Evidence map›Paper›PMID 36088628›Full record

Trial reportJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2022

Multiple Vertebral Fractures After Denosumab Discontinuation: FREEDOM and FREEDOM Extension Trials Additional Post Hoc Analyses.

Felicia Cosman, Shuang Huang, Michele McDermott, Steven R Cummings

3 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
4.2field-weighted citation impact, top 5% 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.

NCT00523341 phase3completednot on this map

An Open Label, Single Arm, Extension Study to Evaluate the Long Term Safety and Sustained Efficacy of Denosumab (AMG162) in the Treatment of Postmenopausal Osteoporosis

TypeinterventionalSponsorAmgenRan2007 to 2015Enrolled4,550ConditionsOsteopenia, OsteoporosisArmsDenosumab
NCT06938152 phase4recruitingnot on this mapstarted 2025, after this paper: background citation

Effects of Cycle Therapy With Romosozumab and Denosumab 2 Years vs 1 Year Romosozumab Followed by 1 Year Denosumab in Postmenopausal Osteoporosis Patients-A Randomized Control Trial

TypeinterventionalSponsorNational Taiwan University HospitalRan2025 to 2029Enrolled70ConditionsOsteoporosis, Osteoporosis PostmenopausalArmsRomosozumab followed by Denosumab, Romosozumab and Denosumab Cycle Therapy
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

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Phase 3 study comparing the efficacy and safety of proposed biosimilar RGB-14-P with denosumab in postmenopausal women with osteoporosis: results from the transition (switch) phase.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Trial
  5. A randomised Phase 3 study comparing the efficacy and safety of proposed denosumab biosimilar RGB-14-P and reference denosumab in women with postmenopausal osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
    Trial
  6. Impact of standard versus cyclic teriparatide and denosumab treatment on trabecular bone score: a post-hoc analysis of a randomized 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 · 2025
    Trial
  7. No overshoot of bone turnover after withdrawal of denosumab treatment of adults with Langerhans cell histiocytosis: a prospective 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 · 2025
    Trial
  8. One versus 2 years of alendronate following denosumab: the CARD extension.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024
    Trial
  9. Trial
  10. The comparison of alendronate and raloxifene after denosumab (CARD) study: A comparative efficacy trial.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024
    Trial
  11. Trial
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Letter to the editor regarding "Pre-teriparatide anti-osteoporosis medication therapy and fracture-related hospitalization in patients at very high fracture risk".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
  18. Review
  19. 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
  20. [Interpretation of the 2025 Asian Federation of Osteoporosis Societies (AFOS) Clinical Consensus: Atypical femoral fractures in patients with osteoporosis].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
    Article
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

4 authors at 3 institutions in 1 country.

Felicia CosmanDivision of Endocrinology/Department of Medicine, Columbia University, New York, NY, USA.ORCID 0000-0003-4554-6616
Shuang HuangAmgen Inc., Thousand Oaks, CA, USA.
Michele McDermottAmgen Inc., Thousand Oaks, CA, USA.
Steven R CummingsSan Francisco Coordinating Center, California Pacific Medical Center Research Institute and University of California, San Francisco, CA, USA.
Amgen (United States) · USColumbia University Irving Medical Center · USUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It is uncertain whether the risk of vertebral fracture (VF) and multiple vertebral fractures (MVFs; ≥2 VFs) after denosumab (DMAb) discontinuation is related to treatment duration. A prior analysis of Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) and FREEDOM Extension trials did not find a relationship with DMAb duration and may have underreported MVF incidence because it included women who did not have radiographs. In this post hoc exploratory analysis, the crude incidence and annualized rates of VF and MVF were determined in patients with ≥7 months' follow-up and ≥1 spine radiograph after discontinuing placebo or DMAb. A multivariate analysis was performed to identify predictors of MVF. Clinical characteristics of patients with ≥4 VFs were explored. This analysis included women who discontinued after placebo (n = 327) or DMAb either from FREEDOM or FREEDOM Extension (n = 425). The DMAb discontinuation group was subsequently dichotomized by treatment duration: short-term (≤3 years; n = 262) and long-term (>3 years; n = 213) treatment. For any VF, exposure-adjusted annualized rates per 100 patient-years (95% confidence interval [CI]) were 9.4 (95% CI, 6.4-13.4) for placebo, 6.7 (95% CI, 4.2-10.1) for short-term DMAb, and 10.7 (95% CI, 7.4-15) for long-term DMAb. Annualized rates for MVF were 3.6 (95% CI, 1.9-6.3), 2.9 (95% CI, 1.4-5.4), and 7.5 (95% CI, 4.8-11.1), respectively. Annualized rates for ≥4 VFs were 0.59 (95% CI, 0.1-2.1), 0.57 (95% CI, 0.1-2.1), and 3.34 (95% CI, 1.7-6.0), respectively. In a multivariate regression model, DMAb duration was significantly associated with MVF risk (odds ratio 3.0; 95% CI, 1.4-6.5). Of 15 patients with ≥4 VFs, 13 had DMAb exposure (mean ± standard deviation [SD], 4.9 ± 2.2 years). The risk of MVF after DMAb discontinuation increases with increased duration of DMAb treatment. Patients transitioning off DMAb after 3 years may warrant more frequent administration of zoledronic acid or another bisphosphonate to maintain bone turnover and bone mineral density (BMD) and prevent MVF. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Indexed as

Bone Density Conservation AgentsOsteoporosisOsteoporosis, PostmenopausalOsteoporotic FracturesSpinal FracturesBone DensityDenosumabFemaleFracture FixationFreedomHumansBone Density Conservation AgentsDenosumabANTIRESORPTIVESCLINICAL TRIALSFRACTURE PREVENTIONOSTEOPOROSISTHERAPEUTICS

Identifiers

PMID36088628
PMCPMC10092421
OpenAlexW4295152004

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.