| Osteoporosis is a systematic skeletal disease characterized by low bone mass and microarchitecture deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Postmenopausal osteoporosis is one of the most common metabolic diseases in old women. It has been a troublesome problem for public health and social life. Estrogen replacement therapy (ERT) is currently considered for increasing the bone mineral density of postmenopausal women effectively, however, has been shown to increase the risk of cancer, such as endometrical and breast cancer. As the third generation of selective estrogen receptor modulators, raloxifene can partially mimic the effects of estrogen in bone system while function as an antiestrogen in breast and endometrial tissue instead, but it's mechanism of estrogen like effects on bone remains uncertain. In addition, the clinical observation of raloxifene's preventive and curative effects on postmenopausal woman is rare. Two parts are included in this research. Part 1 the effects of raloxifene on expression of ER-amRNA in OVX rats bone. Objective: To study the effects of raloxifene on expression of ER-a mRNA in OVX rats bone and the relationship among raloxifene, ER-a and bone mineral density(BMD) using OVX female Wistar rats as animal osteoporosis models.Methods: Fifty female virgin Wistar rats of three-point five months old with matched body weight were randomly divided into 5 groups. There were ten rats ineach 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 S group, bilateral ovariectomies wereperformed in the other groups. All rats were killed 12 weeks later. Bone mineraldensity of femur was measured using Dual Energy X-ray Absorptiometry (DEXA)in vitro after sacrifice. The tibia and femor were dissected out and mRNA levelsof ER-a and beta-actin were studied using reverse transcription polymerase chainreaction technique.Results: The expression of bone ER-a mRNA in OVX group was significantlylower than that of S group, E group and RL group (p<0.01). there was nostatistically differences in the last 3 groups (p>0.05)Conclusion: raloxifene can up-regulate the expression of ER-a mRNA whichmay reduce osteoclastic bone resorption and decrease loss of bone mass.Part2 the clinical observation of raloxifene's preventive and curative effects onpostmenopausal woman.Objective: to determine the effects of raloxifene hydrochloride on BMD,biochemical markers of bone metabolism, breast and uterine.Method: A total of 224 women aged 41 to 70 years with ostopenia orosteoporosis were randomized to 60mg/d of raloxifene or to identically appearingplacebo pills, in addition, all women received supplemental calcium andcholecalciferol, respectively, for 12 months. BMD of lumber and femoral neckwere measured by DEXA at beginning, the sixth month and the end of the study,biochemical markers of bone metabolism such as Ca, P BGP and ALP weredetermined before and after drug administration. Mammograms of breastultrasonography and uterine ultrasonography were optional at the beginning andthe end.Results: (1) The BMD was increased in the spine by 2.59% and in the femoral by41.59% in the raloxifene treated group. There was no significantly changed in the placebo group. (2) For biochemical markers of bone metabolism, serum osteocalcin and ALP, percentage decrease were 31.8% and 25.0 % in raloxifene treated subjects. Corresponding values in placebo were 8.0% and 15.6% decrease (raloxifene compared to placebo, both P < 0.01), no statistically differences were found in serum calcium and phosphate between the 2 groups. (3) Compared to placebo, raloxifene produced no significant increase in the incidence of both breast cancer and neoplasmas. (4) The change in the endometrium was little, no endometrial thickness and bleeding was found.Conclusi...
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