ArticleOncotarget2014
Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The Global Prevalence of Vitamin D Deficiency and Insufficiency in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- Impact of denosumab therapy on periapical healing following root canal treatment: a 10-year retrospective case-control study.BMC oral health · 2026Article
- The Presence of SFRP1 Reduces the High Risk of Metastasis in RANKL-Expressing Canine Mammary Cancers.Animals : an open access journal from MDPI · 2026Article
- Primary Hyperparathyroidism with Severe Vitamin D Deficiency in Chronic Kidney Disease.Internal medicine (Tokyo, Japan) · 2025Article
- Rheumatoid Arthritis and Osteoporosis as Prototypes of Immunosenescence in Osteoimmunology: Molecular Pathways of Inflammaging and Targeted Therapies.International journal of molecular sciences · 2025Review
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- Article
- Reduced osteoprotegerin expression by osteocytes may contribute to rebound resorption after denosumab discontinuation.JCI insight · 2023Article
- Antiresorptive-Type and Discontinuation-Timing Affect ONJ Burden.Journal of dental research · 2021Article
- Novel Pharmaceutical Strategy for Selective Abrogation of TSP1-Induced Vascular Dysfunction by Decoy Recombinant CD47 Soluble Receptor in Prophylaxis and Treatment Models.Biomedicines · 2021Article
- RANKL regulates male reproductive function.Nature communications · 2021Article
- Cancer Treatment-Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy.Current treatment options in oncology · 2021Review
- Effects ofFrontiers in pharmacology · 2021Article
- Denosumab in the treatment of giant cell tumor of the spine. Preliminary report, review of the literature and protocol proposal.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020Review
- Molecular mechanisms and clinical management of cancer bone metastasis.Bone research · 2020Review
- The Interplay between Circulating Tumor Cells and the Immune System: From Immune Escape to Cancer Immunotherapy.Diagnostics (Basel, Switzerland) · 2018Review
- IDK1 is a rat monoclonal antibody against hypoglycosylated bone sialoprotein with application as biomarker and therapeutic agent in breast cancer skeletal metastasis.The journal of pathology. Clinical research · 2018Article
- Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.Journal of proteome research · 2016Article
- Design of a RANK-Mimetic Peptide Inhibitor of Osteoclastogenesis with Enhanced RANKL-Binding Affinity.Molecules and cells · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone homeostasis critically relies on the RANKL-RANK-OPG axis which can be targeted by the fully human monoclonal antibody denosumab in conditions with increased bone resporption such as bone metastases. The binding site and therefore the molecular mechanism by which this antibody inhibits RANKL has not been characterized so far. Here, we used random peptide phage display library screenings to identify the denosumab epitope on RANKL. Alignments of phage derived peptide sequences with RANKL suggested that this antibody recognized a linear epitope between position T233 and Y241. Mutational analysis confirmed the core residues as critical for this interaction. The spatial localization of this epitope on a 3-dimensional model of RANKL showed that it overlapped with the major binding sites of OPG and RANK on RANKL. We conclude that denosumab inhibits RANKL by both functional and molecular mimicry of the natural decoy receptor OPG.
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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.