Reduction Of Bone Quality In A Murine Model Of Essential Hypertension Relative To Age

Autoimmune and inflammatory diseases such as obesity and cancer are highly linked to altered bone growth and osteoporosis. Hypertension (HTN) is an inflammatory condition associated with reduced bone mineral density and increased risk for fragility fractures in adults. As cases of pediatric HTN rise in the United States, HTN may increase bone loss in children and future risk for osteoporosis. We hypothesized that HTN-induced osteoporosis in young mice reduces bone quality like that of aging. To assess this, 3.5- or 16-month-old male C57BL/6J mice received Angiotensin (Ang) II (490 ng/kg/day) or vehicle infusion by subcutaneous osmotic mini-pumps. After 6-weeks of infusion, the lumbar vertebral bodies (VB) were harvested, and analyzed by high-resolution micro-computed tomography and finite element analysis. In young mice, Ang-II induced HTN caused reductions in bone volume fraction (33.4 ± 0.8 vs 25.4 ± 1.1 %, p<0.0001) and trabecular thickness (66.4 ± 1.1 vs 54.3 ± 1.5 μm, p<0.0001). HTN reduced the estimated failure force (24.3 ± 0.7 vs 16.1 ± 1.1 N, p<0.0001) in young mice. In contrast to young mice, in aged mice Ang-II infusion did not induce bone loss; however, at baseline, the old mice exhibited reduced bone quality like that of hypertensive young mice: bone volume fraction (22.5 ± 0.7 vs 25.4 ± 1.1 %, p=0.2928), trabecular thickness (58.0 ± 1.5 vs 54.3 ± 1.1 μm, p=0.3866), and estimated failure force (17.6 ± 0.8 vs 16.1 ± 1.1 N, p=0.6517). To ascertain the impact of inflammation in the bone marrow microenvironment, the bone marrow was analyzed by flow cytometry. The number of CD4 + T cells producing IL-17A was increased in hypertensive vs normotensive young mice (230.0 ± 8.9 vs 167.3 ± 16.6 cells per 1 million events, p=0.0035), as were dendritic cells (408.3 ± 29.1 vs. 229.1 ± 20.5 cells per 1 million events, p<0.0001). CD4 + T cells producing IFN-γ also rose (2845 ± 129 vs 2437 ± 174 cells per 1 million events, p=0.07) in young hypertensive mice. Both normotensive and hypertensive old mice experienced overactive inflammatory responses compared to the young group. Thus, HTN mimics aspects of aging on bone health, causing inflammation in the bone marrow and osteoporosis. Efforts to detect and treat HTN in children may deter untoward events related to bone loss in adulthood.