ArticleBone2014
Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis.
Article in Bone, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 79 citations in OpenAlex.
- Prognostic analysis of percutaneous vertebroplasty (PVP) combined withWorld journal of surgical oncology · 2023Trial
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- An immunocompetent osteoblastic model of mammary cancer bone metastasis established by syngeneic intratibial injection of PyMT mammary carcinoma cells in FVB/N mice.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of breast cancer dormancy in bone metastasis.Clinical & experimental metastasis · 2026Review
- A Computational Model of Tumor Interactions with Bone-Resident Cells Predicts Tumor-Type-Specific Responses to Perturbations.bioRxiv : the preprint server for biology · 2026Article
- Advanced models of lobular breast cancer metastasis capture clinical organ tropism, endocrine response, and bone remodeling.bioRxiv : the preprint server for biology · 2026Article
- Doxorubicin induces bone loss and modifies multiple cell populationsJournal of bone oncology · 2026Article
- Aortic valve stenosis and osteoporosis: insights from a mouse model.BMC cardiovascular disorders · 2025Article
- RANKL Drives Bone Metastasis in Mammary Cancer: Protective Effects of Anti-Resorptive Treatments.International journal of molecular sciences · 2025Article
- Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology, and resorptive activity.JBMR plus · 2025Article
- The osteoblast in regulation of tumor cell dormancy and bone metastasis.Journal of bone oncology · 2024Article
- MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Anti-RANKL Therapy Prevents Glucocorticoid-Induced Bone Loss and Promotes Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy.Calcified tissue international · 2023Article
- MiR-662 is associated with metastatic relapse in early-stage breast cancer and promotes metastasis by stimulating cancer cell stemness.British journal of cancer · 2023Article
- SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches.Cell research · 2023Article
- Improving the Antitumor Effect of Chemotherapy with Ocoxin as a Novel Adjuvant Agent to Treat Prostate Cancer.Nutrients · 2023Article
- The CDK4/6 Inhibitor Palbociclib Inhibits Estrogen-Positive and Triple Negative Breast Cancer Bone Metastasis In Vivo.Cancers · 2023Article
- Review
- Spine Metastases in Immunocompromised Mice after Intracardiac Injection of MDA-MB-231-SCP2 Breast Cancer Cells.Cancers · 2022Article
- Expression of Neurokinin B Receptor in the Gingival Squamous Cell Carcinoma Bone Microenvironment.Diagnostics (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionBone metastasis is the most common complication of advanced breast cancer. The associated cancer-induced bone disease is treated with bone-sparing agents like zoledronic acid. Clinical trials have shown that zoledronic acid also reduces breast cancer recurrence in bone; potentially by modifying the bone microenvironment surrounding disseminated tumour cells. We have characterised the early effects of zoledronic acid on key cell types of the metastatic niche in vivo, and investigated how these modify the location of breast tumour cells homing to bone.
methodsFemale mice were treated with a single, clinically achievable dose of zoledronic acid (100μg/kg) or PBS. Bone integrity, osteoclast and osteoblast activity and number/mm trabecular bone on 1, 3, 5 and 10days after treatment were assessed using μCT, ELISA (TRAP, PINP) and bone histomorphometry, respectively. The effect of zoledronic acid on osteoblasts was validated in genetically engineered mice with GFP-positive osteoblastic cells. The effects on growth plate cartilage were visualised by toluidine blue staining. For tumour studies, mice were injected i.c. with DID-labelled MDA-MB-231-NW1-luc2 breast cancer cells 5days after zoledronic acid treatment, followed by assessment of tumour cell homing to bone and soft tissues by multiphoton microscopy, flow cytometry and ex vivo cultures.
resultsAs early as 3days after treatment, animals receiving zoledronic acid had significantly increased trabecular bone volume vs. control. This rapid bone effect was reflected in a significant reduction in osteoclast and osteoblast number/mm trabecular bone and reduced bone marker serum levels (day 3-5). These results were confirmed in mice expressing GFP in osteoblastic linage cells. Pre-treatment with zoledronic acid caused accumulation of an extra-cellular matrix in the growth plate associated with a trend towards preferential [1] homing of tumour cells to osteoblast-rich areas of bone, but without affecting the total number of tumour cells. The number of circulating tumour cells was reduced in ZOL treated animals.
conclusionA single dose of zoledronic acid caused significant changes in the bone area suggested to contain the metastatic niche. Tumour cells arriving in this modified bone microenvironment appeared to preferentially locate to osteoblast-rich areas, supporting that osteoblasts may be key components of the bone metastasis niche and therefore a potential therapeutic target in breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.