Journal of Bone Oncology最新文献

{"title":"Bone metastasis in colorectal cancer: Pathophysiology, prognostic factors, survival outcomes, and treatment strategies – A comprehensive review","authors":"Lea Hatoum ,&nbsp;Rita El Murr ,&nbsp;Ahmad Assi ,&nbsp;Rami Mohanna ,&nbsp;Amer Sebaaly ,&nbsp;Hampig-Raphaël Kourie","doi":"10.1016/j.jbo.2025.100727","DOIUrl":"10.1016/j.jbo.2025.100727","url":null,"abstract":"<div><h3>Background</h3><div>Colorectal cancer ranks as the third most prevalent cancer globally, with over 1.9 million new cases and 930,000 deaths in 2020. While the liver and lungs are the most common site of colorectal cancer metastases, bone metastasis is relatively rare but clinically significant. The rarity of bone metastasis in colorectal cancer, early diagnosis challenges, and the poorly understood mechanisms underlying bone metastasis have resulted in lesser research compared to other metastatic sites of colorectal cancer.</div></div><div><h3>Objective</h3><div>The goal of this review is to summarize pathophysiology, clinical presentation, risk and prognostic factors, survival outcomes, and treatment options for bone metastasis in colorectal cancer. Results: Bone metastasis occurred in 6 to 10 % of colorectal cancer patients, with the spine and pelvis being the most common sites. Bone metastasis from colorectal cancer may result from hematogenous dissemination and retrograde venous flow through Batson’s plexus. Early diagnosis can be challenging, and Positron Emission Tomography / Computed Tomography (PET/CT) provided the best accuracy for diagnosing bone metastasis in colorectal cancer. Isolated bone metastasis, low neutrophil-to-lymphocyte ratio (NLR) (high NLR with HR: 1.54), low alkaline phosphatase levels, N0 stage colorectal cancer were associated with a better prognosis and survival. High carcinoembryonic antigen (OR: 2.368, HR: 3.300), alkaline phosphatase (OR: 6.89, HR: 2.12), and CA 19–9 levels (HR: 1.5), Lactate dehydrogenase (HR: 1.961), perineural invasion (HR: 3.457), right sided location (HR: 1.84), multiples bone metastasis sites (HR: 1.452), hypercalcemia (HR: 3.75), pathologic fracture (HR:1.91) and more than two extra-bone metastatic organs (HR: 2.357) were linked to worse prognosis. The therapeutic approach for colorectal cancer patients with bone metastasis consists of a multidisciplinary strategy including systemic chemotherapy, palliative surgery, radiotherapy and bisphosphonate.</div></div><div><h3>Conclusion</h3><div>Early diagnosis and management of bone metastasis in colorectal cancer patients is essential to improve quality of life and survival. Further research is needed to identify methods for early detection and develop tailored treatment strategies.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100727"},"PeriodicalIF":3.5,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520108","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":"Soft tissue recurrence in giant cell tumor of Bone: A comprehensive review of pathogenesis, imaging features, and clinical management","authors":"Khodamorad Jamshidi ,&nbsp;Hamed Naghizadeh ,&nbsp;Sadegh Saberi ,&nbsp;Farshad Zand Rahimi ,&nbsp;Aidin Arabzadeh ,&nbsp;Seyyed Saeed Khabiri","doi":"10.1016/j.jbo.2025.100725","DOIUrl":"10.1016/j.jbo.2025.100725","url":null,"abstract":"<div><h3>Background</h3><div>Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm with a high risk of recurrence. Among its patterns of relapse, soft-tissue recurrence (STR) is an uncommon but clinically significant entity, often presenting as ossified or non-ossified perilesional nodules. Despite its rarity, STR poses diagnostic and therapeutic challenges that require clarification.</div></div><div><h3>Methods</h3><div>A comprehensive literature review was performed across PubMed, Embase, and Google Scholar from 1980 through January 2025, focusing on the epidemiology, pathogenesis, imaging features, histopathology, management, and outcomes of STR in GCTB. Case reports, series, and retrospective studies explicitly distinguishing STR from intraosseous recurrence were included, and findings were synthesized narratively.