Atorvastatin Attenuates Bone Loss and Aortic Valve Atheroma in LDLR-/- Mice

Atherosclerosis and osteoporosis are the leading causes of mortality and morbidity. The objective of this study was to test this hypothesis in experimental hypercholesterolemia to determine whether statins play a protective role in this process. LDLR(-/-) mice (n = 60) were allocated to the following groups: group I (n = 20), normal diet; group II (n = 20), 0.25% (w/w) cholesterol diet (w/w), and group III (n = 20), 0.25% (w/w) cholesterol diet + atorvastatin for 48 weeks. Examination of aortic valves (AVA) and femurs for atherosclerosis and calcification markers included micro-CT, special stains, and calcein incorporation. The cholesterol diet induced bone formation in calcified AVA and an increase in macrophage infiltration. Hyperlipidemic bones expressed an increase in osteoclast cells and a decrease in bone formation. Atorvastatin reduced atherosclerosis and bone mineralization in AVA and increased mineralization within femur bones (p < 0.05). Atherosclerosis is present in hyperlipidemic bones and valves as characterized by macrophage and osteoclast infiltration, and it is attenuated by atorvastatin, which may have implications for therapy in the future.