Effects Of Raloxifene On The Prevention And Treatment Of Osteoporosis In OVX Rats

Objective: Postmenopausal osteoporosis is one of the most common metabolic bone diseases for old women. It has been a troublesome problem for public health and social life. Estrogen replacement therapy (ERT) is currently considered to be the optimal therapy for preventing bone loss in postmenopausal women. Chronic estrogen therapy, however, has been shown to increase the risk of certain types of cancer, such as endometrical and breast cancer. Raloxifene is a new drug, which is a selective estrogen receptor modulator that partially mimics the effects of estrogens in bone system while functioning as an antiestrogen in breast and endometrial tissue instead, we evaluated the therapeutic effects of raloxifene on osteoporosis of ovariectomized (OVX) rats.Methods: Fifty female virgin Wistar rats of three-point-five months old according to their body weight were randomly divided into five groups. There are ten rats in each bundle. Sham-operation group (S) , OVX group (O) , estrogen treated group (E) , low-dose raloxifene treated group (RL) , high-dose raloxifene treated group (RH.) . Sham-operation was performed in Sham group, bilateral ovariectomies were performed in the other groups. All rats were killed 12 weeks later. Bone mineral density (BMD) of lumbar vertebrae and femur was measured in vitro after sacrifice. The mechanical strength of lumbar vertebrae and the femur in all groups was measured. The morphological and dynamic parameters for proximal tibia metaphysis histomorphometry were investigated. The microstructure of cancellous bone at the lumbar vertebrae of groups was studied. Uterus was removed for pathohistologic examiation and weight measurement .Results: (1) OVX resulted in destruction of lumbar vertebrae microstructure and reduction of trabecular bone mass, biomechanical properties for femur and lumbar vertebrae. (2) Compared with O group , Maximal loading in the fifth lumbar vertebrae compressive test increased (P<0.05) in RL group. Bending energy increased (P<0.05) in femoral 3-point bending test in E group. Elastic loading, bending energy and coefficient of bending stiffness increased (P<0.05 or P<0.01) in femoral 3-point bending test in RL group. Elastic loading increased (P<0.01) in femoral 3-point bending test in RH group. BMD in vitro of lumbar vertebral and whole femur significantly increased in E, RL group (P<0.01 ) . Static histomorphometric parameters (percent of trabecular area) were significantly increased (P<0.05 or P<0.01 ) , dynamic histomorphometric parameters were significantly decreased ( percent eroded perimeter and percent labeled perimeter ) ( P<0.01 ) in E and RL group. Three-D structure of lumbar vertebrae was recovered in E and RL group. (3) Endometrium was atrophyic and uterine weight decreased in O group. The changes in endometrium for RL and RH group as those for O group.Conclusion: These results showed that low-lose Raloxifene might exhibit similar effects as estrogen on postmenopausal osteoporosis by inhibiting the increased bone turnover in OVX rats without any estrogenic effects on the uterus. So it is believed that Raloxifene is an another choice for preventing bone loss by estrogen deficiency in females.