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Bone metastasis along with osteolysis is a common complication of advanced breast cancer, which directly destroys bone function and becomes one of the major causes of cancer-related mortality. It is crucial to develop a new strategy to achieve effective cancer therapy and inhibition of osteolytic bone metastasis. Metal ruthenium (Ru) complexes exhibit therapeutic potential in cancer chemotherapy. However, the clinical applications of Ru complexes were limited by poor bioavailability, lacking targeting, nonspecific distribution. Therefore, in this study, engineering of cell membrane biomimetic modification was used to construct a highly biocompatible nanoplatform with carrying Ru metal complex of RuPOP and Se nanoparticles (SeNPs). Strikingly, the obtained RPSR nanoparticles can efficiently inhibit the proliferation, invasion and migration of breast cancer cells (MDA-MB-231 cells) in vitro. More importantly, RPSR nanoparticles can induce cycle arrest, apoptosis by generating excessive intracellular (reactive oxygen species, ROS) to disrupt the normal redox balance and induce DNA damage in tumor cells. Furthermore, RPSR nanoparticles can also reshape bone microenvironment by regulating selenoproteins to inhibit osteoclasts and avoid osteolytic bone metastasis induced by tumor development. Taken together, this study not only provides an effective cell membrane biomimetic strategy to enhance the shortcomings of metal complexes, but also demonstrates potential clinical significance for the combined treatment of anti-cancer and bone metastasis inhibition. [ABSTRACT FROM AUTHOR]

Bone is a common site of metastasis for lung cancer. The "seed and soil" hypothesis suggests that the bone marrow microenvironment ("soil") may provide a conducive survival environment for metastasizing tumor cells ("seeds"). The bone marrow microenvironment, comprising a complex array of cells, includes bone marrow adipocytes (BMAs), which constitute about 70% of the adult bone marrow volume and may play a significant role in tumor bone metastasis. BMAs can directly provide energy for tumor cells, promoting their proliferation and migration. Furthermore, BMAs participate in the tumor microenvironment's osteogenesis regulation, osteoclast(OC) regulation, and immune response through the secretion of adipokines, cytokines, and inflammatory factors. However, the precise mechanisms of BMAs in lung cancer bone metastasis remain largely unclear. This review primarily explores the role of BMAs and their secreted adipokines (leptin, adiponectin, Nesfatin-1, Resistin, chemerin, visfatin) in lung cancer bone metastasis, aiming to provide new insights into the mechanisms and clinical treatment of lung cancer bone metastasis. [ABSTRACT FROM AUTHOR]

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23 (FGF23), sclerostin (SCL), and lipocalin 2 (LCN2) as prognostic tumor biomarkers and potential therapeutic targets in bone metastasis. Both OC and ucOC could be useful targets for the prevention of bone metastasis in breast cancer. Moreover, elevated OC level may be a metastatic marker of prostate cancer. FGF23 is particularly important for those forms of cancer that primarily affect bone and/or are characterized by bone metastasis. In other tumor entities, increased FGF23 level is enigmatic. SCL plays a significant role in the pathogenesis of both osteolytic and osteoblastic lesions, as its levels are high in metastatic breast and prostate cancers. Elevated expression levels of LCN2 have been found in aggressive subtypes of cancer. However, its role in antimetastasis varies significantly between different cancer types. Anyway, all aforementioned bone-derived factors can be used as promising tumor biomarkers. As metastatic bone disease is generally not curable, targeting bone factors represents a new trend in the prevention of bone metastasis and patient care. [ABSTRACT FROM AUTHOR]

Background: The limitation in spatial resolution of bone scintigraphy, combined with the vast variations in size, location, and intensity of bone metastasis (BM) lesions, poses challenges for accurate diagnosis by human experts. Deep learning-based analysis has emerged as a preferred approach for automating the identification and delineation of BM lesions. This study aims to develop a deep learning-based approach to automatically segment bone scintigrams for improving diagnostic accuracy., Methods: This study introduces a deep learning-based segmentation model structured around an encoder-decoder architecture. The model employs a multi-attention learning scheme to enhance the contrast of the skeleton outline against the background and a multi-scale learning strategy to highlight the hotspots within skeletal areas. The multi-attention strategies include the Non-local Attention scheme and the vision transformer (ViT), while the multi-scale learning incorporates the multi-scale feature learning strategy and the multi-pooling learning strategy. This combination enables the proposed model to accurately detect and extract lesions of varying sizes with high randomness in location and intensity., Results: Experimental evaluation conducted on clinical data of single photon emission computed tomography (SPECT) bone scintigrams showed the superior performance of the proposed model, achieving the highest-ever dice similarity coefficient (DSC) score of 0.6720. A comparative analysis on the same dataset demonstrated increased scores of 5.6%, 2.03%, and 7.9% for DSC, Precision, and Recall, respectively, compared to the existing models., Conclusions: The proposed segmentation model can be used as a promising tool for automatically extracting metastasis lesions from SPECT bone scintigrams, offering significant support to the development of deep learning-based automated analysis for characterizing BM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1246/coif). The authors have no conflicts of interest to declare., (2025 AME Publishing Company. All rights reserved.)

