This is a review article designed to address the effects of soy isoflavones on bone metabolism in postmenopausal women and their place in the prevention and treatment of postmenopausal osteoporosis. Soy isoflavones are natural products that could be used as an alternative to menopausal hormone therapy because they are structurally and functionally related to 17beta-estradiol. In vitro and animal studies have shown that they act in multiple ways to exert their bone-supporting effects. They act on both osteoblasts and osteoclasts through genomic and nongenomic pathways. Epidemiological studies and clinical trials suggest that soy isoflavones have beneficial effects on bone mineral density, bone turnover markers, and bone mechanical strength in postmenopausal women. However, there are conflicting results related to differences in study design, estrogen status of the body, metabolism of isoflavones among individuals, and other dietary factors. The long-term safety of soy isoflavone supplements remains to be demonstrated.
"Isoflavones make up the most common and well-known form of phytoestrogens, and in particular isoflavones (genistein and daidzein) from soy have received considerable attention in the management of postmenopausal bone loss   . Although the relative affinity of all isoflavones to the ER is lower than for estradiol, they can induce conformational changes that result in transcription activation. "
[Show abstract][Hide abstract] ABSTRACT: Objective. To investigate the effect by which daily consumption of a novel red clover (RC) extract influences bone health, inflammatory status, and cardiovascular health in healthy menopausal women. Design. A 12-week randomized, double-blinded, placebo-controlled trial involving 60 menopausal women receiving a daily dose of 150 mL RC extract containing 37.1 mg isoflavones (33.8 mg as aglycones) or placebo. Methods. Bone parameters were changes in bone mineral density (BMD), bone mineral content (BMC), and T-score at the lumbar spine and femoral neck. Bone turnover (CTx) and inflammatory markers were measured in plasma and finally blood pressure (BP) was evaluated. Results. RC extract had positive effect on bone health, and only the women receiving the placebo experienced a decline in BMD (p < 0.01) at the lumbar spine. T-score at the lumbar spine only decreased in the placebo group (p < 0.01). CTx decreased in the RC group with -9.94 (±4.93)%, although not significant. Conclusion. Daily consumption of RC extract over a 12-week period was found to have a beneficial effect on bone health in menopausal women based on BMD and T-score at the lumbar spine and plasma CTx levels. No changes in BP or inflammation markers were found and no side effects were observed.
Evidence-based Complementary and Alternative Medicine 08/2015; 2015(6):689138. DOI:10.1155/2015/689138 · 1.88 Impact Factor
"All the reviewers indicate that further research is needed to better understand the relationship of soy foods to bone health, and that a number of factors are impeding clear interpretation of the results. The two most comprehensive reviews offer differences in study design, type of isoflavone or soy food preparation utilized, estrogen status of the participants, and other dietary factors as key limitations on our understanding of the meaning of the results of this body of work [Poulsen and Kruger, 2008; Atmaca et al. 2008]. An additional important consideration is the bone health endpoints studied. "
[Show abstract][Hide abstract] ABSTRACT: Numerous studies have investigated the relationship between soy foods, soy protein, or isoflavone extracts and markers of bone health and osteoporosis prevention, and have come to conflicting conclusions. Research on dietary patterns, rather than on specific food ingredients or individual foods, may offer an opportunity for better understanding the role of soy foods in bone health. Evidence is reviewed regarding the question of whether soy foods contribute to a dietary pattern in humans that supports and promotes bone health. Soy foods are associated with improved markers of bone health and improved outcomes, especially among Asian women. Although the optimal amounts and types of soy foods needed to support bone health are not yet clear, dietary pattern evidence suggests that regular consumption of soy foods is likely to be useful for optimal bone health as an integral part of a dietary pattern that is built largely from whole plant foods.
Therapeutic advances in musculoskeletal disease 12/2011; 3(6):293-300. DOI:10.1177/1759720X11417749
"Of all the natural alternatives currently under investigation, genistein, an isoflavone abundant in soy, has received most attention. Numerous studies using cultured bone cells, ovariectomized rat models and clinical trials support the conclusion that genistein might provide an alternative to prevent postmenopausal bone loss [Setchell and Lydeking-Olsen, 2003; Ullmann et al., 2005; Atmaca et al., 2008]. In traditional Chinese Medicine, osteoporosis is considered to be a disorder caused by the insufficiency of kidney yang, and the herbs perceived to be able to tonify the kidney yang have been used for more than 1000 years and today are still being used for osteoporosis treatment. "
[Show abstract][Hide abstract] ABSTRACT: There has been a strong interest in searching for natural therapies for osteoporosis. Genistein, an isoflavone abundant in soy, and icariin, a prenylated flavonol glycoside isolated from Epimedium Herb, have both been identified to exert beneficial effects in preventing postmenopausal bone loss. However, the relative potency in osteogenesis between the individual phytoestrogen flavonoids remains unknown. The present study compared ability of genistein and icariin in enhancing differentiation and mineralization of cultured rat calvarial osteoblasts in vitro. Dose-dependent studies in osteoblast differentiation measuring alkaline phosphatase (ALP) activity revealed optimal concentrations of genistein and icarrin for stimulating osteogenesis to be both at 10(-5) M. Time course studies comparing the two compounds both at 10(-5) M demonstrated that icariin treatment always produced higher ALP activity, more and larger areas of CFU-F(ALP) colonies and mineralized nodules, more osteocalcin secretion, and calcium deposition, and a higher level of mRNA expression of osteogenesis-related genes COL1α2, BMP-2, OSX, and RUNX-2. However, they inhibited the proliferation of osteoblasts to a similar degree. In conclusion, although future in vivo studies are required to investigate whether icariin is more efficient in improving bone mass and/or preventing bone loss, our in vitro studies have demonstrated that icariin has a stronger osteogenic activity than genistein. In addition, while the prenyl group on C-8 of icariin could be the active group that takes part in osteoblastic differentiation and explains its greater potency in osteogenesis, mechanisms of action, and reasons for the relative potency of icariin versus genistein need to be further studied.
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