Journal of Bone Oncology最新文献

{"title":"Comprehensive analysis of cancer and non-cancer mortality in patients with bone metastases: A population-based study","authors":"Xia Yan ,&nbsp;Hongyu Liu ,&nbsp;Xueqi Bai ,&nbsp;Jin Xu ,&nbsp;Xiaojun Lou ,&nbsp;Lai Wang","doi":"10.1016/j.jbo.2025.100708","DOIUrl":"10.1016/j.jbo.2025.100708","url":null,"abstract":"<div><h3>Purpose</h3><div>To characterize causes of death in patients with bone metastases and to support data-driven approaches to survivorship planning and clinical decision-making in this population.</div></div><div><h3>Methods</h3><div>Using data from the SEER registry (2010–2021), we identified 186,404 patients with newly diagnosed bone metastases. Causes of death were classified as related to the cancer-specific, non-cancer, or subsequent cancer. Standardized mortality ratios (SMRs) were calculated to assess excess non-cancer mortality relative to the general population.</div></div><div><h3>Results</h3><div>During follow-up, 133,393 patients (71.5 %) died from the primary cancer, 11,062 (5.9 %) from non-cancer causes, and 929 (0.5 %) from other malignancies. Although cancer remained the predominant cause of death, non-cancer mortality increased over time (from 6.3 % in 2010 to 9.5 % in 2021). Cardiovascular disease, COPD, and cerebrovascular events were the most common non-cancer causes. The greatest excess mortality was observed for HIV-related infection conditions (SMR: 13.24), septicemia (10.60), suicide (6.68), and pneumonia/influenza (6.04).</div></div><div><h3>Conclusion</h3><div>Non-cancer mortality is an increasingly important contributor to death among patients with bone metastases, underscoring the need for targeted prevention strategies for infections, cardiovascular disease, and other avoidable causes in this vulnerable population.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100708"},"PeriodicalIF":3.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social determinants are associated with clinical presentation of acute pathological fracture in metastatic long-bone disease","authors":"Tom M. de Groot ,&nbsp;Lotte R. van der Linden ,&nbsp;Angad D.S. Bedi ,&nbsp;Andreea A. Lucaciu ,&nbsp;Caleb C. Jang ,&nbsp;Olivier Q. Groot ,&nbsp;Job N. Doornberg ,&nbsp;Paul C. Jutte ,&nbsp;Santiago A. Lozano-Calderon ,&nbsp;J.H. Schwab","doi":"10.1016/j.jbo.2025.100707","DOIUrl":"10.1016/j.jbo.2025.100707","url":null,"abstract":"<div><h3>Background</h3><div>Social Determinants of Health (SDOH) are non-medical factors that influence health, which have gained recognition across medical disciplines. Their impact on survival and disease presentation of patients with metastatic bone disease (MBD) remains unexplored.</div></div><div><h3>Methods</h3><div>This retrospective observational study included 712 undergoing surgery for symptomatic long-bone metastases patients between 2013 and 2022. SDOH were evaluated using Cox Proportional hazards regression for post-operative survival. A multivariate logistic regression analysis was performed to identify associated factors for clinical presentation with a completed pathologic fracture.</div></div><div><h3>Results</h3><div>The median overall survival was 264 days (IQR 74–772). Clinical presentation with a pathologic fracture as the initial symptom of metastatic bone disease (MBD) was observed in 15 % of patients (106/712).</div><div>SDOH factors played a significant role in clinical presentation. Patients with secondary insurance coverage were substantially less likely to present with a pathologic fracture (OR 0.26, 95 % CI 0.14–0.49; p &lt; 0.01). In a sub-analysis of the most common tumors (breast, renal, and lung cancer patients; n = 353), attending college was associated with a significantly lower likelihood of presenting with a pathologic fracture as the initial symptom of metastatic bone disease (OR 0.54, 95 % CI 0.30–0.95; p = 0.03)</div></div><div><h3>Conclusion</h3><div>This study suggests that unfavorable SDOH factors are associated with decreased post-operative survival and a higher likelihood of initial clinical presentation with a completed pathological fracture. Incorporating social determinants into comprehensive care strategies for individuals with MBD may guide targeted interventions and optimize patient management to improve outcomes.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100707"},"PeriodicalIF":3.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgery for osteosarcoma with isolated pulmonary metastases: A SEER-based analysis","authors":"Sheng-Fen Liu","doi":"10.1016/j.jbo.2025.100706","DOIUrl":"10.1016/j.jbo.2025.100706","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma frequently metastasizes to the lungs. The role of surgical intervention in patients with isolated pulmonary metastases and early-stage primary tumors (T1-T2) remains unclear.