Evidence map›Paper›PMID 40057981›Full record

ReviewJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2025

Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.

Shejil Kumar, Mawson Wang, Albert S Kim, Jacqueline R Center, Michelle M McDonald, Christian M Girgis

Registry-linked trialAbstract readReview
In one paragraph

Review in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07406685 (The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation), which is not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT07406685 phase4recruitingnot on this mapstarted 2026, after this paper: background citation

The Comparison of Ibandronate and Zoledronic Acid After Denosumab Discontinuation: A Randomized Non-inferiority Trial

TypeinterventionalSponsorNational Taiwan University HospitalRan2026 to 2030Enrolled52ConditionsPostmenopausal Osteoporosis, Postmenopausal Osteopenia, Primary Osteoporosis, OsteoporosisArmsIbandronate IV, Zoledronic acid IV
3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Letter to the editor regarding "Real-world rebound pattern of serum collagen type I C-telopeptide after denosumab discontinuation and zoledronate rescue in postmenopausal osteoporosis and cancer treatment-induced bone loss".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
  15. Review
  16. Real-world rebound pattern of serum collagen type I C-telopeptide after denosumab discontinuation and zoledronate rescue in postmenopausal osteoporosis and cancer treatment-induced bone loss.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
  17. Article
  18. Review
  19. Article
  20. Review
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

6 authors.

Shejil KumarDepartment of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia.ORCID 0000-0002-1242-2476
Mawson WangDepartment of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia.ORCID 0000-0003-1637-5117
Albert S KimDepartment of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia.ORCID 0000-0001-5832-0224
Jacqueline R CenterFaculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0002-5278-4527
Michelle M McDonaldFaculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0002-3928-2506
Christian M GirgisDepartment of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW 2145, Australia.ORCID 0000-0001-8746-5529

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Denosumab is a highly effective treatment for osteoporosis, and its long-term use is associated with incremental gains in BMD and sustained fracture risk reduction. Stopping denosumab, however, results in a rebound increase in bone turnover, loss of treatment-associated BMD gains, and in the worst case, spontaneous vertebral fractures (VFs). Insights into the risk factors, the underlying mechanisms for rebound-associated bone loss, and true incidence of rebound VFs are emerging. Conventional strategies using bisphosphonates to mitigate post-denosumab rebound display mixed success. Bisphosphonates may preserve bone density following short-term denosumab but the optimal sequential approach after longer-term denosumab remains elusive. Patients at particular risk of are those with prevalent VFs or greater on-treatment BMD gains. To greater understand these risks and strategies to preserve bone after denosumab, an emerging body of translational and preclinical work is shedding new light on the biology of RANKL inhibition and withdrawal. Discovering an effective "exit strategy" to control rebound bone turnover and avoid bone loss after denosumab will improve confidence among patients and clinicians in this highly effective and otherwise safe treatment for osteoporosis. This perspective characterizes the clinical problem of post-denosumab rebound, provides a comprehensive update on human studies examining the use of bisphosphonates following denosumab and explores mechanistic insights from preclinical studies that will be critical in the design of definitive human trials.

Indexed as

Bone RemodelingDenosumabFractures, BoneOsteoporosisWithholding TreatmentAnimalsBone DensityDiphosphonatesHumansDenosumabDiphosphonatesbisphosphonatesBMDbone resorptionbone turnoverdenosumabdiscontinuationfractureosteoporosisreboundsequential therapy

Identifiers

PMID40057981
PMCPMC12406127

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.