Yu Zhong, Su Li Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, Liaoning Province, People’s Republic of ChinaCorrespondence: Su LiDepartment of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No. 44, Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning Province, People’s Republic of ChinaTel +86-24-31916806; +86 13709819060Email lisu@cancerhosp-ln-cmu.comAbstract: Bone tumors are tumors that occur in the bone or its accessory tissues, including primary tumors and metastatic tumors. The main mechanism of bisphosphonate is to inhibit the resorption of destructive bone, inhibit the activity of osteoclasts and reduce the concentration of blood calcium. Therefore, bisphosphonates can be used for malignant hypercalcaemia, pain caused by osteolytic bone metastasis, prevention of osteolytic bone metastasis, multiple myeloma osteopathy, improving radiosensitivity and so on. However, the traditional administration of bisphosphonates can cause a series of adverse reactions. To overcome this disadvantage, it is necessary to develop novel methods to improve the delivery of bisphosphonates. In this paper, the latest research progress of new and improved bisphosphonate drug delivery methods in the treatment of bone tumors is reviewed. At present, the main design idea is to connect bisphosphonate nanoparticles, liposomes, microspheres, microcapsules, couplings, prodrugs and bone tissue engineering to targeted anti-tumors systems, and positive progress has been made in in vitro and animal experiments. However, its safety and effectiveness in human body still need to be verified by more studies.Keywords: bone tumor, bisphosphonate, drug delivery system, tumor bone metastasis, bone defect repair

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23 (FGF23), sclerostin (SCL), and lipocalin 2 (LCN2) as prognostic tumor biomarkers and potential therapeutic targets in bone metastasis. Both OC and ucOC could be useful targets for the prevention of bone metastasis in breast cancer. Moreover, elevated OC level may be a metastatic marker of prostate cancer. FGF23 is particularly important for those forms of cancer that primarily affect bone and/or are characterized by bone metastasis. In other tumor entities, increased FGF23 level is enigmatic. SCL plays a significant role in the pathogenesis of both osteolytic and osteoblastic lesions, as its levels are high in metastatic breast and prostate cancers. Elevated expression levels of LCN2 have been found in aggressive subtypes of cancer. However, its role in anti-metastasis varies significantly between different cancer types. Anyway, all aforementioned bone-derived factors can be used as promising tumor biomarkers. As metastatic bone disease is generally not curable, targeting bone factors represents a new trend in the prevention of bone metastasis and patient care.

Objective To explore the role of the chemokine 12（CXCL12)/chemokine receptor 4（CXCR4）pathway in human lung adenocarcinoma cells-induced differentiation of osteoclast precursor cells into osteoclasts and the possible molecular mechanism. Methods The Abelson leukemia virus-transformed murine monocyte/macrophage-like RAW 264. 7 cells acted as osteoclast precursor cells，and were randomly divided into the treatment group and control group. Both groups were inoculated with RAW 264. 7 cells in the lower Transwell chamber and A549 cells in the upper Transwell chamber. The treatment group was separately treated with a culture medium containing the competitive CXCR4 antagonist AMD3100 at 12. 5，25. 0，50. 0，and 100. 0 μg/mL in the Transwell chamber，and the control group was only given a culture medium. After 7 days of culture，cells in both groups received tartrate-resistant alkaline phosphatase（TRAP）staining to count the number of RAW 264. 7 cells differentiating into osteoclasts. Quantitative PCR was used to measure the mRNA levels of the following osteoclast marker genes in the lower Transwell chamber：cathepsin K（CTSK)，calcitonin receptor（CTR)，TRAP，and receptor activator of nuclear factor-κB（RANK). ELISA was used to determine the levels of CXCL12，interleukin 6（IL-6)，and tumor necrosis factor-α（TNF-α）in the supernatant in the chamber. Results In the treatment group，the numbers of RAW 264. 7 cells differentiating into osteoclasts were 81±3，49±3，34±3，and 11±2 after 12. 5，25. 0，50. 0，and 100. 0 μg/mL AMD3100 treatment，all of which were significantly lower than that in the control group（99±5)，and the number of RAW 264. 7 cells differentiating into osteoclasts decreased significantly with the increased concentrations of AMD3100（all P<0. 05). Compared with the control group，the treatment group showed significantly reduced mRNA expression of the osteoclast marker genes CTSK，CTR，TRAP，and RANK and significantly decreased levels of CXCL12，IL-6，and TNF- α in the cell supernatant after treatment with various concentrations of AMD3100（all P<0. 05). As the concentration of AMD3100 increased，the expression of the osteoclast marker genes and the levels of CXCL12，IL-6，and TNF-α gradually decreased（all P<0. 05). Conclusion Inhibiting the CXCL12/CXCR4 pathway can reduce human lung adenocarcinoma cells-induced differentiation of osteoclast precursor cells into osteoclasts，which may be achieved by reducing the expression of IL-6 and TNF-α. [ABSTRACT FROM AUTHOR]

Objective To analyze the bone imaging characteristics of osteoporotic fractures and evaluate its value in the differential diagnosis of metastatic bone tumors. Methods The clinical and bone imaging data of 53 patients with osteoporotic fractures were retrospectively studied, and the characteristic imaging manifestations of osteoporotic fractures were proposed. Through a reading test, the feasibility and clinical efficacy of bone imaging in the differential diagnosis of osteoporotic fractures and tumor bone metastases were evaluated in 53 patients with osteoporotic fractures and 100 randomly selected patients with bone metastases. Results Osteoporotic fractures were commonly appear as multiple lesions on skeletal scintigraphy. Lesions usually showed high uptakes shipped as “linear” in vertebra, “H” type in sacrum, and “spot” or short line vertical to skeleton courser in rib and other sites, and no dilatational growth or distribution along the bone was found. When the above imaging features were used to identify the bone metastases, the diagnostic sensitivity, specificity and accuracy were 96.2%, 97.0% and 96.7%, respectively. Moreover, both the judgment results between the readers (Kappa value: 0.80-0.89) and the reader himself (Kappa value: 0.82-0.86) have a better consistency. Conclusions In bone scintigraphy, osteoporotic fracture has its characteristic imaging manifestations, which can be used not only in the diagnosis of osteoporotic fractures, but also in the differential diagnosis between the osteoporotic fractures and bone metastases. [ABSTRACT FROM AUTHOR]