Evidence map›Paper›PMID 22967310›Full record

ReviewInternational journal of clinical practice2012

Denosumab: mechanism of action and clinical outcomes.

D A Hanley, J D Adachi, A Bell, V Brown

Open access · bronzeAbstract readReview
In one paragraph

Review in International journal of clinical practice, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
207citing papers in PubMed, 8 pooled it
2.9field-weighted citation impact, top 9% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

207 citing papers in PubMed, 8 syntheses or guidelines pooled it, 353 citations in OpenAlex.

  1. Pooled it
  2. Hypercalcemia after denosumab discontinuation in patients with osteoporosis: a systematic review and case report.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
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  9. 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
  10. 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
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  13. Decreased incidence of shoulder arthroplasty in patients prescribed anti-resorptive therapy for osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
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147 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

D A HanleyDepartments of Medicine, Community Health Sciences and Oncology, University of Calgary, Calgary, AL, Canada. dahanley@ucalgary.ca
J D Adachi
A Bell
V Brown
University of Toronto · CASt. Joseph’s Healthcare Hamilton · CAUniversity of Calgary · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTo describe the mechanisms of action of denosumab, a novel antiresorptive agent, contrasting it with other antiresorptive and anabolic osteoporosis treatments.

methodsPublished papers related to the mechanism of action of approved osteoporosis treatments were sought through MEDLINE searches.

findingsOsteoporotic fractures carry a substantial burden of morbidity and mortality, but pharmacotherapy can prevent such fractures in high-risk individuals. Antiresorptive drugs (e.g. bisphosphonates, oestrogen, denosumab) reduce bone turnover by distinct mechanisms. Denosumab, a recently approved therapy, is a fully human monoclonal antibody that binds the cytokine RANKL (receptor activator of NFκB ligand), an essential factor initiating bone turnover. RANKL inhibition blocks osteoclast maturation, function and survival, thus reducing bone resorption. In contrast, bisphosphonates bind bone mineral, where they are absorbed by mature osteoclasts, inducing osteoclast apoptosis and suppressing resorption. These differences in mechanism influence both the onset and reversibility of treatment. DISCUSSION: Effective pharmacotherapy is necessary for patients at high risk of fracture. Among the treatment options for postmenopausal osteoporosis, there are significant differences in mechanism and dosing. Denosumab acts by a novel mechanism and is administered twice yearly by subcutaneous injection. Identified by Osteoporosis Canada Clinical Practice Guidelines as a first-line agent for treatment of postmenopausal osteoporosis, denosumab represents an important addition to our treatment options.

Indexed as

Antibodies, Monoclonal, HumanizedBone Density Conservation AgentsBone RemodelingDenosumabDiphosphonatesHumansMaleMiddle AgedOsteoporosis, PostmenopausalOsteoporotic FracturesPractice Guidelines as TopicTeriparatideAntibodies, Monoclonal, HumanizedBone Density Conservation AgentsDenosumabDiphosphonatesTeriparatide

Identifiers

PMID22967310
PMCPMC3549483
OpenAlexW1621696727

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.