Evidence map›Paper›PMID 34967731›Full record

ArticleeLife2021

Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages.

Marcia A Munoz, Emma K Fletcher, Oliver P Skinner, Julie Jurczyluk, Esther Kristianto, Mark P Hodson, Shuting Sun, Frank H Ebetino, David R Croucher, Philip M Hansbro and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 22% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. 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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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 at 6 institutions in 2 countries.

Marcia A MunozGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, Australia.ORCID 0000-0001-7603-0351
Emma K FletcherGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, Australia.
Oliver P SkinnerGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, Australia.
Julie JurczylukGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, Australia.
Esther KristiantoVictor Chang Cardiac Research Institute Innovation Centre, Sydney, Australia.
Mark P HodsonVictor Chang Cardiac Research Institute Innovation Centre, Sydney, Australia.ORCID 0000-0002-5436-1886
Shuting SunBioVinc, Pasadena, United States.
Frank H EbetinoBioVinc, Pasadena, United States.
David R CroucherGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, Australia.ORCID 0000-0003-4965-8674
Philip M HansbroCentre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, Australia.
Jacqueline R CenterGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, Australia.ORCID 0000-0002-5278-4527
Michael J RogersGarvan Institute of Medical Research and St Vincent's Clinical School, UNSW Sydney, Sydney, Australia.ORCID 0000-0002-1818-9249
Garvan Institute of Medical Research · AUBioVinc (United States) · USThe University of Queensland · AUUniversity of Southern California · USUniversity of Technology Sydney · AUVictor Chang Cardiac Research Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently labelled bisphosphonate is internalised by alveolar macrophages and large peritoneal macrophages in vivo. Furthermore, a single dose of a nitrogen-containing bisphosphonate (zoledronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia.

Indexed as

AnimalsBone Density Conservation AgentsChemokinesCytokinesFemaleLipopolysaccharidesLungMacrophages, AlveolarMacrophages, PeritonealMevalonic AcidMiceMice, Inbred C57BLProtein PrenylationZoledronic AcidBone Density Conservation AgentsChemokinesCytokinesLipopolysaccharidesMevalonic AcidZoledronic Acidalveolar macrophagebisphosphonateinflammasomemedicinemouseosteoporosispneumoniaprenylation

Identifiers

PMID34967731
PMCPMC8718110
OpenAlexW4200501527

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.