affected the bone concentration, but results were highly variable. Further study should be done on the effectiveness of delivering different antibiotics using this method. Cite this article: Bone Joint Res 2014;3:101–7


Bone & Joint Open
Vol. 5, Issue 12 | Pages 1092 - 1100
8 Dec 2024
Fraser E Spence S Farhan-Alanie OM Doonan J Mahendra A Gupta S

Aims. Limb salvage surgery (LSS) is the primary treatment option for primary bone malignancy. It involves the removal of bone and tissue, followed by reconstruction with endoprosthetic replacements (EPRs) to prevent amputation. Trabecular metal (TM) collars have been developed to encourage bone ingrowth (osseointegration (OI)) into EPRs. The primary aim of this study was to assess whether OI occurs when TM collars are used in EPRs for tumour. Methods. A total of 124 patients from July 2010 to August 2021 who underwent an EPR for tumour under the West of Scotland orthopaedic oncology team were identified. Overall, 81 patients (65%) met the inclusion criteria, and two consultants independently analyzed radiographs at three and 12 months, as well as the last radiograph, using a modified version of the Stanford Radiological Assessment System. Results. OI of the TM collar occurred in approximately 65% of patients at last radiograph. The percentage of patients with OI at three months (65.4%) reflected the 12-month (65%) and long-term (64.4%) follow-up. The median amount of OI across all radiographs was one at all three timepoints, with only five cases (11.1%) showing OI in all four zones at last radiograph. Radiolucency at the bone:collar junction was present in 23 cases (28.4%) at three months, but only four (6.7%) showed progression of this at 12 months. The interobserver reliability was found to be highly reliable in all parameters (p < 0.001). Conclusion. OI occurs in approximately 65% of TM collars, and is similar at three months, 12 months, and last radiograph. The extent of OI at the bone:collar junction was found to have decreased at longer-term follow-up. Furthermore, radiolucency at the bone-collar impact junction does occur in some patients but only a low number will show radiolucency progression at longer-term follow-up. Cite this article: Bone Jt Open 2024;5(12):1092–1100


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. Results. In total, 407,893 unique patients with metastatic bone disease were identified. Of the 14 primary tumours assessed, metastatic bone disease most frequently originated from lung (24.8%), prostatic (19.4%), breast (19.3%), gastrointestinal (9.4%), and urological (6.5%) malignancies. The top five malignant tumours resulting in long bone pathological fracture were renal (5.8%), myeloma (3.4%), female reproductive (3.2%), lung (2.8%), and breast (2.7%). Following treatment of pathological fractures of long bones, 90-day mortality rates were greatest for lung (12.1%), central nervous system (10.5%), lymphoma (10.4%), gastrointestinal (10.1%), and non-renal urinary (10.0%) malignancies. Finally, our study demonstrates improved 90-day and 360-day survival in patients treated for impending pathological fracture compared to completed fracture, as well as significantly lower rates of deep vein thrombosis, pulmonary embolism, urinary tract infection, and blood transfusion. Conclusion. This study defines the contemporary characteristics of primary malignancies resulting in metastatic bone disease. These data should be considered by surgeons when prognosticating patient outcomes during treatment of their metastatic bone disease. Cite this article: Bone Jt Open 2023;4(6):424–431


Bone & Joint Open
Vol. 5, Issue 10 | Pages 944 - 952
25 Oct 2024
Deveza L El Amine MA Becker AS Nolan J Hwang S Hameed M Vaynrub M

Aims. Treatment of high-grade limb bone sarcoma that invades a joint requires en bloc extra-articular excision. MRI can demonstrate joint invasion but is frequently inconclusive, and its predictive value is unknown. We evaluated the diagnostic accuracy of direct and indirect radiological signs of intra-articular tumour extension and the performance characteristics of MRI findings of intra-articular tumour extension. Methods. We performed a retrospective case-control study of patients who underwent extra-articular excision for sarcoma of the knee, hip, or shoulder from 1 June 2000 to 1 November 2020. Radiologists blinded to the pathology results evaluated preoperative MRI for three direct signs of joint invasion (capsular disruption, cortical breach, cartilage invasion) and indirect signs (e.g. joint effusion, synovial thickening). The discriminatory ability of MRI to detect intra-articular tumour extension was determined by receiver operating characteristic analysis. Results. Overall, 49 patients underwent extra-articular excision. The area under the curve (AUC) ranged from 0.65 to 0.76 for direct signs of joint invasion, and was 0.83 for all three combined. In all, 26 patients had only one to two direct signs of invasion, representing an equivocal result. In these patients, the AUC was 0.63 for joint effusion and 0.85 for synovial thickening. When direct signs and synovial thickening were combined, the AUC was 0.89. Conclusion. MRI provides excellent discrimination for determining intra-articular tumour extension when multiple direct signs of invasion are present. When MRI results are equivocal, assessment of synovial thickening increases MRI’s discriminatory ability to predict intra-articular joint extension. These results should be interpreted in the context of the study’s limitations. The inclusion of only extra-articular excisions enriched the sample for true positive cases. Direct signs likely varied with tumour histology and location. A larger, prospective study of periarticular bone sarcomas with spatial correlation of histological and radiological findings is needed to validate these results before their adoption in clinical practice. Cite this article: Bone Jt Open 2024;5(10):944–952


