ADVANTAGES OF RALOXIFENE OVER ALENDRONATE OR ESTROGEN ON NONREPRODUCTIVE AND REPRODUCTIVE TISSUES IN THE LONG-TERM DOSING OF OVARIECTOMIZEDRATS

For the first time, raloxifene or alendronate was administered to rats immediately after ovariectomy for 10 months and compared with estroge n to elucidate mechanisms behind the raloxifene effects observed in no nreproductive and reproductive tissues. Specifically, 75-day-old rats were randomly selected as sham controls (Sham), ovariectomized control s (Ovx) or ovariectomized rats treated with fully efficacious doses of raloxifene (RA), 17 alpha-ethynyl estradiol (EE2) or alendronate (ABP ). Lumbar vertebrae and proximal tibiae were examined by computed tomo graphy (QCT) and by histomorphometry. Histomorphometry showed differen ces in bone architecture between groups when QCT densities were simila r, but tibial trabecular bone analysis by QCT correlated with histomor phometry with r = .86 to .93, depending on the parameter. Both techniq ues confirmed that Ovx had substantially less bone than Sham, with gre ater loss of trabecular bone in the proximal tibia than vertebrae. Bot h techniques showed that RA had effects similar to but not identical w ith EE2 in preventing bone loss in vertebrae and tibiae. ABP partially prevented loss of bone in L-5, but was not significantly different fr om Ovx in the proximal tibia. This may be caused by ABP suppression of bone apposition, beyond effects observed for EE2 or RA. RA appeared t o be more similar to EE2 because ABP significantly depressed bone form ation (bone formation rate, mineral apposition rate) to below RA or EE 2 levels, especially in L-5. Mechanical loading to failure of L-6 vert ebrae showed a rank order of vertebral strength of Sham > RA > EE2 > O vx > ABP, although significant differences were not observed between t reatment groups. These data show that ABP suppression of bone formatio n can affect bone quality with long-term treatment. In other tissues, RA had minimal uterine effects, while significantly lowering serum cho lesterol to below EE2-treated levels. Both EE2 and RA rats had signifi cantly lower body weights than the other groups. ABP had no effect on serum lipids, uterine weight or body weight. Therefore, RA appears to have a broader range of desirable effects on bone, body weight, uteri and cholesterol than ABP or EE2 in ovariectomized rats.