Differential effects of 17β-estradiol and raloxifene on bone and lipid metabolism in rats with chronic kidney disease and estrogen insufficiency

Objective: The aim of this study was to evaluate the effect of 17 beta-estradiol, raloxifene, and 1-alpha,25-dihydroxycholecalciferol or calcitriol on bone and lipid metabolism in chronic kidney disease and estrogen insufficiency. Methods: Six-month-old female Sprague-Dawley rats (n = 48) were ovariectomized and nephrectomized (seven eighths). One week after surgery, the rats were divided into six groups and treated with (1) placebo, (2) 17 beta-estradiol 10 mu g kg(-1) day(-1), (3) raloxifene 1 mg kg(-1) day(-1), (4) calcitriol 10 ng kg(-1) day(-1), (5) 17 beta-estradiol + calcitriol, and (6) raloxifene + calcitriol. A group of untreated animals with chronic kidney disease and normal ovarian function was used as a control group (n = 5). The rats were killed after 8 weeks of treatment. Blood samples were drawn for serum analyses; the right tibia was removed to perform histomorphometric analyses, uteri were used as tissue markers of estrogen replacement, and paraffin-embedded sections of the uterus and the fourth breast were used for histopathologic evaluation. Results: Raloxifene, alone or combined with calcitriol, and 17 beta-estradiol combined with calcitriol significantly diminished total cholesterol level compared with placebo. Qualitative histological and histomorphometric analyses showed that both the single treatments and their combinations were able to increase the trabecular connectivity compared with placebo. The less beneficial results were obtained with 17 beta-estradiol alone, whereas the more beneficial results were obtained with the combined treatments, particularly with raloxifene and calcitriol. Conclusions: In summary, this experimental study demonstrates the advantages of replacing both hormonal deficiencies together. The combination of calcitriol and raloxifene, a selective estrogen receptor modulator, showed a better lipid, uterus, and bone profile.