Aims. For rare cases when a tumour infiltrates into the hip joint, extra-articular resection is required to obtain a safe margin. Endoprosthetic reconstruction following tumour resection can effectively ensure local control and improve postoperative function. However, maximizing bone preservation without compromising surgical margin remains a challenge for surgeons due to the complexity of the procedure. The purpose of the current study was to report clinical outcomes of patients who underwent extra-articular resection of the hip joint using a custom-made osteotomy guide and 3D-printed endoprosthesis. Methods. We reviewed 15 patients over a five-year period (January 2017 to December 2022) who had undergone extra-articular resection of the hip joint due to malignant tumour using a custom-made osteotomy guide and 3D-printed endoprosthesis. Each of the 15 patients had a single lesion, with six originating from the acetabulum side and nine from the proximal femur. All patients had their posterior column preserved according to the surgical plan. Results. Postoperative pathological assessment revealed a negative surgical margin was achieved in all patients. At final follow-up, 13.3% (2/15) died and no recurrence occurred. The overall survival was 81.7% at five years. None of the patients showed any signs of aseptic loosening, and no wound healing issues were observed. In total, 20% (3/15) developed complications, with two cases of early hip dislocation and one case of deep infection. The cumulative incidence of mechanical and non-mechanical failure in this series was 13.7% and 9.3%, respectively, at five years. In this cohort, the mean time to full weightbearing was 5.89 (SD 0.92) weeks and the mean Musculoskeletal Tumor Society score was 24.1 (SD 4.4). Conclusion. For patients with a hip joint tumour who met the inclusion criteria and were deemed suitable for posterior column preservation, a custom-made osteotomy guide combined with 3D-printed endoprosthesis is worth performing when treating patients who require extra-articular resection of the hip joint, as it can achieve adequate margin for local control, maximize bone preservation to maintain pelvic ring integrity, reduce the risk of complications by simplifying the surgical procedure, and allow for more precise reconstruction for better function. Cite this article: Bone Jt Open 2024;5(11):1027–1036


Aims. To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs. Methods. The medical records of 75 patients who underwent surgery between 2000 and 2020 were retrospectively reviewed, and 44 patients who were alive and available for follow-up (at a mean of 9.7 years postoperatively) were included in the study. Leg length discrepancy was measured on whole-leg radiographs, and functional assessment was performed with PROMs (Toronto Extremity Salvage Score (TESS) and Comprehensive Outcome Measure for Musculoskeletal Oncology Lower Extremity (COMMON-LE)) with two different aspects. The thresholds for unfavourable PROMs were determined using anchor questions regarding satisfaction, and the risk factors for unfavourable PROMs were investigated. Results. The thresholds for favourable TESS and COMMON were 64.8 and 70.4 points, respectively. Multivariate analysis showed that age at surgery (p = 0.004) and postoperative leg length discrepancy (p = 0.043) were significant risk factors for unfavourable TESS results, while age at surgery (p < 0.001) was a significant risk factor for unfavourable COMMON-LE results. Following receiver operating characteristic analysis, the threshold for both TESS and COMMON-LE was 29 years of age at surgery. Additionally, a leg length discrepancy of 8.2 mm was the threshold for unfavourable TESS. Conclusion. Patients aged > 29 years at the time of surgery require appropriate preoperative counselling and adequate postoperative physical and socioemotional support. Reconstruction equivalent to the length of the resected bone can reduce the risk of functional disabilities in daily living. Cite this article: Bone Jt Open 2023;4(12):906–913


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


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


Bone & Joint Open
Vol. 5, Issue 9 | Pages 749 - 757
12 Sep 2024
Hajialiloo Sami S Kargar Shooroki K Ammar W Nahvizadeh S Mohammadi M Dehghani R Toloue B

