Evidence map›Paper›PMID 31120440›Full record

ArticleThe Journal of clinical investigation2019

RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass.

Nicolas Bonnet, Lucie Bourgoin, Emmanuel Biver, Eleni Douni, Serge Ferrari

Erratum issued Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT07271771 (The Effect of Denosumab on Muscle and Strength and Insulin Sensitivity), which is not on this map. Cited by 185 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
185citing papers in PubMed, 4 pooled it
11.9field-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.

NCT07271771 phase4recruitingnot on this mapstarted 2024, after this paper: background citation

The Effect of Denosumab on Muscle and Strength and Insulin Sensitivity

TypeinterventionalSponsorAarhus University HospitalRan2024 to 2027Enrolled40ConditionsOsteoporosisArmsDenosumab, Saline (0.9% NaCl)
3 · Its place in the literature

Who cites it

185 citing papers in PubMed, 4 syntheses or guidelines pooled it, 291 citations in OpenAlex.

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  8. Anti-resorptive and anabolic therapies improve Falls Risk Assessment Score (FRAS) in postmenopausal women with type 2 diabetes mellitus.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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  14. Denosumab for Prevention of Acute Onset Immobilization-Induced Alterations of Bone Turnover: A Randomized Controlled Trial.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
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125 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Nicolas BonnetDivision of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland.
Lucie BourgoinDivision of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland.
Emmanuel BiverDivision of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland.
Eleni DouniBiomedical Sciences Research Center "Alexander Fleming," Athens, Greece.
Serge FerrariDivision of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital & Faculty of Medicine, Geneva, Switzerland.
University Hospital of Geneva · CHAgricultural University of Athens · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Receptor activator of Nfkb ligand (RANKL) activates, while osteoprotegerin (OPG) inhibits, osteoclastogenesis. In turn a neutralizing Ab against RANKL, denosumab improves bone strength in osteoporosis. OPG also improves muscle strength in mouse models of Duchenne's muscular dystrophy (mdx) and denervation-induce atrophy, but its role and mechanisms of action on muscle weakness in other conditions remains to be investigated. We investigated the effects of RANKL inhibitors on muscle in osteoporotic women and mice that either overexpress RANKL (HuRANKL-Tg+), or lack Pparb and concomitantly develop sarcopenia (Pparb-/-). In women, denosumab over 3 years improved appendicular lean mass and handgrip strength compared to no treatment, whereas bisphosphonate did not. HuRANKL-Tg+ mice displayed lower limb force and maximal speed, while their leg muscle mass was diminished, with a lower number of type I and II fibers. Both OPG and denosumab increased limb force proportionally to the increase in muscle mass. They markedly improved muscle insulin sensitivity and glucose uptake, and decrease anti-myogenic and inflammatory gene expression in muscle, such as myostatin and protein tyrosine phosphatase receptor-γ. Similarly, in Pparb-/-, OPG increased muscle volume and force, while also normalizing their insulin signaling and higher expression of inflammatory genes in skeletal muscle. In conclusions, RANKL deteriorates, while its inhibitor improves, muscle strength and insulin sensitivity in osteoporotic mice and humans. Hence denosumab could represent a novel therapeutic approach for sarcopenia.

Indexed as

Insulin ResistanceMuscle StrengthAnimalsBone and BonesCell LineDenosumabFemaleHumansMaleMiceMice, TransgenicOrgan SizeOsteoporosisOsteoprotegerinPPAR-betaRANK LigandDenosumabOsteoprotegerinPPAR-betaRANK LigandTNFRSF11B protein, humanTnfrsf11b protein, mouseTNFSF11 protein, humanBone BiologyBone diseaseMuscleMuscle BiologyOsteoporosis

Identifiers

PMID31120440
PMCPMC6668701
OpenAlexW2945787015

What OpenQuestion holds

Textmetadata
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.