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We hypothesized that ovariectomy (OVX)-induced estrogen-deficiency and angiotensin (Ang) II-hypertension together cause a greater decline in bone strength than OVX alone. Ovaries were removed (OVX) or remained intact (Sham) in 12-mo-old, C57BL\/6J mice. Four weeks after surgery, mice received either an infusion of vehicle or angiotensin II at 490\u00a0ng\/kg\/min for 6\u00a0wk to induce hypertension. We monitored blood pressure (BP) and areal BMD (aBMD) before surgery, before infusion, and before euthanasia. OVX augmented the increase in BP in hypertensive mice. OVX, not hypertension, decreased whole-body aBMD. Nonetheless, hypertension lowered cortical bone area and thickness of the femur mid-diaphysis in only the OVX group. As determined by the ultimate force that the femur mid-diaphysis endured during 3-point bending, OVX lowered the strength of cortical bone when mice were hypertensive; and hypertension did the same when mice were estrogen deficient. Hypertension and OVX independently affected trabecular bone, such that reductions in trabecular thickness and tissue mineral density were additive with the lowest mean observed in the OVX-hypertension group. OVX significantly lowered the compressive ultimate force of the lumbar vertebra when controlling for hypertension group. Although hypertension did not significantly affect vertebral strength, OVX-hypertension significantly reduced this parameter. The addition of hypertension to OVX in 12-mo-old female mice weakened bone beyond either effect alone. Thus, hypertension, which commonly occurs after menopause or ovarian loss, increases the likelihood of osteoporosis, and thus indicates a high-risk population.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziag101","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T17:02:39Z","timestamp":1781542959000},"source":"Crossref","is-referenced-by-count":0,"title":["Hypertension worsens bone loss and weakens bone in aged ovariectomized mice"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1823-5751","authenticated-orcid":false,"given":"Elizabeth M","family":"Hennen","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0656-2122","authenticated-orcid":false,"given":"Sasidhar","family":"Uppuganti","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0130-4877","authenticated-orcid":false,"given":"Santosh","family":"Thapa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7229-9601","authenticated-orcid":false,"given":"N\u00e9stor","family":"de la Visitaci\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8171-9609","authenticated-orcid":false,"given":"Priya","family":"Mathiy","sequence":"additional","affiliation":[{"name":"Department of Health Humanities, Pennsylvania State University , Abington, PA 19001 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7155-5630","authenticated-orcid":false,"given":"Gabriel","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1540-6989","authenticated-orcid":false,"given":"Elizabeth","family":"Rendina-Ruedy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["United States"]},{"name":"Department of Nutritional Sciences, College of Allied Health, University of Oklahoma Health Campus , Oklahoma City, OK 73117 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9363-6451","authenticated-orcid":false,"given":"David G","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-7605","authenticated-orcid":false,"given":"Jeffry S","family":"Nyman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37232 ,","place":["United States"]},{"name":"Department of Orthopaedic Surgery, Vanderbilt University Medical Center , Nashville, TN 37232 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