Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women

Marini, Herbert; Minutoli, Letteria; Polito, Francesca; Bitto, Alessandra; Altavilla, Domenica; Atteritano, Marco; Gaudio, Agostino; Mazzaferro, S.; Frisina, Alessia; Frisina, N; Lubrano, Carla; Bonaiuto, Michele; D’Anna, Rosario; Cannata, Maria Letizia; Corrado, Francesco; Adamo, Elena Bianca; Wilson, Steven; Squadrito, Francesco

doi:10.7326/0003-4819-146-12-200706190-00005

Cited by 291 publications

(230 citation statements)

References 44 publications

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“…In the present study on female rats with normal estrogen levels, both low and high doses of genistein treatment were observed to induce significant increase in BMD, BMC and bone volume, as well as inducing thicker and larger trabecular bone in the mandibular subchondral bone. These results were consistent with the above-mentioned studies on appendicular bone or vertebrae [17,18,20,[30][31][32][33][34][35][36] , indicating that the effect of genistein on mandibular subchondral bone is similar to that on appendicular bone or vertebrae. Similar to the biphasic effects of estrogen depending on dosage [37] , genistein was also observed to have a biphasic cell proliferative response, stimulation at low concentrations and inhibition at high concentrations [38][39][40] .…”

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentsupporting

confidence: 82%

“…As shown in Figure 6 and [18,20,[30][31][32][33][34][35][36] . Similarly, oral administration of genistein (54 mg·kg -1 ·d -1 ) increased BMD of the spine and hip in osteopenic postmenopausal Caucasian women with an observation period of 24 months [17] . In the present study on female rats with normal estrogen levels, both low and high doses of genistein treatment were observed to induce significant increase in BMD, BMC and bone volume, as well as inducing thicker and larger trabecular bone in the mandibular subchondral bone.…”

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentmentioning

confidence: 99%

“…Previous animal studies have shown that genistein treatment increased bone mineral density (BMD) and improved bone biomechanical performance in ovariectomized (OVX) rodents [12,13] . Clinical studies have also demonstrated that phytoestrogen can effectively increase the BMD of vertebrae and hip bones in postmenopausal women without side effects, which suggested that genistein plays an important role in the regulation of bone formation and bone resorption [14][15][16][17] . phosDose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone www.chinaphar.com Li YQ et al Acta Pharmacologica Sinica npg phatase (ALP) and osteocalcin (OC) are widely used markers for bone formation.…”

Section: Introductionmentioning

confidence: 99%

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Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Xing

Wang

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats. Methods: Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10 -7 or 10 -4 mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using realtime PCR, and ER silencing was performed. Results: At both the low-and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERβ, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERβ silencing abrogated most of the effects of genistein treatment. Conclusion: In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERβ.

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Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentsupporting

confidence: 82%

Section: Effect Of Er Silencing On the Effect Of Genistein Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Xing

Wang

et al. 2011

Acta Pharmacol Sin

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“…The most common side effects observed with soy proteins and isoflavones in the present study were abdominal bloating, pain and constipation. Similar side effects have been reported in an earlier study also (36). These harmless yet unpleasant symptoms are usually short-lived and may represent intolerance to proteins.…”

Section: Soy Proteins Vs Isoflavones In Postmenopausal Womensupporting

confidence: 86%

Effect of soy proteins Vs soy isoflavones on lipid profile in postmenopausal women

Jassi

Jain

Arora

et al. 2010

Indian J Clin Biochem

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Due to increased longevity and awareness, most women seek help of the clinicians for these symptoms. Estrogen therapy has been recommended to postmenopausal women for alleviation of symptoms and long-term benefits (3).However, recent evidence from studies of Women's Health Initiative showed that the combined estrogen and progestin therapy increased risks of coronary heart disease, stroke, pulmonary embolism and breast cancer (4). Recently, estrogen-like compounds from plants like soy proteins provide a new nutritional dimension to the management of short-term as well as long term effects of estrogen deficit (5). Epidemiological data suggest and indicate that only 25% of Japanese women complain of climacteric symptoms compared with 85% North American women and this difference has been attributed to soy protein consumption in Asian countries (6).The beneficial effects of soy protein have been attributed to its active component -the phytoestrogens or the isoflavones INTRODUCTIONMenopause is a normal life transition in a woman's life when reproductive capacity ceases due to loss of ovarian function resulting in a decrease in circulating estrogen levels (1). It is an objective hormonal event associated with subjectively perceived endocrine transition, resulting in various short-term vasomotor (hot flashes, mood swings, depression, nervousness, irritability) and urogenital symptoms (recurrent vaginitis, dysuria etc) and long-term sequelae-osteoporosis, Alzheimer's disease and Coronary Artery disease (CAD) (2).

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“…Nevertheless, genistein has many other important health benefits, such as lowering the incidence of cardiovascular diseases [12], prevention of osteoporosis, and attenuation of postmenopausal problems [13]. Furthermore, it has been reported that genistein decreases body mass and fat tissue, accompanied by a decreased apetite.…”

Section: Biological Effects Of Genisteinmentioning

confidence: 99%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

560

383

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Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genisteinis mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen-and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.

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Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women

Abstract: Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.

Cited by 291 publications

References 44 publications

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone

Effect of soy proteins Vs soy isoflavones on lipid profile in postmenopausal women

Multi-targeted therapy of cancer by genistein

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