A comparative study of the effects of genistein, estradiol and raloxifene on the murine skeletal system.

Abstract

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. The aim of the present study was to compare the effects of genistein, estradiol and raloxifene on the skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg) or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium content, macrometric parameters and mechanical properties were examined. Also the effects of genistein, estradiol and raloxifene (10(-9)-10(-7) M) on the formation of osteoclasts from neonatal mouse bone marrow cells and the activity of osteoblasts isolated from neonatal mouse calvariae were compared. In vivo, estrogen deficiency resulted in the impairment of bone mineralization and bone mechanical properties. Raloxifene but not estradiol or genistein improved bone mineralization. Estradiol fully normalized the bone mechanical properties, whereas genistein augmented the deleterious effect of estrogen-deficiency on bone strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This difference may explain the lack of genistein effect on bone mineralization observed in ovariectomized rats in the in vivo study. Concluding, our experiments demonstrated profound differences between the activities of genistein, estradiol and raloxifene towards the osseous tissue in experimental conditions.

Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H/HeN mice

“…The early losses in bone mass and strength in OVX mice appeared to be transient and may explain that 6-month-old OVX-C3H mice eventually returned to SHAM levels after 6 months. Our results also showed that, as previously reported, raloxifene was able to maintain BMD and to prevent bone loss due to estrogen deficiency [30][31][32]. However, in this study, raloxifene did not prevent uterus atrophy of 3-month-old ovariectomized mice.…”

Effects of multiple daily genistein treatments on delayed alternation and a differential reinforcement of low rates of responding task in middle-aged rats

“…Although serum genistein levels were elevated, uterine horn weights were not increased. This was not unexpected, as several studies using genistein doses similar to, or higher than ours (up to 20 mg/kg/day), also failed to measure a uterotrophic response (Bitto et al, 2009; Fanti et al, 1998; Moller et al, 2010; Sliwinski et al, 2009). This is also not unexpected given that the uterine horn is rich in ERα and genistein binds preferentially to ERβ.…”

Modulation of bone turnover in orchidectomized rats treated with raloxifene and risedronate

“…ALP is considered an osteoblastic marker. It has a positive effect on osteoblast‐induced bone mineralization and contributes to the pool of Pi available for deposition as hydroxyapatite .…”