</div></div><div><h3>Methods</h3><div>Data from the SEER database were used to identify osteosarcoma patients diagnosed with T1-T2 stage disease and isolated lung metastases. Patients were categorized based on whether they underwent surgery for the primary tumor. Propensity score matching (PSM) was applied to reduce baseline differences.</div></div><div><h3>Results</h3><div>Before PSM, surgery was associated with significantly improved overall survival (OS) (median OS: 19.0 vs 7.0 months, P &lt; 0.001). After PSM, a trend toward better OS persisted (median OS: 13.0 vs 9.0 months, P = 0.253), though not statistically significant. Surgery was also associated with lower cancer-related death rates both before and after PSM.</div></div><div><h3>Conclusions</h3><div>Surgical resection of the primary tumor may confer a survival benefit in T1-T2 osteosarcoma patients with isolated pulmonary metastases. These findings support the continued evaluation of surgical strategies in metastatic osteosarcoma and underscore the need for prospective validation.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100706"},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RGS1 stabilized by METTL3-mediated m6A modification promotes the tumorigenicity and macrophage M2 polarization in osteosarcoma","authors":"Zhizhong Liang ,&nbsp;Yuxia Shi ,&nbsp;Mao Wang ,&nbsp;Liqiang Zhang","doi":"10.1016/j.jbo.2025.100705","DOIUrl":"10.1016/j.jbo.2025.100705","url":null,"abstract":"<div><h3>Background</h3><div>Regulators of G-protein signaling 1 (RGS1) has been reported to be involved in immune cell regulation in many cancer types. However, the specific role and mechanism in osteosarcoma (OS) progression and macrophage activation remain unclear.</div></div><div><h3>Methods</h3><div>Levels of mRNA and protein were examined using qRT-PCR and western blotting. Transwell assay, wound healing assay, EdU assay and flow cytometry were used to investigate OS cell invasion, migration, proliferation and apoptosis. Xenografts in mice were established for in vivo assay. Macrophage M2 polarization was evaluated by detecting CD206 + macrophages by flow cytometry. ELISA analysis detected IL-6 and TGF-β1 levels. Methylated RNA immunoprecipitation assay was applied to explore the specific binding of RGS1 and METTL3 (methyltransferase-like 3).</div></div><div><h3>Results</h3><div>RGS1 was highly expressed in OS tissues and cells. The silencing of RGS1 suppressed OS cell invasion, migration, growth and impaired immune response by inhibiting macrophage M2 polarization and M2 macrophage-mediated release of IL-10 and TGF-β1. Mechanistically, METTL3 promoted RGS1 m6A modification and stabilized its expression. METTL3 deficiency also inhibited OS cell invasion, migration, growth and macrophage M2 polarization, while these effects could be abolished by RGS1 overexpression. Besides that, IL–10 elevation induced by M2 macrophages promoted OS cell oncogenic phenotypes.</div></div><div><h3>Conclusion</h3><div>METTL3 stabilized RGS1 mRNA in an m6A-dependent manner to promote the tumorigenicity and macrophage M2 polarization in osteosarcoma, suggesting a novel insight into the therapy of osteosarcoma.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100705"},"PeriodicalIF":3.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFC-305, an adenosine derivative, inhibits the osteolytic metastases of triple-negative breast cancer","authors":"Claudia Alcira Espinoza-González ,&nbsp;Citlalli Oyuki Mendoza-Chacón ,&nbsp;Pierrick G.J. Fournier ,&nbsp;Gabriela Velasco-Loyden ,&nbsp;Felipe Olvera ,&nbsp;Victoria Chagoya de Sánchez ,&nbsp;Rafael Vazquez-Duhalt ,&nbsp;Patricia Juárez","doi":"10.1016/j.jbo.2025.100704","DOIUrl":"10.1016/j.jbo.2025.100704","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is an aggressive subtype of cancer characterized by limited therapeutic options and a propensity to form metastasis, particularly to bone. Given the mortality and morbidity linked to TNBC, the advancement of novel and effective therapies is essential. This work studies the potential of an adenosine derivative compound (IFC-305) as a therapeutic agent for breast cancer bone metastasis. It focuses on its effects on bone metastasis, including cell viability, migration, cell cycle, and apoptosis <em>in vitro</em>. <em>In vitro</em> assays demonstrated that IFC-305 significantly reduced TNBC cell viability and migration in a dose-dependent manner. Additionally, it promoted cell cycle arrest and decreased the proportion of cells in the S phase, although it did not induce