RALOXIFENE INHIBITS BONE TURNOVER AND PREVENTS FURTHER CANCELLOUS BONE LOSS IN ADULT OVARIECTOMIZED RATS WITH ESTABLISHED OSTEOPENIA

Estrogen (E) treatment has proven to be effective in preventing bone l oss after menopause with, however, some undesirable side effects. Many of these side effects are related to the hormone's actions on reprodu ctive tissues. Raloxifene is an organ-selective estrogen agonist that prevents acute cancellous osteopenia in ovariectomized (OVX'd) growing rats. The effects of raloxifene on adult rats with established bone l oss are not known. We now compare the dose response effects of 4 month s of treatment with raloxifene and estrogen in 8-month-old rats that h ad been OVX'd 2 months before treatment. OVX resulted in increased bod y weight, uterine atrophy and severe cancellous bone loss. Estrogen re sulted in a dose-dependent increase in uterine weight in OVX'd rats wh ereas raloxifene did not promote uterine growth. Both treatments reduc ed body weight and serum cholesterol. Raloxifene and estrogen were eac h effective in stabilizing cancellous bone by preventing additional ca ncellous bone loss, but neither treatment replaced lost bone. These fi ndings provide further evidence that raloxifene is a much more potent estrogen agonist on the skeleton and liver than on the uterus.