</div></div><div><h3>Results</h3><div>STR occurs in approximately 2–3 % of GCTB cases, typically within 6–12 months after surgery. Major risk factors include curettage procedures, pathological fractures, cortical breaches, and unrecognized microscopic soft-tissue extension. Imaging reveals three distinct patterns: peripheral “eggshell” ossification, central nodular calcification, and purely soft-tissue lesions. Histology mirrors primary GCTB, often with osteogenic metaplasia, while molecular testing confirms retention of H3F3A mutations. Surgical excision with clear margins remains the mainstay of treatment, yielding excellent functional outcomes. However, up to 60 % of patients experience multiple recurrences, highlighting the need for vigilant surveillance. Systemic agents such as denosumab or bisphosphonates remain investigational, and radiotherapy is generally contraindicated due to malignant transformation risk.</div></div><div><h3>Conclusion</h3><div>STR represents a rare but distinct subset of GCTB recurrences. Awareness of risk factors, early imaging-based detection, and complete surgical excision are critical for optimal outcomes. Further multicenter studies are required to define surveillance protocols, validate molecular predictors, and clarify the role of systemic therapy in this challenging condition.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100725"},"PeriodicalIF":3.5,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520107","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":"WGCNA-identified COL13A1 drives osteosarcoma metastasis and progression via TGF-β signaling","authors":"Kang-Wen Xiao ,&nbsp;Zhenyi Chen ,&nbsp;Chong Zhang ,&nbsp;Zhiqiang Yang ,&nbsp;Liangyu Guo ,&nbsp;Yuanlong Xie ,&nbsp;Jun Lei ,&nbsp;Lin Cai","doi":"10.1016/j.jbo.2025.100721","DOIUrl":"10.1016/j.jbo.2025.100721","url":null,"abstract":"<div><div>Osteosarcoma (OS) is a malignant bone tumor with high incidence of metastasis. However, the molecular landscape of osteosarcoma remains incompletely understood. Weighted gene co-expression network analysis (WGCNA), differential expressed genes (DEGs), Cox regression, gene set enrichment analysis (GSEA), receiver operating characteristic curve (ROC) and survival analysis were conducted to screen potential targets and molecular mechanism for OS. Seven modules were considered to be closely related to the prognosis of OS. Subsequent immunohistochemistry (IHC), survival and ROC analysis indicated that high expression of COL13A1 was seen in OS tissue and was significantly associated with poor clinical outcome. COL13A1 expression may correlate with inhibition of M1 polarization and could serve as a predictor for immunotherapy response. Further cellular experiments showed that the expression of COL13A1 promoted the proliferation, migration and invasion. Besides, high expression of COL13A1 enhanced TGF-β signaling through β1 integrin and upregulated MMP9 and cyclin D1 expression. Finally, the low expression of COL13A1 limited the weight and lung metastasis of tumor, and reduced bone destruction in the orthotopic tumor-bearing model. COL13A1 was identified as a novel regulator of OS progression via TGF-β signaling, suggesting its potential as a therapeutic target pending further validation.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100721"},"PeriodicalIF":3.5,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520105","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":"Evaluation of Zimmer® segmental distal femur mega-prostheses: Patient survival, surgical outcomes and functional outcome","authors":"Christina Enciso Holm,&nbsp;Jesper Peter Bömers,&nbsp;Allan Villadsen,&nbsp;Michael Mørk Petersen","doi":"10.1016/j.jbo.2025.100722","DOIUrl":"10.1016/j.jbo.2025.100722","url":null,"abstract":"<div><h3>Background</h3><div>Modular knee mega-prostheses are considered the method of choice for reconstruction after resection of malignant bone lesions around the knee. The available literature evaluating Zimmer® Segmental mega-prostheses is sparse. The purpose of the present study is to evaluate the use of Zimmer® Segmental mega-prosthesis for reconstruction of the distal femur, following the resection of bone malignancies and aggressive benign bone tumors.