Evidence map›Paper›PMID 26694598›Full record

ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2016

Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics.

A W Popp, P K Zysset, K Lippuner

Registry-linked trialAbstract readCase Reports
PubMed Publisher
In one paragraph

Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03396315 (Bisphosphonates for Prevention of Post-Denosumab Bone Loss in Premenopausal Women With Idiopathic Osteoporosis), which is not on this map. Cited by 76 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
8.6field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT03396315 phase2completednot on this mapstarted 2018, after this paper: background citation

Bisphosphonates for Prevention of Post-Denosumab Bone Loss in Premenopausal Women With Idiopathic Osteoporosis

TypeinterventionalSponsorColumbia UniversityRan2018 to 2023Enrolled24ConditionsIOP, OsteoporosisArmsAlendronate, Zoledronic Acid
3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.

  1. Effectiveness and safety of bone protective interventions to mitigate bone loss and skeletal fractures experienced by patients with non-metastatic breast cancer: a systematic review and meta-analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Pooled it
  2. 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 · 2022
    Trial
  3. Denosumab After Teriparatide in Premenopausal Women With Idiopathic Osteoporosis.The Journal of clinical endocrinology and metabolism · 2022
    Trial
  4. Trial
  5. Bone Mineral Density After Transitioning From Denosumab to Alendronate.The Journal of clinical endocrinology and metabolism · 2020
    Trial
  6. Trial
  7. Effects of Teriparatide, Denosumab, or Both on Spine Trabecular Microarchitecture in DATA-Switch: a Randomized Controlled Trial.Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry
    Trial
  8. Article
  9. Article
  10. Review
  11. Review
  12. Bone health in patients with cancer: a SEOM-SEIOMM consensus review of risk factors, assessment strategies, and management approaches.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  13. 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 · 2026
    Article
  14. Review
  15. 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 · 2026
    Review
  16. Review
  17. Article
  18. Follow-on osteoporosis therapy after denosumab discontinuation among Medicare beneficiaries.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Article
  19. Review
  20. Article

16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

A W PoppDepartment of Osteoporosis, Inselspital, Bern University Hospital and University of Bern, 3010, Bern, Switzerland. albrecht.popp@insel.ch.ORCID http://orcid.org/0000-0002-5954-7495
P K ZyssetInstitute for Surgical Technology and Biomechanics, University of Bern, Bern, Switzerland.
K LippunerDepartment of Osteoporosis, Inselspital, Bern University Hospital and University of Bern, 3010, Bern, Switzerland. kurt.lippuner@insel.ch.
University of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

unlabelledRebound-associated vertebral fractures may follow treatment discontinuation of highly potent reversible bone antiresorptives, resulting from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone.

introductionThe purposes of this study are to characterize rebound-associated vertebral fractures following the discontinuation of a highly potent reversible antiresorptive therapy based on clinical observation and propose a pathophysiological rationale.

methodsThis study is a case report of multiple vertebral fractures early after discontinuation of denosumab therapy in a patient with hormone receptor-positive non-metastatic breast cancer treated with an aromatase inhibitor.

resultsDiscontinuation of highly potent reversible bone antiresorptives such as denosumab may expose patients to an increased fracture risk due to the joined effects of absent microdamage repair during therapy followed by synchronous excess activation of multiple bone remodelling units at the time of loss-of-effect. We suggest the term rebound-associated vertebral fractures (RVF) for this phenomenon characterized by the presence of multiple new clinical vertebral fractures, associated with either no or low trauma, in a context consistent with the presence of high bone turnover and rapid loss of lumbar spine bone mineral density (BMD) occurring within 3 to 12 months after discontinuation (loss-of-effect) of a reversible antiresorptive therapy in the absence of secondary causes of bone loss or fractures. Unlike atypical femoral fractures that emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, RVF originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of highly potent reversible antiresorptives.

conclusionsStudies are urgently needed to i) prove the underlying pathophysiological processes suggested above, ii) establish the predictive criteria exposing patients to an increased risk of RVF, and iii) determine appropriate treatment regimens to be applied in such patients.

Indexed as

Aromatase InhibitorsBone Density Conservation AgentsBone Diseases, MetabolicBreast NeoplasmsDenosumabDrug Administration ScheduleFemaleHumansMiddle AgedOsteoporotic FracturesSpinal FracturesWithholding TreatmentAromatase InhibitorsBone Density Conservation AgentsDenosumabBone antiresorptivesBone turnoverDenosumabMicrodamage repairRebound-associated vertebral fractures

Identifiers

PMID26694598
OpenAlexW2220606005

What OpenQuestion holds

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Read underepoch 390

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.