Age-related diseases involving degeneration of human skeletal and cardiovascular systems are now critical problems worldwide. The current review focuses on a common pathophysiological association between primary osteoporosis and vascular calcification, and reviews the mechanical response of bone cells and vascular cells to mechanical stress, as well as the coordination mechanism for intercellular signaling. With aging, calcium is lost from bones but deposited in the cardiovascular system. Bone metabolism-related molecules, such as alkaline phosphatase, matrix Gla protein, osteocalcin, osteopontin, and collagen type I; inflammatory cytokines, such as interleukin-1, -6, and tumor necrosis factor; and lipid metabolism related molecules, such as oxidized low density lipoprotein; mediate signaling in primary osteoporosis and vascular calcification. The mechanical microenvironment is a common pathophysiological basis for primary osteoporosis and vascular calcification. Mobilization of calcium from bone to vessel determines the regression rate, which could be controlled using a mechanical microenvironment. We highlight several issues: (1) linked features between primary osteoporosis and vascular calcification, and detailed changes of the mechanical microenvironment in degenerative bone or blood vessels, (2) signaling coordination mechanism between bone and vascular wall cells, and (3) calcium translocation mechanism. The degree to which these issues can be solved will help develop prevention and treatment strategies for age-related regression. Copyright © 2017 Elsevier Ltd. All rights reserved.