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Endocrinology. 1994 May;134(5):2283-8.

The effects of raloxifene on tibia histomorphometry in ovariectomized rats.

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Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905.


Tissue-specific estrogen agonists may be useful in protecting against osteoporosis and the increased risk of coronary heart disease in postmenopausal women with minimal undesired effects on reproductive tissues. The actions of the mixed estrogen agonist/antagonist raloxifene on selected estrogen target tissues were determined in ovariectomized (OVX) rats immediately postovariectomy. Five groups of 75-day-old Sprague-Dawley rats were studied; baseline controls, sham-operated controls, OVX controls, OVX animals treated with estrogen (0.1 mg 17 alpha-ethynyl estradiol/, and OVX animals treated with raloxifene (3 mg/ Fluorochrome labels were given on days 1, 28, and 34. The baseline controls were killed on day 2, and the remaining groups on day 35. Ovariectomy increased tibial longitudinal growth rate as well as measurements related to radial growth and cancellous bone turnover. Ovariectomy decreased cancellous bone area and uterine weight, and increased serum cholesterol, bone elongation, and radial bone growth. Estrogen treatment prevented these changes in OVX rats. Raloxifene prevented cancellous osteopenia as well as the changes in radial bone growth, bone resorption, and blood cholesterol, but was less effective in reducing cancellous bone formation and did not prevent uterine atrophy. These findings suggest that raloxifene is a target-specific, mixed estrogen agonist/antagonist. At the concentration studied, raloxifene had potent estrogenic activity on bone resorption and serum cholesterol, a lesser effect on bone formation, and minimal activity on uterine wet weight.

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