Renin Inhibition Improves Ovariectomy-Induced Osteoporosis of Lumbar Vertebra in Mice

• Published in: Biological & pharmaceutical bulletin Vol. 37; no. 12; pp. 1994 - 1997
• Main Authors: Zhang, Fang-Yi, Yang, Feng-Jian, Yang, Jiu-Lin, Wang, Liang, Zhang, Yan
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.12.2014; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: aliskiren; Amides - therapeutic use; Animals; Antihypertensive Agents - therapeutic use; bone; Female; Fumarates - therapeutic use; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - pathology; Mice; osteoporosis; Osteoporosis - drug therapy; Osteoporosis - etiology; ovariectomy; Ovariectomy - adverse effects; Renin - antagonists & inhibitors; Renin-Angiotensin System - physiology; renin–angiotensin system; X-Ray Microtomography
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b14-00576

The skeletal renin–angiotensin system (RAS) is involved in the progression of osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has deleterious effects on bones. This study was performed to investigate whether suppression of the rate-limiting step of the RAS cascade by the renin inhibitor aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX) mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6 weeks. Micro-computed tomography was performed to detect trabecular bone parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment with aliskiren markedly increased bone volume over total volume (p<0.05), trabecular bone number (p<0.05), connectivity density (p<0.05), and bone mineral density (p<0.05) and reduced trabecular bone separation (p<0.05) compared to vehicle-treated OVX mice. Similarly, the 3D images were consistent with the quantitative data that showed aliskiren could markedly reverse the ovariectomy-induced pathological changes of trabecular bone. Thus, this study indicated that the treatment of estrogen-deficient mice with aliskiren could markedly increase bone mass and improve trabecular bone structure, suggesting its potential application in treating postmenopausal osteoporosis.