CoChat
Sign Up
Cited by 996Bone health and osteoporosis researchBone health and treatmentsMenopause: Health Impacts and Treatments

The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.

10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension

Open access
Bone, Henry G, Wagman, Rachel B, Brandi, Maria L, Brown, Jacques P, Chapurlat, Roland, Cummings, Steven R, Czerwiński, Edward, Fahrleitner-Pammer, Astrid, Kendler, David L, Lippuner, Kurt, Reginster, Jean-Yves, Roux, Christian, Malouf, Jorge, Bradley, Michelle N, Daizadeh, Nadia S, Wang, Andrea, Dakin, Paula, Pannacciulli, Nicola, Dempster, David W, Papapoulos, Socrates·2017·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(17)30138-9
Open this paper in CoChat — free account

Abstract

Background Long-term safety and efficacy of osteoporosis treatment are important because of the chronic nature of the disease. We aimed to assess the long-term safety and efficacy of denosumab, which is widely used for the treatment of postmenopausal women with osteoporosis.Methods In the multicentre, randomised, double-blind, placebo-controlled, phase 3 FREEDOM trial, postmenopausal women aged 60-90 years with osteoporosis were enrolled in 214 centres in North America, Europe, Latin America, and Australasia and were randomly assigned (1:1) to receive 60 mg subcutaneous denosumab or placebo every 6 months for 3 years. All participants who completed the FREEDOM trial without discontinuing treatment or missing more than one dose of investigational product were eligible to enrol in the open-label, 7-year extension, in which all participants received denosumab. The data represent up to 10 years of denosumab exposure for women who received 3 years of denosumab in FREEDOM and continued in the extension (long-term group), and up to 7 years for women who received 3 years of placebo and transitioned to denosumab in the extension (crossover group). The primary outcome was safety monitoring, comprising assessments of adverse event incidence and serious adverse event incidence, changes in safety laboratory analytes (ie, serum chemistry and haematology), and participant incidence of denosumab antibody formation. Secondary outcomes included new vertebral, hip, and non-vertebral fractures as well as bone mineral density (BMD) at the lumbar spine, total hip, femoral neck, and one-third radius. Analyses were done according to the randomised FREEDOM treatment assignments. All participants who received at least one dose of investigational product in FREEDOM or the extension were included in the combined safety analyses. All participants who enrolled in the extension with observed data were included in the efficacy analyses. The FREEDOM trial (NCT00089791) and its extension (NCT00523341) are both registered with ClinicalTrials.gov.Findings Between Aug 3, 2004, and June 1, 2005, 7808 women were enrolled in the FREEDOM study. 5928 (76%) women were eligible for enrolment in the extension, and of these, 4550 (77%) were enrolled (2343 long-term, 2207 crossover) between Aug 7, 2007, and June 20, 2008. 2626 women (1343 long-term; 1283 crossover) completed the extension. The yearly exposure-adjusted participant incidence of adverse events for all individuals receiving denosumab decreased from 165·3 to 95·9 per 100 participant-years over the course of 10 years. Serious adverse event rates were generally stable over time, varying between 11·5 and 14·4 per 100 participant-years. One atypical femoral fracture occurred in each group during the extension. Seven cases of osteonecrosis of the jaw were reported in the long-term group and six cases in the crossover group. The yearly incidence of new vertebral fractures (ranging from 0·90% to 1·86%) and non-vertebral fractures (ranging from 0·84% to 2·55%) remained low during the extension, similar to rates observed in the denosumab group during the first three years of the FREEDOM study, and lower than rates projected for a virtual long-term placebo cohort. In the long-term group, BMD increased from FREEDOM baseline by 21·7% at the lumbar spine, 9·2% at total hip, 9·0% at femoral neck, and 2·7% at the one-third radius. In the crossover group, BMD increased from extension baseline by 16·5% at the lumbar spine, 7·4% at total hip, 7·1% at femoral neck, and 2·3% at one-third radius.Interpretation Denosumab treatment for up to 10 years was associated with low rates of adverse events, low fracture incidence compared with that observed during the original trial, and continued increases in BMD without plateau.Funding Amgen.

Overview

Integrity signals

Registry

Crossref · 10.1016/s2213-8587(17)30138-9

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 36 references

Research works printed but not linked: 3

  1. Dempster, 2016, Effect of 10 years of denosumab treatment on bone histology and histomorphometry in the FREEDOM extension study, J Bone Miner Res, 31, 323
  2. Dempster, 2016, Effects of up to 10 years of denosumab treatment on bone matrix mineralization: results from the FREEDOM extension, J Bone Miner Res, 31, LB-1163
  3. Brown, 2016, Discontinuation of denosumab and associated vertebral fracture incidence: Analysis from FREEDOM and its Extension, J Bone Miner Res, 31, 1100

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Bone, H. G., Wagman, R. B., Brandi, M. L., Brown, J. P., Chapurlat, R., Cummings, S. R., Czerwiński, E., Fahrleitner-Pammer, A., Kendler, D. L., Lippuner, K., Reginster, J.-Y., Roux, C., Malouf, J., Bradley, M. N., Daizadeh, N. S., Wang, A., Dakin, P., Pannacciulli, N., Dempster, D. W., & Papapoulos, S.
Affiliations
  • University of Michigan (US)
  • Amgen (United States) (US)
  • University of Florence (IT)
  • Université Laval (CA)
  • Inserm (FR)
  • University of California, San Francisco (US)
  • University of British Columbia (CA)
  • University Hospital of Bern (CH)
  • University of Liège (BE)
  • Université Paris Descartes (FR)
  • Hospital de Sant Pau (ES)
  • Helen Hayes Hospital (US)
  • Leiden University Medical Center (NL)
Corresponding author
Bone, Henry G
ORCID
Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2017-07
Volume
5
Issue
7
Pages
513-523
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(17)30138-9
OpenAlex
W2619448414
Cited by
996
References
36
Citations by year
2026: 102 · 2025: 121 · 2024: 98 · 2023: 104 · 2022: 128 · 2021: 124 · 2020: 124 · 2019: 81 · 2018: 84 · 2017: 28
FWCI
95.26
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Diabetes & Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • BORIS (University Library Bern) (submittedVersion)
  • Florence Research (University of Florence) (submittedVersion, cc-by-nc-nd)
  • ORBi (University of Liège) (submittedVersion)
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Health Sciences › Medicine › Oncology › Bone health and treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
denosumab, postmenopausal osteoporosis, long-term safety, FREEDOM trial, open-label extension, fracture risk, bone mineral density, adverse events, osteonecrosis of the jaw, osteonecrosis of the femoral head, RANKL inhibitor, osteoporosis treatment
MeSH terms
Denosumab, Aged, Double-Blind Method, Female, Follow-Up Studies, Humans, Middle Aged, Prognosis, Time Factors, Bone Density, Osteoporosis, Postmenopausal, Cross-Over Studies, Bone Density Conservation Agents

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review