</div></div><div><h3>Material and Methods</h3><div>A retrospective study including 59 consecutive patients (F/M = 35/24), mean age 58 (range 17–86) who underwent reconstructions of the distal femur due to malignant bone lesions (n = 51) or aggressive benign bone tumors (n = 8) from 2017 to 2022. All reconstructions were performed with the most recent Zimmer® Segmental System with the XT Distal Femoral Component. Kaplan-Meier survival analysis was used for evaluation of overall survival. Competing risk analysis was used for assessing cumulative incidence of revision and amputation. Patients were followed until death or end of study (December 31st, 2024). Functional outcome and quality of life was evaluated with Musculoskeletal Tumor Society Score (MSTS), European quality of life − 5 Dimensions score (EQ 5D) and Oxford Knee Score (OKS).</div></div><div><h3>Results</h3><div>Twenty-eight (n = 28) patients were alive at follow-up. Overall survival after 5-year was 44 % (CI95%: 30–58 %). The risk of implant failure after 1 and 5 years was 8 % (95 %CI 1–16 %) and 12 % (95 %CI 4–20 %) respectively. One patient (2 %) underwent amputation. Mean MSTS score was 17 (57 %) (range 3–30). Mean EQ 5D index score was 0.88 and mean EQ-5D VAS score was 68. OKS demonstrated a mean score of 31.</div></div><div><h3>Conclusion</h3><div>The Zimmer® Segmental mega-prosthesis in distal femur reconstruction with the improved XT femoral component, demonstrated a relatively low risk of implant failure, and a low risk of amputation. The risk of implant failure was higher among patients who underwent radiotherapy.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100722"},"PeriodicalIF":3.5,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466328","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":"Cutting edge developments in bone oncology – Highlights from the Cancer and Bone Society 2024 annual meeting","authors":"Deanna N. Edwards ,&nbsp;Shreya Patel ,&nbsp;Gabriel M. Pagnotti","doi":"10.1016/j.jbo.2025.100724","DOIUrl":"10.1016/j.jbo.2025.100724","url":null,"abstract":"<div><div>The 2024 Annual Conference of the Cancer and Bone Society (CABS), held jointly with the Bone Research Society at the University of Sheffield, highlighted the Society’s enduring mission to advance understanding of cancer–bone interactions through collaboration, mentorship, and scientific excellence. Established from the early Cancer Induced Bone Disease meetings and re-emerging as an independent body in 2016, CABS continues to serve as a global community bridging basic, translational, and clinical research. This year’s meeting featured a comprehensive scientific program spanning tumor–bone biology, therapeutic innovation, and microenvironmental regulation. Clinical sessions emphasized the evolution of bone-targeted treatments such as bisphosphonates, denosumab, and radiopharmaceuticals, alongside predictive biomarkers to guide personalized care. Presentations on renal cell carcinoma bone metastases, multiple myeloma, and prostate cancer underscored persistent clinical challenges and opportunities for integration of immunotherapies and precision radiotherapy. Molecular sessions revealed how non-coding RNAs, TGF-β/Gli2 signaling, metabolic dependencies, and stromal mediators—including osteomodulin, IL-1β, and adiponectin—govern tumor colonization, dormancy, and resistance. Advances in immuno-oncology demonstrated the potential of γδ CAR-T cells, oncolytic viruses, and immune-metabolic targeting to enhance therapeutic efficacy in the bone microenvironment. Spatial and single-cell profiling provided unprecedented resolution of the metastatic niche, identifying novel osteoblast-derived stromal subsets and neurovascular remodeling as key determinants of disease progression. Complementary preclinical models and computational simulations, including 3D engineered bone marrow constructs and micro–finite element analysis, offered new frameworks to study therapeutic responses