ArticleJCI insight2023
Reduced osteoprotegerin expression by osteocytes may contribute to rebound resorption after denosumab discontinuation.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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Who cites it
39 citing papers in PubMed, 46 citations in OpenAlex.
- Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity.Cell reports. Medicine · 2024Trial
- S100A9 Induces RANKL Expression in Osteocytes Utilizing IL-6/sIL-6R Combination and gp130 Signaling Pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Piezo1 Activation Rescues Anabolic Response to Mechanical Loading in Aged Bone via Connexin 43 Hemichannels.Aging cell · 2026Article
- Discontinuing Long-Term Denosumab in Treating Fragile Bone: Why, for Whom, and How?Clinical pharmacology and therapeutics · 2026Review
- DMP1-Cre expressing cells mediate the gain in bone mass and strength, but not the increase in bone remodeling, induced by ligands of the parathyroid hormone receptor.Bone research · 2026Article
- Preventing post-denosumab bone loss with zoledronate: a 2-year randomized trial in post-menopausal women without and with pre-exposure to bisphosphonates.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Review
- Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Osteocytes regulate osteoprotegerin expression via the p38-MAPK-CREB pathway in rheumatoid arthritis.JBMR plus · 2026Article
- Non-metastatic breast cancer patients discontinuing aromatase inhibitor on denosumab: what next?Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Managing Rebound Bone Loss After Denosumab Discontinuation: Mechanisms, Risk Stratification, and Sequential Therapy.Drug design, development and therapy · 2026Review
- Modeling rebound bone loss following denosumab discontinuation and sequential zoledronate therapy in TgRANKL osteoporotic mice.Frontiers in endocrinology · 2026Article
- Mechanisms and management strategies for exacerbated bone loss following denosumab discontinuation.Frontiers in aging · 2026Review
- Endogenous Osteocyte-Osteoclast Signaling Enables Growth Factor-Free Bone Remodeling, Drug Response, and Cancer Invasion in a Nanoscale Calcified Bone-on-a-Chip Model.bioRxiv : the preprint server for biology · 2025Article
- Article
- Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Review
- Article
- Combination or sequential teriparatide for osteoporosis treatment in denosumab-users: real-world bone mineral density outcomes.Bone reports · 2025Article
- TNFRSF11B-modified umbilical cord mesenchymal stem cells as a novel strategy for bone-related diseases by suppressing osteoclast activity.Journal of orthopaedic surgery and research · 2025Article
- A novel CCL3-HMGB1 signaling axis regulating osteocyte RANKL expression in multiple myeloma.Haematologica · 2025Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Denosumab is an anti-RANKL Ab that potently suppresses bone resorption, increases bone mass, and reduces fracture risk. Discontinuation of denosumab causes rapid rebound bone resorption and bone loss, but the molecular mechanisms are unclear. We generated humanized RANKL mice and treated them with denosumab to examine the cellular and molecular conditions associated with rebound resorption. Denosumab potently suppressed both osteoclast and osteoblast numbers in cancellous bone in humanized RANKL mice. The decrease in osteoclast number was not associated with changes in osteoclast progenitors in bone marrow. Long-term, but not short-term, denosumab administration reduced osteoprotegerin (OPG) mRNA in bone. Localization of OPG expression revealed that OPG mRNA is produced by a subpopulation of osteocytes. Long-term denosumab administration reduced osteocyte OPG mRNA, suggesting that OPG expression declines as osteocytes age. Consistent with this, osteocyte expression of OPG was more prevalent near the surface of cortical bone in humans and mice. These results suggest that new osteocytes are an important source of OPG in remodeling bone and that suppression of remodeling reduces OPG abundance by reducing new osteocyte formation. The lack of new osteocytes and the OPG they produce may contribute to rebound resorption after denosumab discontinuation.
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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.