Evidence map›Paper›PMID 40828611›Full record

ArticleThe Journal of clinical investigation2025

Hypertension promotes bone loss and fragility by favoring bone resorption in mouse models.

Elizabeth M Hennen, Sasidhar Uppuganti, Néstor de la Visitación, Wei Chen, Jaya Krishnan, Lawrence A Vecchi, David M Patrick, Mateusz Siedlinski, Matteo Lemoli, Rachel Delgado and 6 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–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

6 citing papers in PubMed.

  1. Article
  2. Article
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  6. Review
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

16 authors.

Elizabeth M HennenDepartment of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Sasidhar UppugantiDepartment of Veterans Affairs, Tennessee Valley Healthcare System, Murfreesboro, Tennessee, USA.
Néstor de la VisitaciónDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Wei ChenDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jaya KrishnanDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Lawrence A VecchiDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
David M PatrickDepartment of Veterans Affairs, Tennessee Valley Healthcare System, Murfreesboro, Tennessee, USA.
Mateusz SiedlinskiCentre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Matteo LemoliCentre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Rachel DelgadoDivision of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Mark P de CaesteckerDivision of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Wenhan ChangSan Francisco VA Medical Center, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Tomasz J GuzikCentre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Rachelle W JohnsonDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
David G HarrisonDivision of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jeffry S NymanDepartment of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.

Funding

Skeletal Biology and Biomechanics (SBB) CoreP30AR075055 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Wenhan Chang · 2019 to 2026
$7.1M
Mechanisms of Immune Activation in HypertensionR35HL140016 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HARRISON, DAVID G · 2018 to 2024
$5.3M
Integrated Training in Engineering and DiabetesT32DK101003 · NIDDK · VANDERBILT UNIVERSITY · PI Jamey D. Young · 2014 to 2026
$3.9M
Early-Stage Preclinical Validation of Carbon Monoxide Prodrugs for Acute Kidney InjuryR01DK128823 · NIDDK · GEORGIA STATE UNIVERSITY · PI LEO E OTTERBEIN, Binghe Wang · 2022 to 2026
$3.5M
Therapeutic Optimization of Productive Repair After Acute Kidney InjuryUC2DK126122 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVIDSON, ALAN, DE CAESTECKER, MARK P. · 2020 to 2024
$3.2M
UCSF Core Center for Musculoskeletal Biology and MedicineP30AR066262 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MAJUMDAR, SHARMILA · 2014 to 2018
$3.0M
Common Inflammation Pathways between Aging and Hypertension That Weaken BoneR01AG076785 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David G Harrison, Jeffry Stephen Nyman · 2022 to 2026
$2.5M
Vitamin D and beta-amyloid signaling in hyperparathyroidismRF1AG075742 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHANG, WENHAN, KOH, JAMES · 2023 to 2025
$2.4M
Vanderbilt Hypertension and Blood Pressure Regulation ProgramT32HL144446 · NHLBI · VANDERBILT UNIVERSITY · PI HARRISON, DAVID G · 2019 to 2023
$1.7M
Novel ultrahigh resolution microCT imaging systemS10RR027631 · NCRR · VANDERBILT UNIVERSITY · PI PERRIEN, DANIEL S · 2010 to 2010
$460k
BLRD VA I01 BX005851BLRD VA I01 BX005866BLRD VA IK2 BX005376BLRD VA IK6 BX004835BLRD VA IK6 BX007117NCRR NIH HHS S10 RR027631NHLBI NIH HHS R35 HL140016NHLBI NIH HHS T32 HL144446NIAMS NIH HHS P30 AR066262NIAMS NIH HHS P30 AR075055NIA NIH HHS R01 AG076785NIA NIH HHS RF1 AG075742NIDDK NIH HHS R01 DK128823NIDDK NIH HHS T32 DK101003NIDDK NIH HHS UC2 DK126122
6 · The paper itself

Abstract

Inflammatory diseases contribute to secondary osteoporosis. Hypertension is a highly prevalent inflammatory condition that is clinically associated with reduced bone mineral density and increased risk of fragility fracture. In this study, we showed that a significant loss in bone mass and strength occurs in two preclinical models of hypertension. This accompanied increases in immune cell populations, including monocytes, macrophages, and IL-17A-producing T cell subtypes in the bone marrow of hypertensive mice. Neutralizing IL-17A in angiotensin II-infused mice blunted hypertension-induced loss of bone mass and strength as a result of decreased osteoclastogenesis. Likewise, the inhibition of the CSF1 receptor blunted loss of bone mass and prevented loss of bone strength in hypertensive mice. In an analysis of UK Biobank data, circulating bone remodeling markers exhibited striking associations with blood pressure and bone mineral density in more than 27,000 humans. These findings illustrate a potential mechanism by which hypertension activates immune cells in the bone marrow, encouraging osteoclastogenesis and eventual loss in bone mass and strength.

Indexed as

Bone ResorptionHypertensionOsteoporosisAngiotensin IIAnimalsBone DensityDisease Models, AnimalFemaleHumansInterleukin-17MacrophagesMaleMiceMice, Inbred C57BLOsteoclastsReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAngiotensin IICsf1r protein, mouseIl17a protein, mouseInterleukin-17Receptors, Granulocyte-Macrophage Colony-Stimulating FactorBone biologyBone diseaseBone marrowHypertensionImmunologyInflammation

Identifiers

PMID40828611
PMCPMC12547992

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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.