Evidence map›Paper›PMID 28449657›Full record

Trial reportBMC musculoskeletal disorders2017

Influence of subject discontinuation on long-term nonvertebral fracture rate in the denosumab FREEDOM Extension study.

Jonathan D Adachi, Henry G Bone, Nadia S Daizadeh, Paula Dakin, Socrates Papapoulos, Peyman Hadji, Chris Recknor, Michael A Bolognese, Andrea Wang, Celia J F Lin and 2 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC musculoskeletal disorders, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00523341 (An Open Label, Single Arm, Extension Study to Evaluate the Long Term Safety and Sustained Efficacy of Denosumab), which is not on this map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 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.

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
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Fracture risk following intermission of osteoporosis therapy.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019
    Pooled it
  3. Relationship Between Bone Mineral Density T-Score and Nonvertebral Fracture Risk Over 10 Years of Denosumab Treatment.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019
    Trial
  4. Review
  5. Review
  6. Article
  7. 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

12 authors.

Jonathan D AdachiMcMaster University, 501-25 Charlton Ave E., Hamilton, ON, L8N 1Y2, Canada. jd.adachi@sympatico.ca.
Henry G BoneMichigan Bone and Mineral Clinic, 22201 Moross Rd, Detroit, MI, 48236, USA.
Nadia S DaizadehAmgen Inc., One Amgen Ctr Dr., Thousand Oaks, CA, 91320, USA.
Paula DakinAmgen Inc., One Amgen Ctr Dr., Thousand Oaks, CA, 91320, USA.
Socrates PapapoulosLeiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, Netherlands.
Peyman HadjiKrankenhaus Nordwest, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany.
Chris RecknorUnited Osteoporosis Centers, 2350 Limestone Pkwy, Gainesville, GA, 30501, USA.
Michael A BologneseBethesda Health Research Center, 10215 Fernwood Rd Ste 40, Bethesda, MD, 20817, USA.
Andrea WangAmgen Inc., One Amgen Ctr Dr., Thousand Oaks, CA, 91320, USA.
Celia J F LinAmgen Inc., One Amgen Ctr Dr., Thousand Oaks, CA, 91320, USA.
Rachel B WagmanAmgen Inc., One Amgen Ctr Dr., Thousand Oaks, CA, 91320, USA.
Serge FerrariGeneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDenosumab treatment for up to 8 years in the FREEDOM study and Extension was associated with low fracture incidence. It was not clear whether subjects who discontinued during the study conduct had a higher risk of fracture than those who remained enrolled, thereby underestimating the true fracture risk for the entire trial cohort. Thus, we explored the influence of early withdrawals on nonvertebral fracture incidence during the Extension study.

methodsTo understand the potential effect of depletion of susceptible subjects on fracture incidence, we first evaluated subject characteristics in patients who were enrolled in the Extension vs those who were not. We subsequently employed a Kaplan-Meier multiple imputation (KMMI) approach to consider subjects who discontinued as if they remained enrolled with a 0%, 20%, 50%, and 100% increase in fracture risk compared with participants remaining on study.

resultsExtension enrollees were generally similar to nonparticipants in median age (71.9 and 73.1 years, respectively), mean total hip bone mineral density T-score (-1.9 and -2.0, respectively), and probability of fracture risk by Fracture Risk Assessment Tool (FRAX

conclusionThe observation of continued denosumab efficacy over 8 years of treatment was robust and does not seem to be explained by depletion of susceptible subjects.

trial registrationClincalTrials.gov registration number NCT00523341 ; registered August 30, 2007.

Indexed as

Patient DropoutsAgedAged, 80 and overBone Density Conservation AgentsDenosumabFemaleHip FracturesHumansMaleMiddle AgedOsteoporotic FracturesTreatment OutcomeBone Density Conservation AgentsDenosumabDenosumabExtension studyFREEDOMOsteoporosisSelection bias

Identifiers

PMID28449657
PMCPMC5408481

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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.