apoptosis in 4T1 cells. Furthermore, <em>in vivo</em> experiments using a murine model of bone metastasis revealed that treatment with IFC-305 attenuated osteolytic lesions associated with breast cancer metastasis. Importantly, our findings highlight an interaction between this adenosine derivative and the TGF-β signaling pathway. The derivative compound effectively inhibited SMAD2/3 phosphorylation, a key mediator of TGF-β signaling pathway involved in cell growth, differentiation, migration and metastatic progression. Besides, IFC-305 reduced TGF-β regulated PMPEA1 expression, a gene associated with cancer stemness and tumor invasion. These findings provide evidence for the therapeutic potential of the IFC-305 in treating metastatic breast cancer in the bone and warrant further investigation to fully elucidate its mechanism of action and evaluate its clinical translatability.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"54 ","pages":"Article 100704"},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of rehabilitation treatment for bone metastasis patients without surgical intervention: A propensity score matching analysis","authors":"Ryo Yoshikawa ,&nbsp;Yasumitsu Fujii ,&nbsp;Ryoga Kashima ,&nbsp;Wataru Saho ,&nbsp;Risa Harada ,&nbsp;Daisuke Makiura ,&nbsp;Katsuya Fujiwara ,&nbsp;Junichiro Inoue ,&nbsp;Yoshiki Takeoka ,&nbsp;Ryoko Sawada ,&nbsp;Naomasa Fukase ,&nbsp;Keisuke Oe ,&nbsp;Hitomi Hara ,&nbsp;Kenichiro Kakutani ,&nbsp;Toshihiro Akisue ,&nbsp;Yoshitada Sakai","doi":"10.1016/j.jbo.2025.100703","DOIUrl":"10.1016/j.jbo.2025.100703","url":null,"abstract":"<div><div>Evidence regarding the effectiveness of rehabilitation treatments in patients with bone metastases remains limited. This study evaluated the implementation and effectiveness of rehabilitation in patients with bone metastases who did not undergo surgery. This retrospective study included 200 patients with nonsurgically treated bone metastases at our institution. The patients were categorized into a rehabilitation group (R group, n = 61) and a non-rehabilitation group (N group, n = 139). Over the course of one month, we compared activities of daily living (ADL), assessed using the Barthel Index (BI), quality of life (QOL), measured using the EuroQoL-5 Dimension (EQ-5D), and demographic and clinical characteristics. Propensity score matching was conducted to minimize selection bias. After matching, 31 patients in each group were included in the analysis. No statistically significant differences were observed in baseline BI and EQ-5D scores between the two groups. In the R group, BI improved significantly from 80 (interquartile range [IQR]: 60–100) to 90 (IQR: 70–100), and EQ-5D improved from 0.444 (IQR: 0.282–0.608) to 0.608 (IQR: 0.533–0.768). In contrast, no improvements were observed in either score in the N group. Chemotherapy was identified as a significant factor associated with improvements in BI (odds ratio 4.03) and EQ-5D (odds ratio 5.29). Rehabilitation may be a valuable treatment option for nonsurgically treated patients with bone metastases, warranting further validation in prospective studies.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100703"},"PeriodicalIF":3.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COPB2 as a key regulator of cell growth in human osteosarcoma cells: Potential therapeutic target and prognostic indicator","authors":"Yunpeng Cui ,&nbsp;Xuedong Shi ,&nbsp;Qiwei Wang ,&nbsp;Wence Wu ,&nbsp;Yuanxing Pan ,&nbsp;Bing Wang ,&nbsp;Mingxing Lei","doi":"10.1016/j.jbo.2025.100702","DOIUrl":"10.1016/j.jbo.2025.100702","url":null,"abstract":"<div><h3>Purpose</h3><div>Coatomer protein complex subunit beta 2 (COPB2) is a crucial component of the coatomer protein complex I, responsible for vesicle transport. Previous studies have indicated that COPB2 is highly expressed in malignant tumors and is involved in cell proliferation and apoptosis. However, the role of COPB2 in osteosarcoma and its underlying mechanisms remain unclear. This study aimed to investigate the impact of COPB2 on proliferation, apoptosis, and colony formation in human osteosarcoma cells, as well as to explore potential mechanisms.</div></div><div><h3>Methods</h3><div>Kaplan-Meier survival analysis was conducted to assess the association between COPB2 expression and the prognosis of osteosarcoma patients using data extracted from the Cancer Genome Atlas (TCGA) database. Additionally, COPB2 expression was examined in osteosarcoma tissue samples and four osteosarcoma cell lines using immunohistochemistry and quantitative real-time PCR (qRT-PCR). COPB2 expression was downregulated using siRNA in U2OS and SAOS-2 human osteosarcoma cells. Cell proliferation and colony formation were assessed using Cellomics/Celigo and Giemsa staining, respectively. Flow cytometry was used to evaluate cell cycle distribution and apoptosis. Tumor growth was evaluated in vivo model. Furthermore, the regulation mechanism of COPB2 on osteosarcoma cells was investigated using the Human Phospho-Kinase Array Kit.