title: Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel.
abstract: Both osteoporosis and high blood pressure are major diseases in aging populations. Recent studies demonstrated that some antihypertensive drugs reduced the risk of bone fracture in elderly patients. Although calcium channel blockers (CCB) are widely used as first-line antihypertensive agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of two types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses norepinephrine release from the sympathetic nerve, and amlodipine (L-type CCB). In ovariectomized female spontaneous hypertensive rats, administration of cilnidipine, but not amlodipine, resulted in a significant increase in the ratio of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a decrease in the number of osteoclasts, as assessed by TRAP staining in the proximal tibia. Bone mineral density, moreover, was significantly higher in the cilnidipine group as compared with the amlodipine group and was associated with a significant decrease in a urinary collagen degradation product (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was similar to that of carvedilol (a β-blocker) because β-blockers reduce fracture risks though the inhibition of osteoclast activation. Interestingly, these effects cannot be attributed to the reduction of blood pressure because all three drugs significantly decreased blood pressure. In contrast, both cilnidipine and carvedilol, but not amlodipine, significantly decreased heart rate, indicating that both cilnidipine and carvedilol suppressed sympathetic nervous activity. Overall, our present data showed that cilnidipine (L-/N-type CCB) ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women.
authors: Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors: Hideo
authors: H
authors: Shimizu
authors: Hironori
authors: H
authors: Nakagami
authors: Natsuki
authors: N
authors: Yasumasa
authors: Osako Kiomy
authors: OK
authors: Mariana
authors: Mariko
authors: M
authors: Kyutoku
authors: Hiroshi
authors: H
authors: Koriyama
authors: Futoshi
authors: F
authors: Nakagami
authors: Munehisa
authors: M
authors: Shimamura
authors: Hiromi
authors: H
authors: Rakugi
authors: Ryuichi
authors: R
authors: Morishita
mesh_terms: D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D017311:Amlodipine; C065927:cilnidipine