Site-specific effects of cerivastatin on bone in male Sprague-Dawley rats.
It is well established that age-related bone loss occurs in men and male SD rats. This study was designed to determine whether cerivastatin will prevent age-related bone loss in male Sprague-Dawley (SD) rats. Parathyroid hormone (PTH) was used as a positive control. Nine-month-old male SD rats were divided into six groups. Group 1: baseline controls; group 2: age-matched controls; group 3: low-dose cerivastatin (0.2 mg/kg b wt/day); group 4: medium-dose cerivastatin (0.4 mg/kg b wt/day); group 5: high-dose cerivastatin (0.8 mg/kg b wt/day); group 6: PTH (80 microg/kg b wt, 5 days/week). The animals were treated for 6 months. Cancellous and cortical bones were analyzed using peripheral quantitative computerized tomography (pQCT) densitometry at the proximal tibial metaphysis (PTM), tibial diaphysis, tibio-fibula junction, femoral diaphysis and the neck of the femur. In the PTM, pQCT analyses were done 2 mm distal from the growth plate. The cancellous bone mineral content (Cn. BMC) decreased by 26% (P<0.05), 25% (P<0.05) and 28% (P<0.05) in the low, medium and high doses of cerivastatin groups, respectively, when compared to the age-matched controls. PTH group did not change significantly from the baseline controls but prevented the decrease in Cn. BMC seen in the age-matched controls by 45% (P<0.0001). Cancellous bone mineral density (Cn. BMD) decreased by 20% (P<0.05), 23% (P<0.05) and 27% (P<0.05) in the low, medium and high doses of cerivastatin groups, respectively, when compared to the age-matched controls. Cn. BMD did not change significantly in the PTH-treated group when compared to the baseline controls but prevented the decrease seen in age-matched controls by 47% (P<0.0001). In the neck of the femur, femoral diaphysis, tibial diaphysis and the tibio-fibula junction, cerivastatin did not prevent age-related bone loss in male SD rats while PTH significantly prevented the age-related bone loss. We conclude that cerivastatin, in any of the doses tested, does not prevent age-related bone loss, in male SD rats, at the different bone sites studied; while PTH not only prevented age-related bone loss but also increased bone mass above the baseline controls in all the bone sites studied except the PTM.
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. banu@uthscsa.edu
Jameela
J
Banu
Dike N
DN
Kalu
D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010024:Osteoporosis / Q000188:drug therapy / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000166:cytology / Q000187:drug effects*
D011725:Pyridines; C086276:cerivastatin