</div></div><div><h3>Results</h3><div>Patients with high COPB2 expression exhibited shorter overall survival and disease-free survival compared to those with low COPB2 expression. COPB2 was found to be highly expressed in osteosarcoma tissue samples and cell lines. Silencing of COPB2 significantly inhibited cell proliferation and colony formation. Additionally, COPB2 silencing altered the cell cycle distribution, leading to cell cycle arrest in the G2 phase, and promoted cell apoptosis in osteosarcoma cells. Further investigations revealed that COPB2 silencing inhibited tumor growth and lung metastases of osteosarcoma cells in vivo, and its effects on cell proliferation and apoptosis may be mediated through the regulation of kinase phosphorylation levels.</div></div><div><h3>Conclusions</h3><div>COPB2 expression is increased in osteosarcoma cells and plays a crucial role in cell growth regulation. Silencing of COPB2 inhibits cell proliferation, colony formation, and promotes cell apoptosis. Furthermore, COPB2 silencing inhibits tumor growth in vivo, suggesting its potential as an important therapeutic target in treating osteosarcoma.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100702"},"PeriodicalIF":3.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yin Yang 1 protein-activated N-acetyltransferase 10 drives cell malignant progression of osteosarcoma through ac4C acetylation of integrin β3","authors":"Fan Yang,&nbsp;Mao Wang","doi":"10.1016/j.jbo.2025.100701","DOIUrl":"10.1016/j.jbo.2025.100701","url":null,"abstract":"<div><h3>Background</h3><div>N-acetyltransferase 10 (NAT10) acts as the “writer” of N4-acetylcytidine (ac4C) modification in tumor progression, including osteosarcoma (OS). Its molecular mechanism in OS remains not fully clear. This study endeavored to disclose the upstream and downstream mechanism of NAT10 related to Yin Yang 1 protein (YY1) and integrin β3 (ITGB3) in OS.</div></div><div><h3>Methods</h3><div>Gene mRNA and protein levels were assayed via real-time quantitative PCR and Western blotting. Cell counting kit-8, EdU assay, flow cytometry/TUNEL staining assay, transwell assay, and scratch assay were conducted to assess cell viability, proliferation, apoptosis, invasion, and migration. Interaction analysis was completed through ac4C RNA immunoprecipitation (ac4c RIP), RIP, chromatin IP and dual-luciferase reporter assay. <em>In vivo</em> assay was carried out using xenograft models in mice.</div></div><div><h3>Results</h3><div>OS tissues and cells showed the high expression of NAT10. Cell proliferation, invasion, and migration were suppressed but apoptosis was enhanced in NAT10-silenced OS cells. GSE237541 dataset has predicted the inhibition of ITGB3 after NAT10 knockdown, and PACES website predicted ac4C site in ITGB3. Furthermore, it was found that NAT10 could up-regulate ITGB3 expression by mediating ac4C acetylation. ITGB3 overexpression recused OS cell progression inhibition caused by NAT10 knockdown. Jaspar predicted the binding between YY1 and NAT10 promoter. YY1 could activate the transcriptional regulation of NAT10 to increase NAT10 expression, and YY1 depletion blocked cell malignant behaviors via reducing NAT10 expression. More importantly, YY1 interacted with NAT10 to up-regulate ITGB3 expression. <em>In vivo</em>, NAT10/ITGB3 axis also promoted OS tumor growth in mice.</div></div><div><h3>Conclusion</h3><div>YY1 was firstly affirmed to regulate transcription of NAT10, and NAT10 was firstly indicated to mediate ac4C modification of ITGB3. YY1-activated NAT10 could affect ITGB3 and then modulated the malignant development of OS.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100701"},"PeriodicalIF":3.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteofibrous dysplasia, osteofibrous Dysplasia-Like adamantinoma, and adamantinoma: A Single-center retrospective analysis","authors":"Wei Chen ,&nbsp;Qinglin Jin ,&nbsp;Shaohua Du ,&nbsp;Shuangwu Dai ,&nbsp;Changhe Hou ,&nbsp;Zixiong Lei ,&nbsp;Lin Zhong ,&nbsp;Qingzhu Wei ,&nbsp;Haomiao Li","doi":"10.1016/j.jbo.2025.100700","DOIUrl":"10.1016/j.jbo.2025.100700","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to comprehensively investigate and contrast the imaging manifestations, pathological features, surgical interventions, and prognostic outcomes of <strong>Osteofibrous Dysplasia(OFD)</strong>, <strong>Osteofibrous Dysplasia-Like Adamantinoma(OFD-AD)</strong>, and <strong>Adamantinoma(AD)</strong>. By synthesizing disease profiles and exploring their evolutionary relationships, we sought to identify more effective diagnostic and therapeutic strategies for these conditions.