ReviewFrontiers in endocrinology2022
The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies.
Review in Frontiers in endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 79 citations in OpenAlex.
- Long-term effect of neoadjuvant denosumab treatment in high-risk early breast cancer (GeparX).ESMO open · 2025Trial
- Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.World journal of experimental medicine · 2026Review
- The Liver-Bone Axis in Steatotic Liver Disease.Calcified tissue international · 2026Review
- The investigation of molecular mechanisms influencing variations of sternum calcification in ducks by integrating transcriptomic and metabolomic analyses.Poultry science · 2026Article
- Role of the Antioxidant Lycopene in Bone Health: Emphasis on the RANKL/RANK/OPG Signaling Pathway.Food science & nutrition · 2026Review
- SGLT2 Inhibitors: Dual Effects on Erythropoiesis and Bone Metabolism.Journal of bone metabolism · 2026Review
- Metabolic checkpoints in bone remodeling: from dysregulation to targeted therapies.Clinics (Sao Paulo, Brazil) · 2026Review
- Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.Biomolecules · 2026Review
- From Bone Marrow Reserve to Metastatic Niche: How Neutrophil-Lineage Cells Shape Skeletal Colonization.International journal of molecular sciences · 2026Review
- Salivary RANKL/OPG and Periodontal Status Among Users of Heated Tobacco and Electronic Cigarettes Versus Non-Smokers: A Prospective Observational Study.Healthcare (Basel, Switzerland) · 2026Article
- Systematic review and meta-analysis of AI in lung cancer metastasis imaging for diagnosis and prognosis.NPJ digital medicine · 2026Article
- Recombinant LGR4 extracellular domain attenuates osteoclastogenesis and prevents bone metastasis via RANKL inhibition.Journal of bone oncology · 2026Article
- Humic Acid Therapy Mitigates Estrogen Deficiency-Induced Alveolar Bone Loss and Modulates the RANKL/OPG Balance.Biomedicines · 2026Article
- Advancements in Skeletal Tumour Management: Linking Metastatic Biology With Surgical Reconstruction.Cureus · 2026Review
- A conceptual blueprint for "turning cold to hot" in Osteosarcoma: from TME stratification hypotheses to adaptive therapeutic prospects.Cell communication and signaling : CCS · 2026Review
- Can Blood Cell Count-Based Inflammatory Markers Reflect the Risk of Osteoporosis? A Cross-Sectional and Genetic Analysis.Immunity, inflammation and disease · 2026Article
- FXR in bone metabolism: An emerging regulator.iScience · 2026Review
- Independent Risk Factors and a New Nomogram for Predicting Breast Cancer Risk for Bone Metastasis in Chinese Women: A Retrospective Study with External Validation.Journal of clinical medicine · 2026Article
- Bone and Infections: An Osteoimmunological Interplay.International journal of molecular sciences · 2026Review
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With the markedly increased diagnosis and incidence of cancer in the population, tumor bone metastasis has become a frequent event in tumor patients. Healthy bone integrity is maintained by a delicate balance between bone formation and bone resorption. Unfortunately, many tumors, such as prostate and breast, often metastasize to the bone, and the alterations to the bone homeostasis can particularly favor tumor homing and consequent osteolytic or osteoblastic lesions. Receptor activator of NF-κB ligand (RANKL), its receptor RANK, and osteoprotegerin (OPG) are involved in the regulation of the activation, differentiation, and survival of osteoclasts, which play critical roles in bone metastasis formation. High rates of osteoclastic bone resorption significantly increase fracture risk, cause severe bone pain, and contribute to homing tumor cells in bone and bone marrow. Consequently, suppression of the RANK/RANKL/OPG system and osteoclastic activity can not only ameliorate bone resorption but may also prevent tumor bone metastases. This review summarizes the important role of the RANK/RANKL/OPG system and osteoclasts in bone homeostasis and its effect on tumor bone metastasis and discusses therapeutic strategies based on RANKL inhibition.
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Registered trials
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.