Evidence map›Paper›PMID 24646104›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2014

Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT).

Toshitaka Nakamura, Toshio Matsumoto, Toshitsugu Sugimoto, Takayuki Hosoi, Takami Miki, Itsuo Gorai, Hideki Yoshikawa, Yoshiya Tanaka, Sakae Tanaka, Teruki Sone and 9 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00680953 (A Randomized, Double-Blind, Placebo-controlled Phase 3 Study Evaluating Efficacy and Safety of Denosumab in Japanese Osteoporotic Subjects With Prevalent Fragility Vertebral Fracture), which is not on this map. Cited by 92 papers, 21 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 21 pooled it
9.8field-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.

NCT00680953 phase3completednot on this map

A Randomized, Double-Blind, Placebo-controlled Phase 3 Study Evaluating Efficacy and Safety of Denosumab in Japanese Osteoporotic Subjects With Prevalent Fragility Vertebral Fracture(s)

TypeinterventionalSponsorDaiichi Sankyo Co., Ltd.Ran2008 to 2012Enrolled1,262ConditionsOsteoporosisArmsDenosumab, Placebo, Alendronate sodium hydrate
3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 21 syntheses or guidelines pooled it, 165 citations in OpenAlex.

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  3. Impact of anti-osteoporosis medication on refracture prevention following osteoporotic vertebral fracture: 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 · 2025
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  8. Denosumab vs. bisphosphonates in primary osteoporosis: a meta-analysis of comparative safety in randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2024
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  13. Denosumab is not associated with risk of malignancy: systematic review and meta-analysis of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021
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32 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

19 authors at 13 institutions in 1 country.

Toshitaka NakamuraNational Center for Global Health and Medicine (T.Nakam.), Tokyo 162-8655, Japan; Department of Medicine and Bioregulatory Sciences (T.Matsu.), University of Tokushima Graduate School of Medical Sciences, Tokushima 770-8503, Japan; Internal Medicine 1 (T.Su.), Shimane University Faculty of Medicine, Izumo 693-8501, Japan; Kenkoin Clinic (T.H.), Tokyo 104-0061, Japan; Department of Geriatric (T.Mi.), Osaka City University Medical School, Osaka 545-8585, Japan; Hori Hospital (I.G.), Yokohama 246-0021, Japan; Department of Orthopedic Surgery (H.Y.), Osaka University Graduate School of Medicine, Suita 565-0871, Japan; The First Department of Internal Medicine (Y.T.), University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Orthopaedic Surgery Faculty of Medicine (S.T.), The University of Tokyo, Tokyo 113-8655, Japan; Department of Nuclear Medicine (T.So.), Kawasaki Medical School (M.F.), Kurashiki 701-0192, Japan; Tamana Central Hospital (T.Nakan.), Tamana 865-0064, Japan; Division of Radiology (M.I.), Nagasaki University School of Medicine, Nagasaki 852-8501, Japan; Department of Biostatistics (S.M.), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Osaka University Graduate School of Dentistry (T.Y.), Suita 565-0871, Japan; Daiichi Sankyo Co Ltd (H.T., K.W., T.O.), Tokyo 140-8710, Japan; and Research Institute and Practice for Involutional Diseases (M.S.), Azumino 399-8101, Japan.
Toshio Matsumoto
Toshitsugu Sugimoto
Takayuki Hosoi
Takami Miki
Itsuo Gorai
Hideki Yoshikawa
Yoshiya Tanaka
Sakae Tanaka
Teruki Sone
Tetsuo Nakano
Masako Ito
Shigeyuki Matsui
Toshiyuki Yoneda
Hideo Takami
Ko Watanabe
Taisuke Osakabe
Masataka Shiraki
Masao Fukunaga
Daiichi-Sankyo (Japan) · JPOsaka University · JPKawasaki Medical School · JPKurashiki Medical Center · JPMinebeaMitsumi (Japan) · JPNagasaki University · JPNagoya University · JPNational Center for Global Health and Medicine · JPOsaka City University · JPShimane University · JPThe University of Tokyo · JPTokushima University · JPUniversity of Occupational and Environmental Health Japan · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextDenosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian postmenopausal women with osteoporosis.

objectiveThe objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo. DESIGN AND

settingA randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted. PATIENTS: Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures.

interventionSubjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D.

main outcome measureThe primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo.

resultsDenosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194-0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study.

conclusionThese results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.

Indexed as

AgedAged, 80 and overAlendronateAntibodies, Monoclonal, HumanizedDenosumabFemaleHumansJapanMaleMiddle AgedOsteoporosisOsteoporosis, PostmenopausalOsteoporotic FracturesPlacebosRisk FactorsTreatment OutcomeAlendronateAntibodies, Monoclonal, HumanizedDenosumabPlacebos

Identifiers

PMID24646104
PMCPMC4191553
OpenAlexW2085717531

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.