Effects Of Estradiol Valerate, Alfacalcidol And Cimadronate On Osteoporosis Of Ovariectomized Rats

Osteoporosis is a bone disease characterized by low bone mass, microarchitectural deterioration of bone tissue leading to enhanced bone fragility, and a consequent increase in fracture risk. It is very important to prevent and treat this disease. Estradiol velerate is an oral regimen of estrogen. Estrogen replacement therapy in postmenopausal women have been proven efficacious in reducing the incidence of skeletal fracture. But most of these studies are conducted with prophylactic application, and the effects of this drug for established osteoporosis are still unknown. The vitamin D metabolites alfacalcidol will thus be changed into active vitamin D 1,25(OH)₂vitaminD₃in vivo. Now alfacalcidol is widely used, but the results of therapy in osteoporosis with alfacalcidol is conflicting. Cimadronate is a third generation bisphosphonate, expected to be antiresorptive without inhibiting bone formation when given in proper doses, without impairment upon bone mineralization. This compound is under clinical development for osteoporosis treatment.Purpose: To evaluate, by means of histomorphometry, peripheral quantitative computed tomography(pQCT), bone biomechanics and measurement bone turnover marker, the effects of estrogen, cimadronate and alfacalcidol on osteoporosis of rats induced by ovariectomy(OVX), and to determine the value of pQCT in measuring bone architecture and biomechanic properties, after correlated study of the parameters of pQCT with histomorphometric and biomechanical parameters.Materials and Methods: Ninety-one virgin female Wistar rats six months old were randomly divided into 11 groups: (1) baseline (base) were scarified when 6 months old before OVX, and those in the other 10 groups were either bilaterally OVX or sham-operated (sham) as follows: (2)sham; (3)OVX baseline (OVXb); (4)OVX end (OVXe); (5).OVX+17β-estradiol 20 μg/kg/d (O+E); (6)OVX+ estradiol valerate 800 μg/kg/d po. (O+VE); (7) OVX+alfacalcidol 0.1 μg/kg/d po. ( imported O+VDi); (8) OVX+alfacacidol 0.1 μg/kg/d po. (domestic, O+VDd); (9) OVX+cimadronate 0.05mg/kg/d po.; (O+Cl) (10) OVX+cimadronate 0.1mg/kg/d po. (O+Cm); (11) OVX+cimadronate 0.2mg/kg/d (O+Ch). Those of group3 were sacrificed 6 weeks after...