title: Protective effect of amlodipine against osteoporosis in stroke-prone spontaneously hypertensive rats.
abstract: Hypertensive patients have an increasing risk of osteoporosis. A recent case-controlled study has demonstrated that anti-hypertensive therapy reduced a risk of fracture in these patients. In this study, we investigated whether amlodipine protects against the reduction in bone density in stroke-prone spontaneously hypertensive rats (SHR-sp). Oral dosing of amlodipine (0.5 and 3.0mg/kg/day) was started when SHR-sp were 3 months old, and continued for 3 months. At the end of the experiment, bone density of femur and serum concentrations of calcium, parathyroid hormone (PTH) and C-telopeptide of type I collagen (CTx), reflecting osteoclast activity, were measured. The bone density dose-dependently increased by the treatment with amlodipine. In addition, amlodipine reduced serum concentrations of calcium, PTH and CTx. This study showed that amlodipine prevents the reduction in bone density during the repeated dosing in SHR-sp. Amlodipine might exert its effect through a direct inhibition of osteoclast function and/or suppression of PTH secretion and subsequent inhibition of osteoclast activity.
authors.affiliation: Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, Japan.
authors.forename: Kentarou
authors.initials: K
authors.lastname: Ushijima
authors.forename: Yuwang
authors.initials: Y
authors.lastname: Liu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maekawa
authors.forename: Eiko
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Yuya
authors.initials: Y
authors.lastname: Motosugi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Tsuruoka
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D004198:Disease Susceptibility; D004334:Drug Administration Schedule; D005269:Femur / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010024:Osteoporosis / Q000097:blood / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke
chemical_list: D000959:Antihypertensive Agents; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D017311:Amlodipine; D002118:Calcium