Aims. The ulna is an extremely rare location for primary bone tumours of the elbow in paediatrics. Although several reconstruction options are available, the optimal reconstruction method is still unknown due to the rarity of proximal ulna tumours. In this study, we report the outcomes of osteoarticular ulna allograft for the reconstruction of proximal ulna tumours. Methods. Medical profiles of 13 patients, who between March 2004 and November 2021 underwent osteoarticular ulna allograft reconstruction after the resection of the proximal ulna tumour, were retrospectively reviewed. The outcomes were measured clinically by the assessment of elbow range of motion (ROM), stability, and function, and radiologically by the assessment of allograft-host junction union, recurrence, and joint degeneration. The elbow function was assessed objectively by the Musculoskeletal Tumor Society (MSTS) score and subjectively by the Toronto Extremity Salvage Score (TESS) and Mayo Elbow Performance Score (MEPS) questionnaire. Results. The mean follow-up of patients was 60.3 months (SD 28.5). The mean elbow flexion-extension ROM was 95.8° (SD 21). The mean MSTS of the patients was 84.4 (SD 8.2), the mean TESS was 83.8 (SD 6.7), and the mean MEPS was 79.2 (SD 11.5). All the patients had radiological union at the osteotomy site. Symptomatic osteoarthritic change was observed in three patients (23%), one of whom ended up with elbow joint fusion. Two patients (15.4%) had recurrence during the follow-up period. Surgical complications included two allograft fractures, two plate fractures, three medial instabilities, and two infections. Conclusion. Osteoarticular ulna allograft reconstruction provides acceptable functional outcomes. Despite a high rate of complications, it is still a valuable reconstruction method, particularly in skeletally immature patients who need their distal humerus physis for the rest of hand growth. Cite this article: Bone Jt Open 2024;5(9):749–757


Bone & Joint Open
Vol. 4, Issue 6 | Pages 442 - 446
12 Jun 2023
Toda Y Iwata S Kobayashi E Ogura K Osaki S Fukushima S Mawatari M Kawai A

Aims. The risk of postoperative complications after resection of soft-tissue sarcoma in the medial thigh is higher than in other locations. This study investigated whether a vessel sealing system (VSS) could help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Methods. Of 285 patients who underwent wide resection for soft-tissue sarcoma between 2014 and 2021 at our institution, 78 patients with tumours in the medial thigh were extracted from our database. Information on clinicopathological characteristics, preoperative treatment, surgical treatment (use of VSS, blood loss volume, operating time), and postoperative course (complications, postoperative haemoglobin changes, total drainage volume, and drainage and hospitalization durations) were obtained from medical records. We statistically compared clinical outcomes between patients whose surgery did or did not use VSS (VSS and non-VSS groups, respectively). Results. There were 24 patients in the VSS group and 54 in the non-VSS group. There were no significant differences between the two groups in terms of clinicopathological background. The total drainage volume in the VSS group was significantly less than that in the non-VSS group (1,176 ml vs 3,114 ml; p = 0.018). Moreover, the drainage and hospitalization durations were significantly shorter in the VSS group compared to the non-VSS group (p = 0.017 and p = 0.024, respectively). Conclusion. Our results suggest that use of VSS can help reduce the risk of postoperative complications after wide resection of soft-tissue sarcoma in the medial thigh. Cite this article: Bone Jt Open 2023;4(6):442–446


Bone & Joint Open
Vol. 5, Issue 5 | Pages 385 - 393
13 May 2024
Jamshidi K Toloue Ghamari B Ammar W Mirzaei A

Aims. Ilium is the most common site of pelvic Ewing’s sarcoma (ES). Resection of the ilium and iliosacral joint causes pelvic disruption. However, the outcomes of resection and reconstruction are not well described. In this study, we report patients’ outcomes after resection of the ilium and iliosacral ES and reconstruction with a tibial strut allograft. Methods. Medical files of 43 patients with ilium and iliosacral ES who underwent surgical resection and reconstruction with a tibial strut allograft between January 2010 and October 2021 were reviewed. The lesions were classified into four resection zones: I. 1. , I. 2. , I. 3. , and I. 4. , based on the extent of resection. Functional outcomes, oncological outcomes, and surgical complications for each resection zone were of interest. Functional outcomes were assessed using a Musculoskeletal Tumor Society (MSTS) score and Toronto Extremity Salvage Score (TESS). Results. The mean age of the patients was 17 years (SD 9.1). At a mean follow-up of 70.8 months (SD 50), the mean functional outcomes were 24.2 points (SD 6.3) for MSTS and 81 points (SD 11) for TESS. The mean MSTS and TESS scores were associated with the iliac resection zone (< 0.001). Nine patients (20.9%) had local recurrence. The recurrence was not associated with the zone of iliac resection (p = 0.324). The two-year disease-free survival of the patients was 69.4%. The mean time to graft union was longer in patients with the I. 4. resection zone (p < 0.001). The complication rate was 34.9%, and nerve palsy (11.6%) was the most common. The rate of surgical complications was not associated with the resection zone. Conclusion. Reconstruction using tibial strut allograft is an efficient procedure after the resection of the ilium and iliosacral ES. Functional outcomes and complications of iliac ES depend on the resection zone, and inferior outcomes could be generally expected when more segments of the pelvic ring are resected, even if it is reconstructed. Cite this article: Bone Jt Open 2024;5(5):385–393


