Potential Contribution of Action of Renin Angiotensin System to Bone Metabolism

Bone metabolism is closely regulated by hormones and cytokines, which have effects on both bone resorption and deposition. Since renin-angiotensin system (RAS) has been known to play an important role to regulate remodeling in several tissues, we focused on the potential role of RAS in bone metabolism. It is known that the receptors of angiotensin II are expressed in culture osteoclasts and osteoblasts, and angiotensin II is postulated to be able to act upon the cells involved in bone metabolism: osteoblasts and osteoclasts; and to regulate blood flow in bone marrow capillaries. In in vitro system, angiotensin II induced the differentiation and activation of osteoclasts responsible for bone resorption and the proliferation of osteoblast-rich populations of cells. As it has been known that osteoclast differentiation is regulated by a variety of hormones, local factors and inflammatory cytokines, such as IL-1 and TNF-α, RAS might also be involved in this autocrine system. In another aspect of RAS, angiotensin II can also regulate blood flow in bone marrow capillaries. Since recent evidence suggests that blood flow can be important to the development of matured bone, the blockade of reninangiotensin system may improve blood flow in bone marrow capillaries, which consequently enhances bone formation. Of importance, sub-analysis of recent clinical study demonstrated that the usage of angiotensin-converting enzyme inhibitors significantly reduced the fracture risk. RAS might be a novel target to treat the subgroups of hypertensive patients with osteoporosis.