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ResearchIn-Press PreviewBone biologyImmunologyInflammation Open Access | 10.1172/JCI184325

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

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 and Jeffry S. Nyman9

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Hennen, E. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Uppuganti, S. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by de la Visitación, N. in: PubMed | Google Scholar |

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Chen, W. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Krishnan, J. in: PubMed | Google Scholar |

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Vecchi III, L. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Patrick, D. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Siedlinski, M. in: PubMed | Google Scholar |

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Lemoli, M. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Delgado, R. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by de Caestecker, M. in: PubMed | Google Scholar |

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Chang, W. in: PubMed | Google Scholar |

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Guzik, T. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Johnson, R. in: PubMed | Google Scholar

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Harrison, D. in: PubMed | Google Scholar |

1Department of Biomedical Engineering, Vanderbilt University, Nashville, United States of America

2Department of Orthopedic Surgery, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

3Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

4Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, United States of America

5Department of Internal and Agricultural Medicine and Omicron Medical Genomi, Collegium Medicum, Jagiellonian University, Krakow, Poland

6Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom

7Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States of America

8San Francisco VA Medical Center, Department of Medicine, UCSF, San Francisco, United States of America

9Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, United States of America

Find articles by Nyman, J. in: PubMed | Google Scholar

Published August 19, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI184325.
Copyright © 2025, Hennen et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 19, 2025 - Version history
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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.

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