and fracture risk. The meeting also celebrated the growing leadership of Early-Stage Investigators (ESIs), whose contributions extended beyond research presentations to creative networking and mentorship events. These efforts reflected CABS’ commitment to inclusivity, community building, and sustaining the next generation of leaders in cancer and bone research. Collectively, the 2024 CABS Annual Conference captured a transformative moment in the field—where mechanistic discoveries, advanced modeling, and translational collaboration converge to improve outcomes for patients with skeletal malignancies. As CABS looks ahead to the 2026 meeting in Tampa, Florida, the Society remains steadfast in fostering global partnerships and advancing integrative approaches to conquer cancer in bone.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100724"},"PeriodicalIF":3.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466329","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":"Benign and malignant bone lesion diagnosis based on self-supervised and radiomics fusion using SPECT/CT images","authors":"Weiming Xie ,&nbsp;Xiaozhou Bai ,&nbsp;Miao Liu ,&nbsp;Haonan Shangguan ,&nbsp;Ying Zhan ,&nbsp;Xiaodan Wu ,&nbsp;Yingxin Dai ,&nbsp;Yusong Pei ,&nbsp;Guoxu Zhang ,&nbsp;Zhiguo Wang ,&nbsp;Zhaomin Yao","doi":"10.1016/j.jbo.2025.100723","DOIUrl":"10.1016/j.jbo.2025.100723","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to improve the diagnostic accuracy of SPECT/CT imaging in distinguishing benign from malignant bone lesions by integrating self-supervised deep learning and radiomics, reducing subjectivity in traditional image interpretation for more reliable clinical decision-making.</div></div><div><h3>Methods</h3><div>We developed a multi-scale, multi-modal framework combining radiomics with self-supervised learning. The novel SPECT-guided model, SPARC-Net, uses functional SPECT data as semantic priors to extract discriminative features from CT scans without manual annotations. Deep features from SPARC-Net were fused with radiomics to form a unified representation. The model was trained and validated on 741 confirmed bone lesion cases using five-fold cross-validation, with interpretability assessed via Grad-CAM.</div></div><div><h3>Results</h3><div>The fused model achieved 82.3 % accuracy, 0.890 AUC, 72.3 % F1 score, 79.3 % precision, 66.6 % sensitivity, and 90.7 % specificity, outperforming single-modality models. Grad-CAM confirmed the model focused on metabolically active regions identified by SPECT.</div></div><div><h3>Conclusion</h3><div>SPARC-Net, integrating SPECT-guided self-supervised learning with CT-based radiomics, improves classification of benign and malignant lesions, enhancing the accuracy, robustness, and interpretability of SPECT/CT imaging for bone tumor diagnosis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100723"},"PeriodicalIF":3.5,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466325","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":"Bone disease burden does not impact overall survival in newly diagnosed patients with multiple myeloma − a single center, retrospective imaging analysis on 119 patients","authors":"Evangelos Terpos ,&nbsp;Vassilis Koutoulidis ,&nbsp;Ioannis Ntanasis-Stathopoulos ,&nbsp;Stylianos Mavropoulos-Papoudas ,&nbsp;Maria Douka ,&nbsp;Maria Gavriatopoulou ,&nbsp;Panagiotis Malandrakis ,&nbsp;Vasiliki Spiliopoulou ,&nbsp;Foteini Theodorakakou ,&nbsp;Despina Fotiou ,&nbsp;Magdalini Migkou ,&nbsp;Nikolaos Kanellias ,&nbsp;Evangelos Eleutherakis-Papaiakovou ,&nbsp;Efstathios Kastritis ,&nbsp;Lia-Angela Moulopoulos ,&nbsp;Meletios A Dimopoulos","doi":"10.1016/j.jbo.2025.100720","DOIUrl":"10.1016/j.jbo.2025.100720","url":null,"abstract":"<div><h3>Background</h3><div>Multiple myeloma (MM) frequently presents with myeloma bone disease (MBD), manifesting as osteolytic lesions and skeletal-related events (SREs), significantly impairing quality of life and increasing morbidity. Whole-body low-dose computed tomography (WBLDCT) has become the standard for assessing bone involvement at diagnosis, but its prognostic significance remains unclear. The aim of this study was to evaluate the burden of MBD in newly diagnosed MM patients using WBLDCT and examined associations between imaging characteristics and survival outcomes.