The Study Of The Effects Of Atorvastatin/E₂ In Ovariectomized Rat Osteoporosis

Objectives: Osteoporosis(OP) is a common chronic disease of the osseous system characterized by low bone mineral density(BMD),deterioration in bone microarchitecture, decreased bone strength and increased fracture risk. It is due to an imbalance in the dynamic ongoing processes of bone formation and bone resorption and is more prevalent in postmenopausal women. Currently available osteoporosis therapies like E2, bisphosphonates,selective estrogen receptor modulators(SERMs) are anti-resorptive agents.The side-effects and limited efficacy of the presently available therapies has encouraged extensive research into the pathophysiology of the disease and newer drug targets for its treatment. Statins, the novel anti-resorptive agent,are in development for the treatment of osteoporosis. The aim of the present study is to evaluate the effects of treatment with atorvastatin and estrogen on ovariectomized osteoporosis rat model.Methods: Fifty 12-weeks old SD female rats were randomly divided into five groups: Sham group, ovariectomized group(VOX group), estrogen group(E2 group), atorvastatin group(Ator group) and atorvastatin/estrogen group(Ator/E2 group). One weeks post-surgery, the Sham group and the VOX group were treated daily by oral gavage with physiological saline, and the E2 group,Ator group and Ator/E2 group were fed with estradiol valerate(1 mg/kg/day)or atorvastatin or both drug for 12 weeks. All rats were sacrificed after 12 weeks, and the serum was collected. Uterus, femur and tibia were harvested.Then follows were measured: uterus index, serum E2, CT, serum Ca and P,ALP level and BMD.Results:1 The effects of atorvastatin and E2 on body weight and uterus index of ovariectomized female rats with osteoporosis.The body weight has no significant deviation among 5 groups.Ovariectomized operation caused a significant decrease in uterus index,compared with the Sham group(P < 0.01). Meanwhile, atorvastatin/E2 treatment markedly increased the uterus index, compared with the VOX group(P < 0.01).2 The effects of atorvastatin and E2 on serum E2 and CT of ovariectomized female rats with osteoporosis.Ovariectomized operation caused a significant decrease in serum E2 and CT levels, compared with the Sham group(P < 0.01). Meanwhile,atorvastatin/E2 treatment markedly increased the serum E2 and CT levels,compared with the VOX group(P < 0.01).3 The effects of atorvastatin and E2 on serum Ca and P of ovariectomized female rats with osteoporosis.The serum Ca and P have no significant deviation among 5 groups.4 The effects of atorvastatin and E2 on ALP and BGP of ovariectomized female rats with osteoporosis.Ovariectomized operation caused a significant increased in serum E2 and CT levels, compared with the Sham group(P < 0.01). Meanwhile,atorvastatin/E2 treatment markedly decreased the serum ALP and BGP levels,compared with the VOX group(P < 0.01).5 The effects of atorvastatin and E2 on femur BMD and tibia BMD of ovariectomized female rats with osteoporosis.Ovariectomized operation caused a significant decrease in femur BMD and tibia BMD, compared with the Sham group(P < 0.01). Meanwhile,atorvastatin/E2 treatment markedly decreased the femur BMD and tibia BMD,compared with the VOX group(P < 0.01).6 The effects of atorvastatin and E2 on femur bone ashes and tibia bone ashes of ovariectomized female rats with osteoporosis.Ovariectomized operation caused a significant decreased in femur bone ashes and tibia bone ashes, compared with the Sham group(P < 0.01).Meanwhile, atorvastatin/E2 treatment markedly increased the femur bonashes and tibia bone ashes, compared with the VOX group(P < 0.01).7 The effects of atorvastatin and E2 on biomechanical properties of the femur of ovariectomized female rats with osteoporosis.Ovariectomized operation caused a significant decrease in the Elastic load and Max load of the femur, compared with the Sham group(P < 0.01).Meanwhile, atorvastatin/E2 treatment markedly increased the Elastic load and Max load of the femur, compared with the VOX group(P < 0.01).Conclusions: Atorvastatin/E2 treatment markedly increased the uterus index, serum E2 and CT, femur BMD and tibia BMD, femur bone ashes and tibia bone ashes, the Elastic load and Max load of the femur, increased the serum E2 and CT levels, and did not affect the serum Ca and P level, and have preventive and therapeutic effect to postmenopausal osteoporosis.