When high blood pressure was induced in young mice, they had bone loss and osteoporosis-related bone damage similar to older mice, according to new research presented today at the American Heart Association’s Hypertension Scientific Sessions 2022 conference, held Sept. 7-10, 2022. , in San Diego. The meeting is a scientific exchange focusing on recent advances in basic and clinical research on high blood pressure and its relationship to heart and kidney disease, stroke, obesity and genetics.
High blood pressure and osteoporosis are common diseases and people can have both at the same time. In this study, researchers examined inflammation linked to high blood pressure in mice and found that it could be linked to osteoporosis.
“Bone marrow is where both new bone and new immune cells are produced. We suspect that more pro-inflammatory immune cells in the bone marrow could damage the bone and make it weaker,” said lead study author Elizabeth Maria Hennen, a PhD candidate in biomedical engineering at Vanderbilt University in Nashville, Tennessee. “By understanding how hypertension contributes to osteoporosis, we may be able to reduce the risk of osteoporosis and better protect people against fragility fractures and a lower quality of life later in life.”
In the study, researchers compared young mice with induced hypertension to older mice without hypertension to assess the possible relationship of hypertension with bone aging. The human age equivalent was about 20-30 years old for the young mice and about 47-56 years old for the older mice, Hennen said. A group of 12 young mice (4 months old) were given angiotensin II, a hormone that leads to high blood pressure. The young mice received 490 nanograms/kilogram angiotensin II for six weeks. A group of 11 older mice (16 months old) also received 490 nanograms/kg of angiotensin II for six weeks. Two control groups of 13 young mice and 9 old mice were given a buffer solution that did not contain angiotensin II, and these mice did not develop high blood pressure.
After six weeks, researchers analyzed the bones of mice from all four groups using microcomputed tomography, an advanced imaging technique. Bone health was determined by bone strength and density. Mathematical algorithms were used to estimate the possible effects of hypertension and aging on bone microstructure and strength in the mice.
Compared to the young mice without hypertension, the young mice with induced hypertension had a significant reduction of 24% in the bone volume fraction, an 18% reduction in the thickness of the spongy trabecular bone at the end of long bones, such as femurs and the spine, and a 34% reduction in the estimated failure force, the ability of bones to withstand various types of force.
“Failure power translates into weaker bones. In the spine, bone weakness can lead to vertebral fractures later in life,” Hennen said.
In contrast, the older mice that received the angiotensin II infusion did not show comparable bone loss. During the study, however, the old mice, with or without high blood pressure, showed reduced bone quality comparable to that of the hypertensive young mice.
“In these mice, which were hypertensive at a younger age, bones essentially aged as if they were 15-25 human years older,” Hennen said.
To assess the impact of inflammation on the bone health of the mice, researchers analyzed the bone marrow using flow cytometry. This tool allowed researchers to identify individual cells and sort specific immune cells. In the hypertensive young mice, they found an increase in the number of inflammatory signaling molecules, indicating an increase in inflammation in the bones compared to the young mice that were not given angiotensin II.
“This increase in active immune cells tells us that the older mice are generally more inflamed, and that a sustained state of inflammation, whether they had high blood pressure or not, can have an impact on bone health,” he said. hens. “It was found that high blood pressure adjusted the bone remodeling process toward bone loss, rather than bone gain or bone balance, in the hypertensive young mice. As a result, bones will be weaker, leading to an increased risk of osteoporosis and fragility fractures in humans.” this may mean that we need to screen for osteoporosis in people with high blood pressure.”
Hennen adds that these findings could help researchers identify the immune cells and mechanisms involved in human bone health. This in-depth knowledge may lead to new approaches to prevent osteoporosis in early adulthood.
The study limitations include that it is descriptive only, so additional research is needed to examine how specifically the different types of immune cells may contribute to bone loss. In addition, it is not known whether a similar association exists in humans, so similar studies in humans are needed to confirm these findings.
Co-authors are: Mingfang Ao, Ph.D.; Nestor de la Visitacion, Ph.D.; Wei Chen, MD, Ph.D.; Sasidhar Uppuganti, MS; Elizabeth Rendina-Ruedy, Ph.D.; Jeffry S. Nyman, Ph.D.; and David G. Harrison, MD
The study was funded by the National Institutes of Health, Vanderbilt University and Vanderbilt University Medical Center.