Evidence map›Paper›PMID 39424806›Full record

ArticleBone research2024

Mapping RANKL- and OPG-expressing cells in bone tissue: the bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect.

Bilal M El-Masri, Christina M Andreasen, Kaja S Laursen, Viktoria B Kofod, Xenia G Dahl, Malene H Nielsen, Jesper S Thomsen, Annemarie Brüel, Mads S Sørensen, Lars J Hansen and 8 more

Abstract read
In one paragraph

Article in Bone research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

55 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  6. Artificial intelligence virtual bone organoids (AIVBOs).Journal of orthopaedic translation · 2026
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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

18 authors.

Bilal M El-MasriDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0003-4963-4859
Christina M AndreasenDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0002-2624-5677
Kaja S LaursenDepartment of Forensic Medicine, Aarhus University, Aarhus, Denmark.
Viktoria B KofodDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.
Xenia G DahlDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0002-4922-2478
Malene H NielsenDanish Spatial Imaging Consortium, University of Southern Denmark, Odense, Denmark.
Jesper S ThomsenDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-9386-6679
Annemarie BrüelDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID http://orcid.org/0000-0003-4833-0888
Mads S SørensenDepartment of Otorhinolaryngology - Head and Neck Surgery and Audiology, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Lars J HansenDepartment of Otorhinolaryngology - Head and Neck Surgery and Audiology, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Albert S KimSkeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0001-5832-0224
Victoria E TaylorSkeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Caitlyn MassarottiSkeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Michelle M McDonaldSkeletal Diseases Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-3928-2506
Xiaomeng YouDepartment of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2132-1404
Julia F CharlesDepartment of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5875-314X
Jean-Marie DelaisseDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0001-7370-1500
Thomas L AndersenDepartment of Clinical Research, University of Southern Denmark, Odense, Denmark. thomas.levin.andersen@rsyd.dk.ORCID http://orcid.org/0000-0002-6981-7276

Funding

Mechanisms of bone fragility in Autosomal Dominant Osteopetrosis type II: from human to mouse and backR01AR078914 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Thomas Levin Geiser Andersen, Julia F Charles · 2022 to 2026
$2.2M
NIAMS NIH HHS R01 AR078914Velux Fonden (Velux Foundation) VELUX25723
6 · The paper itself

Abstract

Denosumab is a monoclonal anti-RANKL antibody that inhibits bone resorption, increases bone mass, and reduces fracture risk. Denosumab discontinuation causes an extensive wave of rebound resorption, but the cellular mechanisms remain poorly characterized. We utilized in situ hybridization (ISH) as a direct approach to identify the cells that activate osteoclastogenesis through the RANKL/OPG pathway. ISH was performed across species, skeletal sites, and following recombinant OPG (OPG:Fc) and parathyroid hormone 1-34 (PTH) treatment of mice. OPG:Fc treatment in mice induced an increased expression of RANKL mRNA mainly in trabecular, but not endocortical bone surface cells. Additionally, a decreased expression of OPG mRNA was detected in bone surface cells and osteocytes of both compartments. A similar but more pronounced effect on RANKL and OPG expression was seen one hour after PTH treatment. These findings suggest that bone surface cells and osteocytes conjointly regulate the activation of osteoclastogenesis, and that OPG:Fc treatment induces a local accumulation of osteoclastogenic activation sites, ready to recruit and activate osteoclasts upon treatment discontinuation. Analysis of publicly available single-cell RNA sequencing (scRNAseq) data from murine bone marrow stromal cells revealed that Tnfsf11

Indexed as

DenosumabOsteoclastsOsteogenesisOsteoprotegerinRANK LigandAnimalsBone and BonesFemaleHumansMaleMiceMice, Inbred C57BLOsteocytesDenosumabOsteoprotegerinRANK Ligand

Identifiers

PMID39424806
PMCPMC11489716

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Registered trials

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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.