[Hormones and osteoporosis update. Effect of angiotensin II on 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 induced the differentiation and activation of osteoclasts responsible for bone resorption. Of importance, angiotensin II significantly induced the expression of RANKL (receptor activator of NF-kappaB ligand) in osteoblasts, leading to the activation of osteoclasts, while these effects were completely blocked by an angiotensin II type 1 receptor blockade. In a rat ovariectomy model of estrogen deficiency, administration of angiotensin II accelerated the increase in TRAP activity, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. 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-alpha, RAS might also be involved in this autocrine system. 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.
Nakagami
Hironori
H
Division of Geno Therapy Science, Osaka University.
Morishita
Ryuichi
R
D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001842:Bone and Bones / Q000378:metabolism*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D016207:Cytokines; D053245:RANK Ligand; D000804:Angiotensin II