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on patients diagnosed with OFD, OFD-AD, or AD at our institution between 2015 and 2022. The analysis included a detailed comparison of clinical presentations, imaging findings, and pathological characteristics. We also evaluated the impact of different diagnostic and treatment modalities on patient prognosis and explored potential disease evolution and transformation patterns.</div></div><div><h3>Results</h3><div>Fifty patients were included in this study: 16 with OFD, 27 with OFD-AD, and 7 with AD. The median age of onset was 14 years for OFD, 6 years for OFD-AD, and 33 years for AD. All diagnoses were confirmed through a combination of clinical evaluation, imaging (X-rays and MRI), and pathological examination. Among the patients, 2 (both with OFD-AD) were managed with observation only. Thirty-seven patients underwent intralesional resection (16 OFD, 20 OFD-AD, and 1 AD), and 11 patients had complete resection (5 OFD-AD and 6 AD). After a minimum follow-up of 24 months (range: 24–––90 months, median: 56 months), 12 patients experienced tumor recurrence (OFD: 2/16, 12.5 %; OFD-AD: 9/25, 36 %; AD: 1/6, 17 %). One patient had concurrent OFD-AD in the fibula and AD in the tibia. In another case, an OFD-AD recurrence 4 years after surgery was later diagnosed as OFD, and an OFD recurrence 2 years after surgery was reclassified as OFD-AD. No distant metastases were observed in any patient.</div></div><div><h3>Conclusion</h3><div>OFD, OFD-AD, and AD exhibit similarities in clinical and imaging presentations, and their pathological features may represent different stages of a common lesion’s evolution. These diseases have distinct age − related onset patterns and variable recurrence risks. Thus, accurate diagnosis and personalized treatment strategies based on patient characteristics are crucial for effective disease management.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100700"},"PeriodicalIF":3.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demethylzeylasteral inhibits proliferation and metastasis of osteosarcoma cells by modulating the PI3K/AKT/Autophagy pathways","authors":"Xuhui Yuan ,&nbsp;Jiayu Li ,&nbsp;Bo Yu ,&nbsp;Feng Cai ,&nbsp;Binqi Chen ,&nbsp;Jun Liu ,&nbsp;Yuanxiang Peng ,&nbsp;Duo Zeng ,&nbsp;Qi Liao ,&nbsp;Lang Liu","doi":"10.1016/j.jbo.2025.100699","DOIUrl":"10.1016/j.jbo.2025.100699","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma (OS) remains a highly aggressive malignancy with limited treatment options, necessitating the discovery of novel therapeutic agents. Demethylzeylasteral (DEM), a compound previously shown to exert anti-tumor properties in several malignancies, has not been sufficiently explored for its potential in OS treatment.</div></div><div><h3>Purpose</h3><div>This study focused on the anti-tumor properties of DEM on OS cells as well as the potential mechanisms.</div></div><div><h3>Methods</h3><div>OS cell lines (MG63 and 143B) were exposed to varying concentrations of DEM, followed by assessment of diverse cell functions. RNA sequencing was implemented to identify the molecular pathways affected by DEM exposure. The mechanistic underpinnings of DEM’s action were also studied via a series of assays. Additionally, the therapeutic potential was validated utilizing xenograft models.</div></div><div><h3>Results</h3><div>DEM evidently repressed OS cell proliferation in a dose- and time-dependent fashion, arrested cells in G2/M phase, and facilitated apoptosis through the modulation of the BCL2/BAX ratio. Furthermore, DEM suppressed cell migration and invasion by reversing EMT-related protein expression. RNA sequencing revealed that DEM primarily affected autophagy-related pathways, particularly through the PI3K/AKT signaling. DEM treatment led to an elevation in ROS generation and enhanced autophagic activity, as demonstrated by elevated LC3B puncta formation and autophagy-related protein expression. <em>In vivo</em>, DEM effectively suppressed tumor growth while showing a favorable safety profile.</div></div><div><h3>Conclusion</h3><div>This study provides comprehensive evidence that DEM exerts potent anti-tumor properties in OS via the PI3K/AKT pathway, highlighting the significance of DEM as a therapeutic candidate for OS.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"53 ","pages":"Article 100699"},"PeriodicalIF":3.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}