ReviewJournal of bone and mineral metabolism2021
Discovery of the RANKL/RANK/OPG system.
Review in Journal of bone and mineral metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 129 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- Effects of kaempferol on bone loss in animal models of osteoporosis: a systematic review and meta-analysis.Frontiers in endocrinology · 2026Pooled it
- Risk of low bone mineral density in patients with haemophilia: a systematic review and meta-analysis.Journal of orthopaedic surgery and research · 2024Pooled it
- Inhibition of BMP-Smad1/5 signaling with DMH1 attenuates joint degeneration in a rat model of cuff tear arthropathy.Osteoarthritis and cartilage open · 2026Article
- Anti-RANKL antibody treatment mitigates subchondral bone loss and cartilage degeneration without affecting synovial inflammation in a mouse model of rotator cuff tear arthropathy.Bone & joint research · 2026Article
- Bone as a Biomarker of Ageing and Senescence: Connecting Musculoskeletal Health to Longevity via Diet, Nutrition and Exercise.Biology · 2026Review
- DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.Journal of biomedical science · 2026Review
- Article
- Angiotensin converting enzyme-2 activation mitigates glucocorticoids-induced osteoporosis in rats by modulating oxidative stress, inflammation and the RANKL/OPG pathway.Pflugers Archiv : European journal of physiology · 2026Article
- Article
- Histomorphologic Assessment of Osteoregeneration in a Rabbit Femur Model With Xenograft, Bone Morphogenetic Protein-2, Platelet-Rich Plasma, and Denosumab.Plastic and reconstructive surgery. Global open · 2026Article
- Fibroblast-like cells accumulate late in human coronary atherosclerosis contributing to necrotic core formation.Cardiovascular research · 2026Article
- RANKL Attenuates Sepsis-Associated Acute Lung Injury Through the OPG/RANKL/RANK/TLR4 Pathway.Immunity, inflammation and disease · 2026Article
- MST4 as a key driver of osteoclast activation in osteoporosis.Journal of pharmaceutical analysis · 2026Article
- Research progress on the effects of macrophage‑derived exosomes on muscle factors IGF‑1 and FGF‑2 mediating musculoskeletal crosstalk molecular signaling pathway on bone metabolism (Review).International journal of molecular medicine · 2026Review
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
- Gout Inflammation Time Programming: Molecular Clock from Crystal Triggering to Tissue Remodeling.International journal of molecular sciences · 2026Review
- RANKL promotes airway inflammation via pro-inflammatory alveolar macrophage activation in COPD.Respiratory research · 2026Article
- Effect of moderate-intensity treadmill exercise on bone quality in adult rats and the underlying mechanisms.BMC musculoskeletal disorders · 2026Article
- The contested association between MASLD and osteoporosis: a narrative review of heterogeneous evidence and modifying factors.Archives of osteoporosis · 2026Review
- The impact of garlic and its active metabolites on degenerative musculoskeletal diseases.Frontiers in pharmacology · 2026Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Almost a quarter century has passed since discovery of receptor activator of NF-κB ligand (RANKL). This discovery had a major impact on identification of mechanisms regulating osteoclast differentiation and function, establishment of a research field bridging bone and the immune system (osteoimmunology), and development of a fully human anti-RANKL neutralizing antibody (denosumab). Denosumab is now clinically available for treatment of osteoporosis and cancer-induced bone diseases in the US, Europe and many other countries, including Japan. Denosumab is a so-called blockbuster drug, with sales of 5.0 billion US dollars in 2019. This is a real success story from bench to bedside. In this review, the pivotal roles of the RANKL/RANK/OPG system in osteoclast differentiation and function are shown. RANKL is a ligand required for osteoclast generation, RANK is the receptor for RANKL, and osteoprotegerin (OPG) is a decoy receptor for RANKL. The review covers recent results showing the importance of RANKL on osteoblasts in regulation of osteogenesis and the role of RANKL-RANK dual signaling in coupling of bone resorption and formation, including demonstration of RANKL reverse signaling that we had previously hypothesized. Possible applications of anti-RANKL antibody in treatment of cancer are also discussed.
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What OpenQuestion holds
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.