Bone & Joint Open
Vol. 5, Issue 4 | Pages 350 - 360
23 Apr 2024
Wang S Chen Z Wang K Li H Qu H Mou H Lin N Ye Z

Aims. Radiotherapy is a well-known local treatment for spinal metastases. However, in the presence of postoperative systemic therapy, the efficacy of radiotherapy on local control (LC) and overall survival (OS) in patients with spinal metastases remains unknown. This study aimed to evaluate the clinical outcomes of post-surgical radiotherapy for spinal metastatic non-small-cell lung cancer (NSCLC) patients, and to identify factors correlated with LC and OS. Methods. A retrospective, single-centre review was conducted of patients with spinal metastases from NSCLC who underwent surgery followed by systemic therapy at our institution from January 2018 to September 2022. Kaplan-Meier analysis and log-rank tests were used to compare the LC and OS between groups. Associated factors for LC and OS were assessed using Cox proportional hazards regression analysis. Results. Overall, 123 patients with 127 spinal metastases from NSCLC who underwent decompression surgery followed by postoperative systemic therapy were included. A total of 43 lesions were treated with stereotactic body radiotherapy (SBRT) after surgery and 84 lesions were not. Survival rate at one, two, and three years was 83.4%, 58.9%, and 48.2%, respectively, and LC rate was 87.8%, 78.8%, and 78.8%, respectively. Histological type was the only significant associated factor for both LC (p = 0.007) and OS (p < 0.001). Treatment with targeted therapy was significantly associated with longer survival (p = 0.039). The risk factors associated with worse survival were abnormal laboratory data (p = 0.021), lesions located in the thoracic spine (p = 0.047), and lumbar spine (p = 0.044). This study also revealed that postoperative radiotherapy had little effect in improving OS or LC. Conclusion. Tumour histological type was significantly associated with the prognosis in spinal NSCLC metastasis patients. In the presence of post-surgical systemic therapy, radiotherapy appeared to be less effective in improving LC, OS, or quality of life in spinal NSCLC metastasis patients. Cite this article: Bone Jt Open 2024;5(4):350–360


Bone & Joint Open
Vol. 5, Issue 3 | Pages 210 - 217
13 Mar 2024
Mthethwa PG Marais LC Aldous CM

Aims. The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa. Methods. We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis. Results. This study comprised 77 patients at a three-year minimum follow-up. The predictors of poor OS were: the median age of ≤ 19 years (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.92 to 0.99; p = 0.021); median duration of symptoms ≥ five months (HR 0.91; 95% CI 0.83 to 0.99; p < 0.037); metastasis at diagnosis (i.e. Enneking stage III) (HR 3.33; 95% CI 1.81 to 6.00; p < 0.001); increased alkaline phosphatase (HR 3.28; 95% CI 1.33 to 8.11; p < 0.010); palliative treatment (HR 7.27; 95% CI 2.69 to 19.70); p < 0.001); and amputation (HR 3.71; 95% CI 1.12 to 12.25; p < 0.032). In contrast, definitive surgery (HR 0.11; 95% CI 0.03 to 0.38; p < 0.001) and curative treatment (HR 0.18; 95% CI 0.10 to 0.33; p < 0.001) were a protective factor. The Kaplan-Meier median survival time was 24 months, with OS of 57.1% at the three years. The projected five-year event-free survival was 10.3% and OS of 29.8% (HR 0.76; 95% CI 0.52 to 1.12; p = 0.128). Conclusion. In this series of high-grade conventional osteosarcoma of the appendicular skeleton from South Africa, 58.4% (n = 45) had detectable metastases at presentation; hence, an impoverished OS of five years was 29.8%. Large-scale future research is needed to validate our results. Cite this article: Bone Jt Open 2024;5(3):210–217