ReviewJournal of clinical medicine2021
Denosumab Discontinuation and the Rebound Phenomenon: A Narrative Review.
Review in Journal of clinical medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 5 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
111 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Pooled it
- Preclinical effects of naringin on bone outcomes in animal models of osteoporosis: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Adynamic bone disorder in chronic kidney disease: meta-analysis and narrative review of potential biomarkers as diagnosis and therapeutic targets.Renal failure · 2025Pooled it
- Rebound hypercalcemia after denosumab cessation during follow-up after surgical treatment for parathyroid carcinoma: case report and literature review.Archives of endocrinology and metabolism · 2024Pooled it
- Efficacy of Antiresorptive Treatment in Osteoporotic Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.The journal of nutrition, health & aging · 2022Pooled it
- Effect of artificial gravity on calcaneal bone marrow adipose tissue and mineral content in female and male participants in 60 days of bed rest.Experimental physiology · 2026Trial
- Effect of a single-dose denosumab on mineral homeostasis in infertile men: insights from a pilot intervention study and a randomized controlled trial.BMC medicine · 2025Trial
- Denosumab in patients with osteogenesis imperfecta and a historical control study with alendronate.Frontiers in endocrinology · 2025Trial
- Efficacy and Safety of Denosumab vs Zoledronic Acid in OI Adults: A Prospective, Open-Label, Randomized Study.The Journal of clinical endocrinology and metabolism · 2024Trial
- Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Trial
- The Effect of Zoledronic Acid on Bone Microarchitecture and Strength after Denosumab and Teriparatide Administration: DATA-HD Study Extension.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Trial
- Denosumab for Prevention of Acute Onset Immobilization-Induced Alterations of Bone Turnover: A Randomized Controlled Trial.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Trial
- Multiple Vertebral Fractures After Denosumab Discontinuation: FREEDOM and FREEDOM Extension Trials Additional Post Hoc Analyses.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Trial
- Effects of denosumab treatment on the expression of receptor activator of nuclear kappa-B ligand (RANKL) and TNF-receptor TNFRSF9 after total hip arthroplasty-results from a randomized placebo-controlled 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 · 2022Trial
- Efficacy of sequential romosozumab-denosumab therapy in patients on hemodialysis: association with bone mineral density improvement and TRACP-5b rebound.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Plant-based macronutrients and micronutrients in combating osteoporosis: research insights and molecular pathways.RSC advances · 2026Review
- Clinical Significance of Bone Turnover Markers in Osteoporosis: Fracture Risk Assessment and Treatment Monitoring.Journal of menopausal medicine · 2026Review
- Pathophysiology, diagnosis and management of secondary osteoporosis.Nature reviews. Endocrinology · 2026Review
- Challenges in Sequential Antiresorptive Therapy After Long-Term Denosumab Discontinuation: A Case Report and Narrative Review of the Literature.Journal of clinical medicine · 2026Review
- The therapeutic window: timing dentoalveolar surgery to minimize MRONJ risk in denosumab-treated osteoporotic patients.JBMR plus · 2026Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Denosumab is a potent antiresorptive agent that substantially increases bone mineral density and reduces fracture rates at all skeletal sites for as long as it is administered. However, its favorable skeletal effects reverse quickly upon its discontinuation, because of a vast increase of osteoclast number and activity, which leads to a subsequent profound increase of bone turnover above pre-treatment values, a phenomenon commonly described as "rebound phenomenon". More importantly, most patients experience rapid, profound bone loss due to this burst of bone resorption that may lead in a minority of these patients to occurrence of fractures, especially multiple vertebral fractures. Therefore, subsequent antiresorptive treatment is mandatory, although the optimal regimen is yet to be clarified. In the present review, we outline what is currently known regarding the negative effects of denosumab discontinuation on different aspects of bone status, the factors that may affect them, and strategies to prevent them.
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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.