2. Academic Validation
  3. Hypertension promotes bone loss and fragility by favoring bone resorption in mouse models

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

  • J Clin Invest. 2025 Aug 19:e184325. doi: 10.1172/JCI184325.
Elizabeth M Hennen 1,  Sasidhar Uppuganti 2,  Néstor de la Visitación 3,  Wei Chen 3,  Jaya Krishnan 3,  Lawrence A Vecchi Iii 3,  David M Patrick 4,  Mateusz Siedlinski 5,  Matteo Lemoli 6,  Rachel Delgado 7,  Mark P de Caestecker 7,  Wenhan Chang 8,  Tomasz J Guzik 6,  Rachelle W Johnson 3,  David G Harrison 3,  Jeffry S Nyman 9
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America.
  • 2 Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America.
  • 3 Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America.
  • 4 Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America.
  • 5 Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland.
  • 6 Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.
  • 7 Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America.
  • 8 San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America.
  • 9 Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America.
PMID: 40828611 DOI: 10.1172/JCI184325
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 for fragility fracture. In this study, we showed that a significant loss in bone mass and strength occurs in two pre-clinical 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 (ang) II-infused mice blunted hypertension-induced loss of bone mass and strength due to decreased osteoclastogenesis. Likewise, the inhibition of the CSF-1 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 > 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.

Keywords

Bone biology; Bone disease; Bone marrow; Hypertension; Immunology; Inflammation.

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