Protective effect of amlodipine against osteoporosis in stroke-prone spontaneously hypertensive rats.
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.
Ushijima
Kentarou
K
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, Japan.
Liu
Yuwang
Y
Maekawa
Tomohiro
T
Ishikawa
Eiko
E
Motosugi
Yuya
Y
Ando
Hitoshi
H
Tsuruoka
Shu-ichi
S
Fujimura
Akio
A
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
D000959:Antihypertensive Agents; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D017311:Amlodipine; D002118:Calcium