ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2009
Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 10 of them syntheses that pooled it.
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Who cites it
189 citing papers in PubMed, 10 syntheses or guidelines pooled it, 432 citations in OpenAlex.
- Efficacy and safety of denosumab in treatment of osteoporosis in patients with rheumatoid arthritis: a meta-analysis and systematic review.BMC musculoskeletal disorders · 2025Pooled it
- Comparing the Efficacy of Antiosteoporotic Drugs in Preventing Periprosthetic Bone Loss Following Total Hip Arthroplasty: A Systematic Review and Bayesian Network Meta-Analysis.Orthopaedic surgery · 2024Pooled it
- Meta-analysis of the effects of denosumab and romosozumab on bone mineral density and turnover markers in patients with osteoporosis.Frontiers in endocrinology · 2023Pooled it
- Denosumab is not associated with risk of malignancy: systematic review and meta-analysis of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- The Efficacy of Denosumab in Patients With Rheumatoid Arthritis: A Systematic Review and Pooled Analysis of Randomized or Matched Data.Frontiers in immunology · 2021Pooled it
- Safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density: a meta-analysis.International journal of clinical and experimental pathology · 2014Pooled it
- Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.PLoS genetics · 2013Pooled it
- Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis.Clinical pharmacokinetics · 2011Pooled it
- Genome-wide association meta-analysis of cortical bone mineral density unravels allelic heterogeneity at the RANKL locus and potential pleiotropic effects on bone.PLoS genetics · 2010Pooled it
- OPG and RANK polymorphisms are both associated with cortical bone mineral density: findings from a metaanalysis of the Avon longitudinal study of parents and children and gothenburg osteoporosis and obesity determinants cohorts.The Journal of clinical endocrinology and metabolism · 2010Pooled it
- Denosumab in Giant Cell Rich Tumors of Bone: An Open-Label Multicenter Phase II Study.The oncologist · 2023Trial
- Denosumab improves bone mineral density and microarchitecture in rheumatoid arthritis: randomized controlled trial by HR-pQCT.Journal of bone and mineral metabolism · 2023Trial
- Trial
- The effect of denosumab in breast cancer patients receiving adjuvant aromatase inhibitors: 36-month results.Journal of bone and mineral metabolism · 2021Trial
- Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial.Annals of the rheumatic diseases · 2019Trial
- Efficacy of denosumab with regard to bone destruction in prognostic subgroups of Japanese rheumatoid arthritis patients from the phase II DRIVE study.Rheumatology (Oxford, England) · 2019Trial
- Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis.The Journal of clinical endocrinology and metabolism · 2018Trial
- Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial.Annals of the rheumatic diseases · 2016Trial
- Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2014Trial
- Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2013Trial
129 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RANKL is a TNF family member that mediates osteoclast formation, activation, and survival by activating RANK. The proresorptive effects of RANKL are prevented by binding to its soluble inhibitor osteoprotegerin (OPG). Recombinant human OPG-Fc recognizes RANKL from multiple species and reduced bone resorption and increased bone volume, density, and strength in a number of rodent models of bone disease. The clinical development of OPG-Fc was discontinued in favor of denosumab, a fully human monoclonal antibody that specifically inhibits primate RANKL. Direct binding assays showed that denosumab bound to human RANKL but not to murine RANKL, human TRAIL, or other human TNF family members. Denosumab did not suppress bone resorption in normal mice or rats but did prevent the resorptive response in mice challenged with a human RANKL fragment encoded primarily by the fifth exon of the RANKL gene. To create mice that were responsive to denosumab, knock-in technology was used to replace exon 5 from murine RANKL with its human ortholog. The resulting "huRANKL" mice exclusively express chimeric (human/murine) RANKL that was measurable with a human RANKL assay and that maintained bone resorption at slightly reduced levels versus wildtype controls. In young huRANKL mice, denosumab and OPG-Fc each reduced trabecular osteoclast surfaces by 95% and increased bone density and volume. In adult huRANKL mice, denosumab reduced bone resorption, increased cortical and cancellous bone mass, and improved trabecular microarchitecture. These huRANKL mice have potential utility for characterizing the activity of denosumab in a variety of murine bone disease models.
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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.