</div></div><div><h3>Methods</h3><div>In this retrospective, single center, analysis of 119 MM patients, WBLDCT was performed at diagnosis prior to treatment initiation. Imaging findings, including vertebral compression fractures (VCFs), lesion number, cortical destruction, and appendicular skeleton medullary cavity (ASMC) patterns, were recorded. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and Cox regression models.</div></div><div><h3>Results</h3><div>VCFs were significantly associated with inferior PFS (18.1 vs. 33.6 months; p = 0.013) and OS (51.5 months vs. not reached; p = 0.023) in univariate analyses. However, in multivariable models, no imaging parameter, including VCFs, retained independent prognostic significance. Other imaging variables (lesion count, ASMC subtype, cortical destruction) were not predictive of outcomes.</div></div><div><h3>Conclusions</h3><div>While VCFs identified on WBLDCT correlate with poor outcomes in univariate analysis, they do not serve as independent prognostic markers when adjusting for established clinical factors. These findings suggest that in the era of novel anti-myeloma therapeutics, the bone disease burden at diagnosis may not impact prognosis significantly.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100720"},"PeriodicalIF":3.5,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417510","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":"Multimodal deep learning for bone tumor diagnosis with clinical imaging, pathology, and blood biomarkers","authors":"Hang Sang ,&nbsp;Tao Lin ,&nbsp;Lincong Luo ,&nbsp;Mingrui Liu ,&nbsp;Jiaying Li ,&nbsp;Xiang Luo ,&nbsp;Jianlin Shen ,&nbsp;Shizhen Zhong ,&nbsp;Lin Xu ,&nbsp;Wenhua Huang","doi":"10.1016/j.jbo.2025.100718","DOIUrl":"10.1016/j.jbo.2025.100718","url":null,"abstract":"<div><div>Accurate classification of bone tumors as benign, malignant, or intermediate is crucial for patient treatment decisions. Misclassification may result in overtreatment of benign cases or delayed intervention for aggressive tumors, significantly impacting patient prognosis. However, current methods rely heavily on single-modality imaging analysis, making it difficult to handle variable lesion locations and complex cancer types. To address these limitations, we propose a novel multimodal deep learning framework that integrates clinical images, pathological slices, and blood biomarkers for automated bone tumor detection and three-class classification. The framework operates in two stages: first, a YOLOv5-based detection model localizes tumor regions on clinical images. Next, a classification model utilizes ResNet to extract deep features from both the clinical images and pathological slices, while abnormal blood biomarkers are transformed into descriptive text by a large language model and subsequently encoded into semantic features using BioBERT. Finally, features from all three modalities are integrated via a fusion module to capture complementary information and enable accurate tumor classification. The evaluation was performed using two distinct datasets: a clinical imaging dataset for bone tumor detection, and a separate multi-modal cohort comprising clinical imaging, pathology, and blood biomarkers for tumor classification. The detection model demonstrated strong localization capabilities, achieving a test [email protected] of 0.7925. For the classification task, ablation studies validated the complementary contribution of each modality. Notably, our multimodal fusion approach outperformed unimodal baselines, attaining a macro-average precision of 0.9056, F1-score of 0.8736, and AUC of 0.9759 in tumor classification—outperforming existing models.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100718"},"PeriodicalIF":3.