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 mug/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. (C) 2004 Elsevier Inc. All rights reserved.