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364074","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":"Establishment and comprehensive characterization of a subline with highly bone-metastatic propensity derived from the lung adenocarcinoma A549 cell line","authors":"Yujian Xu ,&nbsp;Yahan Qin ,&nbsp;Wenjun Chai ,&nbsp;Ke Xue ,&nbsp;Xiaoli Liu ,&nbsp;Jing Li ,&nbsp;Yue Cao ,&nbsp;Lei Sun ,&nbsp;Hongyu Pan ,&nbsp;Mingxia Yan","doi":"10.1016/j.jbo.2025.100719","DOIUrl":"10.1016/j.jbo.2025.100719","url":null,"abstract":"<div><div>Bone metastasis is a major cause of mortality in lung adenocarcinoma, but the mechanisms remain poorly understood. Here, we established a highly bone-metastatic subline, A549-BM5, from the A549 cell line through five rounds of <em>in vivo</em> selection. A549-BM5 cells exhibited enhanced migration and invasion, and preferentially colonized specific skeletal sites in mouse models. In the bone microenvironment, they promoted the recruitment and differentiation of osteoblasts and osteoclasts, disrupting bone homeostasis. Transcriptomic and proteomic profiling revealed dysregulation in pathways such as EMT, adhesion, and bone morphogenesis. We further applied a random forest model to identify potential therapeutic targets associated with bone metastasis. Compared to existing A549-based models, A549-BM5 offers earlier metastasis onset, stable bone tropism, and broader interaction with the bone niche. This model provides a valuable platform for mechanistic studies and therapeutic development targeting lung cancer bone metastasis.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100719"},"PeriodicalIF":3.5,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364075","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":"Transient increase in skeletal-related events after discontinuation of high-dose denosumab in cancer patients","authors":"Nokitaka Setsu ,&nbsp;Nobuhiko Yokoyama ,&nbsp;Taito Esaki ,&nbsp;Masafumi Yamaguchi ,&nbsp;Eriko Tokunaga ,&nbsp;Takahito Negishi","doi":"10.1016/j.jbo.2025.100717","DOIUrl":"10.1016/j.jbo.2025.100717","url":null,"abstract":"<div><h3>Background</h3><div>Denosumab is widely used to prevent skeletal-related events (SREs) in patients with bone metastases. However, rebound bone resorption after discontinuation is recognized. In osteoporosis, discontinuation of low-dose denosumab increases multiple vertebral fractures, but data on high-dose discontinuation remain limited.</div></div><div><h3>Methods</h3><div>Among 493 patients treated with high-dose denosumab at our institution (2014–2023), 78 met eligibility criteria. SREs during and after treatment were compared using each patient as their own control. SREs were defined as pathological fracture, spinal cord compression, or radiotherapy/surgery for metastatic bone pain. Hypercalcemia, benign fragility fractures, and serum ALP level were also assessed.</div></div><div><h3>Results</h3><div>A total of 11 SREs were observed during denosumab and 24 after discontinuation. Post-discontinuation incidence was 14.1 per 1,000 person-months, 3.3 times higher than during treatment (95 % CI, 1.4–7.8). The increase was significant at 6–15 months, peaking at 12–15 months (IRR 8.7, 95 % CI, 2.8–27.5), and declined thereafter. Fewer denosumab doses were also associated with a higher risk of SREs after discontinuation. Two benign fragility fractures occurred during denosumab and four after discontinuation. Grade ≥ 3 hypercalcemia occurred only after discontinuation (3 cases). Transient ALP elevation at 9–18 months was observed in patients with post-discontinuation SREs, and ALP ≥ 95 U/L at 6 months predicted subsequent SREs (AUC 0.80).</div></div><div><h3>Conclusion</h3><div>SREs increased significantly 6–15 months after high-dose denosumab discontinuation. Elevated ALP was associated with post-discontinuation SREs. These findings emphasize that discontinuation contributes to SRE risk, possibly via rebound bone resorption, and underscore the importance of continuation of therapy whenever possible.</div></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"55 ","pages":"Article 100717"},"PeriodicalIF":3.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269709","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}